Effects of antidiabetic agents on platelet characteristics with implications in Alzheimer's disease: Mendelian randomization and colocalization study.

Background: Observational studies have found a potential link between the use of thiazolidinediones (TZDs) and a lower risk of Alzheimer's disease (AD) development. Platelets were the great source of amyloid-ß (Aß) and involved in the development of AD. This study aimed to assess the correlation between antidiabetic agents and platelet characteristics, hoping to provide a potential mechanism of TZDs neuroprotection in AD. Method: Drug-targeted Mendelian randomization (MR) was performed to systematically illustrate the long-term effects of antidiabetic agents on platelet characteristics. Four antidiabetic agent targets were considered. Positive control analysis for type 2 diabetes (T2D) was conducted to validate the selection of instrumental variables (IVs). Colocalization analysis was used to further strengthen the robustness of the results. Result: Positive control analysis showed an association of four antidiabetic agents with lower risk of T2D, which was consistent with their mechanisms of action and previous evidence from clinical trials. Genetically proxied TZDs were associated with lower platelet count (ß[IRNT] = -0.410 [95 % CI -0.533 to -0.288], P = 5.32E-11) and a lower plateletcrit (ß[IRNT] = -0.344 [95 % CI -0.481 to -0.206], P = 1.04E-6). Colocalization suggested the posterior probability of hypothesis 4 (PPH4) > 0.8, which further strengthened the MR results. Conclusion: Genetically proxied TZDs were causally associated with lower platelet characteristics, particularly platelet count and plateletcrit, providing insight into the involvement of platelet-related pathways in the neuroprotection of TZDs against AD. Future studies are warranted to reveal the underlying molecular mechanism of TZDs' neuroprotective effects through platelet pathways.

In Situ Integration of a Flame Retardant Quasisolid Gel Polymer Electrolyte with a Si-Based Anode for High-Energy Li-Ion Batteries.

Silicon (Si) stands out as a promising high-capacity anode material for high-energy Li-ion batteries. However, a drastic volume change of Si during cycling leads to the electrode structure collapse and interfacial stability degradation. Herein, a multifunctional quasisolid gel polymer electrolyte (QSGPE) is designed, which is synthesized through the in situ polymerization of methylene bis(acrylamide) with silica-nanoresin composed of nanosilica and a trifunctional cross-linker in cells, leading to the creation of a "breathing" three-dimensional elastic Li-ion conducting framework that seamlessly integrates an electrode, a binder, and an electrolyte. The silicon particles within the anode are encapsulated by buffering the QSGPE after cross-linking polymerization, which synergistically interacts with the existing PAA binder to reinforce the electrode structure and stabilize the interface. In addition, the formation of the LiF- and Li3N-rich SEI layer further improves the interfacial property. The QSGPE demonstrates a wide electrochemical window until 5.5 V, good flame retardancy, high ionic conductivity (1.13 × 10-3 S cm-1), and a Li+ transference number of 0.649. The advanced QSGPE and cell design endow both nano- and submicrosized silicon (smSi) anodes with high initial Coulombic efficiencies over 88.0% and impressive cycling stability up to 600 cycles at 1 A g-1. Furthermore, the NCM811//Si cell achieves capacity retention of ca. 82% after 100 cycles at 0.5 A g-1. This work provides an effective strategy for extending the cycling life of the Si anode and constructing an integrated cell structure by in situ polymerization of the quasisolid gel polymer electrolyte.

Study on the material basis of Zhujing pill in treating fundus lesions through component analysis and network pharmacology.

Zhujing pill (ZP) is a famous Chinese herbal formula that has been widely used to treat diabetic retinopathy, macular degeneration, retinitis pigmentosa and other fundus lesions. In this study, the material basis and mechanism of ZP in the treatment of fundus lesions were evaluated via the high-performance liquid chromatography fingerprint, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, network pharmacology and molecular docking. A total of 32 common components were found and 31 components were identified in 15 batches of ZP samples. Moreover, 134 common key targets and 17 putative active components that are connected to fundus lesions were identified. Molecular docking revealed that quercetin, kaempferol, isorhamnetin, 5-O-feruloylquinic acid, plantagoside and 2'-acetylacteoside have the ability to interact with the core targets such as AKT1, TP53, TNF, IL-6 and Jun. Our findings revealed that the therapeutic effects of ZP on fundus lesions are mediated by multiple components, targets and pathways, including at least six active ingredients and 11 targets. The study provides new ideas for further research on the material basis and mechanisms of traditional Chinese medicine prescriptions.

