Cost-effectiveness analysis of durvalumab, tremelimumab, and etoposide-platinum in first-line treatment of extensive-stage small cell lung cancer.

BACKGROUND: Durvalumab plus etoposide-platinum (DEP) showed sustained overall survival improvements in patients with extensive-stage small-cell lung cancer (ES-SCLC) compared to etoposide-platinum (EP), but adding tremelimumab to DEP (DTEP) did not significantly improve outcomes. A third-party payer perspective is taken here to evaluate the cost-effectiveness of DTEP, DEP, and EP for ES-SCLC. METHODS: The cost-effectiveness was evaluated by partitioning survival models into 3 mutually exclusive health states. In this model, clinical characteristics and outcomes were obtained from the CASPIAN. Model robustness was evaluated through 1-way deterministic and probabilistic sensitivity analyses. Outcome measurements included costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio, life-years, incremental net health benefit, and incremental net monetary benefit. The analysis was conducted with a 10-year lifetime horizon in a United States setting. RESULTS: Compared with EP, DEP, and DTEP were associated with an increment of 0.480 and 0.313 life-years, and an increment of 0.247 and 0.165 QALYs, as well as a $139,788 and $170,331 increase in cost per patient. The corresponding ICERs were $565,807/QALY and $1033,456/QALY, respectively. The incremental net health benefit and incremental net monetary benefit of DEP or DTEP were -0.685 QALYs and -$102,729, or -0.971 QALYs and -$145,608 at a willingness to pay threshold of $150,000/QALY, respectively. Compared with DTEP, DEP was dominated. DTEP and DEP were 100% unlikely to be cost-effective if the willingness to pay threshold was $150,000/QALY. DEP was cost-effective compared to EP when durvalumab was priced below $0.994/mg. Compared with EP, DEP, and DTEP were unlikely to be considered cost-effective across all subgroups. CONCLUSION: DEP and DTEP were not cost-effective options in the first-line treatment for ES-SCLC compared with EP, from the third-party payer perspective in the United States. Compared with DTEP, DEP was dominated.

Replenishment of mitochondrial Na+ and H+ by ionophores potentiates cutaneous wound healing in diabetes.

Diabetic foot ulcer (DFU) is a highly morbid complication in patients with diabetes mellitus, necessitating the development of innovative pharmaceuticals to address unmet medical needs. Sodium ion (Na+) is a well-established mediator for membrane potential and osmotic equilibrium. Recently, Na+ transporters have been identified as a functional regulator of regeneration. However, the role of Na+ in the intricate healing process of mammalian wounds remains elusive. Here, we found that the skin wounds in hyponatremic mice display a hard-to-heal phenotype. Na+ ionophores that were employed to increase intracellular Na+ content could facilitate keratinocyte proliferation and migration, and promote angiogenesis, exhibiting diverse biological activities. Among of them, monensin A emerges as a promising agent for accelerating the healing dynamics of skin wounds in diabetes. Mechanistically, the elevated mitochondrial Na+ decelerates inner mitochondrial membrane fluidity, instigating the production of reactive oxygen species (ROS), which is identified as a critical effector on the monensin A-induced improvement of wound healing. Concurrently, Na+ ionophores replenish H+ to the mitochondrial matrix, causing an enhancement of mitochondrial energy metabolism to support productive wound healing programs. Our study unfolds a new role of Na+, which is a pivotal determinant in wound healing. Furthermore, it directs a roadmap for developing Na+ ionophores as innovative pharmaceuticals for treating chronic dermal wounds in diabetic patients.

Effects of Aerobic Exercise Combined With Attentional Bias Modification in the Care of Male Patients With a Methamphetamine Use Disorder.

