GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase.

Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent risk factor for poor prognosis in PDAC. Furthermore, we demonstrated that MUC21 promoted the metastasis and PNI of PDAC cells by activating JNK and inducing epithelial-mesenchymal transition (EMT). Mechanistically, glial cell-derived neurotrophic factor, secreted by Schwann cells, phosphorylates the intracellular domain S543 of MUC21 via CDK1 in PDAC cells, facilitating the interaction between MUC21 and RAC2. This interaction leads to membrane anchoring and activation of RAC2, which in turn activates the JNK/ZEB1/EMT axis, ultimately enhancing the metastasis and PNI of PDAC cells. Our results present a novel mechanism of PNI, suggesting that MUC21 is a potential prognostic marker and therapeutic target for PDAC.

[Effect and safety of self-draining ureteral stent with thread in kidney transplant reci-pients].

OBJECTIVE: To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation. METHODS: This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024. The ureteral stent with thread group, in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation. On the 9th day after the operation, the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed. The ureteral stent could be removed along with the suture. As to the cystoscope group, a ureteral stent was routinely placed during kidney transplantation, and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation. The pain scores [numerical rating scale (NRS)-11] during catheter removal and the incidence of urinary tract infections were observed and compared between the two groups. t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups, and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups. P < 0.05 was considered statistically significant. RESULTS: As of March 2024, all the recipients were followed up for an average of 6 months (3 to 12 months) postoperatively. A total of 46 kidney transplantation patients were included, with 21 in the ureteral stent with thread group and 25 in the cystoscope group. There were no statistically significant differences between the two groups in age distribution, male-to-female ratio, and deceased versus live donor grafts. Three months after renal transplantation, there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group (P=0.007). No significant urinary fistula, wound infection, or ureteral stenosis occurred in either group. No stent-related complications, stent migration, or stone formation were observed. The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4, respectively, with no statistically significant difference (t=0.29, P=0.773). However, the pain scores during ureteral stent removal were 4.9±1.6 and 3.0±1.0 in the two groups, respectively, with a statistically significant diffe-rence (t=5.017, P < 0.001). The total costs of indwelling and removing ureteral stents in the cystoscopy group and the ureteral stent with thread group were 6 452.0 (5 539.5, 6 452.0) yuan and 3 225.0 (3 225.0, 3 225.0) yuan, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Compared with the conventional transplanted kidney ureteral stent, the self-discharge ureteral stent technique with sutures is simpler, has a shorter ureteral stent inlay time, reduces the symptoms of bladder spasms, significantly reduces the cost of catheterization, and has fewer postoperative urinary system complications. It is a worthy improved surgical method to be promoted.

In situ visualizing reveals potential drive of lattice expansion on defective support toward efficient removal of nitrogen oxides.

As a sustainable and promising approach of removing of nitrogen oxides (NOx), catalytic reduction of NOx with H2 is highly desirable with a precise understanding to the structure-activity relationship of supported catalysts. In particular, the dynamic evolution of support at microscopic scale may play a critical role in heterogeneous catalysis, however, identifying the in situ structural change of support under working condition with atomic precision and revealing its role in catalysis is still a grand challenge. Herein, we visually capture the surface lattice expansion of WO3-x support in Pt-WO3-x catalyst induced by NO in the exemplified reduction of NO with H2 using in situ transmission electron microscopy and first reveal its important role in enhancing catalysis. We find that NO can adsorb on the oxygen vacancy sites of WO3-x and favorably induce the reversible stretching of W-O-W bonds during the reaction, which can reduce the adsorption energy of NO on Pt4 centers and the energy barrier of the rate-determining step. The comprehensive studies reveal that lattice expansion of WO3-x support can tune the catalytic performance of Pt-WO3-x catalyst, leading to 20% catalytic activity enhancement for the exemplified reduction of NO with H2. This work reveals that the lattice expansion of defective support can tune and optimize the catalytic performance at the atomic scale.

SETMAR Facilitates the Differentiation of Thyroid Cancer by Regulating SMARCA2-Mediated Chromatin Remodeling.

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

An insulin-like signalling pathway model for Fasciola gigantica.

