Indole-3-aldehyde Alleviates High-Fat Diet-Induced Gut Barrier Disruption by Increasing Intestinal Stem Cell Expansion.

High-fat diet (HFD) feeding is known to cause intestinal barrier disruption, thereby triggering severe intestinal inflammatory disease. Indole-3-aldehyde (IAld) has emerged as a potential candidate for mitigating inflammatory responses and maintaining intestinal homeostasis. However, the role of IAld in the HFD-related intestinal disruption remains unclear. In this study, 48 7 week-old male C57BL/6J mice were assigned to four groups: the normal chow diet (NCD) group received a NCD; the HFD group was fed an HFD; the HFD + IAld200 group was supplemented with 200 mg/kg IAld in the HFD; and the HFD + IAld600 group was supplemented with 600 mg/kg IAld in the HFD. The results showed that dietary IAld supplementation ameliorated fat accumulation and metabolic disorders, which are associated with reduced intestinal permeability. This reduction potentially led to decreased systemic inflammation and enhanced intestinal barrier function in HFD-fed mice. Furthermore, we found that IAld promoted intestinal stem cell (ISC) proliferation by activating aryl hydrocarbon receptors (AHRs) in vivo and ex vivo. These findings suggest that IAld restores the HFD-induced intestinal barrier disruption by promoting AHR-mediated ISC proliferation.

Transient receptor potential melastatin 8 contributes to the interleukin-33-mediated cold allodynia in a mouse model of neuropathic pain.

ABSTRACT: Cold allodynia is a common complaint of patients suffering from neuropathic pain initiated by peripheral nerve injury. However, the mechanisms that drive neuropathic cold pain remain elusive. In this study, we show that the interleukin (IL)-33/ST2 signaling in the dorsal root ganglion (DRG) is a critical contributor to neuropathic cold pain by interacting with the cold sensor transient receptor potential melastatin 8 (TRPM8). By using the St2-/- mice, we demonstrate that ST2 is required for the generation of nociceptor hyperexcitability and cold allodynia in a mouse model of spared nerve injury (SNI). Moreover, the selective elimination of ST2 function from the Nav1.8-expressing nociceptor markedly suppresses SNI-induced cold allodynia. Consistent with the loss-of-function studies, intraplantar injection of recombinant IL-33 (rIL-33) is sufficient to induce cold allodynia. Mechanistically, ST2 is co-expressed with TRPM8 in both mouse and human DRG neurons and rIL-33-induced Ca2+ influx in mouse DRG neurons through TRPM8. Co-immunoprecipitation assays further reveal that ST2 interacts with TRPM8 in DRG neurons. Importantly, rIL-33-induced cold allodynia is abolished by pharmacological inhibition of TRPM8 and genetic ablation of the TRPM8-expressing neurons. Thus, our findings suggest that the IL-33/ST2 signaling mediates neuropathic cold pain through downstream cold-sensitive TRPM8 channels, thereby identifying a potential analgesic target for the treatment of neuropathic cold pain.

Nd:YVO4/YVO4 cascaded Raman laser pumped dual-wavelength signal wave MgO:PPLN-OPO with wide range adjustable wavelength interval.

This article presents a dual-wavelength signal wave output system capable of generating a broad range of adjustable wavelength intervals. The setup involved the creation of a dual-wavelength cascaded Raman laser featuring composite cavities operating at 1176 nm and 1313 nm. Experimental investigations were carried out on an external cavity MgO:PPLN-OPO driven by the cascaded Raman laser. By setting the crystal polarization period to 27.6-34.4 µm and the temperature to 50-130°C, adjustable tunable output of dual-wavelength signal wave at 1176 nm-MgO:PPLN-OPO (1550-2294 nm) and 1313 nm-MgO:PPLN-OPO (1768-2189 nm) was achieved with a wavelength interval of 0-218 nm. Under the conditions of a period of 34.4 µm, temperature of 90°C, and an incident Raman power of 2.6 W, the highest conversion efficiency of Raman to dual-wavelength signal wave (2212, 2182 nm) was 34.2%. Furthermore, the maximum output power of dual-wavelength signal wave was recorded at 1.02 W with an incident Raman power of 3.33 W.