OBJECTIVE: It remains unclear which individual or combined strategies are most beneficial for methamphetamine use disorders (MUDs). We compared the effects of aerobic exercise, attentional bias modification, and combined intervention on male patients with MUD. METHOD: One hundred male patients with MUD were randomly assigned to combined intervention, aerobic exercise, attentional bias modification, or control groups (25 patients per group). The 8-week intervention protocol included three 60-minute sessions of aerobic exercises per week. Primary outcomes included high- and low-frequency heart rate variability, executive function, and cardiorespiratory fitness measured by customized software, computerized tests, and the Harvard step test, respectively. Secondary outcomes included psychiatric symptoms, drug craving, training acceptability, and persistence. RESULTS: Participant characteristics were matched between groups at baseline. Executive function, heart rate variability, cardiorespiratory fitness, drug craving, and most psychiatric symptoms had significant time-group interactions at posttest (p < .05, η2 = .08-.28). Compared with the attentional bias modification and control groups, the combined intervention and aerobic exercise groups improved significantly in executive function, heart rate variability, cardiorespiratory fitness, and most secondary outcomes. In addition, high-frequency heart rate variability and cardiorespiratory fitness in the aerobic exercise group were significantly higher than those in the combined intervention group. CONCLUSIONS: Combination strategies showed comparable efficacy to aerobic exercise alone in improving executive function, psychiatric symptoms, and drug craving and significantly exceeded other conditions. For heart rate variability and cardiorespiratory fitness, aerobic exercise alone was the most effective. For acceptability and persistence, combination strategies were preferred over single-domain training and health education intervention.

ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores.

Macroautophagy is a process that cells engulf cytosolic materials by autophagosomes and deliver them to lysosomes for degradation. The biogenesis of autophagosomes requires ATG2 as a lipid transfer protein to transport lipids from existing membranes to phagophores. It is generally believed that endoplasmic reticulum is the main source for lipid supply of the forming autophagosomes; whether ATG2 can transfer lipids from other organelles to phagophores remains elusive. In this study, we identified a new ATG2A-binding protein, ANKFY1. Depletion of this endosome-localized protein led to the impaired autophagosome growth and the reduced autophagy flux, which largely phenocopied ATG2A/B depletion. A pool of ANKFY1 co-localized with ATG2A between endosomes and phagophores and depletion of UVRAG, ANKFY1 or ATG2A/B led to reduction of PI3P distribution on phagophores. Purified recombinant ANKFY1 bound to PI3P on membrane through its FYVE domain and enhanced ATG2A-mediated lipid transfer between PI3P-containing liposomes. Therefore, we propose that ANKFY1 recruits ATG2A to PI3P-enriched endosomes and promotes ATG2A-mediated lipid transfer from endosomes to phagophores. This finding implicates a new lipid source for ATG2A-mediated phagophore expansion, where endosomes donate PI3P and other lipids to phagophores via lipid transfer.

Single cell RNA-sequencing reveals the cellular senescence of placental mesenchymal stem/stromal cell in preeclampsia.

INTRODUCTION: Preeclampsia (PE) is a severe obstetric complication closely associated with placental dysfunction. Placental mesenchymal stem/stromal cells (PMSCs) modulate placental development while PE PMSCs are excessively senescent to disturb placental function. Nevertheless, the senescence mechanism of PE PMSCs remains unclear. METHODS: PE-related single-cell RNA sequencing datasets (GSE173193), data of chip detection (GSE99007) and bulk transcriptome RNA sequencing datasets (GSE75010) were extracted from the GEO database. Firstly, the functional enrichment analyses of the differentially expressed genes (DEGs) in PMSCs were conducted. Then, the clusters of PE PMSCs were distinguished according to the expressions of senescence-related genes (SRGs) by consensus clustering analysis. Cell cycle analysis, senescence ß-galactosidase, Transwell, and tube formation were conducted. Next, the expressions of the senescence-associated secretory phenotype (SASPs) were displayed. The characteristic genes of PE were screened by the least absolute shrinkage and selection operator analysis. CTSZ was suppressed in PMSCs and the cellular senescence levels were evaluated. RESULTS: In this study, The DEGs in PMSCs were closely associated with cellular senescence. The score of SRGs was significantly higher and most of the SASPs were abnormally expressed in the senescent group. Seven characteristic genes of PE were identified, thereinto, CTSZ reduction may accelerate the senescence in PMSCs in vitro. DISCUSSION: Combined with bioinformatic analysis and lab experiments, our study emphatically revealed the abnormal cellular senescence in PE PMSCs, in which CTSZ, one of the PE characteristic genes, regulated the cellular senescence levels in PMSCs. These findings might help to deepen the understanding of the senescence mechanism of PMSCs in PE.

EMC10 modulates hepatic ER stress and steatosis in an isoform specific manner.

