Distinct phenotyping of critical patients with demand-capacity imbalance initiating acute renal replacement therapy by consensus clustering.

BACKGROUND: Certain patient subpopulations requiring dialysis initiation show varied survival rates and chances of ending renal replacement therapy (RRT). Consensus clustering can help identify these subgroups and their dialysis outcomes. METHODS: The study included patients who were over 18 years old with urine output above 400 ml per day and an estimated glomerular filtration rate over 15 ml/min/1.73 m2. They underwent acute RRT because of systemic demand-capacity imbalance. Using consensus clustering with 33 clinical variables and urea:creatinine ratio (UCR) to the variables to investigate the catabolic demand. Endpoints were all-cause mortality and being dialysis-free at 180-day follow-up after RRT initiation. RESULTS: Of 946 patients (mean 63 ± 17 years and 649 men, 68.6 %) three distinct phenotypes were identified. 509 (53.8%) patients died and 364 (38.5%) patients were weaned off dialysis. Cluster 2 showed better survival (60.23% vs. 53.18% [cluster 1] vs. 45.85% [cluster 3], P < 0.01) and higher possibility to be weaned off RRT (45.24% vs. 38.44% [cluster 1] vs. 31.62% [cluster 3], P < 0.01). High UCR had increased mortality (59.16% vs. 47.75%, P < 0.01) and a lower weaning rates (33.27%; 45.72%, P < .01). UCR with the clustering phenotype improved risk stratification. CONCLUSIONS: Among critical patients undergoing RRT due to systemic demand-capacity imbalance, more than half of the patients died. We identified distinct phenotypes in demand-capacity imbalance in a heterogeneous cohort of patients initializing RRT. Additionally, we found that pre-dialysis UCR as a novel predictor for mortality and the likelihood of being dialysis-free.

Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.

BACKGROUND: Chimeric antigen receptor (CAR)-T cells face many obstacles in solid tumor therapy, including heterogeneous antigen expression and inefficient T cell persistence. Guanylyl cyclase C (GUCY2C) has been identified as a suitable tumor antigen for targeted therapy due to its intestinal-restricted expression pattern in normal tissues and steady overexpression in gastrointestinal tumors, especially colorectal cancer. An antigen-sensitive and long-lasting CAR-T cell targeting GUCY2C was investigated in this study. METHODS: Using constructed tumor cell lines with various GUCY2C expression densities, we screened out an antigen-sensitive single chain variable fragment (scFv) that enabled CAR-T cells to efficiently eradicate the GUCY2C lowly expressed tumor cells. CAR-T cells with different compositions of the hinge, transmembrane and costimulatory domains were also constructed for selection of the long-lasting CAR-T format with durable antitumor efficacy in vitro and in tumor-bearing mice. The underlying mechanism was further investigated based on mutation of the hinge and transmembrane domains. RESULTS: We found that the composition of the antigen-sensitive scFv, CD8α hinge, CD8α transmembrane, and CD28 costimulatory domains boosted CAR-T cells to rapidly kill tumors, maintain high expansion capacity, and long-term efficacy in various colorectal cancer models. The durable antitumor function was attributed to the optimal CAR tonic signaling that conferred CAR-T cells with autonomous activation, proliferation, survival and cytokine release in the absence of antigen stimulation. The tonic signaling was associated with the length and the cysteine residues in the CD8α hinge and transmembrane domains. CONCLUSIONS: This study demonstrated a potent GUCY2C-targeted CAR-T cell for gastrointestinal tumor therapy and highlights the importance of adequate tonic signaling for effective CAR-T cell therapy against solid tumors.

Effect of glyceryl monopalmitate on the gelatinization, rheological and retrogradation properties of Japonica rice starch.

