Effectiveness of a Full Course Health Education in the Care of Patients with Chronic Kidney Disease Receiving Peritoneal Dialysis.

Background: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis face numerous challenges that can impact their health behaviors, treatment adherence, and overall quality of life. A comprehensive health education program tailored for CKD patients on peritoneal dialysis is imperative to enhance the effectiveness of treatment and address these issues. Objective: The primary objective was to evaluate the impact of a full course health education program on health behaviors, treatment adherence, quality of life, and the occurrence of adverse events in CKD patients receiving peritoneal dialysis. Methods: A total of 98 CKD patients on peritoneal dialysis at our hospital between October 2019 and October 2022 were selected. The patients were randomly assigned to receive either routine care (n=52) or participate in a full-course health education program (n=46). The comparative assessments included health behavior scores, treatment adherence, Kidney Disease Targeted Area (KDTA) scores, monitoring adverse events, and tracking readmissions. Results: Patients in the observation group who underwent the full course health education program exhibited significant improvements in health behavior scores and treatment adherence (P < .05). Notably, the observation group demonstrated higher levels of medication compliance, timely reviews, and catheter maintenance. Moreover, full-course health education contributed to an enhanced quality of life, reflected in higher KATA scores, and led to a reduction in adverse events and readmission rates compared to routine care (P < .05). Conclusions: This study concludes that a full-course health education program is effective in improving health behaviors, treatment adherence, and quality of life while reducing adverse events among CKD patients undergoing peritoneal dialysis.

Ursolic acid attenuates cholestasis through NRF2-mediated regulation of UGT2B7 and BSEP/MRP2.

Ursolic acid (UA), a pentacyclic triterpenoid, exhibits various pharmacological actions, such as anti-inflammation, anti-tumor, anti-diabetes, heart protection, and liver protection. However, the role of nuclear factor E2-related factor 2 (NRF2)-mediated regulation of uridine diphosphate glucuronosyltransferase (UGT2B7) and bile salt export pump (BSEP)/multidrug resistance-associated protein 2 (MRP2) in UA against cholestatic liver injury has not been cleared. The purpose of this study is to explore the effect of UA on cholestatic liver injury and its potential mechanism. The results of the liver pathology sections and blood biochemical indices demonstrated that UA significantly attenuated the cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) in a dose-dependent manner. The mRNA and protein levels of UGT2B7 and BSEP/MRP2 were remarkably increased in the liver of ANIT rats and HepG2 cells pretreated with UA, but this activation was suppressed with NRF2 silenced. In conclusion, our findings demonstrate that UA prevents cholestasis, which may be associated with NRF2-mediated regulation of UGT2B7, BSEP/MRP2.

The Impact of Emotional Care on Poor Mood, Quality of Life and Self-Efficacy in Patients with Chronic Primary Kidney Disease.

Objective: To investigate the impact of affective care on poor mood, quality of life, and self-efficacy in patients with chronic primary kidney disease. Methods: Between January 2020 and January 2021, 112 patients treated in our hospital were divided into a control group (n=55, receiving conventional care) and a research group (n=57, using emotional nursing in addition to conventional care), and the anxiety self-assessment scale (SAS) scores, depression self-assessment scale (SDS) scores, kidney disease quality of life (KDQOL-SF) scores, and the quality of life (KDQOL-SF) scores developed by the Center for Chronic Disease Education, Stanford University, USA were compared before and aftercare. The results of the study group were compared with those of the KDQOL-SF, the Self-Efficacy Scale developed by the Center for Chronic Disease Education and Research, Stanford University, USA, and the adherence to care. Results: After the intervention, the research group had lower SAS and SDS scores than the control group (P < .05). After the intervention, all KDQOL-SF scores and all self-efficacy scores were higher in the research group than in the control group (P < .05). The research group had a higher nursing care adherence rate of 92.98% than the control group of 78.18% (P < .05). Conclusion: Emotional nursing can help improve the poor mood of patients with chronic primary kidney disease, improve their quality of life, and strengthen their self-efficacy, and the overall nursing compliance of patients is higher, which is of high clinical application.

Titanium-Based Superlattice with Fe(III)-Regulable Bandgap and Performance for Optimal and Synergistic Sonodynamic-Chemotherapy Guided by Magnetic Resonance Imaging.

