Deoxyshikonin triggers apoptosis in cervical cancer cells through p38 MAPK-mediated caspase activation.

Deoxyshikonin (DSK) is a biological component derived from Lithospermum erythrorhizon. Although DSK possesses potential anticancer activities, whether DSK exerts anticancer effects on cervical cancer cells is incompletely explored. This study was aimed to investigate the anticancer activity of DSK against cervical cancer cells and its molecular mechanisms. Cell viability was evaluated by MTT assay. Level of phosphorylation and protein was determined using Western blot. Involvement of signaling kinases was assessed by specific inhibitors. Our results revealed that DSK reduced viability of human cervical cell in a dose-dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa and SiHa cells. Apoptosis microarray was used to elucidate the involved pathways, and the results showed that DSK dose-dependently diminished cellular inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-8/9/3. Furthermore, we observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK (p38), and only inhibition of p38 diminished the DSK-mediated pro-caspases cleavage. Taken together, our results demonstrate that DSK has anti-cervical cancer effects via the apoptotic cascade elicited by downregulation of IAPs and p38-mediated caspase activation. This suggests that DSK could act as an adjuvant to facilitate cervical cancer management.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Analysis of the impact of temperature on the spectral shift in ultraviolet hyperspectral imaging spectrometers.

The imaging spectrometer's high performance in practical applications may be compromised by environmental factors, particularly temperature variations, posing a challenge to its stability. Temperature fluctuations can induce spectral shift, directly impacting the accuracy of spectral measurements, subsequently influencing the precision of radiometric measurements. To address this issue, this study investigates a dual-channel UV imaging spectrometer. This instrument boasts a wavelength calibration accuracy of 0.01 nm. This paper conducts an in-depth analysis of the various mechanisms through which temperature changes influence the spectral line offset in the imaging spectrometer, integrating actual orbital temperature data to discuss the instrument's temperature load settings. The impact of temperature on spectral shift is examined using finite element analysis and optical design software. Estimations of spectral shift were made based on temperature variations. Simulation results indicated that the maximum deviation of spectral shift is estimated at 0.018 nm under a temperature condition of 16 ± 1°C. Under a more controlled orbital temperature condition (16 ± 0.3°C), the maximum deviation of spectral shift decreased to 0.01 nm. Experimental data revealed that at 16 ± 1°C, the maximum deviation of spectral shift did not exceed 0.01 nm. This effectively corroborates our theoretical analysis. The relationship between temperature and spectral shift offers a crucial theoretical foundation for calibrating spectral measurements and managing the thermal conditions of the instrument.

Constructing B─N─P Bonds in Ultrathin Holey g-C3N4 for Regulating the Local Chemical Environment in Photocatalytic CO2 Reduction to CO.

The lack of intrinsic active sites for photocatalytic CO2 reduction reaction (CO2RR) and fast recombination rate of charge carriers are the main obstacles to achieving high photocatalytic activity. In this work, a novel phosphorus and boron binary-doped graphitic carbon nitride, highly porous material that exhibits powerful photocatalytic CO2 reduction activity, specifically toward selective CO generation, is disclosed. The coexistence of Lewis-acidic and Lewis-basic sites plays a key role in tuning the electronic structure, promoting charge distribution, extending light-harvesting ability, and promoting dissociation of excitons into active carriers. Porosity and dual dopants create local chemical environments that activate the pyridinic nitrogen atom between the phosphorus and boron atoms on the exposed surface, enabling it to function as an active site for CO2RR. The P-N-B triad is found to lower the activation barrier for reduction of CO2 by stabilizing the COOH reaction intermediate and altering the rate-determining step. As a result, CO yield increased to 22.45 µmol g-1 h-1 under visible light irradiation, which is ≈12 times larger than that of pristine graphitic carbon nitride. This study provides insights into the mechanism of charge carrier dynamics and active site determination, contributing to the understanding of the photocatalytic CO2RR mechanism.

Psychobiotics Lactiplantibacillus plantarum JYLP-326: Antidepressant-like effects on CUMS-induced depressed mouse model and alleviation of gut microbiota dysbiosis.

BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.

Size Dependent Specific Heat Capacity of PbSe Nanocrystals.

Specific heat capacity is one of the most fundamental thermodynamic properties of materials. In this work, we measured the specific heat capacity of PbSe nanocrystals with diameters ranging from 5 to 23 nm, and its value increases significantly from 0.2 to 0.6 J g-1 °C-1. We propose a mass assignment model to describe the specific heat capacity of nanocrystals, which divides it into four parts: electron, inner, surface, and ligand. By eliminating the contribution of ligand and electron specific heat capacity, the specific heat capacity of the inorganic core is linearly proportional to its surface-to-volume ratio, showing the size dependence. Based on this linear relationship, surface specific heat capacity accounts for 40-60% of the specific heat capacity of nanocrystals with size decreasing. It can be attributed to the uncoordinated surface atoms, which is evidenced by the appearance of extra surface phonons in Raman spectra and ab initio molecular dynamics (AIMD) simulations.

Reliability of MEMS inertial devices in mechanical and thermal environments: A review.

The reliability of MEMS inertial devices applied in complex environments involves interdisciplinary fields, such as structural mechanics, material mechanics and multi-physics field coupling. Nowadays, MEMS inertial devices are widely used in the fields of automotive industry, consumer electronics, aerospace and missile guidance, and a variety of reliability issues induced by complex environments arise subsequently. Hence, reliability analysis and design of MEMS inertial devices are becoming increasingly significant. Since the reliability issues of MEMS inertial devices are mainly caused by complex mechanical and thermal environments with intricate failure mechanisms, there are fewer reviews of related research in this field. Therefore, this paper provides an extensive review of the research on the reliability of typical failure modes and mechanisms in MEMS inertial devices under high temperature, temperature cycling, vibration, shock, and multi-physical field coupling environments in the last five to six years. It is found that though multiple studies exist examining the reliability of MEMS inertial devices under single stress, there is a dearth of research conducted under composite stress and a lack of systematic investigation. Through analyzing and summarizing the current research progress in reliability design, it is concluded that multi-physical field coupling simulation, theoretical modeling, composite stress experiments, and special test standards are important directions for future reliability research on MEMS inertial devices.

Biomimetic Multimodal Receptors for Comprehensive Artificial Human Somatosensory System.

Electronic skin (e-skin) capable of acquiring environmental and physiological information has attracted interest for healthcare, robotics, and human-machine interaction. However, traditional 2D e-skin only allows for in-plane force sensing, which limits access to comprehensive stimulus feedback due to the lack of out-of-plane signal detection caused by its 3D structure. Here, a dimension-switchable bioinspired receptor is reported to achieve multimodal perception by exploiting film kirigami. It offers the detection of in-plane (pressure and bending) and out-of-plane (force and airflow) signals by dynamically inducing the opening and reclosing of sensing unit. The receptor's hygroscopic and thermoelectric properties enable the sensing of humidity and temperature. Meanwhile, the thermoelectric receptor can differentiate mechanical stimuli from temperature by the voltage. The development enables a wide range of sensory capabilities of traditional e-skin and expands the applications in real life.

Identification and Structural Characterization of Twisted Atomically Thin Bilayer Materials by Deep Learning.

Two-dimensional materials are expected to play an important role in next-generation electronics and optoelectronic devices. Recently, twisted bilayer graphene and transition metal dichalcogenides have attracted significant attention due to their unique physical properties and potential applications. In this study, we describe the use of optical microscopy to collect the color space of chemical vapor deposition (CVD) of molybdenum disulfide (MoS2) and the application of a semantic segmentation convolutional neural network (CNN) to accurately and rapidly identify thicknesses of MoS2 flakes. A second CNN model is trained to provide precise predictions on the twist angle of CVD-grown bilayer flakes. This model harnessed a data set comprising over 10,000 synthetic images, encompassing geometries spanning from hexagonal to triangular shapes. Subsequent validation of the deep learning predictions on twist angles was executed through the second harmonic generation and Raman spectroscopy. Our results introduce a scalable methodology for automated inspection of twisted atomically thin CVD-grown bilayers.

