Pregnane X receptor (PXR) deficiency promotes hepatocarcinogenesis via induction of Akr1c18 expression and prostaglandin F2α (PGF2α) levels.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Pregnane X receptor (PXR), a xenobiotic-sensing nuclear receptor, plays a critical role in the metabolism of endogenous and exogenous substances in the liver. Here, we investigate whether PXR plays a role in pathogenesis of HCC. We show that liver tumors were developed in diethylnitrosamine (DEN)-treated in PXR knockout (KO) mice. Hepatic levels of prostaglandin F2α (PGF2α) and aldo-keto reductase family 1 member C18 (Akr1c18), a prostaglandin synthase of catalyzing reduction of PGH2 to PGF2α, were significantly elevated in DEN-treated PXR KO mice. Hepatic mRNA levels of alpha fetoprotein (AFP), cyclin D1 (Ccnd1), fibroblast growth factor 21 (FGF21), and inflammatory cytokine interleukin 6 (IL-6) were significantly increased in DEN-treated PXR KO mice. Other members of Akr1c family, liver metabolizing enzymes including Cyp1a2, Cyp2b10 and Cyp3a11, and bile acid synthesis enzyme Cyp7a1 mRNA levels were significantly decreased in DEN-treated PXR KO mice. Our findings revealed that PXR deficiency promoted DEN-induced HCC in mice via induction of Akr1c18 expression and PGF2α levels and the increased PGF2α levels synthetized by Akr1c18 enhanced hepatocytes proliferation and induced inflammatory cytokine production, which accelerated liver tumor development after DEN treatment, suggesting that PXR deficiency may create a microenvironment that is more prone to DEN-induced liver tumors and targeting PXR and Akr1c18 to reduce PGF2α biosynthesis may be a potential and novel therapeutic strategy for HCC.

Gelation and Plugging Performance of Low-Concentration Partially Hydrolyzed Polyacrylamide/Polyethyleneimine System at Moderate Temperature and in Fractured Low-Permeability Reservoir.

HPAM/PEI gel is a promising material for conformance control in hydrocarbon reservoirs. However, its use in low-permeability reservoirs is limited by the high polymer concentrations present. In this study, the gelation performance of an HPAM/PEI system with HPAM < 2.0 wt.% was systematically investigated. The gelation time for HPAM concentrations ranging from 0.4 to 2.0 wt.% varied from less than 1 h to 23 days, with the highest gel strength identified as grade H. The hydrodynamic radius manifested the primary effect of HPAM on the gelation performance. Branched PEI provided superior gelation performance over linear PEI, and the gelation performance was only affected when the molecular weight of the PEI varied significantly. The optimal number ratio of the PEI-provided imine groups and the HPAM-provided carboxylic acid functional groups was approximately 1.6:1~5:1. Regarding the reservoir conditions, the temperature had a crucial effect on the hydrodynamic radius of HPAM. Salts delayed the gelation process, and the order of ionic influence was Ca2+ > Na+ > K+. The pH controlled the crosslinking reaction, primarily due to the protonation degree of PEI and the hydrolysis degree of HPAM, and the most suitable pH was approximately 10.5. Plugging experiments based on a through-type fracture showed that multi-slug plugging could significantly improve the plugging performance of the system, being favorable for its application in fractured low-permeability reservoirs.

A c-di-GMP signaling module controls responses to iron in Pseudomonas aeruginosa.

Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a bacterial second messenger that modulates various processes including biofilm formation, motility, and host-microbe symbiosis. Numerous studies have conducted comprehensive analysis of c-di-GMP. However, the mechanisms by which certain environmental signals such as iron control intracellular c-di-GMP levels are unclear. Here, we show that iron regulates c-di-GMP levels in Pseudomonas aeruginosa by modulating the interaction between an iron-sensing protein, IsmP, and a diguanylate cyclase, ImcA. Binding of iron to the CHASE4 domain of IsmP inhibits the IsmP-ImcA interaction, which leads to increased c-di-GMP synthesis by ImcA, thus promoting biofilm formation and reducing bacterial motility. Structural characterization of the apo-CHASE4 domain and its binding to iron allows us to pinpoint residues defining its specificity. In addition, the cryo-electron microscopy structure of ImcA in complex with a c-di-GMP analog (GMPCPP) suggests a unique conformation in which the compound binds to the catalytic pockets and to the membrane-proximal side located at the cytoplasm. Thus, our results indicate that a CHASE4 domain directly senses iron and modulates the crosstalk between c-di-GMP metabolic enzymes.

FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma.

BACKGROUND: Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper. AIM: To explore the identification of potential biomarkers for STAD disease based on cuproptosis. METHODS: A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas. RESULTS: Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11. CONCLUSION: Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

[Effects of Biochar Application on the Structure and Function of Fungal Community in Continuous Cropping Watermelon Soil].