BACKGROUND: The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. RESULTS: The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. CONCLUSIONS: This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.

Preparation of mesoporous biogas residue biochar via a self-template strategy for efficient removal of ciprofloxacin: Effect of pyrolysis temperature.

Biochar preparation and application is an anticipated pathway for the resource utilization of biogas residue. In this study, biochars were prepared by the pyrolysis of biogas residue from food waste anaerobic digestion (named as BRBCs) under various pyrolysis temperatures (300, 500, 700, and 900 °C), and the effect of pyrolysis temperatures on the physicochemical characteristics of BRBCs was examined. The adsorption performance toward ciprofloxacin (CIP), a typical antibiotic in waterbodies, was also investigated. The results showed that pyrolysis temperature significantly changed the physicochemical properties of BRBCs. In addition, the minerals in the biogas residue, especially SiO2, were rearranged to form a mesoporous structure in biochar through a self-template strategy (without activator). BRBC prepared at 900 °C exhibited a high specific surface area and pore volume, well-developed mesopore structure, and more carbon structure defects, and exhibited the largest CIP adsorption capacity with 70.29 mg g-1, which was ascribed to the combined interaction of pore diffusion, π-π interactions, hydrogen bonding, complexation, and electrostatic forces. Furthermore, the adsorption of CIP by BRBC900 was well described by two-compartment kinetic and Langmuir isotherm models. BRBC900 showed good adsorption performance toward CIP at pH 7-9. The adsorption of CIP by BRBC is a spontaneous, exothermic, entropy-increasing process. Moreover, BRBC also presented a good recycling potential. Therefore, the preparation of mesoporous biochar based on a self-template strategy not only provides an option for the resource utilization of biogas residue but also offers a new option for the treatment of antibiotic wastewater.

High-Performance Trimethylamine Sensor Based on an Imine Covalent Organic Framework.

As trimethylamine (TMA) is widely used in agriculture and industry, inhalation of TMA can cause very serious negative effects on human health. However, most of the current gas sensors for detecting TMA are commonly performed at high temperatures and cannot meet market needs. Inspired by this, we prepared imine covalent organic frameworks (TB-COF) synthesized from two monomers, 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 1,3,5-benzotricarboxaldehyde (BTCA), using acetic acid as a catalyst at room temperature. Based on this, three sensors were prepared for gas sensitivity testing, namely, TA, BT, and TB-COF sensors. The three sensors were tested for 15 different gases at room temperature. From the whole gas sensitivity data, the TB-COF sensor made by compositing TA and BT has a higher sensitivity (6845.9%) to TMA at 500 ppm, which is 6.1 and 5.4 times higher than the response of TA and BT sensors, respectively. The TB-COF sensor adsorbs and desorbs TMA in a controlled 23 s cycle with a low detection limit of 28.6 ppb. This result indicates that TB-COF prepared at room temperature can be used as a gas-sensitive sensing material for real-time monitoring of TMA. The gas sensing results demonstrate the great potential of COFs for sensor development and application and provide ideas for further development of COFs-based gas sensors.

SENP1 regulates intermittent hypoxia-induced microglia mediated inflammation and cognitive dysfunction via wnt/ß-catenin pathway.

Obstructive sleep apnea syndrome (OSAS), characterized by repeated narrow or collapse of the upper airway during sleep, resulting in periodic reductions or cessations in ventilation, consequent hypoxia, hypercapnia, increased sympathetic activity and sleep fragmentation, places a serious burden on society and health care. Intermittent hypoxia (IH), which cause central nervous system (CNS) inflammation, and ultimately lead to neuropathy, is thought to be a crucial contributor to cognitive impairment in OSAS. Wnt signaling pathway exerts an important role in the regulation of CNS disorders. Particularly, it may be involved in the regulation of neuroinflammation and cognitive dysfunction. However, its underlying mechanism remains poorly understood. Accumulating evidence demonstrated that Wnt signaling pathway may inhibited in a variety of neurological disorders. Recently studies revealed that SUMOylation was participated in the regulation of neuroinflammation. Members of Wnt/ß-catenin pathway may be targets of SUMOylation. In vitro and in vivo molecular biology experiments explored the regulatory mechanism of SUMOylation on Wnt/ß-catenin in IH-induced neuroinflammation and neuronal injury, which demonstrated that IH induced the SUMOylation of ß-catenin, microglia mediated inflammation and neuronal damage. Moreover, SENP1 regulated the de-SUMOylation of ß-catenin, triggered Wnt/ß-catenin pathway, and alleviated neuroinflammation and neuronal injury, thus improving IH-related mice cognitive dysfunction.

