Application of capsaicin and calcium phosphate-loaded MOF system for tumor therapy involving calcium overload.

Calcium overload therapy refers to the condition of intracellular Ca2+ overload, which causes mitochondrial damage and leads to the uncontrolled release of apoptotic factors into the cytoplasm through the open mitochondrial permeability pore. Based on this, it is playing an increasingly important role in the field of oncology due to its good efficacy and small side effects. However, the regulation of calcium homeostasis by cancer cells themselves, insufficient calcium ions (Ca2+) in tumor sites and low efficiency of calcium entering tumor have limited its efficacy, resulting in unsatisfactory therapeutic effect. Therefore, a novel CAP/BSA@TCP-ZIF-8 nanoparticle drug carrier system was constructed that can provide Ca2+ from exogenous sources for pH-controlled degradation and drug release at the same time. Both in vivo and in vitro experiments have proved that the nanomaterial can activate TRPV1 channels and provide exogenous Ca2+ to cause Ca2+ overload and apoptosis, thus achieving anti-tumor effects.

Polydopamine Nanocarriers with Cascade-Activated Nitric Oxide Release Combined Photothermal Activity for the Therapy of Drug-Resistant Bacterial Infections.

Antibiotic abuse leads to increased bacterial resistance, and the surviving planktonic bacteria aggregate and secrete extracellular polymers to form biofilms. Conventional antibacterial agents find it difficult to penetrate the biofilm, remove the bacteria wrapped in it, and produce an excellent therapeutic effect. In this study, a dual pH- and NIR-responsive nanocomposite (A-Ca@PDA) was developed to remove drug-resistant bacteria through a cascade of catalytic nitric oxide (NO) release and photothermal clearance. NO can melt in the outer package of the biofilm, facilitating the nanocomposites to have better permeability. Thermal therapy further inhibits the growth of planktonic bacteria. The locally generated high temperature and the burst release of NO together aggravate the biofilm collapse and bacterial death after NIR irradiation. The nanocomposites achieved a remarkable photothermal conversion efficiency of 47.5%, thereby exhibiting significant advancements in energy conversion. The nanocomposites exhibited remarkable efficacy in inhibiting multidrug-resistant (MDR) Escherichia coli and MDR Staphylococcus aureus, thus achieving an inhibition rate of >90%. Moreover, these nanocomposites significantly improved the wound-healing process in the MDR S. aureus-infected mice. Thus, this novel nanocomposite offers a novel strategy to combat drug-resistant bacterial infections.

Four-Phonon Enhanced the Thermoelectric Properties of ScSX (X = Cl, Br, and I) Monolayers.

Recently, the FeOCl-type two-dimensional materials have attracted significant attention owing to their versatile applications in fields such as thermoelectricity and photocatalysis. This study aims to systematically investigate the thermoelectric properties of ScSX (X = Cl, Br, and I) monolayers by a combination of the first-principles calculations and the machine-learning interatomic potential approach. These monolayers are indirect semiconductors with band gaps of 3.22 (ScSCl), 3.27 (ScSBr), and 2.87 eV (ScSI), respectively. The lattice thermal conductivity is decreased by 25.72% (20.90%), 44.05% (40.00%), and 30.96% (34.76%) for ScSCl, ScSBr, and ScSI along the x-axis (y-axis) when the four-phonon scattering is introduced, indicating its important role in phonon transport. Anharmonic phonon scattering yields high Grüneisen parameter and scattering rate values, hence causing these low lattice thermal conductivities. Additionally, the large Seebeck coefficients and electrical conductivities of n-type doped ScSX monolayers contribute to their excellent power factors (24.69, 25.66, and 24.99 mW/K2·m for ScSCl, ScSBr and ScSI at 300 K, respectively). Based on the excellent power factor and low thermal conductivity, the maximum values of the figure of merit are calculated to be 2.68, 3.39, and 3.21 for ScSCl, ScSBr, and ScSI monolayers at 700 K, respectively. Our research provides valuable insights into the phonon thermal transport of ScSX monolayers and suggests a promising approach to address high-order anharmonicity.