BACKGROUND & AIMS: Endoplasmic reticulum (ER) membrane protein complex subunit 10 (EMC10) has been implicated in obesity. Here we investigated the roles of the two isoforms of EMC10, including a secreted isoform (scEMC10) and an ER membrane-bound isoform (mEMC10), in MASLD. METHODS: Manifold steatotic mouse models and HepG2 cells were employed to investigate the role of EMC10 in the regulation of hepatic PERK-eIF2α-ATF4 signaling and hepatosteatosis. The therapeutic effect of scEMC10-neutralizing antibody on mouse hepatosteatosis was explored. Associations of MASLD with serum scEMC10 and hepatic mEMC10 were determined in two cohorts of participants with MASLD. RESULTS: scEMC10 promoted, while mEMC10 suppressed the activation of hepatocytic PERK-eIF2α-ATF4 signaling. Emc10 gene knockout exacerbated, while hepatic overexpression of mEMC10 ameliorated hepatic ER stress and steatosis in mice challenged with either a MCD diet or tunicamycin, highlighting a direct, suppressive role of mEMC10 in MASLD via modulation of hepatic ER stress. Overexpression of scEMC10 promoted, whereas neutralization of circulating scEMC10 prevented hepatosteatosis in mice with fatty liver, suggesting a progressive role of scEMC10 in MASLD. Clinically, serum scEMC10 increased, while hepatic mEMC10 decreased in participants with MASLD. Correlative analysis indicated serum scEMC10 positively, whereas hepatic mEMC10 negatively correlated with liver fat content and serum ALT, AST, and GGT. CONCLUSIONS: These findings demonstrate a novel, isoform specific role for EMC10 in the pathogenesis of MASLD and identify the secreted isoform as a tractable therapeutic target for MASLD via antibody-based neutralization. IMPACT AND IMPLICATIONS: We have shown the role of EMC10 in the regulation of energy homeostasis and obesity. In this study, we determine the distinct roles of the two isoforms of EMC10 in the regulation of hepatic ER stress and steatosis in mice, and associations of MASLD with different EMC10 isoforms in humans. Our findings delineate a novel regulatory axis for hepatosteatosis and identify EMC10 as a modulator of the PERK-eIF2α-ATF4 signaling cascade that may be of broad physiological significance. Moreover, our pre-clinical and clinical studies clearly provide the foundations for translation of scEMC10 modulation for the treatment of MASLD.

Thiamethoxam-Induced Intergenerational Sublethal Effects on the Life History and Feeding Behavior of Rhopalosiphum padi.

Thiamethoxam, a second-generation neonicotinoid insecticide is widely used for controlling sap-sucking insect pests including Rhopalosiphum padi. The current study aimed to investigate the life-history parameters and feeding behavior of R. padi following treatments with sublethal concentrations of thiamethoxam. The lethal concentration 50 (LC50) value of thiamethoxam against adult R. padi was 11.458 mg L-1 after 48 h exposure. The sublethal concentrations of thiamethoxam (LC5 and LC10) significantly decreased the adult longevity, fecundity, and reproductive days in the directly exposed aphids (F0 generation). In the progeny R. padi (F1), the developmental durations and total prereproductive period (TPRP) were decreased while the adult longevity, fecundity, and reproductive days (RPd) were increased at both thiamethoxam concentrations. The demographic parameters including the net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) were prolonged only at the LC5 of thiamethoxam. The EPG results indicated that the sublethal concentrations of thiamethoxam increases the total duration of non-probing (Np) while reducing the total duration of E2 in directly exposed aphids (F0). Interestingly, the E2 were significantly increased in the progeny generation (F1) descending from previously exposed parental aphids (F0). Overall, this study showed that thiamethoxam exhibited high toxicity against directly exposed individuals (F0), while inducing intergenerational hormetic effects on the progeny generation (F1) of R. padi. These findings provided crucial details about thiamethoxam-induced hormetic effects that might be useful in managing resurgences of this key pest.

The Interaction between Human Microbes and Advanced Glycation End Products: The Role of Klebsiella X15 on Advanced Glycation End Products' Degradation.