BACKGROUND: Starch-based food is easy to retrograde during cold storage after gelatinization, which leads to quality fission and a relatively short shelf life. Some lipids can effectively enhance the storage stability of starch gels by the formation of starch-lipid complexes. The present study aimed to investigate the effects of glyceryl monopalmitate (GMP) on gelatinization, rheological and retrogradation properties of Japonica rice starch (JS) at different conditions and to analyze the correlation between the physical-chemical properties and structural characteristics of the JS-GMP complex. RESULTS: The addition of GMP to JS could retard the process of starch gelatinization through forming JS-GMP complexes. The resulting JS-GMP pastes were typical pseudoplastic fluids with shear thinning, and their solid-like properties were prominent (tan δ < 1). In addition, the retrogradation of JS-GMP complex was more inhibited during storage at -18 than at 4 °C. The added amount of GMP was negatively and highly associated with the minimum viscosity, consistency coefficient, hardness and elasticity, whereas it was positively and highly correlated with the breakdown value, fluid characteristic index and relative crystallinity. The relative crystallinity of JS was affected by GMP in an approximate dose-dependent manner. CONCLUSION: The addition of GMP can influence the gelatinization properties, rheological properties and retrogradation characteristics of JS, and the formation of JS-GMP complex could improve the quality and storage stability of starch gel, which provides ideas for the quality control of starch-based food. © 2024 Society of Chemical Industry.

Drug-induced thrombotic microangiopathy after adjuvant chemotherapy in malignant ovarian germ cell tumor: A case report and literature review.

OBJECTIVE: We presented a rare case of drug-induced thrombotic microangiopathy (DI-TMA) following chemotherapy with the regimen of bleomycin, etoposide, and cisplatin (BEP) in a patient with malignant ovarian germ cell tumor (MOGCT). The objective is to highlight the difficulty in diagnosing and treating DI-TMA associated with BEP chemotherapy. CASE REPORT: A 21-year-old woman presented with a pelvic mass. Fertility-sparing staging surgery was performed, and a diagnosis of endodermal sinus tumor was confirmed. The patient received the first course of adjuvant chemotherapy with BEP regimen, but she developed symptoms of anemia, thrombocytopenia, and acute kidney injury. DI-TMA was diagnosed after thorough examinations, and she improved gradually by three courses of plasma exchange. Adjuvant chemotherapy was discontinued due to DI-TMA, and she kept disease-free for 17 months after the operation. CONCLUSION: DI-TMA, a rare lethal complication in MOGCT patients receiving the BEP regimen, requires prompt diagnosis and appropriate treatments.

A Phase 3 Study of Pembrolizumab versus Placebo for Previously Treated Patients from Asia with Hepatocellular Carcinoma: Health-Related Quality of Life Analysis from KEYNOTE-394.

Introduction: KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods: HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results: The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, -8.4; 95% CI: -11.7 to -5.1) versus pembrolizumab (-4.0; 95% CI: -6.4 to -1.6; difference vs. placebo: 4.4; 95% CI: 0.5-8.4; nominal p = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (-6.9; 95% CI: -9.4 to -4.5) versus pembrolizumab (-2.7; 95% CI: -4.5 to -1.0; difference vs. placebo: 4.2; 95% CI: 1.2-7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58-1.25; nominal p = 0.1993). Conclusion: Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.

GLP-1 receptor agonists' impact on cardio-renal outcomes and mortality in T2D with acute kidney disease.

Previous studies have explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in reducing cardiovascular events in type 2 diabetes. Here we show that GLP-1 RAs are associated with lower risks of mortality, major cardiovascular events (MACEs), and major adverse kidney events (MAKEs) in type 2 diabetes patients with acute kidney disease (AKD). Utilizing global data from the TriNetX database (2002/09/01-2022/12/01) and propensity score matching, we compare 7511 GLP-1 RAs users to non-users among 165,860 AKD patients. The most common causes of AKI are sepsis (55.2%) and cardiorenal syndrome (34.2%). After a median follow-up of 2.3 years, GLP-1 RAs users exhibit reduced risks of mortality (adjusted hazard ratio [aHR]: 0.57), MACEs (aHR: 0.88), and MAKEs (aHR: 0.73). External validation in a multicenter dataset of 1245 type 2 diabetes patients with AKD supports the favorable outcomes. These results emphasize the potential of GLP-1 RAs in individualized treatment for this population.

Unveiling the enigma of acute kidney disease: predicting prognosis, exploring interventions, and embracing a multidisciplinary approach.

Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed "KAMPS" (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce "MAND-MASS," an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.

