Androcin 18-1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction.

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18-1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18-1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18-1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18-1 in drug development for glioblastoma treatment.

Smoking and osteoimmunology: Understanding the interplay between bone metabolism and immune homeostasis.

Smoking continues to pose a global threat to morbidity and mortality in populations. The detrimental impact of smoking on health and disease includes bone destruction and immune disruption in various diseases. Osteoimmunology, which explores the communication between bone metabolism and immune homeostasis, aims to reveal the interaction between the osteoimmune systems in disease development. Smoking impairs the differentiation of mesenchymal stem cells and osteoblasts in bone formation while promoting osteoclast differentiation in bone resorption. Furthermore, smoking stimulates the Th17 response to increase inflammatory and osteoclastogenic cytokines that promote the receptor activator of NF-κB ligand (RANKL) signaling in osteoclasts, thus exacerbating bone destruction in periodontitis and rheumatoid arthritis. The pro-inflammatory role of smoking is also evident in delayed bone fracture healing and osteoarthritis development. The osteoimmunological therapies are promising in treating periodontitis and rheumatoid arthritis, but further research is still required to block the smoking-induced aggravation in these diseases. Translational potential: This review summarizes the adverse effect of smoking on mesenchymal stem cells, osteoblasts, and osteoclasts and elucidates the smoking-induced exacerbation of periodontitis, rheumatoid arthritis, bone fracture healing, and osteoarthritis from an osteoimmune perspective. We also propose the therapeutic potential of osteoimmunological therapies for bone destruction aggravated by smoking.

Scalable Synthesis of Si Nanosheets as Stable Anodes for Practical Lithium-Ion Batteries.

Silicon (Si) is regarded as a promising anode material because of its outstanding theoretical capacity, abundant existence, and mature infrastructure, but it suffers from an inherent volume expansion problem. Herein, a facile, scalable, and cost-effective route to produce Si nanosheets (Si NSs) using a low-cost silica fume as the start materials is proposed. After coated with carbon, the as-prepared Si-NSs@C material delivers ultrahigh capability (2770 mAh g-1 at 0.1 C), high initial Coulombic efficiency (87.9%), and long cycling lifespan (100 cycles at 0.5 C with a capacity decay rate of 0.3% per cycle). Beyond proof of concept, this work demonstrates a Si-NSs based pouch cell with an impressive capacity retention of 70.9% after 400 cycles, making it more promising for practical application. Revealed by the theoretical simulation, kinetics analysis, and in situ thickness/pressure detection, it is found that the superior performance of Si-NSs is attributed to the improved diffusivity and reversibility of Li+ ions and low expansion.

Comparison of focusing property and radiation force between autofocusing Bessel beams and focused Gaussian beams.

As abruptly autofocusing beams, autofocusing Bessel beams (ABBs) have been proven to be a class solution for the Helmholtz equation [Opt. Express31, 33228 (2023)10.1364/OE.500383]. In this paper, we use the Fresnel number as the basic parameter and accurately compare the focusing property and radiation force of ABBs versus focused Gaussian beams (FGBs) under the same Fresnel number. Unlike FGBs, ABBs can achieve autofocusing without the need for an initial focusing phase. Our analysis of the beam width defined by power in the bucket, revealed that FGBs exhibit uniform focusing along the straight line, whereas ABBs demonstrate accelerated focusing along the elliptic curve. At the same Fresnel number, FGBs exhibit a higher peak intensity in the focal plane, yet ABBs excel in gradient force on particles. In comparison to FGBs, ABBs exhibit smaller potential well widths, allowing for stable and precise trapping of high refractive index particles at the focal point. While FGBs are considered suitable for laser processing and ablation due to their high peak power density, ABBs possess significant advantages in optical manipulation due to their great gradient force. Furthermore, we conduct a comparative analysis between ABBs and circular Airy beams (CABs). The peak intensity and gradient force exhibited by CABs are slightly lesser than those of ABBs. CABs are appropriate for multi-point trapping along the axis, whereas ABBs are more suited for precise single-point trapping.