The top 100 highly cited articles on neck pain: A bibliometric analysis.

Objective: Neck pain has emerged as a significant public health concern. This study is to unveil the present state of neck pain research, thereby furnishing invaluable insights for prospective research endeavours and clinical applications. Methods: The study was initiated by searching the Web of Science Core Collection database, focusing on "neck pain". From the amassed results, the top 100 most cited references were imported into CiteSpace and VOSviewer, enabling a rigorous bibliometric analysis. To ensure precision, synonymous terms conveying similar meanings were harmonized. The bibliometric study encompassed countries, research institutions, authors, journals, and keyword analysis. Results: The investigation centered on a curated compilation of 100 articles, disseminated across a diverse array of 36 scholarly journals. These seminal articles originated from 24 distinct countries, reflecting contributions from a wide spectrum of 188 research institutions. Impressively, a collaborative effort involving 385 authors emerged. Noteworthy core research countries included the United States and Australia, with the University of Queensland and the University of Toronto asserting notable influence. Prolific authors such as J. David Cassidy and Pierre Cote garnered attention. Present research endeavours pivot around the incidence of neck pain, the identification of risk factors, the efficacy evaluation of treatment modalities, and a pronounced focus on high-quality randomized controlled trials and systematic reviews. Conclusion: The study shines a light on key research countries, influential institutions, prominent authors, and prevalent trends, effectively contributing to comprehending the knowledge landscape and research dynamics in the field of neck pain.

Interlayer bond polarizability model for interlayer phonons in van der Waals heterostructures.

Raman scattering provides essential insights into phonons, electronic structures and electron-phonon coupling within solids through the intensity of Raman peaks, which cannot be easily quantified using the classical bond polarizability model. The interlayer bond polarizability model (IBPM) had been developed to understand the Raman intensity of layer-breathing modes (LBMs) in two-dimensional materials. However, the quantitative understanding of the LBM intensity of a van der Waals heterostructure (vdWH) remains challenging. Here, in polynary vdWHs comprising twisted multilayer graphene (tMLG), MoS2 and hBN, we observed a series of LBMs, whose intensity is markedly dependent on the excitation energy and twist angle of the tMLG constituent. An improved IBPM is proposed to quantitatively understand the Raman intensity of LBMs in the tMLG-based vdWHs, including the emergence or absence of a specific LBM when the excitation energy is resonant with the electronic states of tMLG or MoS2 constituents. This work underscores the significant potential of the improved IBPM in accurately understanding and predicting the intensity profile of LBM in polynary vdWHs, even for the case of Raman scattering with excitation energies selectively resonant with the electronic states of the corresponding specific constituents.

Quantitative Characterization of Inorganic Pores in Sinian Doushantou Dolomitic Shale Based on FIB-SEM in Western Hubei Province, China.

Unlike traditional shale gas reservoirs, where organic matter pores dominate, inorganic pores are the primary reservoir space in the Sinian (Ediacaran) high-maturity Doushantou dolomitic shale in western Hubei Province, China. The inorganic pore characteristics of Doushantuo shale and its influence on shale gas aggregation were investigated by examining the TOC content, thermal maturity, mineralogical composition, and field-emission scanning electron microscopy (SEM) and focused ion beam scanning electron microscopy (FIB-SEM) of drill cores. The results show that the shale mineral composition in the study area is primarily dolomite and plate-shaped interparticle-intercrystalline pores associated with dolomite are widespread inorganic pores in dolomitic shale. Interparticle-intercrystalline pores account for 75% of the total pores, with a pore size distribution mainly between 50 and 300 nm, as extracted from the 3D pore network model (PNM). Compared with organic pores, interparticle-intercrystalline pores provide greater space for gas storage and have a strong coupling relationship with the hydrocarbon generation and evolution of organic matter. Therefore, the inorganic pores in the Doushantuo Formation play a vital role in the enrichment and accumulation of shale gas. This study aims to establish a scientific basis for understanding the enrichment mechanism of shale gas in Doushantuo dolomitic shale and other inorganic pore-dominated shales in southern China.