Soft and Damping Thermal Interface Materials with Honeycomb-Board-Mimetic Filler Network for Electronic Heat Dissipation.

High-power-density electronic devices under vibrations call for soft and damping thermal interface materials (TIMs) for efficient heat dissipation. However, integrating low hardness, high damping, and superior heat transfer capability into one TIM is highly challenging. Herein, soft, damping, and thermally conductive TIMs are designed and prepared by constructing a honeycomb-board-mimetic boron nitride nanosheet (BNNS) network in a dynamic polyimine via one-step horizontal centrifugal casting. The unique filler network makes the TIMs perform a high through-plane thermal conductivity (> 7.69 W m-1 K-1) and a uniform heat transfer process. Meanwhile, the hierarchical dynamic bonding of the polyimine endows the TIMs with low compressive strength (2.16 MPa at 20% strain) and excellent damping performance (tan δ > ≈0.3 at 10-2-102 Hz). The resulting TIMs also exhibit electrical insulation and remarkable recycling ability. Compared with the commercial ones, the TIMs provide better heat dissipation (4.1 °C) for a high-power 5G base station and less temperature fluctuation (1.8 °C) for an automotive insulated gate bipolar transistor (IGBT) under vibrations. This rational design offers a viable approach to prepare soft and damping TIMs for effective heat dissipation of high-power-density electronic devices under vibrations.

Acupuncture and related acupoint therapies for smoking cessation: An umbrella review and updated meta-analysis.

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Rapid and sustained resolution in generalized pustular psoriasis with IL-17A inhibitors required high adherence: a 96-week analysis in a real-life setting.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease often requiring long-term therapy. We aimed to evaluate the use of Interleukin (IL)-17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. METHODS: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96-week follow-up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). RESULTS: Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91-1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High-adherence therapy (MPR ≥ 80%) was significantly superior to the low-adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low-adherence group. No new safety signals occurred. CONCLUSION: IL-17A inhibitors led to effective and sustained improvement in GPP patients, and high-adherence therapy had long-term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long-term clinical management.

Short-term effectiveness and potential factors of ustekinumab based on real-world data in Chinese psoriasis patients.

BACKGROUND: As one of the most effective biologic treatments for psoriasis, the short-term effectiveness of ustekinumab has yet to be studied extensively. OBJECTIVE: The purpose of this study was to evaluate the short-term effectiveness and potential factors within four weeks after the first-dose ustekinumab treatment based on real-world data. METHODS: The study enrolled 98 patients with moderate-to-severe psoriasis, given ustekinumab 45 mg at week 0, week 4, and then every 12 weeks. Based on clinical data collected at baseline and week 4, we investigated the short-term effectiveness of ustekinumab after the first dose and potential factors associated with the treatment. For evaluation, we collected demographic information, body data, medical history, laboratory examination results, Psoriasis Area and Severity Index (PASI), body surface area (BSA), and dermatology life quality index (DLQI). Response rates were calculated based on the number of patients that achieved a 75/90/100% reduction in PASI (PASI 75/90/100), and the primary treatment goal was to achieve PASI 75. RESULTS: The response rates for PASI 75/90/100 at week 4 were 30.5%, 18.9%, and 16.8%, respectively. For PASI 75, the response rate was higher in patients without metabolic syndrome (MS) (without MS vs. with MS: 36.9% vs. 5.9%, p = 0.013); the serum triglyceride (TG) level was significantly lower in patients achieving PASI 75 (expressed as mean ± standard deviation, achieved vs. unachieved: 1.82 ± 1.79 vs. 3.59 ± 8.89, p = 0.010). For PASI 100, the response rates were higher in female patients (female vs. male: 26.3% vs. 10.5%, p = 0.044) and patients with a family history of psoriasis (with family history vs. without family history: 44.4% vs. 13.9%, p = 0.042). In addition, the possibility of achieving PASI 75/90/100 went up along with the serum high-density lipoprotein cholesterol (HDL-C) level (expressed as adjusted odds ratio < 95% confidence interval>: PASI 75: 28.484 < 2.035-248.419>, p = 0.011; PASI 90: 28.226 < 2.828-281.729>, p = 0.004; PASI 100: 12.175 < 1.876-79.028>, p = 0.009). CONCLUSION: In this study, nearly one-third of patients achieved PASI 75 after only the first-dose ustekinumab treatment. Sex, family history of psoriasis, MS, serum TG level might affect the short-term effectiveness, and serum HDL-C level may be a potential factor. The possibility of achieving treatment goals (PASI 75/90/100) at week 4 increased along with serum HDL-C levels.