This study was conducted to clarify the long-term effects of biochar application on the structure and function of the fungal community in continuous cropping watermelon soil. Taking watermelon root soil as the research object, Illumina NovaSeq high-throughput sequencing and FUNGuild platform were used to analyze the differences in soil fungal community composition, diversity, and function after 3-year biochar additions of 7.5, 15.0, and 30.0 t·hm-2 and to explore the correlation between soil environmental factors and fungal community structure under the control of biochar. The results showed that compared to that in the absence of biochar (control), the soil pH, available phosphorus, available potassium, total nitrogen, organic matter, and cation exchange capacity increased, but available nitrogen decreased with biochar addition. High-throughput sequencing results showed that biochar amendment improved the fungal community structure in continuous cropping watermelon soil and increased the richness and diversity of soil fungi. A total of 922 OTU were obtained from all soil samples, and the species annotation results indicated that the dominant fungal groups were Ascomycota, Basidiomycota, Mortierellomycota, Chytridiomycota, and Glomeromycota, with these phyla accounting for 85.70 %-92.45 % of the total sequences.The relative abundance of Ascomycota and Basidiomycota decreased, whereas the abundance of Mortierellomycota and Glomeromycota increased with biochar addition.At the genus level, the application of biochar increased the relative abundance of Mortierella and Rhizophlyctis but decreased the abundance of Fusarium. The Mantel test showed that soil available potassium, available nitrogen, organic matter, and pH were the main environmental factors leading to the shift in the soil fungal community composition.The functional prediction with FUNGuild showed that the many nutrient types among the different treatments were saprotrophic, pathotrophic, and symbiotrophic. The relative abundance of pathotrophs significantly decreased, but the abundance of symbiotrophs significantly increased with the medium and high doses of biochar treatment. In conclusion, the application of biochar changed the soil physicochemical properties, promoted the development of soil fungal community structure and functional groups in a healthy and beneficial direction, and improved the quality of continuous cropping watermelon soil.

Influence of protonic acid on the structure and properties of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) in oxidation polymerization.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is widely used because of its excellent performance. We report the synthesis of two PEDOT:PSS dispersions. The two dispersions differ by the addition of additional protonic acid in the oxidative polymerization system. Although there are examples of the introduction of acids into the polymerization system, the effects of acid on the structure and properties of these materials, in particular their mechanisms of action, have not been elucidated. We describe the chemical structure and molecular weight of two PEDOT polymers using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, UV-vis-NIR spectroscopy, and density functional theory calculations. The carrier concentration, carrier mobility, and surface morphology of the composites are characterized by UV-vis-NIR spectroscopy, electron spin resonance, Raman spectra, Hall effect measurements, and atomic force microscopy. The crystallinity of PEDOT:PSS was measured by X-ray diffraction patterns. We show that the addition of a proper amount of protonic acid to the oxidative polymerization system can effectively reduce the formation of the terminal carbonyl group of PEDOT chains, which is conducive to the growth of polymer chains, and further improve the carrier concentration, which leads to an improvement of conductivity. Our results highlight the optimization of the chemical structure of PEDOT in order to increase its molecular weight and ultimately its conductivity.

The effect of developmental care on the length of hospital stay and family centered care practice for very low birth weight infants in neonatal intensive care units: A cluster randomized controlled trial.

BACKGROUND: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. OBJECTIVE: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DESIGN: Cluster-randomized controlled trial. SETTING(S) AND PARTICIPANTS: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. METHODS: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. RESULTS: The length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451-0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. CONCLUSIONS: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. REGISTRATION: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.

Association between serum total bilirubin and diabetic kidney disease in US diabetic patients.

Background: Bilirubin has been widely reported to be a protective factor against diabetic kidney disease (DKD) in Asian populations. However, few large-sample analyses have been conducted in American populations. This study aimed to investigate the association between serum total bilirubin (STB) level and DKD in a US diabetic cohort. Methods: This cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Univariate and multivariate logistic regression analyses were performed to assess the association between STB level and DKD. Three models were conducted to control the potential confounding factors. Subgroup analysis was carried out for further validation. Results: Among the 5,355 participants, the median age [interquartile range (IQR)] was 62 [52-71] years; 2,836 (52.96%) were male, and 1,576 (29.43%) were diagnosed with DKD. In the entire cohort, no significant association between STB level and DKD was observed in any logistic regression models (p > 0.05). Subgroup analysis revealed that, in U.S. diabetic males, STB levels > 11.98 µmol/L were associated with a nearly 30% lower risk of DKD than STB levels ≤ 8.55 µmol/L. Additionally, a moderate STB level (8.56-11.98 µmol/L) was found associated with a nearly 25% lower risk of DKD in U.S. diabetic patients over 65 years old. Conclusion: The association of STB level with DKD may depict differences across diverse populations, among which the impact of race, sex, and age requires thorough consideration and relevant inferences should be interpreted cautiously.