Design of a Shock-Protected Structure for MEMS Gyroscopes over a Full Temperature Range.

Impact is the most important factor affecting the reliability of Micro-Electro-Mechanical System (MEMS) gyroscopes, therefore corresponding reliability design is very essential. This paper proposes a shock-protected structure (SPS) capable of withstanding a full temperature range from -40 °C to 80 °C to enhance the shock resistance of MEMS gyroscopes. Firstly, the shock transfer functions of the gyroscope and the SPS are derived using Single Degree-of-Freedom and Two Degree-of-Freedom models. The U-folded beam stiffness and maximum positive stress are deduced to evaluate the shock resistance of the silicon beam. Subsequently, the frequency responses of acceleration of the gyroscope and the SPS are simulated and analyzed in Matlab utilizing the theoretical models. Simulation results demonstrate that when the first-order natural frequency of the SPS is approximately one-fourth of the gyroscope's resonant frequency, the impact protection effect is best, and the SPS does not affect the original performance of the gyroscope. The acceleration peak of the MEMS gyroscope is reduced by approximately 23.5 dB when equipped with the SPS in comparison to its counterpart without the SPS. The anti-shock capability of the gyroscope with the SPS is enhanced by approximately 13 times over the full-temperature range. After the shock tests under the worst case, the gyroscope without the SPS experiences a beam fracture failure, while the performance of the gyroscope with the SPS remains normal, validating the effectiveness of the SPS in improving the shock reliability of MEMS gyroscopes.

Prescription of glucagon-like peptide 1 agonists and risk of subsequent open-angle glaucoma in individuals with type 2 diabetes mellitus.

Background: The glucagon-like peptide 1 receptor agonist (GLP-1RA) is an antidiabetic medication with vascular protection and anti-inflammatory properties. Theoretically, the use of GLP-1RA should inhibit the development of open-angle glaucoma (OAG) as both vascular damage and inflammation are associated with OAG. Therefore, our objective was to investigate the association between the application of GLP-1RA and the subsequent OAG in individuals with type 2 diabetes mellitus (T2DM). Methods: We conducted a retrospective cohort study by using data from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T2DM were divided into those who used GLP-1RA and those who did not, forming the GLP-1RA and control groups. The primary outcome was the occurrence of OAG based on diagnostic codes. Cox proportional hazard regression was employed to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for OAG. Results: 91 patients in the control group developed OAG, and 40 patients in the GLP-1RA group developed OAG. After adjustment for all covariates, the GLP-1RA group exhibited a significantly lower incidence of OAG compared with the control group (aHR: 0.712, 95% CI: 0.533-0.936. P = 0.0025). In the subgroup analyses, the association between GLP-1RA use and OAG incidence was more pronounced in patients with T2DM using GLP-1RA and aged younger than 60 years (P = 0.0438). Conclusion: The prescription of GLP-1RA is associated with a lower incidence of subsequent OAG in individuals with T2DM, and this association was more significant in patients with T2DM under the age of 60 years.

Application of the Five-Step Phase-Shifting Method in Reflective Ghost Imaging for Efficient Phase Reconstruction.

The conventional approach to phase reconstruction in Reflective Ghost Imaging (RGI) typically involves the introduction of three reference screens into the reference path, deeming the Fourier transform step indispensable. However, this method introduces complexity to the system and raises concerns regarding potential errors in phase retrieval. In response to these challenges, we advocate for adopting the Five-Step Phase-Shifting (FSPS) method in the RGI system. This method presents two key advantages over traditional approaches: (1) It streamlines the phase reconstruction process by eliminating the requirement for a Fourier inverse transform. (2) It avoids the need to insert objects into the reference optical path, simplifying the computation of reference optical path intensity and enabling seamless application to Computational Ghost Imaging (CGI), overcoming the constraints of Dual-Arm Ghost Imaging (DAGI). We substantiate the theoretical proposition through numerical simulations involving two intricate objects. Furthermore, our discussion delves into exploring the influence of varying reflective angles on the phase reconstruction performance.