Exploring the regulatory role of FBXL19-AS1 in triple-negative breast cancer through the miR-378a-3p/OTUB2 axis.

The regulatory potential of long noncoding RNA (lncRNA) FBXL19-AS1 has been highlighted in various cancers, but its effect on triple-negative breast cancer (TNBC) remains unclear. Here, we aimed to elucidate the role of FBXL19-AS1 in TNBC and its underlying mechanism. RT-qPCR was employed to detect the expressions of FBXL19-AS1 and miR-378a-3p in tissues and cells. Immunohistochemical staining and western blot were utilized to detect the expression levels of proteins. Cell activities were detected using flow cytometry, CCK-8, and transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were deployed to investigate interactions of different molecules. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathways were used to analyze the downstream pathway. In vivo xenograft model was conducted to detect the effect of FBXL19-AS1 on tumor growth. FBXL19-AS1 was overexpressed in TNBC tissues and cell lines compared with counterparts. FBXL19-AS1 knockdown suppressed TNBC cell activities, whereas its overexpression exhibited the opposite effect. Mechanistically, FBXL19-AS1 was found to interact with miR-378a-3p. Further analysis revealed that miR-378a-3p exerted tumor-suppressive effects in TNBC cells. Additionally, miR-378a-3p targeted and downregulated the expression of ubiquitin aldehyde binding 2 (OTUB2), a deubiquitinase associated with TNBC progression. In vivo experiments substantiated the inhibitory effects of FBXL19-AS1 knockdown on TNBC tumorigenesis, and a miR-378a-3p inhibitor partially rescued these effects. The downstream pathway of the miR-378a-3p/OTUB2 axis was explored, revealing connections with proteins involved in modifying other proteins, removing ubiquitin molecules, and influencing signaling pathways, including the Hippo signaling pathway. Western blot analysis confirmed changes in YAP and TAZ expression levels, indicating a potential regulatory network. In summary, FBXL19-AS1 promotes exacerbation in TNBC by suppressing miR-378a-3p, leading to increased OTUB2 expression. The downstream mechanism may be related to the Hippo signaling pathway. These findings propose potential therapeutic targets for TNBC treatment.

KLF11 promotes the proliferation of breast cancer cells by inhibiting p53-MDM2 signaling.

Abnormal Krüppel-like factor 11 (KLF11) expression is frequently found in tumor tissues and is associated with cancer prognosis, but its biological functions and corresponding mechanisms remain elusive. Here, we demonstrated that KLF11 functions as an oncoprotein to promote tumor proliferation in breast cancer cells. Mechanistically, at the transcription level, KLF11 decreased TP53 mRNA expression. Notably, KLF11 also interacted with and stabilized MDM2 through inhibiting MDM2 ubiquitination and subsequent degradation. This increase in MDM2 in turn accelerated the ubiquitin-mediated proteolysis of p53, leading to the reduced expression of p53 and its target genes, including CDKN1A, BAX, and NOXA1. Accordingly, data from animals further confirmed that KLF11 significantly upregulated the growth of breast cancer cells and was inversely correlated with p53 expression. Taken together, our findings reveal a novel mechanism for breast cancer progression in which the function of the tumor suppressor p53 is dramatically weakened.

Lipopolysaccharide modification enhances the inhibitory effect of clodronate liposomes on hepatic fibrosis by depletion of macrophages and hepatic stellate cells.

Hepatic fibrosis is a complex chronic liver disease in which both macrophages and hepatic stellate cells (HSCs) play important roles. Many studies have shown that clodronate liposomes (CLD-lipos) effectively deplete macrophages. However, no liposomes have been developed that target both HSCs and macrophages. This study aimed to evaluate the therapeutic efficacy of lipopolysaccharide-coupled clodronate liposomes (LPS-CLD-lipos) and the effects of liposomes size on hepatic fibrosis. Three rat models of hepatic fibrosis were established in vivo; diethylnitrosamine (DEN), bile duct ligation (BDL), and carbon tetrachloride (CCl4). Hematoxylin and eosin staining and serological liver function indices were used to analyze pathological liver damage. Masson's trichrome and Sirius red staining were used to evaluate the effect of liposomes on liver collagen fibers. The hydroxyproline content in liver tissues was determined. In vitro cell counting kit-8 (CCK-8) and immunofluorescence assays were used to further explore the effects of LPS modification and liposomes size on the killing of macrophages and HSCs. Both in vitro and in vivo experiments showed that 200 nm LPS-CLD-lipos significantly inhibited hepatic fibrosis and the abnormal deposition of collagen fibers in the liver and improved the related indicators of liver function. Further results showed that 200 nm LPS-CLD-lipos increased the clearance of macrophages and induced apoptosis of hepatic stellate cells, significantly. The present study demonstrated that 200 nm LPS-CLD-lipos could significantly inhibit hepatic fibrosis and improve liver function-related indices and this study may provide novel ideas and directions for hepatic fibrosis treatment.