TMX2 potentiates cell viability of hepatocellular carcinoma by promoting autophagy and mitophagy.

The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment.Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.

Prevalence and risk evaluation of cardiovascular disease in the newly diagnosed prostate cancer population in China: A nationwide, multi-center, population-based cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Assembled RhRuFe Trimetallene for Water Electrolysis.

Industrializing water electrolyzers demands better electrocatalysts, especially for the anodic oxygen evolution reaction (OER). The prevailing OER catalysts are Ir or Ru-based nanomaterials, however, they still suffer from insufficient stability. An alternative yet considerably less explored approach is to upgrade Rh, a known stable but moderately active element for OER electrocatalysis, via rational structural engineering. Herein, a precise synthesis of assembled RhRuFe trimetallenes (RhRuFe TMs) with an average thickness of 1 nm for boosting overall water splitting catalysis is reported. Favorable mass transport and optimized electronic structure collectively render RhRuFe TMs with an improved OER activity of an overpotential of 330 mV to deliver 10 mA cm-2, which is significantly lower than the Rh/C control (by 601 mV) and reported Rh-based OER electrocatalysts. In particular, the RhRuFe TMs-based water splitting devices can achieve the current density of 10 mA cm-2 at a low voltage of 1.63 V, which is among the best in the Rh-based bifunctional catalysts for electrolyzers. The addition of Fe in RhRuFe TMs can modulate the strain/electron distribution of the multi-alloy, which regulates the binding energies of H* and OH* in hydrogen and oxygen evolution reactions for achieving the enhanced bifunctional OER and HER catalysis is further demonstrated.

The effect of internal orifice narrowing in laparoscopic inguinoscrotal hernia repair to prevent seroma formation: a prospective double-blind randomized controlled trial.

OBJECTIVES: Seroma represents the most prevalent postoperative complication following laparoscopic inguinal hernia repair, particularly in the case of large inguinoscrotal hernias. This randomized controlled trial was undertaken with the objective of assessing the effects of internal orifice narrowing achieved by suturing the divided distal hernia sac in laparoscopic repair of indirect inguinoscrotal hernias. METHODS: A total of 58 patients aged 18 years or older, were randomized into two groups: Group I, which underwent internal orifice narrowing, and Group II, which served as the control without narrowing. The study's primary endpoint was the incidence and volume of seroma in the inguinal region on postoperative days 1 and 7, as well as at 1, 3, and 6 months following the procedure. Secondary outcomes encompassed metrics like total operative time, acute and chronic pain levels, duration of hospital stay, recurrence rates, and the occurrence of any additional complications. RESULTS: In comparison to the control group, the experimental group exhibited a significantly lower incidence of seroma formation at 7 days (P = 0.001). Furthermore, the ultrasonic assessment indicated a reduced seroma volume in the operative group on postoperative day 7 (8.84 ± 17.71 vs. 52.39 ± 70.78 mL; P < 0.001). Acute pain levels and hospital stay were similar between the two groups (1.22 ± 0.76 vs. 1.04 ± 0.53, P = 0.073; 1.22 ± 0.07 vs. 1.19 ± 0.08, P = 0.627, respectively). Notably, neither chronic pain nor early recurrence, nor any other postoperative complications were observed in either group throughout the follow-up period, which extended for at least 6 months (range: 6-18 months). CONCLUSION: In the context of laparoscopic inguinoscrotal hernia repair, the incidence and volume of seroma can be significantly reduced through the implementation of internal orifice narrowing achieved by suturing the divided distal hernia sac. And, this reduction in seroma formation was not associated elevation in postoperative pain levels or recurrence rates.