Integration of cognitive tasks into artificial general intelligence test for large models.

During the evolution of large models, performance evaluation is necessary for assessing their capabilities. However, current model evaluations mainly rely on specific tasks and datasets, lacking a united framework for assessing the multidimensional intelligence of large models. In this perspective, we advocate for a comprehensive framework of cognitive science-inspired artificial general intelligence (AGI) tests, including crystallized, fluid, social, and embodied intelligence. The AGI tests consist of well-designed cognitive tests adopted from human intelligence tests, and then naturally encapsulates into an immersive virtual community. We propose increasing the complexity of AGI testing tasks commensurate with advancements in large models and emphasizing the necessity for the interpretation of test results to avoid false negatives and false positives. We believe that cognitive science-inspired AGI tests will effectively guide the targeted improvement of large models in specific dimensions of intelligence and accelerate the integration of large models into human society.

Ionizable Lipids from Click Reactions for Lipid Nanoparticle Assembling and mRNA Delivery.

Ionizable lipid-containing lipid nanoparticles (LNPs) are regarded as promising nonviral vectors for gene therapy delivery systems. Rationale design of the ionizable lipid structure based on initial screening of ionizable lipid molecule libraries combined with systematic comparison and analysis on the physical chemical parameters related to delivery efficiency greatly accelerated the discovery of novel LNP candidates for delivering various nucleic acid therapeutics like mRNAs (mRNAs). Based on the copper-catalyzed azide-alkyne click reaction, which is highly efficient and biocompatible, we were able to obtain the lipid molecule library containing a common triazole moiety between different lipid tails and various substituents as hydrophilic head groups. Herein, we systematically investigated the change of pKa values of different ionizable lipid molecules with different substituents as head groups in the click-based lipid library, mapping the pKa value change to different steps in the process of the LNP assembly and mRNA delivery. Systematic analyses on the data including the pKa value of the ionized lipids and the encapsulation and delivery efficiency of mRNA in LNPs with these ionized lipids provided the possibility of rational design on the head and tail structure for the triazole containing ionized lipids to realize highly efficient delivery of different mRNAs.

Ionic crosslinking of alginate/carboxymethyl chitosan fluorescent hydrogel for bacterial detection and sterilization.

Herein, a polysaccharide-based fluorescent hydrogel with multi-responsiveness simply implemented by concurrent effects of ionic crosslinking/rehydration processes is presented. Specifically, the alginate and carboxymethyl chitosan are chosen to prepare the interpenetrating polymer matrix while a pair of metal cations has been selectively sequentially integrated to alter hydrogel mechanical and fluorescent properties. Experimental results indicate the hydrogels show tunable fluorescent emission in response to multiple cations and pH conditions, and display a reversible "ON/OFF" fluorescent response to Mn+/ethylenediaminetetraacetic acid. Moreover, this synergistic ionic crosslinking strategy is proved to be highly effective in preparing multifunctional metallohydrogels possessing robust/anisotropic mechanical properties, typical shape memory and cation/pH-responsive fluorescence performance, and a proof-of-application for bacterial detection and sterilization has also been demonstrated. Therefore, we believe this study would provide new insights into multifunctional luminescent hydrogels for advanced biomedical systems.

Deep learning-based speech analysis for Alzheimer's disease detection: a literature review.