Superlattices have considerable potential as sonosensitizers for cancer therapy because of their flexible and tunable band gaps, although they have not yet been reported. In this study, a Ti-based organic-inorganic superlattice with good electron-hole separation was synthesized, which consisted of orderly layered superlattices of 2,2'-bipyridine-5,5'-dicarboxylic acid (BPDC) and Ti-O layers. In addition, the superlattice was coordinated with Fe(III) and encapsulated doxorubicin (DOX) to prepare Ti-BPDC@Fe@DOX@PEG (TFDP) after biocompatibility modification. TFDP can realize the simultaneous generation of reactive oxygen species and release of DOX under ultrasound irradiation. Moreover, adjusting the Fe(III) content can effectively modulate the band gap of the superlattice and increase the efficiency of sonodynamic therapy (SDT). The mechanisms underlying this modulation were explored. TFDP with Fe(III) can also be used as a contrast agent for magnetic resonance imaging (MRI). Both in vitro and in vivo experiments demonstrated the ability of TFDP to precisely treat cancer using MRI-guided SDT/chemotherapy. This study expands the applications of superlattices as sonosensitizers with flexible and tailored modifications and indicates that superlattices are promising for precise and customized treatments.

Zero Thermal Quenching Phenomenon of Green Emitting Carbon Dots with High Biocompatibility and Stable Multicolor Biological Imaging in a Hot Environment.

Carbon dots are emerging fluorescent nanomaterials with unique physical and chemical properties and a wide range of applications. Herein, we have designed and successfully synthesized thermally stable green emissive nitrogen-doped carbon dots (NCDs) with a photoluminescent quantum yield of 11.32% through facile solvent-free carbonization. NCDs demonstrated zero thermal quenching upon various temperatures modulating from 20 to 80 °C. The green emissive NCDs perform very stably even after heating them at 80 °C for 1 h. The thermal stability mechanism demonstrates that C═O and C═N functional groups control the particle aggregation and protect the fluorescent hub from photo-oxidation and thermal oxidation. Highly biocompatible CDs exhibit bright, stable, and multicolor emissions in T-ca cells under hot circumstances (25-45 °C). Additionally, NCDs offer long-term stability in the biosystem, as evidenced by the fact that the cell retains its brightness about 70% after prolonging the incubation time to 8 days. Furthermore, the fluorescent NCDs are utilized as in vivo imaging agents in the hot environment as they display bright and thermally stable imaging (27-45 °C) under 488 nm excitation. The results confirmed that the produced thermally stable NCDs could be used in biology and related medical fields that require hot environment imaging.

Successful treatment of lung adenocarcinoma complicated with a rare compound EGFR mutation L833V/H835L using aumolertinib: a case report and literature review.

Background: The deletion of exon 19 and the Leu858Arg mutation of exon 21 are the most frequently observed mutations in the epidermal growth factor receptor (EGFR) gene, and patients with these mutations have shown significant benefits from EGFR-tyrosine kinase inhibitors (TKIs). However, there exists a small subgroup of patients with uncommon/rare mutations of EGFR, including compound mutations, which display a high degree of heterogeneity in terms of clinical features and variable sensitivities to EGFR-TKIs. The understanding of these uncommon mutations and their response to targeted therapy is still unclear and requires further investigation. Case presentation: We presented a case of a never-smoking patient with lung adenocarcinoma and brain metastasis. Initially, she received chemotherapy plus immune checkpoint inhibitor as first-line therapy as no EGFR mutations were detected by amplification-refractory mutation system-polymerase chain reaction. However, disease progressed rapidly. Subsequently, next-generation sequencing was carried out and revealed a rare compound mutation, L833V/H835L, in exon 21 of EGFR. As a result, she was switched to second-line therapy with the third-generation TKI aumolertinib, which demonstrated good efficacy. The patient was evaluated for a remarkable progression-free survival of 18 months and an overall survival of 29 months. Conclusion: The present study supports that aumolertinib might be a good treatment option for advanced NSCLC patients with EGFR L833V/H835L mutation, particularly in patients with brain metastasis. Furthermore, conducting a comprehensive screening for gene mutations is crucial in effectively identifying potential oncogenic driver mutations and guiding mutation-targeted therapy decisions in clinical practice.