FS145, the first flea-derived disintegrin, inhibits angiogenesis through specifically binding integrin αvß3.

FS145, a protein containing a WGD motif, was previously described from the salivary transcriptome of the flea Xenopsylla cheopis. Nevertheless, its biological function and complete structure are still uncertain. Herein, FS145 was confirmed to adopt a common αßß structure with the WGD motif exposed on its surface and located right at the top of a loop composed of residues 72-81. Furthermore, FS145 dose-dependently inhibited the proliferation, adhesion, migration, and tube formation of HUVECs by not only binding to integrin αvß3 but also by subsequently inactivating the FAK/Src/MAPK pathway along with the reduction of the expression of MMP-2, MMP-9, VEGFA, bFGF, Ang2, Tie2, HIF-1α, and FAK. Moreover, FS145 also inhibited aortic vessel sprout and showed strong anti-angiogenic activities as assessed ex vivo, by employing the rat aortic ring assay, chick embryo chorioallantoic membrane, and zebrafish embryo models. Altogether, our results suggest that FS145 suppresses angiogenesis ex vivo and in vitro by blocking integrin αvß3. The current study reveals the first anti-angiogenesis disintegrin with WGD motif from invertebrates and provides a beneficial pharmacological activity to inhibit abnormal angiogenesis.

Construction of an abnormal glycosylation risk model and its application in predicting the prognosis of patients with head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck, and the incidence rate is increasing year by year. Protein post-translational modification, recognized as a pivotal and extensive form of protein modification, has been established to possess a profound association with tumor occurrence and progression. This study employed bioinformatics analysis utilizing transcriptome sequencing data, patient survival data, and clinical data from HNSCC to establish predictive markers of genes associated with glycosylation as prognostic risk markers. The R procedure WGCNA was employed to construct a gene co-expression network using the gene expression profile and clinical characteristics of HNSCC samples. Multiple Cox Proportional Hazards Regression Model (Cox regression) and LASSO analysis were conducted to identify the key genes exhibiting the strongest association with prognosis. A risk score, known as the glycosylation-related genes risk score (GLRS), was subsequently formulated utilizing the aforementioned core genes. This scoring system facilitated the classification of samples into high-risk and low-risk categories, thereby enabling the prediction of patient prognosis. The association between GLRS and clinical variables was examined through both univariate and multivariate Cox regression analysis. The validation of six core genes was accomplished using quantitative real-time polymerase chain reaction (qRT-PCR). The findings demonstrated noteworthy variations in risk scores among subgroups, thereby affirming the efficacy of GLRS in prognosticating patient outcomes. Furthermore, a correlation has been observed between the risk-scoring model and immune infiltration. Moreover, significant disparities exist in the expression levels of diverse immune checkpoints, epithelial-mesenchymal transition genes, and angiogenic factors between the high and low-risk groups.

Agar-Derived Slope-Dominated Carbon Anode with Puparium Like Nano-Morphology for Cost-Effective SIBs.

The microstructure of hard carbons (HCs) including interlayer distance and lateral ab direction and pore size distribution plays a key role in regulating the sodium ions storage performance. Herein, by employing the gelatinous agar as a model precursor, series P-doping HCs (P-HC-x, x = 1, 2, 3, 4) are facilely prepared in batches via controllably regulating its crosslinking state by phytic acid (PA) at a low carbonization temperature of 750 °C, in which PA plays three roles (acid, flame retardant, and P-doping precursor) in promoting the final structure of P-HC-x. Among those, the puparium like P-HC-2 with expanded carbon interlayer distance of 3.91 Å and shortened lateral ab direction of 9.4 nm delivers a high reversible capacity of 394 mAh g-1 at 0.1 A g-1 with high increased slope capacity of 363 mAh g-1 as well as an ultrafast charge-discharge feature and a superlong cycle life. Pairing with the Na3 V2 (PO4 )3 cathode, the fabricated sodium-ion full cells exhibit the 132 mAh g-1 reversible capacity at 0.1 A g-1 , and 86% capacity retention after 100 cycles. This work successfully develops slope-dominated high-performance carbon anode, which will provide new insights for the microstructure regulation and design of other precursor-derivedHCs.