Sleep disordered breathing and neurobehavioral deficits in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Sleep disordered breathing (SDB) is broadly recognized to be associated with neurobehavioral deficits, which have significant impacts on developing-aged children and adolescents. Therefore, our study aimed to quantify the proportion of neurobehavioral impairments attributed to SDB in general children and adolescents by population attributable fraction (PAF). METHODS: The study was registered at PROSPERO (ID: CRD42023388143). We collected two types of literature on the prevalence of SDB and the risk of SDB-related neurobehavioral deficits from ten electronic databases and registers, respectively. The pooled effect sizes (Pe, Pc, RR) by random-effects meta-analysis were separately substituted into Levin's formula and Miettinen's formula to calculate PAFs. RESULTS: Three prevalence literature and 2 risk literature, all with moderate/high quality, were included in the quantitative analysis individually. The prevalence of SDB was 11% (95%CI 2%-20%) in children and adolescents (Pe), while the SDB prevalence was 25% (95%CI 7%-42%) in neurobehavioral patients (Pc). SDB diagnosis at baseline was probably associated with about threefold subsequent incidence of neurobehavioral deficits (pooled RR 3.24, 95%CI 1.25-8.41), after multi-adjustment for key confounders. Up to 19.8% or 17.3% of neurobehavioral consequences may be attributed to SDB from Levin's formula and Miettinen's formula, respectively. CONCLUSIONS: A certain number of neurobehavioral consequences may be attributable to SDB. It is essential for clinicians to identify and treat SDB timely, as well as screen for SDB in patients with neurobehavioral impairments. More longitudinal studies of SDB and neurobehavioral deficits are needed in the future to further certify the association between them.

An automatic diagnostic system for the urodynamic study applying in lower urinary tract dysfunction.

OBJECTIVE: To establish an automatic diagnostic system based on machine learning for preliminarily analysis of urodynamic study applying in lower urinary tract dysfunction (LUTD). METHODS: The eight most common conditions of LUTDs were included in the present study. A total of 527 eligible patients with complete data, from the year of 2015 to 2020, were enrolled in this study. In total, two global parameters (patients' age and sex) and 13 urodynamic parameters were considered to be the input for machine learning algorithms. Three machine learning approaches were applied and evaluated in this study, including Decision Tree (DT), Logistic Regression (LR), and Support Vector Machine (SVM). RESULTS: By applying machine learning algorithms into the 8 common LUTDs, the DT models achieved the AUC of 0.63-0.98, the LR models achieved the AUC of 0.73-0.99, and the SVM models achieved the AUC of 0.64-1.00. For mutually exclusive diagnoses of underactive detrusor and acontractile detrusor, we developed a classification model that classifies the patients into either of these two diseases or double-negative class. For this classification method, the DT models achieved the AUC of 0.82-0.85 and the SVM models achieved the AUC of 0.86-0.90. Among all these models, the LR and the SVM models showed better performance. The best model of these diagnostic tasks achieved an average AUC of 0.90 (0.90 ± 0.08). CONCLUSIONS: An automatic diagnostic system was developed using three machine learning models in urodynamic studies. This automated machine learning process could lead to promising assistance and enhancements of diagnosis and provide more useful reference for LUTD treatment.

Reconstruction of the TGF-ß signaling pathway of Fasciola gigantica.

In the present study, we reconstructed the transforming growth factor beta (TGF-ß) signaling pathway for Fasciola gigantica, which is a neglected tropical pathogen. We defined the components involved in the TGF-ß signaling pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (FgESP) was predicted via signal peptide annotation. The core components of the TGF-ß signaling pathway have been detected in F. gigantica; classical and nonclassical single transduction pathways were constructed. Four ligands have been detected, which may mediate the TGF-ß signaling pathway and BMP signaling pathway. Two ligand-binding type II receptors were detected, and inhibitory Smad7 was not detected. TLP, BMP-3, BMP-1, and ActRIb showed higher transcription in 42-day juvenile and 70-day juvenile, while ActRIIa, Smad1, ActRIIb, Smad8, KAT2B, and PP2A showed higher transcription in egg. TLM, Ski, Smad6, BMPRI, p70S6K, Smad2, Smad3, TgfßRI, Smad4, and p300 showed higher transcription in metacercariae. Four ligands, 2 receptors and 3 Smads are predicted to be present in the FgESP, suggesting their potential extrinsic function. This study should help to understand signal transduction in the TGF-ß signaling pathway in F. gigantica. In addition, this study helps to illustrate the complex mechanisms involved in developmental processes and F. gigantica - host interaction and paves the way for further characterization of the signaling pathway in trematodes.