BACKGROUND: Alzheimer's disease has become one of the most common neurodegenerative diseases worldwide, which seriously affects the health of the elderly. Early detection and intervention are the most effective prevention methods currently. Compared with traditional detection methods such as traditional scale tests, electroencephalograms, and magnetic resonance imaging, speech analysis is more convenient for automatic large-scale Alzheimer's disease detection and has attracted extensive attention from researchers. In particular, deep learning-based speech analysis and language processing techniques for Alzheimer's disease detection have been studied and achieved impressive results. METHODS: To integrate the latest research progresses, hundreds of relevant papers from ACM, DBLP, IEEE, PubMed, Scopus, Web of Science electronic databases, and other sources were retrieved. We used these keywords for paper search: (Alzheimer OR dementia OR cognitive impairment) AND (speech OR voice OR audio) AND (deep learning OR neural network). CONCLUSIONS: Fifty-two papers were finally retained after screening. We reviewed and presented the speech databases, deep learning methods, and model performances of these studies. In the end, we pointed out the mainstreams and limitations in the current studies and provided a direction for future research.

Research on nonstroke dementia screening and cognitive function prediction model for older people based on brain atrophy characteristics.

BACKGROUND: Brain atrophy is an important feature in dementia and is meaningful to explore a brain atrophy model to predict dementia. Using machine learning algorithm to establish a dementia model and cognitive function model based on brain atrophy characteristics is unstoppable. METHOD: We acquired 157 dementia and 156 normal old people.s clinical information and MRI data, which contains 44 brain atrophy features, including visual scale assessment of brain atrophy and multiple linear measurement indexes and brain atrophy index. Five machine learning models were used to establish prediction models for dementia, general cognition, and subcognitive domains. RESULTS: The extreme Gradient Boosting (XGBoost) model had the best effect in predicting dementia, with a sensitivity of 0.645, a specificity of 0.839, and the area under curve (AUC) of 0.784. In this model, the important brain atrophy features for predicting dementia were temporal horn ratio, cella media index, suprasellar cistern ratio, and the thickness of the corpus callosum genu. CONCLUSION: For nonstroke elderly people, the machine learning model based on clinical head MRI brain atrophy features had good predictive value for dementia, general cognitive impairment, immediate memory impairment, word fluency disorder, executive dysfunction, and visualspatial disorder.

Simple, Skin-Attachable, and Multifunctional Colorimetric Sweat Sensor.

In situ analysis of sweat provides a simple, convenient, cost-effective, and noninvasive approach for the early diagnosis of physical illness in humans and is particularly useful in family care. In this study, a flexible and skin-attachable colorimetric sweat sensor for multiplexed analysis is developed using a simple, cost-effective, and convenient method. The obtained sweat sensor can be used to simultaneously detect glucose, lactate, urea, and pH value in sweat, as well as sweat loss and skin temperature. Only 2.5 µL of sweat is enough for the whole test, and the sweat loss and chemical-sensing results can be read out conveniently by naked eyes or a smartphone. In addition, body temperature can also be detected with an additional electrical circuit. Our sweat sensor provides a new, cost-effective, and convenient approach for in vitro diagnosis of multiple components in sweat, and the easy fabrication and cost-effectiveness make our sensor commercializable in the near future.

The Association between Dietary Protein Intake and the Risk of Pancreatic Cancer: Evidence from 14 Publications.

Many studies have been published to assess the association about dietary protein intake on the risk of pancreatic cancer, but with inconsistent result. This meta-analysis aimed to evaluate whether protein intake could affect the risk of pancreatic cancer. A systematic literature search was performed in PubMed, EMBASE and Web of Science up to October 1, 2019. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effect model. A total of 14 studies (12 case-control studies and two cohort studies) were included. Overall, total protein intake had no significant association on the risk of pancreatic cancer (RR = 1.02, 95%CI= 0.85-1.22, I2=45.7%). Subgroup analyses showed such relationships were almost not influenced by study design and geographic location. Interestingly, when we performed the subgroup analysis by protein type, the opposite association was found in animal protein intake (RR = 1.37, 95%CI= 0.93-2.01) and vegetable protein intake (RR = 0.78, 95%CI= 0.54-1.14), although these two groups were not statistically significant. In conclusion, this meta-analysis indicated that dietary total protein intake may be not associated with the risk of pancreatic cancer. However, protein type may be affecting the result which was found from our research. Therefore, studies with detailed information, especially protein type, are warranted to further confirm these findings.