Comparison of Biomarkers of Exposure in a Controlled Study of Smokers Switched from Conventional Cigarettes to Heated Tobacco Products.

The heated tobacco product (HTP) heats rather than burns tobacco to release an aerosol with significantly fewer toxicants than conventional cigarette smoke and has received global attention in recent years. To investigate whether changes in biomarkers of exposure could be detected after switching from conventional cigarettes (CCs) to HTPs, 224 subjects from four cities in China participated in this study. Nine biomarkers containing tobacco-specific nitrosamines (TSNAs), volatile organic compounds (VOCs), and the biomarkers for acrolein and crotonaldehyde were determined by UPLC-MS/MS. The levels of the sum of nine biomarkers in CCs were 5.4 and 5.2 times higher than in an Original-HTP and Menthol-HTP, respectively. Among the nine biomarkers, 3HPMA and 3HMPMA accounted for the highest proportions. Switching from CCs to HTPs is good for both men and women because the changes in each biomarker in urine samples were the same in men and women. Among all the subjects, subjects aged 20-39 years had the greatest reduction in biomarker residues in urine. The findings of the present study provided useful information for the health risk research of HTPs in China.

Pharmacological effects of nicotine salts on dopamine release in the nucleus accumbens.

With the growing number of individuals regularly using e-cigarettes, it has become increasingly important to understand the psychobiological effects of nicotine salts. Nicotine increases the release of dopamine (DA) into the nucleus accumbens (NAc), causing feelings of satisfaction. However, the differences in the DA-increasing effects of different nicotine salts have not been reported. In this study, we used a G protein-coupled receptor-activated DA fluorescent probe (GRABDA1m) and optical fiber photometric recording equipment to monitor the dynamic changes and kinetics of DA release in the NAc of mice exposed to different e-cigarette aerosols, including nicotine, nicotine benzoate, nicotine tartrate, nicotine lactate, nicotine levulinic acid, nicotine malate, and nicotine citrate. The results of this study were as follows: 1) Different types of nicotine salts could increase the release of DA in the NAc. 2) The slopes and half-effective concentrations of the fitted curves were different, suggesting that each nicotine salt had a difference in the efficiency of increasing DA release with concentration changes. 3) The absorption rates of different nicotine salts containing the same original nicotine concentration were significantly different by measuring the blood nicotine content. The effect of nicotine salts on increasing DA was directly proportional to the blood nicotine level. In conclusion, by observing the effects of nicotine salts on DA release in real time in vivo, differences in the pharmacological effects of nicotine salts are revealed to better understand the mechanism underlying the regulatory effects of nicotine salts on the brain.

Hydrogen bonding-induced high-performance stretchable organic semiconductors: a Review.

Semiconductors are widely used in electron devices. With the development of wearable soft-electron devices, conventional inorganic semiconductors are unable to meet the demand because of their high rigidity and high cost. Thus, scientists construct organic semiconductors with high charge mobility, low cost, eco-friendly, stretchable, etc. Due to the excellent performance of stretchable organic semiconductors, they can be widely used as wearable soft-electron devices, such as stretchable organic field-effect transistors (OFETs), organic solar cells (OSCs), etc. Contains flexible display devices and flexible power sources, which are of great interest for applications of future electron devices. However, there are still some challenges that need to be solved. Commonly, enhancing the stretchability may cause the degradation of charge mobility, because of the destruction of the conjugated system. Currently, scientists find that hydrogen bonding can enhance the stretchability of organic semiconductors with high charge mobility. Thus in this review, based on the structure and design strategies of hydrogen bonding, various hydrogen bonding induced stretchable organic semiconductors are introduced. In addition, the applications of the hydrogen bonding induced stretchable organic semiconductors are reviewed. Finally, the stretchable organic semiconductors design concept and potential evolution trends are discussed. The final goal is to outline a theoretical scaffold for the design of high-performance wearable soft-electron devices, which can also further advance the development of stretchable organic semiconductors for applications.

