A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets for breast cancer.

BACKGROUND: Adhesion G protein-coupled receptors (aGPCRs), a distinctive subset of the G protein-coupled receptor (GPCR) superfamily, play crucial roles in various physiological and pathological processes, with implications in tumor development. Despite the global prevalence of breast cancer (BRCA), specific aGPCRs as potential drug targets or biomarkers remain underexplored. METHODS: UALCAN, GEPIA, Kaplan-Meier Plotter, MethSurv, cBiopportal, String, GeneMANIA, DAVID, Timer, Metascape, and qPCR were applied in this work. RESULTS: Our analysis revealed significantly increased transcriptional levels of ADGRB2, ADGRC1, ADGRC2, ADGRC3, ADGRE1, ADGRF2, ADGRF4, and ADGRL1 in BRCA primary tumors. Further analysis indicated a significant correlation between the expressions of certain aGPCRs and the pathological stage of BRCA. High expression of ADGRA1, ADGRF2, ADGRF4, ADGRG1, ADGRG2, ADGRG4, ADGRG6, and ADGRG7 was significantly correlated with poor overall survival (OS) in BRCA patients. Additionally, high expression of ADGRF2 and ADGRF4 indicated inferior recurrence-free survival (RFS) in BRCA patients. The RT-qPCR experiments also confirmed that the mRNA levels of ADGRF2 and ADGRF4 were higher in BRCA cells and tissues. Functional analysis highlighted the diverse roles of aGPCRs, encompassing GPCR signaling and metabolic energy reserves. Moreover, aGPCRs may exert influence or actively participate in the development of BRCA through their impact on immune status. CONCLUSION: aGPCRs, particularly ADGRF2 and ADGRF4, hold promise as immunotherapeutic targets and prognostic biomarkers in BRCA.

Cyclometalated gold(III)-hydride under oriented external electric fields: a new strategy to modulate its reactivity?

Selected gold complexes have been regarded as promising anti-cancer agents because they can bind with protein targets containing thiol or selenol moieties, but their clinical applications were hindered by the unbiased binding towards off-target thiol-proteins. Recently, a novel gold(III)-hydride complex (abbreviated as 1) with visible light-induced thiol reactivity has been reported as potent photo-activated anticancer agents (Angew. Chem. Int. Ed., 2020, 132, 11139). To explore new strategies to stimuli this potential antitumor drug, the effect of oriented external electric fields (OEEFs) on its geometric structure, electronic properties, and chemical reactivity was systematically investigated. Results reveal that imposing external electric fields along the Au-H bond of 1 can effectively activate this bond, which is conducive to its dissociation and the binding of Au site to potential targets. Hence, this study provides a new OEEF-strategy to activate this reported gold(III)-hydride, revealing its potential application in electrochemical therapy. We anticipate this work could promote the development of more electric field-activated anticancer agents. However, further experimental research should be conducted to verify the conclusions obtained in this work.

A Super-Resolution and 3D Reconstruction Method Based on OmDF Endoscopic Images.

In the field of endoscopic imaging, challenges such as low resolution, complex textures, and blurred edges often degrade the quality of 3D reconstructed models. To address these issues, this study introduces an innovative endoscopic image super-resolution and 3D reconstruction technique named Omni-Directional Focus and Scale Resolution (OmDF-SR). This method integrates an Omnidirectional Self-Attention (OSA) mechanism, an Omnidirectional Scale Aggregation Group (OSAG), a Dual-stream Adaptive Focus Mechanism (DAFM), and a Dynamic Edge Adjustment Framework (DEAF) to enhance the accuracy and efficiency of super-resolution processing. Additionally, it employs Structure from Motion (SfM) and Multi-View Stereo (MVS) technologies to achieve high-precision medical 3D models. Experimental results indicate significant improvements in image processing with a PSNR of 38.2902 dB and an SSIM of 0.9746 at a magnification factor of ×2, and a PSNR of 32.1723 dB and an SSIM of 0.9489 at ×4. Furthermore, the method excels in reconstructing detailed 3D models, enhancing point cloud density, mesh quality, and texture mapping richness, thus providing substantial support for clinical diagnosis and surgical planning.

A case of ascetic fluid Mycobacterium aubagnense infection in a patient with severe peritoneal effusion.