Public trust in general practitioners and its association with primary care contracts: a cross-sectional study of community residents in China.

OBJECTIVES: This study aimed to assess the level of public trust in general practitioners (GPs) and its association with primary care contract services (PCCS) in China. STUDY DESIGN: Cross-sectional study. METHODS: Between September and December 2021, 4158 residents across eastern, central, and western China completed a structured self-administered questionnaire. Trust was assessed using the Chinese version of Wake Forest Physician Trust Scale. Multivariable linear regression models were established to identify predictors of trust. The effect size of PCCS on trust was estimated by the average treatment effect for the treated (ATT) through propensity score matching. RESULTS: The study participants had a mean Wake Forest Physician Trust Scale score of 36.82 (standard deviation = 5.45). Enrollment with PCCS (ß = 0.14, P < 0.01), Han ethnicity (ß = 0.03, P < 0.05), lower educational attainment (ß = -0.06, P < 0.01), higher individual monthly income (ß = 0.03, P < 0.05), better self-rated health (ß = 0.04, P < 0.05), chronic conditions (ß = 0.07, P < 0.01), and higher familiarity with primary care services (ß = 0.12, P < 0.01) and PCCS (ß = 0.21, P < 0.01) were associated with higher trust in GPs. The ATT of PCCS exceeded 1 (P < 0.05). CONCLUSIONS: PCCS are associated with higher levels of trust in GPs. PCCS may become an effective tool to attract public trust in GPs, although the relationship between the two may be bi-directional.

Enhancing Aboveground Biomass Prediction through Integration of the SCDR Paradigm into the U-Like Hierarchical Residual Fusion Model.

Deep learning methodologies employed for biomass prediction often neglect the intricate relationships between labels and samples, resulting in suboptimal predictive performance. This paper introduces an advanced supervised contrastive learning technique, termed Improved Supervised Contrastive Deep Regression (SCDR), which is adept at effectively capturing the nuanced relationships between samples and labels in the feature space, thereby mitigating this limitation. Simultaneously, we propose the U-like Hierarchical Residual Fusion Network (BioUMixer), a bespoke biomass prediction network tailored for image data. BioUMixer enhances feature extraction from biomass image data, facilitating information exchange and fusion while considering both global and local features within the images. The efficacy of the proposed method is validated on the Pepper_Biomass dataset, which encompasses over 600 original images paired with corresponding biomass labels. The results demonstrate a noteworthy enhancement in deep regression tasks, as evidenced by performance metrics on the Pepper_Biomass dataset, including RMSE = 252.18, MAE = 201.98, and MAPE = 0.107. Additionally, assessment on the publicly accessible GrassClover dataset yields metrics of RMSE = 47.92, MAE = 31.74, and MAPE = 0.192. This study not only introduces a novel approach but also provides compelling empirical evidence supporting the digitization and precision improvement of agricultural technology. The research outcomes align closely with the identified problem and research statement, underscoring the significance of the proposed methodologies in advancing the field of biomass prediction through state-of-the-art deep learning techniques.

Delafossite CuGaO2-Based Chemiresistive Sensor for Sensitive and Selective Detection of Dimethyl Disulfide.

Dimethyl disulfide (DMDS) is a common odor pollutant with an extremely low olfactory threshold. Highly sensitive and selective detection of DMDS in ambient humid air background, by metal oxide semiconductor (MOS) sensors, is highly desirable to address the increased public concern for health risk. However, it has still been a critical challenge up to now. Herein, p-type delafossite CuGaO2 has been proposed as a promising DMDS sensing material owing to its striking hydrophobicity (revealed by water contact angle measurement) and excellent partial catalytic oxidation properties (indicated by mass spectroscopy). The present CuGaO2 sensor shows a selective DMDS response, with satisfied humidity resistance performance and long-term stability at a relatively low operation temperature of 140 °C. An ultrahigh response of 100 to 10 ppm DMDS and a low limit of detection of 3.3 ppb could be achieved via a pulsed temperature modulation strategy. A smart sensing system based on a CuGaO2 sensor has been developed, which could precisely monitor DMDS vapor in ambient humid air, even with the presence of multiple interfering gases, demonstrating the practical application capability of MOS sensors for environmental odor monitoring.