CY-09 Alleviates the Depression-like Behaviors via Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation in Lipopolysaccharide-Induced Mice.

Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, and cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by a variety of stimuli to promote the maturation and secretion of pro-inflammatory cytokines, has been considered to be involved in the pathophysiology of depression. In this study, the putative role of CY-09, a selective and direct inhibitor of NLRP3, was evaluated in the lipopolysaccharide (LPS)-induced mice. The results of the study indicated that CY-09 significantly decreased the levels of NLRP3 in the hippocampus of LPS-induced mice. In addition, CY-09 increased the sucrose preference and shortened the immobility time in LPS-induced mice, suggesting the antidepressant-like effects of inhibiting NLRP3 inflammasome. Biochemical analysis showed that LPS significantly activated the NLRP3/ASC/cytokine signaling pathway and caused microglial activation, while CY-09 prevented the changes. Moreover, CY-09 increased the brain-derived neurotrophic factor (BDNF) only in microglia but not in the whole hippocampus. Meanwhile, CY-09 did not promote neurogenesis in the hippocampus of LPS mice. In conclusion, the results of the study showed that the antidepressant-like effects of NLRP3 inhibitor CY-09 were mediated by alleviating neuroinflammation in microglia and independent of the neurotrophic function in the hippocampus.

Emission and Gas/Particle Partitioning Characteristics of Nicotine in Aerosols for Electronic Cigarettes.

Nicotine is a dependence-producing component in electronic cigarettes. The nicotine release characteristics of electronic cigarettes are closely connected with human exposure and respiratory health. In this paper, a theoretical model was established to study the effects of the compositions of e-liquids and the heating powers of device on the emission and gas/particle partitioning characteristics of nicotine in aerosols at equilibrium. The simulation results of nicotine emissions were compared with the experimental data. The errors between them were within a reasonable range. At a larger heating power level, a higher nicotine yield and a larger vaporization amount of e-liquids could be observed. Under the same heating power condition, a higher vegetable glycerin content in e-liquids could result in a lower nicotine emission. When the heating powers supplied by the device increased, a larger mass fraction of particle-phase nicotine in aerosols at equilibrium would appear. As more propylene glycol was added into e-liquids, a lower mass fraction of gas-phase nicotine would exist in aerosols at equilibrium. The results may provide more information for the industry to set technical standards for electronic cigarettes and for the government department to make regulatory policies.

Progress in quantification of nicotine content and form distribution in electronic cigarette liquids and aerosols.

Each electronic cigarette (e-cigarette) is a battery-powered system which converts electronic cigarette liquids (e-liquids) into the inhalable phase by heating the solution when it is in use. After four generations of development, e-cigarettes tend to be more customized and user-operable. The main components in the e-liquid and the aerosol are vegetable glycerin, propylene glycol, nicotine, organic acid and some flavor ingredients. Among them, nicotine is closely associated with the irritation and physiological satisfaction caused by tobacco products, and it is the core functional substance of e-cigarettes. For this reason, the quantification of nicotine content and nicotine form distribution mainly focuses on the components of the e-liquid and the released aerosol. Up to now, various technologies and methods have been applied in the analysis and research of nicotine content and nicotine form distribution in the e-liquid and its aerosol. GC-MS is often used as the most viable tool for the analysis of volatile organic compounds and can be widely applied in the measurement of nicotine related chemicals; there are a number of quantitation strategies using LC-MS, LC-MS/MS or 1H NMR for the analysis of e-cigarette samples. We also reviewed the four main methods for determining the distribution of nicotine forms, which are pH value derivation, solvent extraction, SPME and NMR methods. These research methods are of great significance to the upgrading and development of e-cigarette products.

Identification of the in vitro antiviral effect of BmNedd2-like caspase in response to Bombyx mori nucleopolyhedrovirus infection.

