Arntl-induced upregulation of DUSP1 inhibits tumor progression in esophageal squamous cell carcinoma by inactivating ERK signaling.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a primary histological type of esophageal carcinoma with high morbidity. Aryl hydrocarbon receptor nuclear translocator-like (ARNTL) is a circadian clock gene associated with the progression of multiple tumors. However, its roles and mechanisms in ESCC remain unknown. METHODS: ARNTL expression was analyzed using TCGA database and detected using qRT-PCR, and ARNTL-related pathways were analyzed through GSEA. Cell functional behaviors were assessed in vitro by measuring cell viability, proliferation, and apoptosis. Cell growth in the murine model was investigated through xenograft model and immunofluorescence assays of PCNA and Ki67. The downstream targets of ARNTL were analyzed through sequencing and identified via luciferase report, ChIP, and RNA pull-down analyses. Dual-specificity protein phosphatase-1 (DUSP1) expression was analyzed using GEO datasets and measured using qRT-PCR and western blotting. Protein expression was examined via western blotting. RESULTS: ARNTL expression was decreased in esophageal carcinoma and associated with histological types, and elevated expression of ARNTL repressed ESCC cell viability and proliferation and facilitated cell apoptosis. ARNTL upregulation reduced tumor cell growth in murine models and decreased PCNA and Ki67 levels. Furthermore, DUSP1 was downregulated upon ARNTL silencing in ESCC. ARNTL could bind and positively regulate DUSP1 transcription. Additionally, DUSP1 silencing reversed the influences of ARNTL upregulation on cell viability, proliferation, and apoptosis in ESCC cells. ARNTL attenuated the activation of the ERK signaling by decreasing ERK phosphorylation through upregulation of DUSP1. CONCLUSION: ARNTL hinders cell growth and contributes to cell apoptosis by inactivating ERK signaling through transcriptional upregulation of DUSP1 in ESCC.

• ARNTL is differentially expressed in ESCC and associated with cell apoptosis.• ARNTL augments cell apoptosis.• ARNTL increases DUSP1 transcription.• ARNTL inhibits activation of the ERK signaling by upregulating DUSP1.• DUSP1 silencing reverses the effects of ARNTL in esophageal squamous cell carcinoma.

Cutting-edge microneedle innovations: Transforming the landscape of cardiovascular and metabolic disease management.

Cardiovascular diseases (CVDs) and metabolic disorders (MDs) have surfaced as formidable challenges to global health, significantly imperiling human well-being. Recently, microneedles (MNs) have garnered substantial interest within the realms of CVD and MD research. Offering a departure from conventional diagnostic and therapeutic methodologies, MNs present a non-invasive, safe, and user-friendly modality for both monitoring and treatment, thereby marking substantial strides and attaining pivotal achievements in this avant-garde domain, while also unfurling promising avenues for future inquiry. This thorough review encapsulates the latest developments in employing MNs for both the surveillance and management of CVDs and MDs. Initially, it succinctly outlines the foundational principles and approaches of MNs in disease surveillance and therapy. Subsequently, it delves into the pioneering utilizations of MNs in the surveillance and management of CVDs and MDs. Ultimately, this discourse synthesizes and concludes the primary findings of this investigation, additionally prognosticating on the trajectory of MN technology.

[Preparation and performance evaluation of fast dissolving polymer microneedles piggybacked with sitagliptin].

The dramatic rise in the number of obese/overweight people is a global public health challenge that urgently requires novel and effective therapies. In this study, we designed a fast dissolving polymer microneedle array patch (SGN-PVP/PVA-MN) with sitagliptin as a model drug for treating obesity, focusing on the preparation process of the patch. We then characterized the morphology and dimensions of SGN-PVP/PVA-MN. Furthermore, we delved into the mechanical properties, solubility, skin-puncturing capability, and transdermal drug diffusion and release kinetics of SGN-PVP/PVA-MN. The results demonstrated that SGN-PVP/PVA-MN exhibited favorable morphology and mechanical properties, effectively penetrating the stratum corneum and creating microchannels for rapid transdermal drug diffusion. The in vitro transdermal diffusion assays revealed the release of 64.5% of the drug within 2 min and 95.7% within 10 min. With rapid dissolution and high drug diffusion efficiency, SGN-PVP/PVA-MN is poised to serve as an effective and safe treatment option for the individuals with obesity.