Correction: Chen et al. The Effect of High-Quality RDX on the Safety and Mechanical Properties of Pressed PBX. Materials 2022, 15, 1185.

Error in Figure [...].

The Effect of High-Quality RDX on the Safety and Mechanical Properties of Pressed PBX.

In order to investigate and compare the effects of RDX crystal quality on the safety and mechanical properties of pressed PBX, different RDX-based PBXs were prepared by a water suspension granulation method. The surface morphology, thermal decomposition properties, impact sensitivity, and mechanical properties of high-quality RDX (H-RDX) and PBX were characterized by SEM, optical microscope, DSC, impact sensitivity tester, and universal material testing machines. The results have shown that the H-RDX crystal has a smoother surface, regular shape, higher density, fewer defects, better thermal stability, and lower impact sensitivity than raw RDX. The activation energy of H-RDX-based PBX is 26.0% higher than that of raw RDX-based PBX, and H50 increased by 2.8 cm, indicating that the application of H-RDX to PBX can effectively improve its thermal stability and reduce the impact sensitivity in the safety performance. However, the compressive strength of pressed H-RDX-based PBX is 36% lower than that of pressed raw RDX-based PBX, showing that H-RDX results in the deterioration of the compressive strength of pressed PBX in mechanical performance. Fortunately, this study found a strategy on how to effectively improve mechanical performance, which is changing the type of binder and increasing the pressing pressure. Under the same pressing conditions, the order of compressive strength of PBX prepared by the three binders is FKM DS2603 > Viton A > PVAc. Moreover, the compressive strength of H-RDX-based PBX with FKM DS2603 can be increased by 33.7% compared with PVAc. When the pressing pressure is 200 MPa, the average compressive strength of H-RDX-based PBX with FKM DS2603 reaches 10.00 MPa, which can basically meet application requirements.

An ab initio study of two-dimensional anisotropic monolayers ScXY (X = S and Se; Y = Cl and Br) for photocatalytic water splitting applications with high carrier mobilities.

Recently, metal oxyhalides have been broadly studied due to their hierarchical structures and promising functionalities. Herein, a thorough study of newly modeled monolayers ScXY (X = S and Se; Y = Cl and Br), a class of derivates of ScOBr monolayers, was conducted using first-principles calculations. We theoretically confirm that these ScXY monolayers are mechanically, dynamically, and thermally stable. Young's modulus and Poisson's ratio calculated for all these ScXY monolayers obviously exhibit anisotropic properties. All these monolayers are indirect-gap semiconductors with bandgaps in the range of 2.35-3.18 eV, and their conduction band minimum (CBM) and valence band maximum (VBM) can straddle the reduction and oxidation potential of water very well, respectively. Particularly, ScSeCl and ScSeBr monolayers have the most propitious bandgaps and band alignments to be used as promising photocatalysts, and the predicted carrier mobility is much larger than that of many other two-dimensional materials. Moreover, the predicted anisotropic carrier mobilities and indirect bandgaps will diminish the recombination and facilitate the migration of photo-generated electron and hole pairs. Moreover, biaxial strain (-5% to 5%) effects on the band alignments and bandgaps are discussed. Our findings highlight that ScSeCl and ScSeBr monolayers are envisioned to act as promising photocatalytic and photoelectronic materials with anisotropic ultrahigh carrier mobilities.

Generation and application of a monoclonal antibody specific for the ORF121 of cyprinid herpesvirus 2.