High biocompatible nitrogen and sulfur Co-doped carbon dots for Hg(II) detection and their long-term biological stability in living cells.

Fluorescent carbon dots have been highly reported nanomaterials in recent times because of their excellent physio-chemical properties and various field of applications. Herein, a one-step hydrothermal approach was used to synthesize high biocompatible nitrogen and sulfur co-doped carbon dots, and examined their chemical sensing (Hg2+) and biological imaging properties. The N,S-CDs exhibited blue light, demonstrating a high quantum yield of up to 44.5% and excitation-independent fluorescent characteristics. Cytotoxicity was observed by CCK-8 assay using T-ca cells as a target source. Cell viability was recorded over 80% even after 7 days of treatment with a concentration up to 400 µg/mL, indicating low-toxicity of N,S-CDs. Notably, the bright blue fluorescence of N,S-CDs was quenched by introducing toxic Hg2+ ions into the solution. The detection limit was calculated to be about ∼3.5 nM, which is quite impressive compared to previous reports. Because of their low-toxicity, nano-size, and environment friendly properties, N,S-CDs could be excellent fluorescent agents for bio-imaging applications. The biological stability of fluorescent N,S-CDs was tested over time, and the findings were significant even after 8 days of incubation with T-ca cells. Because of good biocompatibility and bright fluorescence, N,S-CDs were suitable for in vivo imaging.

Characterization and protective effect against ultraviolet radiation of a novel exopolysaccharide from Bacillus marcorestinctum QDR3-1.

Although exopolysaccharide (EPS) has been applied to various fields, EPS for UVR-mediated oxidative stress repair still needs further exploration. In this study, a novel EPS was isolated from the fermentation medium of Bacillus sp. QDR3-1 and its yield was 4.8 g/L (pH 8.0, 12 % glucose, 30 °C and 6 % NaCl). The pure fraction (named EPS-M1) was purified by DEAE-cellulose and Sephadex G-100 column. EPS-M1 was a heteropolysaccharide composed of Man, Glc, Gal, and Fuc with a molecular weight of 33.8 kDa. Scanning electron microscopy (SEM) observed a rough surface and reticular structure of EPS-M1, and EPS-M1 formed spherical aggregates in aqueous solution observed in atomic force microscopy (AFM). Thermal analysis revealed that the degradation temperature of EPS-M1 was 306 °C. Moreover, methylation and NMR analysis determined that EPS-M1 was consisted of →3)-Manp-(1→, →2,6)-Manp-(1→, →4,6)-Glcp-(1→, →3)-Glcp-(1→, →4)-Galp-(1→, →4)-Fucp-(1→, and T-Manp-(1→. Furthermore, the cytotoxicity and the repair ability of UVR-mediated cell damage of EPS-M1 were studied with L929 cells. The results showed that EPS-M1 had good biocompatibility and it could mitigate UVR-mediated cell damage by regulating the levels of cellular reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (MMP) and Caspase-3/7 activity. Overall, the structure analysis and the protective effects of EPS against L929 cells exposed to UVR provided an experimental basis for EPS in practical applications.

An auto-inhibited state of protein kinase G and implications for selective activation.

Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory (AI) pseudo-substrate sequences to PKG Iα and Iß that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation by cGMP is not well understood. Here, we present a crystal structure of PKG Iß in which the AI sequence and the cyclic nucleotide-binding (CNB) domains are bound to the catalytic domain, providing a snapshot of the auto-inhibited state. Specific contacts between the PKG Iß AI sequence and the enzyme active site help explain isoform-specific activation constants and the effects of phosphorylation in the linker. We also present a crystal structure of a PKG I CNB domain with an activating mutation linked to Thoracic Aortic Aneurysms and Dissections. Similarity of this structure to wildtype cGMP-bound domains and differences with the auto-inhibited enzyme provide a mechanistic basis for constitutive activation. We show that PKG Iß auto-inhibition is mediated by contacts within each monomer of the native full-length dimeric protein, and using the available structural and biochemical data we develop a model for the regulation and cooperative activation of PKGs.