The effect of budesonide-formoterol powder inhalation on cough and lung function following thoracoscopic pulmonary surgery: a retrospective cohort study.

OBJECTIVES: To explore whether portable budesonide-formoterol powder inhalation can ameliorate cough symptoms and improve pulmonary function recovery in patients who underwent thoracoscopic lung surgery. METHODS: Clinical data of patients who underwent thoracoscopic pulmonary resection at Henan Provincial People's Hospital between December 2022 and May 2023 were extracted. To evaluate the impact of continuous post-operative use of portable budesonide-formoterol powder inhalation, patients were divided into two groups: the control group and the case group. Next, we compared the Leicester cough score and pulmonary function indexes of the patients before surgery, one month and six month after the operation. RESULTS: A total of 188 cases were included, and the baseline demographic characteristics of both groups were well-balanced. The internal consistency of the LCQ-MC scale, as indicated by Cronbach's α coefficients, were all greater than 0.8, and there was no significant difference in LCQ-MC scores between the two groups before the operation (Z=-1.173, P=0.241). Postoperatively, the LCQ-MC score in the case group was significantly higher than that in the control group (18.66 vs. 16.79, P<0.01), with a notable statistically significant difference in the reduction of LCQ-MC scores between the two groups (1.32 vs. 3.30, P<0.01). Analysis of lung function revealed that patients in the case group exhibited significant improvements in FEV1/FVC, FVC, FEV1, PEF, MMEF75/25, MVV, DLCO and the RV/TLC indexes compared to the control group (P<0.01). CONCLUSIONS: Portable budesonide-formoterol powder inhalation can alleviate cough symptoms and promote pulmonary function recovery in patients following thoracoscopic lung surgery.

Long-term survival outcomes of esophagectomy with off-pump CABG versus esophagectomy alone.

BACKGROUND: This study aimed to evaluate the long-term survival outcomes of esophagectomy with off-pump coronary artery bypass grafting (OPCABG) vs. esophagectomy alone. METHODS: A total of 1798 patients who received esophagectomy between January 2010 and February 2020 were included and divided into the 38 patients who underwent OPCABG followed by esophagectomy (OP + ES group) and 1760 patients had only esophagectomy (ES group). Propensity score matching (PSM) and Cox multivariable analyses were performed to compare postoperative complications, disease-free survival (DFS), and overall survival (OS) between the two groups. RESULTS: There were 37 patients in the OP + ES group matched with 74 in the ES group. The matched OP + ES group had higher total postoperative complications than the ES group, especially more pulmonary infections (P = 0.001) and arrhythmias (P = 0.018), but no other postoperative complications were the difference. The DFS was similar and the OS was a significant difference between the matching 2 groups (log-rank, P = 0.132 and 0.04, respectively). Although pT 3/4 stage, pN (+), and tumor length > 3.0 cm were independently associated with worse OS and DFS in multivariable analysis, CAD and EF < 55% were also found to be a predictive factor for OS and DFS in univariate analysis. CONCLUSION: OPCABG followed by esophagectomy for esophageal cancer associated with coronary artery disease has equivalent DFS and recurrence pattern to esophagectomy for esophageal cancer alone, but with a disadvantage in OS.

Enhancing Brain-Computer Interface Performance by Incorporating Brain-to-Brain Coupling.

Human cooperation relies on key features of social interaction in order to reach desirable outcomes. Similarly, human-robot interaction may benefit from integration with human-human interaction factors. In this paper, we aim to investigate brain-to-brain coupling during motor imagery (MI)-based brain-computer interface (BCI) training using eye-contact and hand-touch interaction. Twelve pairs of friends (experimental group) and 10 pairs of strangers (control group) were recruited for MI-based BCI tests concurrent with electroencephalography (EEG) hyperscanning. Event-related desynchronization (ERD) was estimated to measure cortical activation, and interbrain functional connectivity was assessed using multilevel statistical analysis. Furthermore, we compared BCI classification performance under different social interaction conditions. In the experimental group, greater ERD was found around the contralateral sensorimotor cortex under social interaction conditions compared with MI without any social interaction. Notably, EEG channels with decreased power were mainly distributed around the frontal, central, and occipital regions. A significant increase in interbrain coupling was also found under social interaction conditions. BCI decoding accuracies were significantly improved in the eye contact condition and eye and hand contact condition compared with the no-interaction condition. However, for the strangers' group, no positive effects were observed in comparisons of cortical activations between interaction and no-interaction conditions. These findings indicate that social interaction can improve the neural synchronization between familiar partners with enhanced brain activations and brain-to-brain coupling. This study may provide a novel method for enhancing MI-based BCI performance in conjunction with neural synchronization between users.