Radiomics and Deep Learning in Nasopharyngeal Carcinoma: A Review.

Nasopharyngeal carcinoma is a common head and neck malignancy with distinct clinical management compared to other types of cancer. Precision risk stratification and tailored therapeutic interventions are crucial to improving the survival outcomes. Artificial intelligence, including radiomics and deep learning, has exhibited considerable efficacy in various clinical tasks for nasopharyngeal carcinoma. These techniques leverage medical images and other clinical data to optimize clinical workflow and ultimately benefit patients. In this review, we provide an overview of the technical aspects and basic workflow of radiomics and deep learning in medical image analysis. We then conduct a detailed review of their applications to seven typical tasks in the clinical diagnosis and treatment of nasopharyngeal carcinoma, covering various aspects of image synthesis, lesion segmentation, diagnosis, and prognosis. The innovation and application effects of cutting-edge research are summarized. Recognizing the heterogeneity of the research field and the existing gap between research and clinical translation, potential avenues for improvement are discussed. We propose that these issues can be gradually addressed by establishing standardized large datasets, exploring the biological characteristics of features, and technological upgrades.

Peripheral Mechanism of Cancer-Induced Bone Pain.

Cancer-induced bone pain (CIBP) is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis. CIBP constitutes a specific pain state with distinct characteristics; however, it shares similarities with inflammatory and neuropathic pain. At present, although various therapies have been developed for this condition, complete relief from CIBP in patients with cancer is yet to be achieved. Hence, it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs. Herein, we focused on the peripheral mechanism associated with the initiation of CIBP, which involves tissue injury in the bone and changes in the tumor microenvironment (TME) and dorsal root ganglion. The nerve-cancer and cancer-immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis, ultimately leading to CIBP. The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.

Succinate signaling attenuates high-fat diet-induced metabolic disturbance and intestinal barrier dysfunction.

Succinate is a vital signaling metabolite produced by the host and gut microbiota. Succinate has been shown to regulate host metabolic homeostasis and inhibit obesity-associated inflammation in macrophages by engaging its cognate receptor, SUCNR1. However, the contribution of the succinate-SUCNR1 axis to intestinal barrier dysfunction in obesity remains unclear. In the present study, we explored the effects of succinate-SUCNR1 signaling on high-fat diet (HFD)-induced intestinal barrier dysfunction. Using a SUCNR1-deficient mouse model under HFD feeding conditions, we identified the effects of succinate-SUCNR1 axis on obesity-associated intestinal barrier impairment. Our results showed that HFD administration decreased goblet cell numbers and mucus production, promoted intestinal pro-inflammatory responses, induced gut microbiota composition imbalance, increased intestinal permeability, and caused mucosal barrier dysfunction. Dietary succinate supplementation was sufficient to activate a type 2 immune response, trigger the differentiation of barrier-promoting goblet cells, suppress intestinal inflammation, restore HFD-induced mucosal barrier impairment and intestinal dysbiosis, and eventually exert anti-obesity effects. However, SUNNR1-deficient mice failed to improve the intestinal barrier function and metabolic phenotype in HFD mice. Our data indicate the protective role of the succinate-SUCNR1 axis in HFD-induced intestinal barrier dysfunction.

Decoupling the Conflicting Roles of Photoactivation and Boosting Chemiresistor Response by Pulsed UV Light Modulation.