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens in sericulture, and the underlying antiviral mechanism in silkworm is still unclear. Bombyx mori Nedd2-like caspase (BmNc) has been identified as a candidate antiviral gene from previous transcriptome data, since it is differentially expressed in the midgut of differentially resistant silkworm strains following BmNPV infection. However, the molecular mechanism by which BmNc responds to BmNPV is unknown. In this study, the relationship between BmNc and BmNPV was confirmed by its significantly different expression in different tissues of differentially resistant strains after BmNPV infection. Moreover, the antiviral role of BmNc was confirmed by the significantly higher fluorescence signals of BV-eGFP after knockdown of BmNc in BmN cells, and a reduced signal after overexpression. This was further verified by the capsid gene vp39 expression, DNA copy number, and GP64 protein level in the RNAi and overexpression groups. Furthermore, the antiviral phenomenon of BmNc was found to be associated with apoptosis. In brief, BmNc showed a relatively high expression level in the metamorphosis stages, and the effect of BmNc on BmNPV infection following RNAi and overexpression was eliminated after treatment with the inducer, Silvestrol, and the inhibitor, Z-DEVD-FMK, respectively. Therefore, it is reasonable to conclude that BmNc is involved in anti-BmNPV infection via the mitochondrial apoptosis pathway. The results provide valuable information for elucidating the molecular mechanism of silkworm resistance to BmNPV infection.

A numerical study on capillary-evaporation behavior of porous wick in electronic cigarettes.

A mathematical model based on heat and mass transfer processes in the porous wick of electronic cigarettes was established to describe the atomization of e-liquids according to max liquid temperature, vaporization rate and thermal efficiency in a single puff. Dominant capillary-evaporation effects were defined in the model to account for the effects of electrical power, e-liquid composition and porosity of the wick material on atomization and energy transmission processes. Liquid temperature, vaporization rate, and thermal efficiency were predicted using the mathematical model in 64 groups, varying with electrical power, e-liquid composition and wick porosity. Experimental studies were carried out using a scaled-model test bench to validate the model's prediction. A higher PG/VG ratio in the e-liquid promoted energy transfer for vaporization, and the e-liquid temperature was comparatively reduced at a relatively high power, which was helpful to avoid atomizer overheating. Compared with the other factors, wick porosity affected the thermal efficiency more significantly. The vaporization rate increased with a higher wick porosity in a certain range. The modelling results suggested that a greater wick porosity and a higher PG ratio in e-liquids helped to improve the overall thermal efficiency.

Vaporization characteristics and aerosol optical properties of electronic cigarettes.

The aerosols generated from electronic cigarettes have a significant impact on the human respiratory system. Understanding the vaporization characteristics and aerosol optical properties of electronic cigarettes is important for assessing human exposure to aerosols. An experimental platform was designed and built to simulate the atomization process of electronic cigarette and detect the laser transmissivity of aerosols. The optical properties of single particles and polydispersed particle system for aerosols in the visible wavelength ranges of 400-780 nm were analyzed based on Mie theory. The results show that a higher heating power supplied by coil results in a larger average vaporization rate of e-liquid. Meanwhile, the steady-state transmissivity of the laser beam for aerosols reduces as the heating power increases. Under the same heating power and puffing topography, the total particulate mass (TPM) of aerosols generated by the e-liquid composed of higher vegetable glycerin (VG) content decreases. The scattering efficiency factor of aerosol particle of electronic cigarette increases with an increase in particle size. The volume scattering coefficients of a polydispersed particle system of aerosols decrease as the incident visible wavelengths increase. A higher VG content in e-liquid results in decreased TPM and particle number concentration of aerosols and increased the volume scattering coefficient in the visible wavelength range. It can explain an interesting phenomenon that a lower TPM and a better visual effect brought by the aerosols generated by the e-liquid with a higher VG content could be observed concurrently. The mass indexes (e.g., TPM, average vaporization rate, average mass concentration) and optical indexes (e.g., volume scattering coefficient, laser transmissivity) are suggested to be used for the comprehensive evaluation of relative amounts of aerosols. The results have potential significances for the objective and quantitative assessments of aerosols generated from electronic cigarettes.

Research on the Role of Combined Chemotherapy and Radiotherapy in Patients With N+ Non-Metastatic Metaplastic Breast Carcinoma: A Competing Risk Analysis Model Based on the SEER database, 2000 to 2015.