BACKGROUND: Mycobacterium aubagnense, which was first characterized in 2006, is a non-tuberculosis mycobacterium (NTM) that has only been isolated from respiratory secretions and joint fluid. With only four cases globally, the microbe has rarely been reported in human clinical cases and the strain has not been isolated from ascites. CASE PRESENTATION: To the best of our knowledge, this is the first time that M. aubagnense has been isolated from ascites samples of a patient with severe peritoneal effusion and normal liver functions. Anti-NTM therapy with moxifloxacin, ethambutol, and isoniazid combined with furosemide and spironolactone diuretic therapy relieved the symptoms after six months. CONCLUSIONS: Increased puncture and drainage of ascites combined with diuretic treatment did not significantly relieve the ascites, leading to relapse with aggravated symptoms. The subsequent anti-NTM treatment with moxifloxacin, ethambutol, and isoniazid alleviated the degree of ascites. Therefore, we postulated that M. aubagnense infection was the potential cause of the difficult reduction of ascites in this patient. However, the ascites repeatedly occurred in the patient, which was attributed to M. aubagnense resistance due to insufficient medication time and repeated medication. The patient's underlying diseases may also result in ascites. Therefore, there is a need for careful analysis of the clinical significance of M. aubagnense.

Biochar inoculated with Rhodococcus biphenylivorans altered microecological regulation by promoting quorum sensing and electron transfer: Up-regulation of related genes and enhancement of phenol and ammonia degradation.

Bioaugmentation is an efficient method for improving the efficiency of coking wastewater removal. Nevertheless, how different immobilization approaches affect the efficiency of bioaugmentation remains unclear, as does the corresponding mechanism. With the assistance of immobilized bioaugmentation strain Rhodococcus biphenylivorans B403, the removal of synthetic coking wastewater was investigated (drying agent, alginate agent, and absorption agent). The reactor containing the absorption agent exhibited the highest average removal efficiency of phenol (99.74 %), chemical oxygen demand (93.09 %), and NH4+-N (98.18 %). Compared to other agents, the covered extracellular polymeric substance on the absorption agent surface enhanced electron transfer and quorum sensing, and the promoted quorum sensing benefited the activated sludge stability and microbial regulation. The phytotoxicity test revealed that the wastewater's toxicity was greatly decreased in the reactor with the absorption agent, especially under high phenol concentrations. These findings showed that the absorption agent was the most suitable for wastewater treatment bioaugmentation.

Calcium deficiency is associated with malnutrition risk in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) often have the condition of malnutrition, which can be presented as sarcopenia, micronutrient deficiencies, etc. Trace elements (magnesium, calcium, iron, copper, zinc, plumbum and manganese) belonging to micronutrients, are greatly vital for the assessment of nutritional status in humans. Trace element deficiencies are also the main manifestation of malnutrition. Calcium (Ca) has been proved to play an important part in maintaining body homeostasis and regulating cellular function. However, there are still a lack of studies on the association between malnutrition and Ca deficiency in IBD. This research aimed to investigate the role of Ca for malnutrition in IBD patients. METHODS: We prospectively collected blood samples from 149 patients and utilized inductively coupled plasma mass spectrometry to examine their venous serum trace element concentrations. Logistic regression analyses were used to investigate the association between Ca and malnutrition. Receiver operating characteristic (ROC) curves were generated to calculate the cutoffs for determination of Ca deficiency. RESULTS: Except Ca, the concentrations of the other six trace elements presented no statistical significance between non-malnutrition and malnutrition group. In comparison with the non-malnutrition group, the serum concentration of Ca decreased in the malnutrition group (89.36 vs 87.03 mg/L, p = 0.023). With regard to ROC curve, Ca < 87.21 mg/L showed the best discriminative capability with an area of 0.624 (95% CI: 0.520, 0.727, p = 0.023). Multivariate analyses demonstrated that Ca < 87.21 mg/L (OR = 3.393, 95% CI: 1.524, 7.554, p = 0.003) and age (OR = 0.958, 95% CI: 0.926, 0.990, p = 0.011) were associated with malnutrition risk. Serum Ca levels were significantly lower in the malnutrition group than those in the non-malnutrition group among UC patients, those with severe disease state or the female group. CONCLUSIONS: In patients with IBD, Ca deficiency is an independent factor for high malnutrition risk.

A retrospective study of 3D measurement and analysis applied in the morphological evaluation of achalasia cardia.