UV photoactivation has been widely employed to trigger the response of semiconductor chemiresistors at room temperature (RT). Generally, continuous UV (CU) irradiation is applied, and an apparent maximal response could be obtained via optimizing UV intensity. However, owing to the conflicting roles of (UV) photoactivation in the gas response process, we do not think the potential of photoactivation has been fully explored. Herein, a pulsed UV light modulation (PULM) photoactivation protocol has been proposed. Pulsed UV-on facilitates the generation of surface reactive oxygen species and refreshes the surface of chemiresistors, while pulsed UV-off avoids the side effects of UV-induced desorption of the target gas and the decline of base resistance. PULM enables decoupling those conflicting roles of CU photoactivation, resulting in a drastic boost of response to trace (20 ppb) NO2 from 1.9 (CU) to 131.1 (PULM UV-off), and a decline of limit of detection from 2.6 ppb (CU) to 0.8 ppb (PULM) for a ZnO chemiresistor. This work highlights that PULM allows full exploitation of the potential of nanomaterials for sensitively detecting trace (ppb-level) toxic gas molecules and opens a new opportunity for designing highly sensitive, low-power consumed RT chemiresistors for ambient air quality monitoring.

Bifunctional role of PDMS membrane in designing humidity-tolerant H2S chemiresistors with high selectivity.

A thermally evaporated hydrophobic PDMS membrane could significantly mitigate humidity interference/poisoning (without a decline in response at 50% RH for nearly 3 months) and enhance the selectivity of a CuCrO2 chemiresistor toward erosive H2S, offering an avenue for the practical applications of (H2S) chemiresistors in an ambient humid air atmosphere.

Succinate communicates pro-inflammatory signals to the host and regulates bile acid enterohepatic metabolism in a pig model.

Succinate is produced by both the host and microbiota with pleiotropic functions in the modulation of intestinal inflammation and metabolic homeostasis, but the mechanisms remain elusive. This study aimed to determine whether dietary succinate influences the intestinal inflammatory response and to analyze the possible mechanisms by which succinate regulates enterohepatic metabolism. Sixteen growing barrows were randomly assigned to two groups, fed with a basal diet that consisted of a typical commercial diet or fed with a basal diet supplemented with 1% sodium succinate. Our data showed that dietary succinate activated the expression of succinate receptor 1 (SUCNR1) and increased the concentrations of pro-inflammatory cytokines in the intestine. Dietary succinate inhibited the expression levels of the ileal Farnesol X receptor (FXR) and its target genes, promoted hepatic bile acid secretion, and altered the bile acid metabolic profile. Then, we demonstrated that the pro-inflammatory cytokines triggered by succinate disrupted the ability of bile acids to activate FXR and fibroblast growth factor 19. Furthermore, dietary succinate reduced the abundance of bile-salt hydrolase enriched bacteria in the ileum. Taken together, dietary succinate activated the pro-inflammatory response via SUCNR1 in the intestine, and the pro-inflammatory cytokines induced by succinate blocked the activation of FXR and its target genes and disturbed bile acid enterohepatic circulation.

Improvement for a full-spectrum modulated nonlinear frequency division multiplexing transmission system.

Nonlinear frequency division multiplexing (NFDM), as a possible technique to overcome the limit imposed by Kerr nonlinearity in conventional coherent optical communication systems, has attracted widespread attention in the communication community in recent years. In order to fully utilize the available degrees of freedom in the nonlinear spectrum, this paper focuses on the full-spectrum (FS) modulated NFDM system. First, we maximize the data rate of discrete spectrum (DS) by optimizing the distribution of eigenvalues in DS part of FS. Then through introducing the probabilistic shaping (PS) into the FS system, and combined with linear minimum mean square (LMMSE) estimators, a 1120 km transmission with BER below the hard decision forward error correction (HD-FEC) threshold at 112 Gbps is achieved, where 128 subcarriers with PS-64QAM are used in the continuous spectrum (CS) and 13 eigenvalues with 64QAM are adopted in the discrete spectrum (DS). The achievable data rate is about 12% higher than that of pure CS modulation. Our work achieves the current FS NFDM system with the largest number of multiplexed eigenvalues, and provides a way to improve the performance of FS systems.