Design of chemically defined synthetic substrate surfaces for the in vitro maintenance of human pluripotent stem cells: A review.

Human pluripotent stem cells (hPSCs) have the potential of long-term self-renewal and differentiation into nearly all cell types in vitro. Prior to the downstream applications, the design of chemically defined synthetic substrates for the large-scale proliferation of quality-controlled hPSCs is critical. Although great achievements have been made, Matrigel and recombinant proteins are still widely used in the fundamental research and clinical applications. Therefore, much effort is still needed to improve the performance of synthetic substrates in the culture of hPSCs, realizing their commercial applications. In this review, we summarized the design of reported synthetic substrates and especially their limitations in terms of cell culture. Moreover, much attention was paid to the development of promising peptide displaying surfaces. Besides, the biophysical regulation of synthetic substrate surfaces as well as the three-dimensional culture systems were described.

Application of lanthanide-doped upconversion nanoparticles for cancer treatment: a review.

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.

Water-soluble green-emitting carbon nanodots with enhanced thermal stability for biological applications.

High stability and water solubility of fluorescent nanomaterials are considered key factors to evaluate their feasibility for fundamental applications. Herein, water-soluble and thermally stable, green-emitting carbon nanodots (CNDs) have been synthesized via a facile hydrothermal method with an average size of 1.9 nm. CNDs showed green emission centered at 544 nm with the photo-luminescence quantum yield (PLQY) of up to 10.1% under the excitation of 400 nm. The obtained CNDs demonstrated high resistance towards photo-bleaching and an ionic (KCl) environment. Moreover, the aqueous solution of CNDs exhibited excellent stability under harsh thermal conditions from 10 °C to 80 °C. The as-prepared CNDs showed stable performance at high temperatures, even after keeping them at 80 °C for 30 min. Furthermore, the green emissive CNDs were incubated in T-ca cancer cells for bio-imaging applications. The results indicated that CNDs can served as an effective thermally-stable bio-imaging agent in T-ca cells at the physiological temperature range of 25 °C-45 °C. Green emission and excellent thermal stability make these CNDs promising fluorescent materials for potential applications in the medical field, which requires long-wavelength fluorescence and high-temperature imaging.

Fluorescent Carbon Dots an Effective Nano-Thermometer in Vitro Applications.

Fluorescent sensing of temperature in nanoscale regions has many advantages and applications in the biological field. Herein, blue emitting carbon dots (CDs) are designed and successfully developed using a one step hydrothermal method. As synthesized CDs exhibit temperature dependent photoluminescent (PL) intensity and PL decay lifetime over the physiological temperature ranging from room temperature (RT) to 70 °C. The PL intensity and PL decay lifetime of the obtained CDs correlate linearly to temperature (RT-70 °C) with correlation coefficient of 0.997 and 0.996, respectively. Additionally, dual mode thermal sensing (PL intensity/lifetime) make these CDs a promising optical nanothermometer over alternative semiconductors quantum dots and CD-based quantum dots. Moreover, the resultant aqueous CDs demonstrate excitation-independent blue emission, and the PL quantum yield (QY) is reached at 44.5%. The obtained CDs illustrate stable performance to high ionic environments and photobleaching even after keeping them for 2 h under continues UV irradiation. Furthermore, blue emitting CDs have low cytotoxicity for T-ca. cells and illuminate deep blue fluorescence under the excitation of 406 nm. As a result, high thermal sensitivity of these fluorescent CDs has potential to detect temperature in living cells in the range of 25-40 °C.

Structural basis for selective inhibition of human PKG Iα by the balanol-like compound N46.