Previous studies have shown that advanced glycation end products (AGEs) are implicated in the occurrence and progression of numerous diseases, with dietary AGEs being particularly associated with intestinal disorders. In this study, methylglyoxal-beta-lactoglobulin AGEs (MGO-ß-LG AGEs) were utilized as the exclusive nitrogen source to investigate the interaction between protein-bound AGEs and human gut microbiota. The high-resolution mass spectrometry analysis of alterations in peptides containing AGEs within metabolites before and after fermentation elucidated the capacity of intestinal microorganisms to enzymatically hydrolyze long-chain AGEs into short-chain counterparts. The 16S rRNA sequencing revealed Klebsiella, Lactobacillus, Escherichia-Shigella, and other genera as dominant microbiota at different fermentation times. A total of 187 potential strains of AGE-metabolizing bacteria were isolated from the fermentation broth at various time points. Notably, one strain of Klebsiella exhibited the most robust growth capacity when AGEs served as the sole nitrogen source. Subsequently, proteomics was employed to compare the changes in protein levels of Klebsiella X15 following cultivation in unmodified proteins and proteins modified with AGEs. This analysis unveiled a remodeled amino acid and energy metabolism pathway in Klebsiella in response to AGEs, indicating that Klebsiella may possess a metabolic pathway specifically tailored to AGEs. This study found that fermenting AGEs in healthy human intestinal microbiota altered the bacterial microbiota structure, especially by increasing Klebsiella proliferation, which could be a key factor in AGEs' role in causing diseases, particularly intestinal inflammation.

Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.

BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.

Hormetic effects of thiamethoxam on Schizaphis graminum: demographics and feeding behavior.

In agroecosystems, insects contend with chemical insecticides often encountered at sublethal concentrations. Insects' exposure to these mild stresses may induce hormetic effects, which has consequences for managing insect pests. In this study, we used an electrical penetration graph (EPG) technique to investigate the feeding behavior and an age-stage, two-sex life table approach to estimate the sublethal effects of thiamethoxam on greenbug, Schizaphis graminum. The LC5 and LC10 of thiamethoxam significantly decreased longevity and fecundity of directly exposed adult aphids (F0). However, the adult longevity, fecundity, and reproductive days (RPd)-indicating the number of days in which the females produce offspring - in the progeny generation (F1) exhibited significant increase when parental aphids (F0) were treated with LC5 of the active ingredient. Subsequently, key demographic parameters such as intrinsic rate of increase (r) and net reproductive rate (R0) significantly increased at LC5 treatment. EPG recordings showed that total durations of non-probing (Np), intercellular stylet pathway (C), and salivary secretion into the sieve element (E1) were significantly increased, while mean duration of probing (Pr) and total duration of phloem sap ingestion and concurrent salivation (E2) were decreased in F0 adults exposed to LC5 and LC10. Interestingly, in the F1 generation, total duration of Np was significantly decreased while total duration of E2 was increased in LC5 treatment. Taken together, our results showed that an LC5 of thiamethoxam induces intergenerational hormetic effects on the demographic parameters and feeding behavior of F1 individuals of S. graminum. These findings have important implications on chemical control against S. graminum and highlight the need for a deeper understanding of the ecological consequences of such exposures within pest management strategies across the agricultural landscapes.

A polydopamine coating enabling the stable cycling of MnO2 cathode materials in aqueous zinc batteries.

MnO2 is a desired cathode candidate for aqueous zinc batteries. However, their cycling stability is seriously limited by active material dissolution, and pre-addition of Mn2+ salts in electrolytes is widely required to shift the dissolution equilibrium. Herein, we synthesize a polydopamine (PDA) coated MnO2 composite material (MnO2/PDA) to realize stable cycling in zinc cells without relying on pre-added Mn2+. The functional groups on PDA exhibit strong coordination ability with the Mn active material. It not only confines dissolved species within the cathode during discharge, but also enhances their deposition back to the cathode during charge to retrieve the active material. Thanks to this effect, the cathode achieves 81.1% capacity retention after 2000 cycles at 1 A g-1 in the 1 M ZnSO4 electrolyte, superior to 37.3% with the regular MnO2 cathode. This work presents an effective strategy to realize the stable cycling of manganese oxide cathode materials in aqueous zinc batteries.

2'-Fucosyllactose Promotes Colonization of Akkermansia muciniphila and Prevents Colitis In Vitro and in Mice.