Explainable Deep-Learning Prediction for Brain-Computer Interfaces Supported Lower Extremity Motor Gains Based on Multistate Fusion.

Predicting the potential for recovery of motor function in stroke patients who undergo specific rehabilitation treatments is an important and major challenge. Recently, electroencephalography (EEG) has shown potential in helping to determine the relationship between cortical neural activity and motor recovery. EEG recorded in different states could more accurately predict motor recovery than single-state recordings. Here, we design a multi-state (combining eyes closed, EC, and eyes open, EO) fusion neural network for predicting the motor recovery of patients with stroke after EEG-brain-computer-interface (BCI) rehabilitation training and use an explainable deep learning method to identify the most important features of EEG power spectral density and functional connectivity contributing to prediction. The prediction accuracy of the multi-states fusion network was 82%, significantly improved compared with a single-state model. The neural network explanation result demonstrated the important region and frequency oscillation bands. Specifically, in those two states, power spectral density and functional connectivity were shown as the regions and bands related to motor recovery in frontal, central, and occipital. Moreover, the motor recovery relation in bands, the power spectrum density shows the bands at delta and alpha bands. The functional connectivity shows the delta, theta, and alpha bands in the EC state; delta, theta, and beta mid at the EO state are related to motor recovery. Multi-state fusion neural networks, which combine multiple states of EEG signals into a single network, can increase the accuracy of predicting motor recovery after BCI training, and reveal the underlying mechanisms of motor recovery in brain activity.

[Preparation and evaluation of chitosan-based light source-loaded soluble microneedles].

The combination of photodynamic therapy and drug delivery microneedle (MN) provides a safe and effective way to treat tumors. In this paper, we designed a controlled and sustained-release drug-loaded microneedle patch (LED-losartan-HEMA/CS-MN, LLH-CSMN) based on chitosan loaded with high-energy photons, investigated its preparation process, and characterized the morphology and size of the microneedle array with losartan as the model drug. The mechanical properties of LLH-CSMN, skin puncture properties, slow release properties and the photothermal properties of high energy photons under long-term operation were investigated. The experimental results showed that the chitosan-based microneedle patch loaded with high-energy photons can effectively open channels on the skin surface for drug delivery and photodynamic therapy. At the same time, the in vitro percutaneous diffusion experiment showed that the microneedles prepared with losartan as the model drug released about 30% of the drug within 1 h, about 60% of the drug in total within 1 d, followed by slow release, and finally released 93% of the drug after 6 d. LLH-CSMN has controllable slow-release characteristics and good long-term photoassisted therapy effect. It provides a new safe and effective way for tumor treatment.

Health risk assessment of drinking groundwater in rural areas of Ru village and surrounding areas in Wutai County, China.

Nitrate pollution in groundwater is a global environmental problem that poses risks to human health. We investigate the health risks of nitrate in rural drinking groundwater in Rucun Township and surrounding areas of Wutai County, and provide a basis for healthy drinking water. By using statistical analysis software (SPSS19) and hydrogeochemical analysis software (AqQA), a qualitative and quantitative evaluation of nitrate health risks was conducted among populations of different ages and genders through water sample collection, chemical analysis, and construction of a human health risk model (HHRA). Through research, it was found that the average concentration of nitrate in the study area is 43.99 mg/L. Groundwater is severely polluted by NO3-, and nitrate pollution areas are mainly concentrated in the main human activity areas, especially in the main agricultural production areas. The Quaternary loess layer, as a permeable layer, cannot prevent groundwater from being polluted by NO3-. Through evaluation, it is believed that there is a health risk of nitrate pollution in rural drinking groundwater in Rucun Township and surrounding areas. Health risk level: infants>children>adult females>adult males. The discovery and evaluation results can provide a basis for the prevention and control of nitrate pollution in groundwater.