Effects of Dietary Indole-3-carboxaldehyde Supplementation on Growth Performance, Intestinal Epithelial Function, and Intestinal Microbial Composition in Weaned Piglets.

As a microbial tryptophan metabolite, indole-3-carboxaldehyde (ICA) has been suggested to confer benefits to host, such as regulation of intestinal barrier function. This study aimed to elucidate the role of ICA in modulating intestinal homeostasis via using a weaned pig model. Twenty-four weaned piglets were randomly allocated into three groups: the control group (a basal diet), ICA100 group (the basal diet supplemented with 100 mg/kg ICA), and ICA200 group (the basal diet supplemented with 200 mg/kg ICA). The experiment lasted 14 d, and pigs from the control and ICA100 groups were slaughtered. The results showed no significant differences in the average daily gain (ADG) and average daily feed intake (ADFI) among the three groups (P > 0.05). However, the ICA100 group had a lower feed to gain ratio (F:G) (P < 0.05). Dietary ICA supplementation did not alter the villus height, crypt depth, and villus height/crypt depth ratio in the small intestine, and did not change the intestinal permeability and antioxidant parameters (P > 0.05). Intriguingly, ICA treatment significantly increased the jejunal, ileal and colonic indexes in piglets (P < 0.05). Besides, the expression of proliferating cell nuclear antigen (PCNA) in the intestine was up-regulated by ICA treatment. Moreover, in vitro experiments demonstrated that 15 µM ICA significantly accelerated the proliferation activity of IPEC-J2 cells, and increased the expression of the ICA receptor aryl hydrocarbon receptor (AHR) and the proliferation markers PCNA and Cyclin D1 (P < 0.05). In addition, dietary ICA supplementation modulated the intestinal flora, increasing the richness estimators and diversity index, decreasing the abundances of phylum Fibrobacterota and genera Alloprevotella, Prevotella, and Parabacteroides, and enriching the abundance of genera Butyrivibrio. These data reveal a beneficial role for the microbial metabolite ICA on intestinal epithelial proliferation, rather than intestinal barrier function, in weaned piglets.

Fumonisin B1 promotes germ cells apoptosis associated with oxidative stress-related Nrf2 signaling in mice testes.

Fumonisins (FBs) are widespread Fusarium toxins commonly found in corn. This study aimed to establish the mechanism of oxidative stress via the Nrf2 signaling pathway associated with FB1-induced toxicity in mice testis. Male mice were fed with 5 mg/kg FB1 diet for 21 or 42 days, the expression of inflammatory related genes, apoptosis related genes and Nrf2 pathway genes were detected by RT-qPCR, Western blot and immunohistochemical. Furthermore, Sertoli cell was treatment with FB1. Cell viability was measured by CCK8 assay, ROS level and apoptosis related genes were detected by immunofluorescence staining. The results showed that FB1 had toxic effects on testis, which could increase the ROS level of Sertoli cells, affect the Keap1-Nrf2 pathway related factors, destroy the oxidative balance of testis, lead to the occurrence of inflammation and the initiation of apoptosis, and finally destroy the testicular tissue structure and affect the formation of sperm.

Pt-Anchored CuCrO2 for Low-Temperature-Operating High-Performance H2S Chemiresistors.

Recent advances in heterogeneous catalysts indicate that single atoms (SAs), anchored/stabilized on metal oxide nanostructures, exhibit not only high catalyst atom efficiency but also intriguing reactivity and selectivity. Herein, isolated Pt SA-anchored CuCrO2 (CCO) has been designed by a glycine-nitrate solution combustion synthesis (SCS) route. The density of isolated Pt SAs achieves the highest value of ∼100 µm-2 for the 1.39 wt % Pt-anchored CCO sample, which results in the drastically boosted H2S response characteristics, including a high response of 1250 (35 times higher than that of pure CCO) at 10 ppm H2S and a low operating temperature of 100 °C. Except for CH4S, the responses of a 1.39 wt % Pt-anchored CCO chemiresistor to diverse vapors with concentrations of 50-100 ppm are less than 2, exhibiting excellent selectivity. Various ex situ characterizations indicate that the spillover catalytic effect of Pt SA sites, other than the conventional sulfuration-desulfuration mechanism, plays a dominant role in the outstanding H2S response characteristics.