Background: Achalasia cardia (AC) is defined as a disorder of esophageal motility whose diagnostic gold standard depends on high-resolution manometry (HRM). The invasiveness of HRM can cause difficulties in diagnosis, treatment, and follow-up for patients with AC. Thus, we aimed to investigate the function of 3D reconstruction and measurement to prove the wide application of this alternative non-invasive approach for AC. Methods: A total of 126 patients with AC and 40 healthy subjects in Tianjin Medical University General Hospital from January 2018 to October 2022 were enrolled in this retrospective study. Chest CT images of these subjects were used to reconstruct the 3D models of the esophagus, stomach, spine, left crus, and right crus. Measurements of esophagus length, volume of esophagus, gastroesophageal insertion angle (His angle), max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, esophagus-spine angle, and spine-lower esophageal sphincter (LES) angle were applied based on the models. Results: Retrocardiac esophagus length, volume of esophagus, max thickness of esophageal wall, esophagus maximum transverse and longitudinal diameter, thoracic esophagus-spine angle, and spine-LES angle in the AC group were higher than those in the control group (all P values <0.05). Among the three subtypes of AC, thoracic esophagus length, intra-abdominal LES length, volume of esophagus, His angle, esophagus maximum transverse and longitudinal diameter, and thoracic esophagus-spine angle all presented statistical differences (all P values <0.05). Correlation analysis revealed that manometric types were positively associated with His angle [r=0.196; 95% confidence interval (CI): 0.009, 0.372; P=0.028] but negatively associated with volume of esophagus (r=-0.480; 95% CI: -0.639, -0.310; P<0.001), esophagus maximum transverse diameter (r=-0.551; 95% CI: -0.679, -0.400; P<0.001), esophagus maximum longitudinal diameter (r=-0.518; 95% CI: -0.649, -0.366; P<0.001), and thoracic esophagus-spine angle (r=-0.324; 95% CI: -0.479, -0.157; P<0.001). Conclusions: This study successfully presented the differences in esophageal length, volume, thickness, and angles between healthy subjects and different AC subtypes on the basis of 3D reconstruction and measurement. Thus, 3D model and measurement can be regarded as a good support for further research and make a valuable contribution to developing non-invasive approaches for AC management.

Yinchen gongying decoction mitigates CCl4-induced chronic liver injury and fibrosis in mice implicated in inhibition of the FoxO1/TGF-ß1/ Smad2/3 and YAP signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis (LF) is a common reversible consequence of chronic liver damage with limited therapeutic options. Yinchen Gongying decoction (YGD) composed of two homologous plants: (Artemisia capillaris Thunb, Taraxacum monochlamydeum Hand.-Mazz.), has a traditionally application as a medicinal diet for acute icteric hepatitis. However, its impact on LF and underlying mechanisms remain unclear. AIM OF THE STUDY: This study aims to assess the impact of YGD on a carbon tetrachloride (CCl4) induced liver fibrosis and elucidate its possible mechanisms. The study seeks to establish an experimental foundation for YGD as a candidate drug for hepatic fibrosis. MATERIALS AND METHODS: LC-MS/MS identified 11 blood-entry components in YGD, and network pharmacology predicted their involvement in the FoxO signaling pathway, insulin resistance, and PI3K-AKT signaling pathway. Using a CCl4-induced LF mouse model, YGD's protective effects were evaluated in comparison to a positive control and a normal group. The underlying mechanisms were explored through the assessments of hepatic stellate cells (HSCs) activation, fibrotic signaling, and inflammation. RESULTS: YGD treatment significantly improved liver function, enhanced liver morphology, and reduced liver collagen deposition in CCl4-induced LF mice. Mechanistically, YGD inhibited HSC activation, elevated MMPs/TIMP1 ratios, suppressed the FoxO1/TGF-ß1/Smad2/3 and YAP pathways, and exhibited anti-inflammatory and antioxidant effects. Notably, YGD improved the insulin signaling pathway. CONCLUSION: YGD mitigates LF in mice by modulating fibrotic and inflammatory pathways, enhancing antioxidant responses, and specifically inhibiting FoxO1/TGF-ß1/Smad2/3 and YAP signal pathways.

The role of potential probiotic strains Lactobacillus reuteri in various intestinal diseases: New roles for an old player.

Lactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., is a gut symbiont that can colonize many mammals. Since it was first isolated in 1962, a multitude of research has been conducted to investigate its function and unique role in different diseases as an essential probiotic. Among these, the basic functions, beneficial effects, and underlying mechanisms of L. reuteri have been noticed and understood profoundly in intestinal diseases. The origins of L. reuteri strains are diverse, with humans, rats, and piglets being the most common. With numerous L. reuteri strains playing significant roles in different intestinal diseases, DSM 17938 is the most widely used in humans, especially in children. The mechanisms by which L. reuteri improves intestinal disorders include protecting the gut barrier, suppressing inflammation and the immune response, regulating the gut microbiota and its metabolism, and inhibiting oxidative stress. While a growing body of studies focused on L. reuteri, there are still many unknowns concerning its curative effects, clinical safety, and precise mechanisms. In this review, we initially interpreted the basic functions of L. reuteri and its related metabolites. Then, we comprehensively summarized its functions in different intestinal diseases, including inflammatory bowel disease, colorectal cancer, infection-associated bowel diseases, and pediatric intestinal disorders. We also highlighted some important molecules in relation to the underlying mechanisms. In conclusion, L. reuteri has the potential to exert a beneficial impact on intestinal diseases, which should be further explored to obtain better clinical application and therapeutic effects.

The role of small intestinal bacterial overgrowth in obesity and its related diseases.

Obesity has become a major public health problem worldwide and its occurrence is increasing globally. Obesity has also been shown to be involved in the occurrence and development of many diseases and pathological conditions, such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), insulin resistance (IR). In recent years, gut microbiota has received extensive attention as an important regulatory part involved in host diseases and health status. A growing body of evidence suggests that gut microbiota dysbiosis has a significant adverse effect on the host. Small intestinal bacterial overgrowth (SIBO), a type of intestinal microbial dysbiosis, has been gradually revealed to be associated with obesity and its related diseases. The presence of SIBO may lead to the destruction of intestinal barrier integrity, increased intestinal permeability, increased endotoxin levels, activation of inflammatory responses, and translocation of bacteria from the colon to the small intestine. However, the causal relationship between SIBO and obesity and the specific mechanisms have not been well elucidated. This review discusses the cross-talk between SIBO and obesity and its related diseases, and expounds its potential mechanisms and interventions, which may help to discover new therapeutic targets for obesity and its related diseases and develop treatment options.

Rare leptin in non-alcoholic fatty liver cirrhosis: A case report.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD)-related cirrhosis is mainly caused by NAFLD by causing inflammation which leads to fibrosis. The role of leptin in NAFLD-related cirrhosis has been rarely reported. CASE SUMMARY: This study presents the case of a 65-year-old male patient who was referred to The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China, for diagnosis and treatment for liver cirrhosis. Initially, the cause of liver cirrhosis was unknown. After radiology, laboratory examination, pathological results and analysis of the patient's signs and symptoms, the case was finally diagnosed with final NAFLD-related cirrhosis. Although this study reports a single case, the findings might expand the understanding of leptin's role in NAFLD-related cirrhosis and might provide a basis for the clinical diagnostic criteria, pathological features and treatment of NAFLD-related cirrhosis. CONCLUSION: Although the occurrence of marasmus NAFLD-related cirrhosis is rare, it needs to be distinguished from other liver diseases, including viral hepatitis, drug-induced liver disease, Wilson's disease and autoimmune liver disease. Aggressive treatment is needed to prevent the progression of NAFLD-related cirrhosis.

Imidazo[1,2-b]pyridazine as Building Blocks for Host Materials for High-Performance Red-Phosphorescent Organic Light-Emitting Devices.

A novel electron-transporting unit, imidazo [1,2-b]pyridazine (IP), was first reported for developing host materials. The IP moiety possesses excellent electron-transporting ability and great thermal stability. Using carbazole as p-type units and IP as n-type units, several bipolar host materials, namely, IP6Cz, IP68Cz, IP36Cz, and IP368Cz, were developed through altering the substitution site of the IP core. Among these four materials, 6-site-substituted IP6Cz and 6,8-site-substituted IP68Cz exhibit the best electroluminescence (EL) performance. IP6Cz- and IP68Cz-based red phosphorescent organic light-emitting diodes using Ir(pq)2acac as the emitter exhibit extremely high EL efficiency with the maximum external quantum efficiency (ηext,max) of 26.9 and 25.2% and an insignificant efficiency roll-off. Moreover, IP6Cz- and IP68Cz-based deep-red devices doped by Ir(piq)2acac also show satisfactory EL performance with a ηext,max of 20.5 and 19.9%, respectively. The influence of different substitution sites of the IP core on the photophysical and electrochemical properties was systematically investigated. This study demonstrates that IP could be a first-rate electron-transporting unit for bipolar materials for red-emitting devices.