Multiscale Canonical Coherence for Functional Corticomuscular Coupling Analysis.

Functional corticomuscular coupling (FCMC) probes multi-level information communication in the sensorimotor system. The canonical Coherence (caCOH) method has been leveraged to measure the FCMC between two multivariate signals within the single scale. In this paper, we propose the concept of multiscale canonical Coherence (MS-caCOH) to disentangle complex multi-layer information and extract coupling features in multivariate spaces from multiple scales. Then, we verified the reliability and effectiveness of MS-caCOH on two types of data sets, i.e., a synthetic multivariate data set and a real-world multivariate data set. Our simulation results showed that compared with caCOH, MS-caCOH enhanced coupling detection and achieved lower pattern recovery errors at multiple frequency scales. Further analysis on experimental data demonstrated that the proposed MS-caCOH method could also capture detailed multiscale spatial-frequency characteristics. This study leverages the multiscale analysis framework and multivariate method to give a new insight into corticomuscular coupling analysis.

Spatiotemporal evolution of dissolved organic matter (DOM) and its response to environmental factors and human activities.

The South-to-North Water Diversion East Project (SNWDP-E) is an effective way to realize the optimal allocation of water resources in China. The North Dasha River (NDR) is the reverse recharge section that receives water from the Yufu River to the Wohushan Reservoir transfer project line in the SNWDP. However, the dissolved organic matter (DOM) evolution mechanism of seasonal water transfer projects on tributary waters has not been fully elucidated. In this paper, the NDR is the main object, and the changes in the composition and distribution of spectral characteristics during the winter water transfer period (WT) as well as during the summer non-water transfer period (NWT) are investigated by parallel factor analysis (PARAFAC). The results showed that the water connectivity caused by water transfer reduces the environmental heterogeneity of waters in the basin, as evidenced by the ammonia nitrogen (NH4+-N) and total phosphorus (TP) in the water body were significantly lower (p<0.05, p<0.01) during the water transfer period than the non-water transfer period. In addition, the fluorescence intensity of DOM was significantly lower in the WT than the NWT (p<0.05) and was mainly composed of humic substances generated from endogenous sources with high stability. While the NWT was disturbed by anthropogenic activities leading to significant differences in DOM composition in different functional areas. Based on the redundancy analysis (RDA) and multiple regression analysis, it was found that the evolution of the protein-like components is dominated by chemical oxygen demand (COD) and NH4+-N factors during the WT. While the NWT is mainly dominated by total nitrogen (TN) and TP factors for the evolution of the humic-like components. This study helps to elucidate the impact of water transfer projects on the trunk basin and contribute to the regulation and management of inter-basin water transfer projects.

Treatment of atrazine-containing wastewater by algae-bacteria consortia: Signal transmission and metabolic mechanism.

Atrazine is a toxic endocrine disruptor. Biological treatment methods are considered to be effective. In the present study, a modified version of the algae-bacteria consortia (ABC) was established and a control was simultaneously set up to investigate the synergistic relationship between bacteria and algae and the mechanism by which atrazine is metabolized by those microorganisms. The total nitrogen (TN) removal efficiency of the ABC reached 89.24% and the atrazine concentration was reduced to below the level recommended by the Environment Protection Agency (EPA) regulatory standards within 25 days. The protein signal released from the extracellular polymeric substances (EPS) secreted by the microorganisms triggered the resistance mechanism of the algae, and the conversion of humic acid to fulvic acid and electron transfer constituted the synergistic mechanism between the bacteria and algae. The mechanism by which atrazine is metabolized by the ABC mainly consists of hydrogen bonding, H-pi interactions, and cation exchange with atzA for hydrolysis, followed by a reaction with atzC for decomposition to non-toxic cyanuric acid. Proteobacteria was the dominant phylum for bacterial community evolution under atrazine stress, and the analysis revealed that the removal of atrazine within the ABC was mainly dependent on the proportion of Proteobacteria and the expression of degradation genes (p < 0.01). EPS played a major role in the removal of atrazine within the single bacteria group (p < 0.01).