PURPOSE: Due to the rarity of metaplastic breast carcinoma (MpBC), no randomized trials have investigated the role of combined chemotherapy and radiotherapy (CCRP) in this condition. We aimed to explore and identify the effectiveness of CCRP in patients with regional lymph node metastasis (N+) non-metastatic MpBC. MATERIALS AND METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database. We assessed the effects of CCRP on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) using Kaplan-Meier analysis, competing risk model analysis, and competing risk regression mode analysis. RESULTS: A total of 707 women and 361 death cases were included in the unmatched cohort, of which 76.45% (276/361) were BCSD, and 23.55% (85/361) were non-breast cancer-specific deaths (non-BCSD). Both the ChemT and CCRP groups had better OS (ChemT group: HR: 0.59, 95% CI: 0.45-0.78, P<0.001; CCRP group: HR: 0.31, 95% CI: 0.23-0.41, P<0.001) and BCSS (ChemT group: HR: 0.63, 95% CI: 0.45-0.87, P<0.001; CCRP group: HR: 0.32, 95%CI: 0.22-0.46, P<0.001) than the non-therapy group. Subjects in the CCRP group tended to have significantly lower cumulative BCSD (Gray's test, P=0.001) and non-BCSD (Gray's test, P<0.001) than the non-therapy group or ChemT group. In competing risk regression model analysis, subjects in the CCRP group had a better prognosis in BCSD (HR: 0.710, 95% CI: 0.508-0.993, P=0.045) rather than the ChemT group (HR: 1.081, 95% CI: 0.761-1.535, P=0.660) than the non-therapy group. CONCLUSION: Our study demonstrated that CCRP could significantly decrease the risk of death for both BCSD and non-BCSD and provided a valid therapeutic strategy for patients with N+ non-metastatic MpBC.

Squish: Near-Optimal Compression for Archival of Relational Datasets.

Relational datasets are being generated at an alarmingly rapid rate across organizations and industries. Compressing these datasets could significantly reduce storage and archival costs. Traditional compression algorithms, e.g., gzip, are suboptimal for compressing relational datasets since they ignore the table structure and relationships between attributes. We study compression algorithms that leverage the relational structure to compress datasets to a much greater extent. We develop Squish, a system that uses a combination of Bayesian Networks and Arithmetic Coding to capture multiple kinds of dependencies among attributes and achieve near-entropy compression rate. Squish also supports user-defined attributes: users can instantiate new data types by simply implementing five functions for a new class interface. We prove the asymptotic optimality of our compression algorithm and conduct experiments to show the effectiveness of our system: Squish achieves a reduction of over 50% in storage size relative to systems developed in prior work on a variety of real datasets.

Derivatization followed by gas chromatography-mass spectrometry for quantification of ethyl carbamate in alcoholic beverages.

A sensitive and rapid analytical methodology based on derivatization followed by gas chromatography-mass spectrometry (GC-MS) was developed for the quantitative determination of the toxic contaminant ethyl carbamate (EC, urethane, C(2)H(5)OCONH(2)) in alcoholic samples. EC was extracted using liquid-liquid extraction technique, and then silylated with bis-(trimethylsilyl)trifluoroacetamide, analysed finally by GC-MS. The isopropyl carbamate was used as the internal standard for quantitative analysis of EC in alcoholic samples. In this work, the sample extraction and derivatization reaction conditions were investigated, and the optimal extraction conditions obtained were: pH 9 and solvent of ethyl acetate, and the derivatization conditions were: derivatization reaction temperature of 80°C and time duration of 30 min. With the optimal conditions, the method validations were also studied. In the validation studies, EC exhibited good linearity with a regression coefficient of 0.9999. The limit of detection and limit of quantification were 0.30 and 5.0 µg/kg, respectively. The precision was less than 8.4%. Finally, the proposed technique was successfully applied to the analysis of EC in 35 kinds of alcoholic samples. The experimental results have demonstrated that the proposed technique is a fast, reliable and low-cost method for determination of EC in alcoholic samples.