Activation of protein kinase G (PKG) Iα in nociceptive neurons induces long-term hyperexcitability that causes chronic pain. Recently, a derivative of the fungal metabolite balanol, N46, has been reported to inhibit PKG Iα with high potency and selectivity and attenuate thermal hyperalgesia and osteoarthritic pain. Here we determined co-crystal structures of the PKG Iα C-domain and cAMP-dependent protein kinase (PKA) Cα, each bound with N46, at 1.98 Å and 2.65 Å, respectively. N46 binds the active site with its external phenyl ring, specifically interacting with the glycine-rich loop and the αC helix. Phe-371 at the PKG Iα glycine-rich loop is oriented parallel to the phenyl ring of N46, forming a strong π-stacking interaction, whereas the analogous Phe-54 in PKA Cα rotates 30° and forms a weaker interaction. Structural comparison revealed that steric hindrance between the preceding Ser-53 and the propoxy group of the phenyl ring may explain the weaker interaction with PKA Cα. The analogous Gly-370 in PKG Iα, however, causes little steric hindrance with Phe-371. Moreover, Ile-406 on the αC helix forms a hydrophobic interaction with N46 whereas its counterpart in PKA, Thr-88, does not. Substituting these residues in PKG Iα with those in PKA Cα increases the IC50 values for N46, whereas replacing these residues in PKA Cα with those in PKG Iα reduces the IC50, consistent with our structural findings. In conclusion, our results explain the structural basis for N46-mediated selective inhibition of human PKG Iα and provide a starting point for structure-guided design of selective PKG Iα inhibitors.

Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.

cGMP-dependent protein kinase (PKG) Iα is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG Iα by interacting with G-kinase-anchoring proteins. The PKG Iα LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG Iα. To understand the molecular details of the PKG Iα LZ and C42-C42' disulfide bond, we determined crystal structures of the PKG Iα wild-type (WT) LZ and C42L LZ. Our data demonstrate that the C42-C42' disulfide bond dramatically stabilizes PKG Iα and that the C42L mutant mimics the oxidized WT LZ structurally.

Identification and structural basis for a novel interaction between Vav2 and Arap3.

Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. It regulates processes including cell migration, neuronal development and phagocytosis through interactions with different proteins. In this study, Arap3, a dual GTPase-activating protein (GAP) for RhoA and Arf6, was first identified to be a novel interaction partner for Vav2 both in vitro and in vivo. ITC and NMR chemical shift perturbation experiments demonstrated that Vav2 SH2 domain was able to interact directly with phosphorylated Y1403 and Y1408 within the C-terminal region of Arap3 with high affinities, with the dissociation constants (Kd) of ≈ 0.27 and ≈ 1.40 µM, respectively. In addition, using different phosphotyrosine peptides, the pY +3 specificity of Vav2 SH2 domain was discovered. The solution structures of Vav2 SH2 domain in free and in complex with the phosphotyrosine peptide pY1408 were therefore determined to understand the structural basis of this recognition specificity. Structural analysis revealed that the presence of a Phe residue in the BG loop (BG6) leads to the formation of a shallow hydrophobic pY +3 pocket on the surface of Vav2 SH2 domain, which determines the pY +3 specificity of Vav2 SH2 domain.

Using attenuated Salmonella typhi as tumor targeting vector for MDR1 siRNA delivery.

OBJECTIVE: To investigate the feasibility of using attenuated Salmonella typhi as an in vivo delivery vector for multidrug-resistance gene (MDR1) small interference RNA (siRNA) in a mouse model bearing human tongue squamous cell cancer. This technique may represent a novel and effective route for the in vivo administration of siRNA against malignant tumors. METHODS: The cisplatin (DDP)-resistant human tongue squamous cell carcinoma cell line Tca8113/DDP, which highly expresses the MDR1 gene, was established by exposure to gradually increasing concentrations of cisplatin. A plasmid MDR1 siRNAwas constructed and transformed into attenuated Salmonella typhi strain SL7207. Tca8113/ DDP cells were infected with recombinant salmonella and expression of the MDR1 gene encoding P-glycoprotein (P-gp) product was detected. Tca8113/DDP tumor-bearing nude mice were established by inoculation by gavage administration of recombinant salmonella and were simultaneously injected intraperitoneally with cisplatin. Tumor growth was observed. RESULTS: Recombinant salmonella-bearing MDR1 siRNA expression plasmids can infect Tca8113/DDP cells in vitro and suppress P-gp expression and reverse DDP tolerance in Tca8113/DDP cells. Oral administration of recombinant salmonella in tumor-bearing nude mice can suppress tumor proliferation and enhance the therapeutic effect of DDP. CONCLUSION: Attenuated Salmonella typhi is expected to act as an in vivo targeting delivery vector for siRNA in tumor tissues.