Enhancement of EEG-EMG coupling detection using corticomuscular coherence with spatial-temporal optimization.

Objective. Corticomuscular coherence (CMC) is widely used to detect and quantify the coupling between motor cortex and effector muscles. It is promisingly used in human-machine interaction (HMI) supported rehabilitation training to promote the closed-loop motor control for stroke patients. However, suffering from weak coherence features and low accuracy in contingent neurofeedback, its application to HMI rehabilitation robots is currently limited. In this paper, we propose the concept of spatial-temporal CMC (STCMC), which is the coherence by refining CMC with delay compensation and spatial optimization.Approach. The proposed STCMC method measures the coherence between electroencephalogram (EEG) and electromyogram (EMG) in the multivariate spaces. Specifically, we combined delay compensation and spatial optimization to maximize the absolute value of the coherence. Then, we tested the reliability and effectiveness of STCMC on neurophysiological data of force tracking tasks.Main results. Compared with CMC, STCMC not only enhanced the coherence significantly between brain and muscle signals, but also produced higher classification accuracy. Further analysis showed that temporal and spatial parameters estimated by the STCMC reflected more detailed brain topographical patterns, which emphasized the different roles between the contralateral and ipsilateral hemisphere.Significance. This study integrates delay compensation and spatial optimization to give a new perspective for corticomuscular coupling analysis. It is also feasible to design robotic neurorehabilitation paradigms by the proposed method.

Ultrasonic-Assisted Method for the Preparation of Carbon Nanotube-Graphene/Polydimethylsiloxane Composites with Integrated Thermal Conductivity, Electromagnetic Interference Shielding, and Mechanical Performances.

Due to the rapid development of the miniaturization and portability of electronic devices, the demand for polymer composites with high thermal conductivity and mechanical flexibility has significantly increased. A carbon nanotube (CNT)-graphene (Gr)/polydimethylsiloxane (PDMS) composite with excellent thermal conductivity and mechanical flexibility is prepared by ultrasonic-assisted forced infiltration (UAFI). When the mass ratio of CNT and Gr reaches 3:1, the thermal conductivity of the CNT-Gr(3:1)/PDMS composite is 4.641 W/(m·K), which is 1619% higher than that of a pure PDMS matrix. In addition, the CNT-Gr(3:1)/PDMS composite also has excellent mechanical properties. The tensile strength and elongation at break of CNT-Gr(3:1)/PDMS composites are 3.29 MPa and 29.40%, respectively. The CNT-Gr/PDMS composite also shows good performance in terms of electromagnetic shielding and thermal stability. The PDMS composites have great potential in the thermal management of electronic devices.

[Preparation and performance evaluation of controlled-release chitosan-based microneedles].

In clinical application, a microneedle system that continuously delivers drugs is of great value for the delivery of some vaccines and hormone drugs. In this study, a controlled-release chitosan-based microneedle array (PVA/CS-MN) was designed, combining microneedle patches with drugs for controlled-release of drugs. Here we report the optimization of the preparation process of PVA/CS-MN. The appearance, morphology, mechanical properties, dissolution and swelling properties, and in vitro penetration properties of the MN arrays were characterized. The PVA/CS-MN prepared by the optimal process showed good morphology and mechanical properties. PVA/CS-MN can smoothly open microchannels on the skin and achieve controllable dissolution and swelling functions. Ascorbic acid (l-ascorbic acid) was used as a model drug to prepare a Vc-PVA/CS-MN. In vitro transdermal diffusion experiments showed that the Vc-PVA/CS-MN released about 57% of the drug within 1 h. About 66.7% of the drug was slowly released within 12 h, and a total of 92% of the drug was released after 7 days. The controllable sustained-release properties and excellent drug delivery efficiency of PVA/CS-MN provide a new option for sustained transdermal drug delivery.

[Preparation and transdermal effect of a tip-loaded bubble-soluble microneedle].