Cyprinid herpesvirus 2 (CyHV-2) is a viral pathogen worldwide and causing high mortality on goldfish and silver crucian carp (Carassius auratus gibelio). In order to establish a stable and sensitive immunological diagnostic approach, the recombinant ORF121 protein encoded by the CyHV-2 ORF121 gene, was selected as a capture antigen to identify cells and tissues infected with CyHV-2 by immunological methods in this study. Firstly, the open reading frame of CyHV-2 ORF121 was cloned into the PGEX-4T-3 vector and expressed in Escherichia coli. Purified recombinant ORF121 protein was then used as an antigen to prepare monoclonal antibodies, and an efficient hybridoma cell line was selected by dot-blot assay. The resulting mAb-3D9 was applied to detect CyHV-2 in infected caudal fin of Carassius auratus gibelio (GiCF) cells and fish tissues by western blotting, immunofluorescence assays and immunohistological asays. The monoclonal antibody could specifically identify CyHV-2 in infected GiCF cells and the gills, the kidney and the spleen tissues, and it could attenuate CPE by CyHV-2 in vitro, suggesting it can be applied for CyHV-2 detection in the crucian carp and ORF121 may be a candidate vaccine against CyHV-2.

Extended Application of Digital Clock Drawing Test in the Evaluation of Alzheimer's Disease Based on Artificial Intelligence and the Neural Basis.

INTRODUCTION: This study aimed to build the supervised learning model to predict the state of cognitive impairment, Alzheimer's Disease (AD) and cognitive domains including memory, language, action, and visuospatial based on Digital Clock Drawing Test (dCDT) precisely. METHODS: 207 normal controls, 242 Mild Cognitive Impairment (MCI) patients, 87 dementia patients, including 53 AD patients, were selected from Shanghai Tongji Hospital. The electromagnetic tablets were used to collect the trajectory points of dCDT. By combining dynamic process and static results, different types of features were extracted, and the prediction models were built based on the feature selection approaches and machine learning methods. RESULTS AND DISCUSSION: The optimal AUC of cognitive impairment's screening, AD's screening and differentiation are 0.782, 0.919 and 0.818, respectively. In addition, the cognitive state of the domains with the best prediction result based on the features of dCDT is action with the optimal AUC 0.794, while the other three cognitive domains got the prediction results between 0.744-0.755. CONCLUSION: By extracting dCDT features, cognitive impairment and AD patients can be identified early. Through dCDT feature extraction, a prediction model of single cognitive domain damage can be established.

Selecting and Analyzing Speech Features for the Screening of Mild Cognitive Impairment.

The total number of patients with Alzheimer's Disease (AD) has exceeded 10 million in China, while the consultation rate is only 14%. Large-scale early screening of cognitive impairment is necessary, however, the methods of traditional screening are expensive and time-consuming. This study explores a speech-based method for the early screening of cognitive impairment by selecting and analyzing speech features to reduce cost and increase efficiency. Specifically, speech-based early screening models are built based on a feature selection method and a self-built dataset including AD patients, Mild Cognitive Impairment (MCI) patients, and healthy controls. This method achieves 10% relative improvement in F1-score to discriminate MCI patients from healthy controls on our dataset. The prediction F1-score reached 70.73% when discriminating MCI patients from healthy controls based on the feature importance list calculated by the auxiliary model that is built to discriminate AD from Control group. Besides, to further assist the medical screening of MCI, we analyze the correlation between brain atrophy features and speech features including acoustic, lexical and duration features. On the basis of key speech feature selection and correlation analysis, the reference interval of speech features is constructed based on the speech data from Control group to provide a reference for evaluating cognitive impairment.Clinical Relevance - We build a speech-based dataset including AD, MCI and Control groups, and provide a feature selection method to improve the effectiveness of the screening of MCI. Apart from this, the correlation between speech features and brain atrophy features is analyzed. Finally, the reference interval of key speech features is established.

Dopant-Free Hole Transporting Material Based on Nonconjugated Adamantane for High-Performance Perovskite Solar Cells.