[1,2,4]Triazolo[1,5- a]pyridine-Based Host Materials for Green Phosphorescent and Delayed-Fluorescence OLEDs with Low Efficiency Roll-Off.

Herein, a series of universal bipolar host materials, 9,9'-([1,2,4]triazolo[1,5- a]pyridine-2,6-diylbis(4,1-phenylene))bis(9 H-carbazole) (TP26Cz1), 3-(2-(4-(9 H-carbazol-9-yl)phenyl)-[1,2,4]triazolo[1,5- a] pyridine-6-yl)-9-phenyl-9 H-carbazole (TP26Cz2), 9,9'-([1,2,4]triazolo[1,5- a]pyridine-2,7-diylbis(4,1-phenylene))bis(9 H-carbazole) (TP27Cz1), and 3-(2-(4-(9 H-carbazol-9-yl)phenyl)-[1,2,4]triazolo[1,5- a]pyridin-7-yl)-9-phenyl-9 H-carbazole (TP27Cz2), using [1,2,4]triazolo[1,5- a]pyridine (TP) as electron-transporting moiety and carbazole as hole-transporting moiety, were designed and synthesized. All four compounds possess remarkable carrier-transporting properties and excellent thermal stability with high glass-transition temperature ( Tg) in the range of 136-144 °C. The hole- and electron-transporting abilities could be regulated by adjusting the linkage mode between the carbazole and TP units, and balanced charge-transporting properties were realized in TP26Cz2 and TP27Cz2. The phosphorescent and thermally activated delayed-fluorescence (TADF) organic light-emitting diodes (OLEDs) based on these host materials exhibit superior performance with high efficiency and low roll-off. For example, TP26Cz2-hosted phosphorescent OLED (PhOLED) exhibits the maximum external quantum efficiency (ηext) of 25.6%, and at the high luminance of 5000 cd m-2, the ηext still remained at 25.2%. TP27Cz1-hosted TADF device exhibits the maximum ηext of 15.5% and only dropped to 15.4% at the luminance of 1000 cd m-2. Moreover, the influence of linking mode of carbazole unit and TP units in these hosts on their photophysical and carrier-transporting properties as well as the electroluminescence (EL) performance of devices was discussed.

[1,2,4]Triazolo[1,5-a]pyridine as Building Blocks for Universal Host Materials for High-Performance Red, Green, Blue and White Phosphorescent Organic Light-Emitting Devices.

The electron-accepting [1,2,4]triazolo[1,5-a]pyridine (TP) moiety was introduced to build bipolar host materials for the first time, and two host materials based on this TP acceptor and carbazole donor, namely, 9,9'-(2-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (o-CzTP) and 9,9'-(5-([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (m-CzTP), were designed and synthesized. These two TP-based host materials possess a high triplet energy (>2.9 eV) and appropriate highest occupied molecular orbital/lowest unoccupied molecular orbital levels as well as the bipolar transporting feature, which permits their applicability as universal host materials in multicolor phosphorescent organic light-emitting devices (PhOLEDs). Blue, green, and red PhOLEDs based on o-CzTP and m-CzTP with the same device configuration all show high efficiencies and low efficiency roll-off. The devices hosted by o-CzTP exhibit maximum external quantum efficiencies (ηext) of 27.1, 25.0, and 15.8% for blue, green, and red light emitting, respectively, which are comparable with the best electroluminescene performance reported for FIrpic-based blue, Ir(ppy)3-based green, and Ir(pq)2(acac)-based red PhOLEDs equipped with a single-component host. The white PhOLEDs based on the o-CzTP host and three lumophors containing red, green, and blue emitting layers were fabricated with the same device structure, which exhibit a maximum current efficiency and ηc of 40.4 cd/A and 17.8%, respectively, with the color rendering index value of 75.