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

[Effect of Combined Application of an Enterobacter and Sulfur Fertilizer on Cadmium and Arsenic Accumulation in Rice].

The aim of this study was to explore the effects of different sulfur fertilizers combined with sulfate-reducing bacteria on the accumulation of cadmium and arsenic in rice and the formation of iron plaque under long-term flooding conditions and to provide a reference for the safe production of rice fields polluted by moderate and mild cadmium and arsenic. We adopted a pot experiment, selecting two sulfur fertilizers, sulfur and calcium sulfate, and Enterobacter M5 with sulfate-reducing ability, and designed six treatments of single application and combined application of different sulfur fertilizers and M5. The results showed that the combined application of calcium sulfate and M5(CM5) had the best effect on reducing available cadmium and arsenic in rice rhizosphere soil. The combined application of sulfur fertilizer or M5 could reduce the content of cadmium and inorganic arsenic in early season rice grains by 8%-51% and 42%-61%, respectively, under flooding conditions. The content of cadmium and inorganic arsenic in late rice grains decreased by 81%-92% and 41%-62%, respectively. The treatment of the combined application of sulfur and M5(SM5) and CM5 had the best effect on reducing cadmium and arsenic content in both early and late season rice grains. SM5 and CM5 could promote the adsorption of cadmium and arsenic by iron plaque, and the extracted cadmium and arsenic content of ACA in both treatments was significantly higher than that of CK. The extracted iron content of ACA in the CM5 treatment was also significantly higher than that of CK, which indicates that the combined application of calcium sulfate and M5 would promote the formation of iron plaque. The results showed that the combined application of sulfur fertilizer and M5 was better than single application in reducing the content of cadmium and arsenic in grains, whereas the combined application of calcium sulfate and M5 was the best and most stable method.

Cuproptosis-Associated lncRNA Gene Signature Establishes New Prognostic Profile and Predicts Immunotherapy Response in Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

Letter to the editor: Aggressive variant prostate cancer: An exemplary case study and comprehensive literature survey.

This article enthusiastically explores the study of highly aggressive variant prostate cancer (AVPC), acknowledging its relatively rare yet highly menacing presence within the realm of prostate cancer. The paper delves into the pathological characteristics of AVPC, diagnostic and therapeutic challenges, and the potential applications of precision medicine and molecular imaging in the future.

High-Performance Ethylene Glycol Sensor Based on Imine Covalent Organic Frameworks.

The colorless and odorless ethylene glycol is prone to unknowingly causing poisoning, making preventive monitoring of ethylene glycol necessary. In this paper, scandium (III) trifluoromethanesulfonate was used as a catalyst to successfully prepare covalent organic framework (COF) nanospheres linked by imines at room temperature. The COF nanospheres were characterized by XRD, SEM, TEM, FT-IR, UV-Vis and BET. The results show that COF nanospheres have rough surfaces and a large number of mesoporous structures, which greatly increase the active sites on the surface of the sensing material and enhance the gas sensing performance. The sensing results showed that the prepared imine-conjugated COF nanospheres exhibited a good response-recovery ability for 10 consecutive response-recovery cycles for ethylene glycol at room temperature and had a theoretical detection limit of 40 ppb. In addition, the responses of COF nanospheres to nearly 20 interfering gases, including HCl, HNO3, phenol, formaldehyde and aniline, are relatively low compared to the response to ethylene glycol, indicating that the COF nanospheres have high selectivity towards ethylene glycol. The COF nanospheres show good sensitivity and selectivity for the detection of ethylene glycol, which should be attributed to the large specific surface area, hydrogen bonding interactions, and high defects. This work provides an effective method for the detection of ethylene glycol and expands the application field of COF materials.