As a new transdermal drug delivery technology, bubble microneedle could achieve painless and precise drug delivery, which has attracted great attention from researchers. In order to improve the utilization rate of the drug carried by microneedle, we proposed a method for preparing a tip-loaded bubble-soluble microneedle. During the molding process of the microneedle, air bubbles were formed in the needle body, and the drug was concentrated on the needle tip. The preparation process of the bubble microneedle was optimized. The effects of foaming agent concentration, drying temperature, and solution viscosity on the forming of bubble microneedles were explored. Furthermore, the transdermal effect of the product was analyzed. The experimental results showed that the bubble microneedle forming process was stable, with the forming rate above 90% and the forming cycle shortened to about 4 h. The drug was mainly concentrated on the tip of the microneedle, with a length of 180 µm, and the length of the bubble was 250 µm. Moreover, the microneedle array can create microchannels on the mouse skin, and the needle bodies can be rapidly dissolved within 5 min. The bubble microneedle could rapidly release about 48% of the drug within 1 min and about 91% of the drug within 5 min. The bubble microstructure of the microneedle array hindered the diffusion of the drug to the substrate, which improves the utilization rate of the drug. This study provides a technical basis for the practical application of microneedle for transdermal drug delivery.

Water Availability, Soil Characteristics, and Confounding Effects on the Patterns of Biocrust Diversity in the Desert Regions of Northern China.

The species diversity of biocrusts is an important community characteristic in determining their multiple ecosystem functions. Hence, understanding the diversity patterns of biocrusts and their environmental drivers is of fundamental importance. However, explain variables often correlated with each other; thus, the confounding effects among them may arise and result in spurious causal relationships and biased ecological inferences. In this study, we investigated the richness of three biocrust-forming components (mosses, lichens, and cyanobacteria-algae) and their environmental variables across six desert regions of northern China. A comparison between conventional redundancy analysis (RDA) and structural equation model (SEM) was conducted to study the environmental driver-richness relationship and the confounding effects. Our results showed that three latent variables related to water availability, soil texture, and soil salinity and sodicity, could account for the main environmental variations and explain the diversity patterns of biocrusts at the intracontinental scale. Water availability was positively and negatively related to the richness of mosses and cyanobacteria-algae, respectively, while soil texture was positively related to the richness of lichens. In addition, environmental variables confounded with each other caused distinct driver-richness relationships between results of RDA and SEM. Therefore, we suggest that future multivariable studies should utilize path analysis in conjunction with conventional canonical ordination to facilitate more rigorous ecological inferences.

Oxygen Plasma-Assisted Defect Engineering of Graphene Nanocomposites with Ultrasmall Co3O4 Nanocrystals for Monitoring Toxic Nitrogen Dioxide at Room Temperature.

Functional adjustment of graphene with metal oxide can in fact progress the affectability of graphene-based gas sensors. However, it could be a huge challenge to upgrade the detecting execution of nitrogen dioxide (NO2) sensors at room temperature. The ultrasmall size of nanocrystals (NCs) and copious defects are two key variables for moving forward gas detecting execution. Herein, we provide an effective strategy that the hydrothermal reaction is combined with room-temperature oxygen plasma treatment to prepare Co3O4 NCs and reduced graphene oxide (RGO) nanohybrids (Co3O4-RGO). Among all of Co3O4-RGO nanohybrids, Co3O4-RGO-60 W exhibits the most superior NO2 sensing properties and achieves the low-concentration detection of NO2. The sensitivity of Co3O4-RGO-60 W to 20 ppm NO2 at room temperature is the highest (72.36%). The excellent sensing properties can mainly depend on the change in the microstructure of Co3O4-RGO. Compared with Co3O4-RGO, Co3O4-RGO-60 W with oxygen plasma treatment shows more favorable properties for NO2 adsorption, including the smaller size of Co3O4 NCs, larger specific surface area, pore size, and more oxygen vacancies (OVs). Especially, OVs make the surface of NCs have a unique chemical state, which can increase active sites and improve the adsorption property of NO2. Besides, the agreeable impact of the p-p heterojunction (Co3O4 and RGO) and the doping of N molecule contribute to the improved NO2 detecting properties. It is demonstrated that the Co3O4-RGO-60 W sensor is expected to monitor NO2 at room temperature sensitively.