Defining the Minimal Important Change and Meaningful Change Value of the Disease Activity Index for Psoriatic Arthritis: A Chinese Longitudinal Study.

OBJECTIVE: To determine the minimal important change (MIC) and meaningful change value (MCV) of the Disease Activity Index for Psoriatic Arthritis (DAPSA) and the effect size (ES) of DAPSA. METHODS: This was a retrospective cohort study, recruiting 106 patients who agreed to participate in the research from the Department of Dermatology, Xiangya Hospital, between November 1, 2019, and April 1, 2023. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs of the DAPSA. The anchor question assessed whether the patient's well-being had changed since their previous visit, employing a 5-point Likert scale that ranged from "much improved" to "much deteriorated." RESULTS: The overall MIC value was 8.4 (95% CI 0.01-16.75). The MIC improvement was 9.5 (95% CI 0.89-18.14) and MIC deterioration was 1.1 (95% CI -9.81 to 12.05). The overall MCV was 10.5 (95% CI 4.34-16.72). MCV improvement was 11.4 (95% CI 5.95-16.95) and MCV deterioration was 1.1 (95% CI -9.81 to 12.05). The ES was 0.6. CONCLUSION: A change in DAPSA of 8.4 is indicative of an MIC, offering physicians an additional means to contextualize the patient's perception of disease activity during treatment, and a change in DAPSA of 10.5 is likely to be regarded as MCV. These values can enhance the utility of DAPSA in psoriatic arthritis clinical trials.

A New Advanced Approach: Design and Screening of Affinity Peptide Ligands Using Computer Simulation Techniques.

Peptides acquire target affinity based on the combination of residues in their sequences and the conformation formed by their flexible folding, an ability that makes them very attractive biomaterials in therapeutic, diagnostic, and assay fields. With the development of computer technology, computer-aided design and screening of affinity peptides has become a more efficient and faster method. This review summarizes successful cases of computer-aided design and screening of affinity peptide ligands in recent years and lists the computer programs and online servers used in the process. In particular, the characteristics of different design and screening methods are summarized and categorized to help researchers choose between different methods. In addition, experimentally validated sequences are listed, and their applications are described, providing directions for the future development and application of computational peptide screening and design.

Multi-Scale Dispersion Engineering on Biomass-Derived Materials for Ultra-Wideband and Wide-Angle Microwave Absorption.

Efficient electromagnetic waves (EMWs) absorbing materials play a vital role in the electronic era. In traditional research on microwave absorbing (MA) materials, the synergistic modulation of material dispersion and structural dispersion of EMWs by incorporating multi-scale effects has frequently been overlooked, resulting in an untapped absorption potential. In this study, the material dispersion customization method based on biomass carbon is determined by quantitative analysis. The study carries out thermodynamic modulation of carbon skeleton, micro-nano porous engineering, and phosphorus atom donor doping in turn. The dielectric properties are improved step by step. In terms of structural dispersion design, inspired by the theory of antenna reciprocity, a Vivaldi antenna-like absorber is innovatively proposed. With the effective combination of material dispersion and structural dispersion engineering by 3D printing technology, the ultra-wideband absorption of 36.8 GHz and the angular stability of close to 60 ° under dual polarization are successfully realized. The work breaks the deadlock of mutual constraints between wave impedance and attenuation rate through the dispersion modulation methods on multiple scales, unlocking the potential for designing next-generation broadband wide-angle absorbers.

Facile fabrication of Ni, Fe-doped δ-MnO2 derived from Prussian blue analogues as an efficient catalyst for stable Li-CO2 batteries.