Akkermansia muciniphila is a potential candidate for ulcerative colitis prevention. Considering that it utilizes 2'-fucosyllactose (2'FL) for growth, 2'FL can be used to enrich the abundance of A. muciniphila in feces. However, whether the crosswalk between 2'FL and A. muciniphila can promote the intestinal colonization of A. muciniphila remains unclear. In this study, we explored the effect and the underlying mechanism of 2'FL on the colonization of A. muciniphila in vitro and in vivo as well as its alleviating effect on colitis. Our results revealed that 2'FL can serve as a carbon source of A. muciniphila to support the growth and increase cell-surface hydrophobicity and the expression of the genes coding fibronectin-binding autotransporter adhesin to promote the adhesion to Caco2/HT29 methotrexate (MTX) cells but not of galactooligosaccharides (GOS) and glucose. Moreover, 2'FL could increase the host mucin formation to promote the adhesion of A. muciniphila to Caco2/HT29 MTX cells but not of GOS and glucose. Furthermore, 2'FL could significantly increase the colonization of A. muciniphila in the gut to alleviate colitis in mice. Overall, the interplay between A. muciniphila and 2'FL is expected to provide an advantageous ecological niche for A. muciniphila so as to confer further health benefits against colitis.

Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion.

Autophagy is crucial for degrading and recycling cellular components. Fusion between autophagosomes and lysosomes is pivotal, directing autophagic cargo to degradation. This process is driven by STX17-SNAP29-VAMP8 and STX7-SNAP29-YKT6 in mammalian cells. However, the interaction between STX17 and YKT6 and its significance remain to be revealed. In this study, we challenge the notion that STX17 and YKT6 function independently in autophagosome-lysosome fusion. YKT6, through its SNARE domain, forms a complex with STX17 and SNAP29 on autophagosomes, enhancing autophagy flux. VAMP8 displaces YKT6 from this complex, leading to the formation of the fusogenic complex STX17-SNAP29-VAMP8. We demonstrated that the YKT6-SNAP29-STX17 complex facilitates both lipid and content mixing driven by STX17-SNAP29-VAMP8, suggesting a priming role of YKT6 for efficient membrane fusion. Our results provide a potential regulation mechanism of autophagosome-lysosome fusion, highlighting the importance of YKT6 and its interactions with STX17 and SNAP29 in promoting autophagy flux.

Aneuploid serves as a prognostic marker and favors immunosuppressive microenvironment in ovarian cancer.

Ovarian cancer is the most lethal gynecologic neoplasm, and most patients experience recurrence and chemoresistance. Even the promising immunotherapy showed limited efficacy in ovarian cancer, probably due to the immunosuppressive microenvironment. However, the behind mechanisms of the immune exclusion or cold phenotype in ovarian cancer still remain to be explored. As a cancer dominated by copy number variations instead of mutations, ovarian cancer contains a high fraction of aneuploid, which might correlate with immune inhibition. Nevertheless, whether or how aneuploid affects ovarian cancer is still unclear. For exploring the role of aneuploid cancer cells and the potential ploidy-immune relationship, herein, the ploidy information was first comprehensively analyzed combining the karyotype data and copy number variation data obtained from Mitelman and cBioPortal databases, respectively. Ovarian cancer showed strong ploidy heterogeneity, with high fraction of aneuploid and recurrent arm-level and whole chromosome changes. Furthermore, clinical parameters were compared between the highly-aneuploid and the near-diploid ovarian cancers. Aneuploid indicated high grade, poor overall survival and poor disease-free survival in ovarian cancer. To understand the biofunction affected by aneuploid, the differentially expressed genes between the highly-aneuploid and the near-diploid groups were analyzed. Transcription data suggested that aneuploid cancer correlated with deregulated MHC expression, abnormal antigen presentation, and less infiltration of macrophages and activated T cells and higher level of T cell exclusion. Furthermore, the ploidy-MHC association was verified using the Human Protein Atlas database. All these data supported that aneuploid might be promising for cancer management and immune surveillance in ovarian cancer.

A systemic lupus erythematosus patient with persistent elevated conjugated bilirubin as the initial symptom: A case report.

RATIONALE: While some systemic lupus erythematosus (SLE) patients may experience varying degrees of liver function abnormalities, only a small portion of these cases have clinical significance, and the majority of patients typically exhibit low levels of serum bilirubin. However, in this article, we present a case of a middle-aged female patient with SLE who exhibited persistent skin jaundice as her initial symptom, offering a fresh perspective on diagnosing and treating patients who exhibit unexplained liver dysfunction and SLE combined with liver injury. PATIENT CONCERNS: A 45-year-old woman was initially admitted to the hospital due to yellowing of the skin and sclera, and her symptoms did not improve significantly during treatment. The results were abnormal after relevant immunological tests. DIAGNOSES: Persistent non-conjugated bilirubin elevation due to lupus hepatitis. INTERVENTIONS: The use of methylprednisolone sodium succinate (40 mg/Qd) and mycophenolate mofetil (0.75 g/d) suppressed immunity, polyolefin choline (20 mL/d) and glutathione (0.6 g/Qd) improved liver function, and nutritional support therapy. OUTCOMES: After 2 weeks of treatment, a significant decrease in the yellow skin and sclera of the patient was observed. LESSONS: Most clinicians overlook that liver function abnormalities are the main manifestation of SLE, resulting in many patients not receiving timely treatment. This study highlights the importance that SLE is also a cause of abnormal liver function.