Antagonistic Effect of Selenium on Fumonisin B1 Promotes Neutrophil Extracellular Traps Formation in Chicken Neutrophils.

Neutrophils are an important component of the innate immune system, and one of their defense mechanisms, neutrophil extracellular traps (NETs), is a hot topic of the current research. This study explored the effects of fumonisin B1 (FB1) on chicken neutrophil production of NETs and its possible molecular mechanism of action. Scanning electron microscopy and fluorescence microscopy were used to observe morphological changes in neutrophils, and a fluorescence microplate reader was used to detect reactive oxygen species (ROS) and extracellular DNA release from neutrophils. Quantitative PCR (qPCR) and western blot were used to determine the expression levels of selenoproteins. The results indicate that FB1 inhibited the zymosan-induced formation of NETs in chicken neutrophils by preventing ROS burst and histone H3 (H3) and neutrophil elastase (NE) release. Moreover, the mRNA expression levels of glutathione peroxidase (GPX), thioredoxin reductase (TXNRD), and deiodinase (DIO) were downregulated in the FB1 group. The protein expression levels of GPX1, GPX2, GPX3, DIO3, and TXNRD1 were consistent with the changes in their gene expressions, suggesting an abnormal selenoprotein expression in response to the toxic effects of FB1. Conversely, selenium (Se) supplementation reduced the toxic effects of FB1 and restored the NETs formation, indicating that Se can be used as a potential drug to prevent and control FB1 toxicity in livestock farming.

Mechanism and Model for Optimizing Polytetrafluoroethylene Distribution to Improve the Electrical and Thermal Conductivity of Treated Carbon Fiber Paper in Fuel Cells.

Employing polytetrafluoroethylene (PTFE)-treated carbon fiber paper (CFP) as the substrate of the gas diffusion layer (GDL) is a common practice to improve water management in proton exchange membrane fuel cells (PEMFCs), but the resulting increase in electrical and thermal resistance is a critical problem that restricts the performance output of PEMFCs. Hence, studying the mechanism and prediction model for both the electrical and thermal conductivity in CFP is essential. This work established a mathematical graph theory model for CFP electrical and thermal conductivity prediction based on the observation and abstraction of the CFP characteristic structures. For the PTFE-treated CFP, the electrical and thermal conductivity of CFP can be effectively increased by optimizing the PTFE distribution in CFP. A "filter net effect" mechanism was proposed to reasonably explain PTFE distribution's influence on the CFP performance. Finally, the equivalent effect of multiple factors on conductivity was revealed using contour maps, which provides inspiration for further reducing the electrical and thermal resistance in CFP.

High-Throughput Screening of Rat Mesenchymal Stem Cell Behavior on Gradient TiO2 Nanotubes.

The dimension of TiO2 nanotubes (TNTs) ranges from several nanometers to hundreds of nanometers. This variety raises the difficulty of screening suitable nanotube dimension for biomedical applications. Herein, we report the use of a simple one-step bipolar anodization method for fabrication of TNT gradients with diameter range from 30 to 100 nm. The gradient TNTs were successfully applied for high-throughput screening of TNT size effect on cell responses, including cell adhesion, proliferation, and differentiation. Results reveal that no significant difference in adherent cell number could be found within the range of 30-87 nm in both the presence and absence of serum proteins. On the contrary, large nanotubes (with outer diameter >87 nm) profoundly reduce cell adhesion in both the presence and absence of serum proteins, indicating TNT size could affect cell adhesion directly without the adsorbed proteins. The size effect on cell behavior becomes prominent with time that cell proliferation and differentiation decrease with increasing nanotube size. This size effect can be comprehended by protein adsorption and the formation of focal adhesion. Another two sample applications of gradient TNTs demonstrate gradient TNTs are promising for high-throughput screening.