Mechanistic insight into the impact of polystyrene microparticle on submerged plant during asexual propagules germination to seedling: Internalization in functional organs and alterations of physiological phenotypes.

Asexual reproduction is one of the most important propagations in aquatic plants. However, there is a lack of information about the growth-limiting mechanisms induced by microplastics on the submerged plant during asexual propagule germination to seedling. Hence, we investigated the effects of two sizes (2 µm, 0.2 µm) and three concentrations (0.5 mg/L, 5 mg/L, and 50 mg/L) of polystyrene microplastics (PSMPs) on Potamogeton crispus turion germination and seedling growth. Both PSMPs sizes were found in P. crispus seedling tissues. Metabolic profile alterations were observed in leaves, particularly affecting secondary metabolic pathways and ATP-binding cassette transporters. Metal elements are indispensable cofactors for photosynthesis; however, alterations in the metabolic profile led to varying degrees of reduced concentrations in magnesium, iron, copper, and zinc within P. crispus. Therefore, the maximum quantum yield of photosystem II significantly decreased in all concentrations with 0.2 µm-PSMPs, and at 50 mg/L with 2 µm-PSMPs. These findings reveal that internalization of microplastics, nutrient absorption inhibition, and metabolic changes contribute to the negative impact on P. crispus seedlings.

Identification of non-canonical antagonistic bacteria via interspecies contact-dependent killing.

BACKGROUND: Canonical biocontrol bacteria were considered to inhibit pathogenic bacteria mainly by secreting antibiotic metabolites or enzymes. Recent studies revealed that some biocontrol bacteria can inhibit pathogenic bacteria through contact-dependent killing (CDK) mediated by contact-dependent secretion systems. The CDK was independent of antibiotic metabolites and often ignored in normal biocontrol activity assay. RESULTS: In this study, we aimed to use a pathogen enrichment strategy to isolate non-canonical bacteria with CDK ability. Rhizosphere soil samples from Chinese cabbage showing soft rot symptom were collected and Pectobacterium carotovorum subsp. carotovorum (Pcc), the pathogen of cabbage soft rot, were added into these samples to enrich bacteria which attached on Pcc cells. By co-culture with Pcc, four bacteria strains (named as PcE1, PcE8, PcE12 and PcE13) showing antibacterial activity were isolated from Chinese cabbage rhizosphere. These four bacteria strains showed CDK abilities to different pathogenic bacteria of horticultural plants. Among them, PcE1 was identified as Chryseobacterium cucumeris. Genome sequencing showed that PcE1 genome encoded a type VI secretion system (T6SS) gene cluster. By heterologous expression, four predicted T6SS effectors of PcE1 showed antibacterial activity to Escherichia coli. CONCLUSION: Overall, this study isolated four bacteria strains with CDK activity to various horticultural plant pathogens, and revealed possible involvement of T6SS of Chryseobacterium cucumeris in antibacterial activity. These results provide valuable insight for potential application of CDK activity in biocontrol bacteria. © 2024 Society of Chemical Industry.

Recovery Dynamics and Prognosis After Dialysis for Acute Kidney Injury.

Importance: The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored. Objective: To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D. Design, Setting, and Participants: This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023. Exposure: Exposure to severe AKI and baseline and post-AKD kidney function. Main Outcomes and Measures: The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission. Results: A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes. Conclusions and Relevance: In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Species-specific functional trait responses of canopy-forming and rosette-forming macrophytes to nitrogen loading: Implications for water-sediment interactions.