Transcatheter tricuspid valve replacement via vena jugularis interna: A case report / 中国胸心血管外科临床杂志

@#We reported a 54-year-old female patient with severe tricuspid regurgitation, who received mechanic valve in the mitral position 15 years ago. The patient’s Society of Thoracic Surgeons score was 8.27%, and was intolerant to open heart surgery, so she was recommended for transcatheter tricuspid valve replacement via right vena jugularis interna. The procedures were guided by echocardiography and X ray fluoroscopy on November 13, 2021, the prosthesis was implanted successfully, and the patient was recoved without any adverse events. After 1 month follow-up, her general condition was apparently improved.

Safety and efficacy of transcatheter tricuspid valve replacement with LuX-Valve in patients with severe tricuspid regurgitation / 中华心血管病杂志

Objectives: To evaluate the safety and efficacy of LuX-Valve on the treatment of severe tricuspid regurgitation (TR). Methods: This is a prospective observational study. From September 2018 to March 2019, 12 patients with severe TR, who were not suitable for surgery, received LuX-Valve implantation in Changhai Hospital. LuX-Valve was implanted under general anesthesia and the guidance of transesophageal echocardiography and X-ray fluoroscopy. Access to the tricuspid valve was achieved via a minimally invasive thoracotomy and transatrial approach. Main endpoints were surgery success and device success. Surgery success was defined as successful implanting the device and withdrawing the delivery system, positioning the valve correctly and stably without severe or life-threatening adverse events. Device success was defined as satisfied valve function (TR severity reduction ≥ 2 grades, tricuspid gradient ≤ 6 mmHg (1 mmHg=0.133 kPa)), absence of malposition, valve failure and reintervention, major adverse events including device related mortality, embolization, conduction system disturbances and new onset shunt across ventricular septum at day 30 post implantation. Results: A total of 12 patients with severe to torrential TR were included in this study. The age was (68.5±6.9) years and 7 were female. All patients had typical right heart failure symptoms. Procedural success was achieved in all cases, there was no intraprocedural mortality or transfer to open surgery. TR significantly improved after LuX-Valve implantation (none/trivial in 8 patients, mild in 3 patients and moderate in 1 patient). The average device time was (9.2±4.2) minutes. Intensive care unit duration was 3.0 (2.0, 4.8) days. One patient died at postoperative day 18 due to non-surgery and device reasons. Transthoracic echocardiography at 30 days after operation showed that TR was significantly reduced (none/trivial in 8 patients, mild in 2 patients and moderate in 1 patient) and device success was achieved in 11 cases. All survived patients experienced a significant improvement in life quality with significantly improvement in New York Heart Association (NYHA) classification (Ⅰ and Ⅱ: 6/11 post operation vs. 0/11 before operation, P=0.012) and there were no device related complications in this patient cohort. Conclusions: LuX-Valve implantation is feasible, safe and effective for the treatment of patients with severe TR.

Throat Infection, Neck and Chest Pain and Cardiac Response: A Persistent Infection-Related Clinical Syndrome / 华中科技大学学报（医学）（英德文版）

Dizziness,chest discomfort,chest depression and dyspnea are a group of symptoms that are common complaints in clinical practice. Patients with these symptoms are usually informed that while neurosis consequent to coronary heart disease is excluded nonetheless they remain unhealthy with no rational explanation or treatment. 165 cases of these symptoms and 85 control subjects were reviewed and underwent further medical history inquiry,routine EKG test and cardiac ultrasound examination. Thirty-five patients received coronary artery angiography to exclude coronary heart disease. Serum myocardial autoantibodies against beta1-adrenoceptor,alpha-myosin heavy chain,M2-muscarinie receptor and adenine-nucleotide translocator were tested,and inflammatory cytokines and high sensitivity C-reaction protein were measured and lymphocyte subclass was assayed by flow cytometry. All patients had a complex of four symptoms or tetralogy: (1) persistent throat or upper respiratory tract infection,(2) neck pain,(3) chest pain and (4) chest depression or dyspnea,some of them with anxiety. Anti-myocardial autoantibodies (AMCAs) were present in all patients vs. 8% in and CD4-CD8+ lymphocytes were significantly higher and CD56+ lymphocytes lower in patients than those in controls (P<0.01). The ratio of serum pathogen antibodies positive against Coxsackie virus-B,cytomegalovirus,Mycoplasma pneumoniae and Chlamydia pneumoniae were all markedly higher in patients. These data led to identification of a persistent respiratory infection-related clinical syndrome,including persistent throat infection,neck spinal lesion,fib cartilage inflammation,symptoms of car-diac depression and dyspnea with or without anxiety.