Rechargeable Li-CO2 batteries are regarded as an ideal new-generation energy storage system, owing to their high energy density and extraordinary CO2 capture capability. Developing a suitable cathode to improve the electrochemical performance of Li-CO2 batteries has always been a research hotspot. Herein, Ni-Fe-δ-MnO2 nano-flower composites are designed and synthesized by in situ etching a Ni-Fe PBA precursor as the cathode for Li-CO2 batteries. Ni-Fe-δ-MnO2 nanoflowers composed of ultra-thin nanosheets possess considerable surface spaces, which can not only provide abundant catalytic active sites, but also facilitate the nucleation of discharge products and promote the CO2 reduction reaction. On the one hand, the introduction of Ni and Fe elements can improve the electrical conductivity of δ-MnO2. On the other hand, the synergistic catalytic effect between Ni, Fe elements and δ-MnO2 will greatly enhance the cycling performance and reduce the overpotential of Li-CO2 batteries. Consequently, the Li-CO2 battery based on the Ni-Fe-δ-MnO2 cathode shows a high discharge capacity of 8287 mA h g-1 and can stabilize over 100 cycles at a current density of 100 mA g-1. The work offers a promising guideline to design efficient manganese-based catalysts for Li-CO2 batteries.

Electrochemical water softening technology: From fundamental research to practical application.

In recent decades, the environmentally benign electrochemical softening process has been gaining widespread interest as an emerging alternative for water softening. But, in spite of decades of research, the fundamental advances in laboratory involving electrolytic cell design and treatment system development have not led to urgently needed improvements in industrially practicable electrochemical softening technique. In this review, we firstly provide the critical insights into the mechanism of the currently widely used cathode precipitation process and its inherent limitations, which seriously impede its wide implementation in industry. To relieve the above limitations, some cutting-edge electrochemically homogeneous crystallization systems have been developed, the effectiveness of which are also comprehensively summarized. In addition, the pros and cons between cathode precipitation and electrochemically homogeneous crystallization systems are systematically outlined in terms of performance and economic evaluation, potential application area, and electrolytic cell and system complexity. Finally, we discourse upon practical challenges impeding the industrial-scale deployment of electrochemical water softening technique and highlight the integration of strong engineering sense with fundamental research to realize industry-scale deployment. This review will inspire the researchers and engineers to break the bottlenecks in electrochemical water softening technology and harness this technology with the broadened industrial application area.

On-Demand Preparation of Boron Nitride Nanosheets for Functional Nanocomposites.

Boron nitride nanosheets (BNNSs) have garnered significant attention across diverse fields; however, accomplishing on-demand, large-scale, and highly efficient preparation of BNNSs remains a challenge. Here, an on-demand preparation (OdP) method combining high-pressure homogenization and short-time ultrasonication is presented; it enables a highly efficient and controllable preparation of BNNSs from bulk hexagonal boron nitride (h-BN). The homogenization pressure and number of cycles are adjusted, and the production efficiency and yield of BNNSs reach 0.95 g g-1 h-1 and 82.8%, respectively, which significantly exceed those attained by using existing methods. The universality of the OdP method is demonstrated on h-BN raw materials of various bulk sizes from various producers. Furthermore, this method allows the preparation of BNNSs having specific sizes based on the final requirements. Both simulation and experimental results indicate that large BNNSs are particularly suitable for enhancing the thermal conductivity and electrical insulation properties of dielectric polymer nanocomposites. Interestingly, the small BNNS-filled photonic nanocomposite films fabricated via the OdP method exhibit superior daytime radiative cooling properties. Additionally, the OdP method offers the benefits of low energy consumption and reduced greenhouse gas emissions and fossil energy use. These findings underscore the unique advantages of the OdP method over other techniques for a high-efficiency and controllable preparation of large BNNSs.

The impacts of biologic treatment on metabolic profiling in psoriasis.