Globally intensified lake eutrophication, attributed to excessive anthropogenic nitrogen loading, emerges as a significant driver of submerged vegetation degradation. Consequently, the impact of nitrogen on the decline of submerged macrophytes has received increasing attention. However, a functional trait-based approach to exploring the response of submerged macrophytes to nitrogen loading and its environmental feedback mechanism was unclear. Our study utilized two different growth forms of submerged macrophytes (canopy-forming Myriophyllum spicatum, and rosette-forming Vallisneria natans) to established "submerged macrophytes-water-sediment" microcosms. We assessed the influence of nitrogen loading, across four targeted total nitrogen concentrations (original control, 2, 5, 10 mg/L), on plant traits, water parameters, sediment properties, enzyme activities, and microbial characteristics. Our findings revealed that high nitrogen (10 mg/L) adversely impacted the relative growth rate of fresh biomass and total chlorophyll content in canopy-forming M. spicatum, while the chlorophyll a/b and free amino acid content increased. On the contrary, the growth and photosynthetic traits of resource-conservative V. natans were not affected by nitrogen loading. Functional traits (growth, photosynthetic, and stoichiometric) of M. spicatum but not V. natans exhibited significant correlations with environmental variables. Nitrogen loading significantly increased the concentration of nitrogen components in overlying water and pore water. The presence of submerged macrophytes significantly reduced the ammonia nitrogen and total nitrogen both in overlying water and pore water, and decreased total organic carbon in pore water. Nitrogen loading significantly inhibited sediment extracellular enzyme activities, but the planting of submerged macrophytes mitigated their negative effects. Furthermore, rhizosphere bacterial interactions were less compact compared to bare control, while eukaryotic communities exhibited increased complexity and connectivity. Path modeling indicated that submerged macrophytes mitigated the direct effects of nitrogen loading on overlying water and amplified the indirect effects on pore water, while also attenuating the direct negative effects of pore water on extracellular enzymes. The findings indicated that the restoration of submerged vegetation can mitigate eutrophication resulting from increased nitrogen loading through species-specific changes in functional traits and direct or indirect feedback mechanisms in the water-sediment system.

[Retracted] MicroRNA­454­3p inhibits cervical cancer cell invasion and migration by targeting c­Met.

[This retracts the article DOI: 10.3892/etm.2018.5714.].

Synergistic anti-tumor effects of lenalidomide and gefitinib by upregulating ADRB2 and inactivating the mTOR/PI3K/AKT signaling pathway in lung adenocarcinoma.

Gefitinib is commonly used to be the first-line therapy for advanced non-small cell lung cancer (NSCLC). Therapeutic effect of gefitinib is reduced due to acquired resistance, and combined treatment is recommended. In this research, we planned to explore the impacts of combined treatment of lenalidomide and gefitinib on gefitinib-sensitive or -resistant NSCLC cells. The co-treatment results demonstrated that enhanced antitumor impact on NSCLC cell growth, migration, invasion, cell cycle process and apoptosis. The tumor-bearing mouse models were established using PC9/GR cells. In vivo assays also showed that lenalidomide and gefitinib synergistically inhibited mouse tumor growth along increased the survival of mice. ADRB2 was identified as a lowly expressed gene in PC9/GR cells and LUAD tumor tissues. LUAD patients with high ADRB2 expression were indicated with favorable survival outcomes. Moreover, ADRB2 was upregulated in lenalidomide and/or gefitinib-treated PC9/GR cells. ADRB2 deficiency partially offsets the suppressive impacts of lenalidomide and gefitinib co-treatment on the viability and proliferation of PC9/GR cells. Additionally, lenalidomide and gefitinib cotreatment significantly inactivated the mTOR/PI3K/AKT signaling pathway compared with each treatment alone. Rescue assays were performed to explore whether lenalidomide and gefitinib synergistically inhibited the growth of PC9/GR cells via the PI3K/AKT pathway. PI3K activator SC79 significantly restored reduced cell proliferation, migration and invasion along with elevated cell cycle arrest and apoptosis caused by lenalidomide and gefitinib cotreatment. In conclusion, lenalidomide and gefitinib synergistically suppressed LUAD progression and attenuated gefitinib resistance by upregulating ADRB2 and inactivating the mTOR/PI3K/AKT signaling pathway in lung adenocarcinoma.