A new dopant-free hole transporting material (HTM) 4',4‴,4‴'',4‴''''-(adamantane-1,3,5,7-tetrayl)tetrakis(N,N-bis(4-methoxyphenyl)-[1,1'-biphenyl]-4-amine) (Ad-Ph-OMeTAD) (named FDY for short), which consists of a nonconjugated 3D bulky caged adamantane (Ad) as the core, triphenyl amines as side arms, and phenyl units as a linking bridge, is synthesized and applied in an inverted planar perovskite solar cell (PSC). As a result, the champion device with FDY as HTM yields an impressive power of conversion efficiency (PCE) of 18.69%, with JSC = 22.42 mA cm-2, VOC = 1.05 V, and FF = 79.31% under standard AM 1.5G illumination, which is ca. 20% higher than that of the device based on PEDOT:PSS (only 15.41%). Notably, the stability of PSC based on FDY is much better than that of devices based on PEDOT:PSS, and the corresponding devices retain over 90% of their initial PCEs after storing for 60 days in a nitrogen glove box without any encapsulation. Even when stored in an open air condition with 50-60% relative humidity for 188 h, the retained PCE is still over 81% of its initial one. All these results demonstrate that the new design strategy by combing the bulky and nonconjugated (aliphatic) adamantane unit as the core and triphenyl amines as side arms can efficiently develop highly efficient HTMs for PSCs, which is different from the traditional way based on conjugated backbones, and it may open a new way for scientists to design small-molecule HTMs for PSCs.

Interpenetrating polysaccharide-based hydrogel: A dynamically responsive versatile medium for precisely controlled synthesis of nanometals.

Herein, we reported an interpenetrating polysaccharide-based hydrogel in which carboxymethyl chitosan (CMC) chains were physically dispersed throughout the thermoplastic elastomer gel network has been developed as a versatile platform for precisely controlled synthesis of nanometals. Results indicated the interpenetrated CMC chains could serve as multifunctional fillers for metal ions adsorption and stabilization while the thermally reconfigurable agarose (Agar) gel medium provides three-dimensional semi-solid framework for entrapping and recollecting of the fabricated nanometals. Specifically, the CMC chains were found to strongly coordinate with silver ions as a dynamically responsive metal-biopolymer complex within the bulk gel network as confirmed by the enhanced mechanical properties and regulated shape memory performances. Moreover, by varying CMC concentrations and coupling with a layer-stacking approach, multiple biochemical gradients could be facilely generated for in-situ synthesis of silver nanoparticles, achieving a narrow size of ~7 nm, confined sphere-shape and high concentrations. The monodispersed nanometals are confirmed to be highly active (e.g., considerable catalytic performance), and which could be easily recycled from the bulk gel system via a heating treatment. Thus, this work would provide a generic methodology for the multifunctional metallogel assembly and great possibility for controllable and largescale synthesis of noble nanometals toward biomedical applications.

Electrochemical synthesis of chitosan/silver nanoparticles multilayer hydrogel coating with pH-dependent controlled release capability and antibacterial property.

By coupling in situ electrochemical synthesis of silver nanoparticles (AgNPs) with the pre-deposited chitosan multilayer hydrogel, a novel type of nanocomposite coating was successfully fabricated on the stainless-steel needle electrode. Experimental results demonstrated the chitosan film can serve as a versatile medium for metal salt adsorption and stabilization, and finally electrochemical reduction of loaded silver ions to nanoparticles. The AgNPs were fabricated with a spherical shape and an average size of ∼15 nm endowing considerable antibacterial property to the hydrogel. Furthermore, the unique layered architecture consisted of porous segments and compact boundaries is almost retained, resulting in a pH-dependent and staged release pattern of silver nanoparticles based on acid triggered dissolution of the multi-membrane layer by layer. Thus, considering the mild synthesizing approach, multi-functionalities and relatively low cytotoxicity, this antibacterial hydrogel would show great potential either to be used as a newly coating material for interfacial improvement of implants or as a free-standing film after being peeled off for wound dressing.