Psoriasis is an immune-mediated inflammatory disease commonly accompanied by various metabolic disorders. It is widely known that biologics could affect the metabolic status and comorbidities in psoriasis patients, however, the effects of biologics on metabolism in psoriasis patients remain poorly understood. The aim of this study was to elucidate the characteristic changes of metabolic profiling in psoriasis vulgaris (PsV) patients before and after applying biologics. Plasma samples were collected from a retrospective cohort of 43 PsV patients. Non-targeted metabolomics analyses were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic profiles before and after applying adalimumab (ADA) or ixekizumab (IXE) for 4 weeks. Additionally, correlation analyses were conducted to investigate the associations between metabolite expression levels and clinical characteristics. The biologics significantly affected the metabolic profiles of PsV patients especially in glycerophospholipids (GPs). First, phosphatidylcholine (PC), unsaturated lysophosphatidylcholine (LPC), unsaturated lysophosphatidic acid (LPA) and unsaturated lysophosphatidylethanolamine (LPE) were significantly up-regulated, whereas phosphatidylethanolamine (PE), saturated LPC, saturated LPA and saturated LPE were predominantly down-regulated after biologic treatment. What is more, the changes in PE and LPA were mainly observed after applying IXE instead of ADA. Second, we also found GPs including PC, unsaturated LPC, unsaturated LPA and unsaturated LPE were primarily negatively correlated with disease severity, whereas, PE, saturated LPC, saturated LPA and saturated LPE displayed inverse correlations. Biologics could affect GP metabolism and facilitate the transition of metabolic status from a pro-inflammatory to an anti-inflammatory phenotype in PsV patients.

Engineering a Dynamic Solvent-Phobic Liquid Electrolyte Interphase for Long-Life Lithium Metal Batteries.

The heterogeneity, species diversity, and poor mechanical stability of solid electrolyte interphases (SEIs) in conventional carbonate electrolytes result in the irreversible exhaustion of lithium (Li) and electrolytes during cycling, hindering the practical applications of Li metal batteries (LMBs). Herein, this work proposes a solvent-phobic dynamic liquid electrolyte interphase (DLEI) on a Li metal (Li-PFbTHF (perfluoro-butyltetrahydrofuran)) surface that selectively transports salt and induces salt-derived SEI formation. The solvent-phobic DLEI with C-F-rich groups dramatically reduces the side reactions between Li, carbonate solvents, and humid air, forming a LiF/Li3PO4-rich SEI. In situ electrochemical impedance spectroscopy and Ab-initio molecular dynamics demonstrate that DLEI effectively stabilizes the interface between Li metal and the carbonate electrolyte. Specifically, the LiFePO4||Li-PFbTHF cells deliver 80.4% capacity retention after 1000 cycles at 1.0 C, excellent rate capacity (108.2 mAh g-1 at 5.0 C), and 90.2% capacity retention after 550 cycles at 1.0 C in full-cells (negative/positive (N/P) ratio of 8) with high LiFePO4 loadings (15.6 mg cm-2) in carbonate electrolyte. In addition, the 0.55 Ah pouch cell of 252.0 Wh kg-1 delivers stable cycling. Hence, this study provides an effective strategy for controlling salt-derived SEI to improve the cycling performances of carbonate-based LMBs.

Risk factor analysis of refracture in the same cemented vertebra after percutaneous kyphoplasty for Kümmell's disease.

OBJECTIVE: The objective of this study was to evaluate the factors that affect refracture in the same cemented vertebra after percutaneous kyphoplasty (PKP) for Kümmell's disease (KD) and establish a risk prediction score. METHODS: A total of 2932 patients who were treated with PKP for KD between January 2019 and December 2021 were retrospectively reviewed. After inclusion and exclusion criteria were applied, 191 patients were included in the study. According to the criteria for refracture, there were 50 patients in the refracture group and 141 patients in the no-refracture group. Twenty-five factors were analyzed. Patient demographics, medical history, imaging data, surgical data, and postoperative management were reviewed. Multivariate logistic regression modeling was used to identify the independent risk factors for refracture. Receiver operating characteristic (ROC) curve analysis was used to assess and establish a risk score system and further predict the risk of refracture. RESULTS: In this study, 50 (26.2%) patients developed a refracture. Through univariate analysis, bone mineral density (BMD) (p < 0.001), compression rate (p = 0.007), classification (i.e., the stages determined by the compression ratios) (p < 0.001), bone cement volume (p < 0.001), volume fraction (p < 0.001), distribution pattern (p = 0.007), non-PMMA endplate contact (p < 0.001), and anti-osteoporosis therapy (p < 0.001) were found to be significant factors for post-cement vertebral refracture after PKP in patients with KD. Three independent risk factors were found to be significant for refracture: small volume fraction, low BMD, and no anti-osteoporosis therapy. One point was assigned for each factor. The incidence rates of refracture in patients with scores of 0, 1, 2, and 3 were 3.7%, 4.4%, 42.0%, and 100%, respectively. The area under the ROC curve for this risk prediction score was 0.888 (p < 0.001), indicating moderate accuracy. CONCLUSIONS: Volume fraction, BMD, and osteoporosis therapy are the main factors influencing the refracture of the same cemented vertebra in KD. On the basis of these factors, the risk prediction score developed in this paper can be used to forecast the incidence of refracture.