Discriminatory fluorescence and FRET in the chiral-perovskite/RhB system.

Förster resonance energy transfer (FRET) holds a significant position in various natural and artificial systems, especially within donor-acceptor systems encompassing chiral components. Despite extensive investigations, a clear understanding of the effects of chirality and FRET on discriminatory fluorescence remains elusive. Here, chiral perovskite nanowires (CPNWs) and achiral rhodamine B (RhB) are employed to examine the FRET and discriminatory fluorescence behavior in a donor-acceptor system involving a chiral nanostructure. A notable FRET from the CPNWs to RhB is observed, along with circular dichroism (CD) and circularly polarized luminescence (CPL) activities in RhB. Although the FRET interaction remains consistent over time, a notable inversion in the polarity preference of the CD and CPL of RhB is observed. This reveals that the discriminatory fluorescence of the acceptor arises from the electromagnetic influence of the chiral donor. These findings elucidate that "chirality", as a property related to spatial orientation, cannot accompany the transfer of energy (which is a scalar) from chiral nanostructures to achiral molecules, which helps advance the understanding of the discriminatory fluorescence in the donor-acceptor system with a chiral nanostructure.

The effects of double-filtration plasmapheresis on coagulation profiles and the risk of bleeding.

BACKGROUND/PURPOSE: Double-filtration plasmapheresis (DFPP) can be used to remove circulating pathogenic molecules. By reclaiming filtered albumin, DFPP reduces the need for albumin and plasma replacement. Large proteins, such as fibrinogen, are removed. Our institution adopts a DFPP treatment protocol consisting of active surveillance of coagulation profiles and prophylactic supplementation of blood products containing fibrinogen. This study aims to investigate the effects of consecutive DFPP treatments on serial coagulation profiles and the risk of bleeding under this protocol. METHODS: Serial laboratory data and bleeding events at a single tertiary medical center were prospectively collected. Prophylactic transfusion of cryoprecipitate or fresh frozen plasma (FFP) was instituted if significant coagulopathy or a clinically evident bleeding event was observed. RESULTS: After the first treatment session, plasma fibrinogen levels decreased from 332 ± 106 mg/dL to 96 ± 44 mg/dL in the 37 study patients. In the following sessions, plasma fibrinogen levels were maintained at around 100 mg/dL under prophylactic transfusion. No major bleeding events were recorded, but five (14%) patients experienced minor bleeding. CONCLUSION: DFPP treatment might be performed safely along with active monitoring of coagulation profiles and prophylactic transfusion of cryoprecipitate or FFP.

Visceral adipose tissue and risk of diabetic nephropathy: A Mendelian randomization study.

OBJECTIVE: Previous observational studies have established a correlation between visceral adipose tissue (VAT) and diabetic nephropathy (DN). However, the causality of this association remains unclear. Therefore, the aim of this study was to investigate the causal association between VAT and DN by employing two-sample Mendelian randomization (MR) methods. METHODS: The primary MR approach employed was the random-effects inverse-variance weighted (IVW) method. Additionally, we employed alternative methods, including the weighted median (WM) approach, MR-Egger regression, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). Sensitivity analyses were conducted to evaluate the robustness of the MR analyses. RESULTS: Genetically predicted higher VAT mass was causally associated with a higher risk of DN. The results of the MR analyses were as follows: IVW(Beta = 0.948, odds ratio (OR) = 2.581, 95 % confidence interval (CI) = 2.100-3.173, p = 1.980e-19), WM (Beta = 1.126, OR = 3.082, 95 % CI = 2.278-4.171, p = 2.997e-13), MR-Egger (Beta = 1.315, OR = 3.724, 95 % CI = 1.981-6.998, p = 6.446e-05), and MR-PRESSO (Beta = 0.914, OR = 2.493, 95 % CI = 2.292-2.695, p = 3.121e-16). No pleiotropy was detected (p = 0.230). CONCLUSIONS: This study provided genetic evidence that higher VAT mass was causally associated with a higher risk of DN.