Synergistic Electronic Interaction of Nitrogen Coordinated Fe-Sn Double-Atom Sites: An Efficient Electrocatalyst for Oxygen Reduction Reaction.

Double-atom site catalysts (DASs) have emerged as a recent trend in the oxygen reduction reaction (ORR), thereby modifying the intermediate adsorption energies and increasing the activity. However, the lack of an efficient dual atom site to improve activity and durability has limited these catalysts from widespread application. Herein, the nitrogen-coordinated iron and tin-based DASs (Fe-Sn-N/C) catalyst are synthesized for ORR. This catalyst has a high activity with ORR half-wave potentials (E1/2 ) of 0.92 V in alkaline, which is higher than those of the state-of-the-art Pt/C (E1/2  = 0.83 V), Fe-N/C (E1/2  = 0.83 V), and Sn-N/C (E1/2  = 0.77 V). Scanning electron transmission microscopy analysis confirmed the atomically distributed Fe and Sn sites on the N-doped carbon network. X-ray absorption spectroscopy analysis revealed the charge transfer between Fe and Sn. Both experimental and theoretical results indicate that the Sn with Fe-NC (Fe-Sn-N/C) induces charge redistribution, weakening the binding strength of oxygenated intermediates and leading to improved ORR activity. This study provides the synergistic effects of DASs catalysts and addresses the impacts of P-block elements on d-block transition metals in ORR.

Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy.

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC.

Expression of a recombinant protein by an acetic acid bacterial host.

We evaluated the suitability of Komagataeibacter europaeus, a vinegar production organism adept at synthetic media growth, as a host for heterologous gene expression. Cryptic plasmids (pGE1 and pGE2 derivatives) from K. europaeus strain KGMA0119 were employed as vectors for heterologous gene expression. The focus was placed on the groES promoter as a potential inducible switch. The groES promoter was fused with the EGFP gene and introduced into a pGE1 derivative to assess its suitability. Ethanol, acetic acid, and heat stresses were examined under various conditions for induction. EGFP transcription surged 600-fold when late logarithmic phase K. europaeus cells, cultured at 30 °C, endured heat stress at 40 °C, coupled with 20% acetic acid and 30% ethanol stress after an additional 6-hour cultivation. This robust induction system was then applied to express two proteins, Tth pol from the thermophilic bacterium Thermus thermophilus strain M1 and UPV230, a restriction enzyme from the acid-tolerant microorganism Ureaplasma parvum, known to cause vaginal infections and miscarriages. Both Tth pol and UPV230 were successfully expressed in K. europaeus cells and purified. The recovery of Tth pol from K. europaeus cells (480 µg protein per liter culture) was approximately half that from E. coli (960 µg protein per liter culture). In contrast, UPV230 recovery from K. europaeus cells (640 µg protein per liter culture) was nearly 10 times higher than that from Escherichia coli (66 µg protein per liter). The data highlights the potential of acetic acid bacteria as a host for producing acidophilic proteins. The shift in recognition from a 6-base sequence to a 4-base sequence of UPV230 was observed, accompanied by a change in structure as the pH transitioned from acidic pH to near-neutral pH.

Phase Retrieval Based on Shaped Incoherent Sources.

Current ghost imaging phase reconstruction schemes require either complex optical systems, iterative algorithms, Fourier transform steps, or entangled photon pairs. These factors may increase the difficulty of system design, lead to phase retrieval errors, or result in excessive time consumption. To tackle this challenge, we propose a five-step phase-shifting method that eliminates the need for complex optical systems, Fourier transform steps, entangled photon pairs, or iterative algorithms. Using five specifically designed incoherent sources, we can generate five distinct ghost imaging patterns. Subsequently, the phase information of the object can be calculated from these five speckle patterns. Additionally, we offer a detailed theoretical explanation for choosing the five-step phase-shifting method over the more commonly used three-step or four-step phase-shifting methods. We demonstrate the applicability of this theoretical proposal through numerical simulations involving two types of complicated objects. The results illustrate that the phase information of the complex object can be successfully and quantitatively reconstructed.