Ultra-Large Scale Stitchless AFM: Advancing Nanoscale Characterization and Manipulation with Zero Stitching Error and High Throughput.

The atomic force microscopy (AFM) is an important tool capable of characterization, measurement, and manipulation at the nanoscale with a vertical resolution of less than 0.1 nm. However, the conventional AFMs' scanning range is around 100 µm, which limits their capability for processing cross-scale samples. In this study, it proposes a novel approach to overcome this limitation with an ultra-large scale stitchless AFM (ULSS-AFM) that allows for the high-throughput characterization of an area of up to 1 × 1 mm2 through a synergistic integration with a compliant nano-manipulator (CNM). Specifically, the compact CNM provides planar motion with nanoscale precision and millimeter range for the sample, while the probe of the ULSS-AFM interacts with the sample. Experimental results show that the proposed ULSS-AFM performs effectively in different scanning ranges under various scanning modes, resolutions, and frequencies. Compared with the conventional AFMs, the approach enables high-throughput characterization of ultra-large scale samples without stitching or bow errors, expanding the scanning area of conventional AFMs by two orders of magnitude. This advancement opens up important avenues for cross-scale scientific research and industrial applications in nano- and microscale.

Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers.

Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high-throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid-phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide-based therapeutics and diagnostic tools for various biomedical challenges.

Non-immobilized GO-SELEX screening of aptamers against cyclosporine A and its application in a AuNPs colorimetric aptasensor.

Cyclosporine A (CsA) is an immunosuppressive drug that is widely used in clinical practice. Due to its narrow therapeutic window and the significant differences between individuals, the therapeutic drug monitoring (TDM) of CsA is required to ensure patient safety. In this study, we screened a novel aptamer, named CsA7, which could specifically recognize CsA, and developed a AuNPs colorimetric aptasensor for the rapid detection of CsA. In the SELEX process, after eight rounds of screening, four aptamer candidate sequences were obtained and subjected to binding affinity and specificity tests. Finally, the CsA7 aptamer (Kd = 41.21 ng mL-1) showed the highest affinity for CsA. Based on CsA7, we also developed a AuNPs colorimetric aptasensor, which had a detection limit of 0.1 ng mL-1 and a quantitative range of 0.1-500 ng mL-1 and showed good selectivity among CsA and its analogs. According to the results, the CsA7 aptamer provides an alternative recognition molecule to the antibody in biosensor applications and shows great potential for the rapid and convenient detection of CsA.

Improving ADMET Prediction Accuracy for Candidate Drugs: Factors to Consider in QSPR Modeling Approaches.

Quantitative Structure-Property Relationship (QSPR) employs mathematical and statistical methods to reveal quantitative correlations between the pharmacokinetics of compounds and their molecular structures, as well as their physical and chemical properties. QSPR models have been widely applied in the prediction of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). However, the accuracy of QSPR models for predicting drug ADMET properties still needs improvement. Therefore, this paper comprehensively reviews the tools employed in various stages of QSPR predictions for drug ADMET. It summarizes commonly used approaches to building QSPR models, systematically analyzing the advantages and limitations of each modeling method to ensure their judicious application. We provide an overview of recent advancements in the application of QSPR models for predicting drug ADMET properties. Furthermore, this review explores the inherent challenges in QSPR modeling while also proposing a range of considerations aimed at enhancing model prediction accuracy. The objective is to enhance the predictive capabilities of QSPR models in the field of drug development and provide valuable reference and guidance for researchers in this domain.