Deciphering the heterogeneity of neutrophil cells within circulation and the lung cancer microenvironment pre- and post-operation.

Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils' automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.

Evaluation of an algorithm-guided photoplethysmography for atrial fibrillation burden using a smartwatch.

BACKGROUND: Wearable devices based on the PPG algorithm can detect atrial fibrillation (AF) effectively. However, further investigation of its application on long-term, continuous monitoring of AF burden is warranted. METHOD: The performance of a smartwatch with continuous photoplethysmography (PPG) and PPG-based algorithms for AF burden estimation was evaluated in a prospective study enrolling AF patients admitted to Beijing Anzhen Hospital for catheter ablation from September to November 2022. A continuous Electrocardiograph patch (ECG) was used as the reference device to validate algorithm performance for AF detection in 30-s intervals. RESULTS: A total of 578669 non-overlapping 30-s intervals for PPG and ECG each from 245 eligible patients were generated. An interval-level sensitivity of PPG was 96.3% (95% CI 96.2%-96.4%), and specificity was 99.5% (95% CI 99.5%-99.6%) for the estimation of AF burden. AF burden estimation by PPG was highly correlated with AF burden calculated by ECG via Pearson correlation coefficient (R2 = 0.996) with a mean difference of -0.59 (95% limits of agreement, -7.9% to 6.7%). The subgroup study showed the robust performance of the algorithm in different subgroups, including heart rate and different hours of the day. CONCLUSION: Our results showed the smartwatch with an algorithm-based PPG monitor has good accuracy and stability in continuously monitoring AF burden compared with ECG patch monitors, indicating its potential for diagnosing and managing AF.

Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA.

Closed-loop process for selective leaching and recovery of palladium from spent auto-exhaust catalysts using iodotrihalide ionic liquids.

The recovery of palladium from spent auto-exhaust catalysts (SAE-catalysts) is of great significance for resource sustainability. Herein, we proposed an efficient closed-loop leaching and recovery method for palladium from SAE-catalysts using iodotrihalide ionic liquids (ILs). Recovery design was explored aimed at green leaching and process simplification. Iodotrihalide ILs exhibited exceptional performance in terms of leaching efficiency (99.1%), selectivity (selectivity > 6.8 ×103) and reusability (over 6 cycles). The mechanism study revealed that excellent leaching performance was attributed to the redox and complexation. Additionally, the chemical reaction-controlled model was best suited to describe the leaching process. Notably, under the optimal conditions determined by the response surface methodology, a high-purity Pd(II) solution (purity > 99.8%) was obtained. More significantly, it was ideal for practical applications due to the low-viscosity (36.0 cP), mild (55 °C) and one-step leaching and recovery. In conclusion, this work provides an eco-friendly method for recovering palladium from SAE-catalysts with its non-high corrosiveness and low environmental impact.

Three cases of systemic lupus erythematosus presenting with ischemic stroke as the initial symptom: Case reports and literature review.

BACKGROUND: Ischemic stroke constitutes a grave complication within the context of systemic lupus erythematosus (SLE), typically manifesting several years postdiagnosis of SLE. Incidents where ischemic stroke precedes and acts as an initial symptom of SLE are comparatively rare in its early stages, and such presentations are frequently misdiagnosed as ischemic cerebrovascular diseases, posing significant diagnostic challenges. CASE REPORTS: This article presents three cases of young females in whom ischemic stroke emerged as the initial manifestation of SLE. It incorporates a review of 17 case reports published over the past two decades, focusing on patients with SLE where ischemic stroke was a primary symptom. This discussion encompasses the clinical presentation, outcomes, and therapeutic approaches for these patients. CONCLUSION: In young patients, particularly females presenting with ischemic stroke and especially in cases accompanied by hematologic or multisystemic involvement, there should be heightened vigilance for SLE-induced ischemic stroke. Early diagnosis and treatment significantly enhance patients' quality of life and survival rates.