Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge.

PURPOSE: To examine whether a 7-day or 24-h recall period of Perioperative Symptom Assessment for Patients Undergoing Lung Surgery (PSA-Lung) was appropriate for symptom assessment after discharge. METHODS: A total of 377 patients were recruited in a cohort study of patients who underwent lung surgery. We measured patient symptoms daily and weekly using the two recall period versions of the PSA-Lung scale, respectively. The psychometric properties of both versions were calculated. Spearman rank correlation coefficients and kappa (k) coefficients were used to measure the association between items score measured by the two version scales each week. Cohen's d effect size and mixed linear model were used to measure responsiveness to change over time. RESULTS: Spearman rank correlation coefficients between the symptom scores generated by the 7-day and 24-h versions (range 0.48-0.77; all P < 0.05). The correlations increased in patients in stable condition (weekly symptom change < 2). Cronbach's α coefficients for both ratings were > 0.87 and both had good test-retest reliability. The longitudinal analysis and Cohen's d effect sizes showed that both ratings had good ability to detect changes in all items. CONCLUSION: The 7-day retrospective scale was as effective as the 24-h retrospective scale in terms of psychometric performance. In the stage where the patient's symptoms change rapidly, it is recommended to use the 24-h retrospective scale for symptom monitoring. On the contrary, in a stable state, it can be considered to use the 7-day retrospective scale for monitoring to reduce the patient's burden.

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

A chromosome-level genome reveals genome evolution and molecular basis of anthraquinone biosynthesis in Rheum palmatum.

BACKGROUND: Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. RESULTS: We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. CONCLUSION: Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.

Transcriptomic divergence of the Rheum palmatum complex derived from top-geoherb and non-geoherb areas provides the insights into geoherbalism properties of rhubarb.

Geoherb usually represents high-quality medicinal herbs with better clinical therapeutic effects, and elucidating the geoherbalism is essential for the quality improvement of traditional Chinese Medicine. However, few researches were conducted to clarify the geoherbalism based on a large scale of transcriptomics. In the present study, we compared the transcriptomes of Rheum palmatum complex derived from top-geoherb and non-geoherb areas to show the geoherbalism properties of rhubarb. A total of 412.32 Gb clean reads were obtained with unigene numbers of 100,615 after assembly. Based on the obtained transcriptome datasets, key enzyme-encoding genes involved in the anthraquinones biosynthesis were also obtained. We also found that 21 anthraquinone-related unigenes were differentially expressed between two different groups, and some of these DEGs were correlated to the content accumulation of five free anthraquinones, indicating that the gene expression profiles may promote the geoherbalism formation of rhubarb. In addition, the selective pressure analyses indicated that most paired orthologous genes between these two groups were subject to negative selection, and only a low proportion of orthologs under positive selection were detected. Functional annotation analyses indicated that these positive-selected genes related to the functions such as gene expression, substance transport, stress response and metabolism, indicating that discrepant environment also enhanced the formation of geoherbalism. Our study not only provided insights for the genetic mechanism of geoherbalism of rhubarb, but also laid more genetic cues for the future rhubarb germplasms improvement and utilization.

KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis.

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in diverse biological processes. Deletion of KAT8 inhibited CRC tumor growth, especially in a high-lactic tumor microenvironment. Therefore, the KAT8-eEF1A2 Kla axis is utilized to meet increased translational requirements for oncogenic adaptation. As a lactyltransferase, KAT8 may represent a potential therapeutic target for CRC.

Epidemiological characteristics of suspected adenomyosis in the Chinese physical examination population: a nested case-control study.

OBJECTIVES: We aimed to explore the epidemiological characteristics of suspected adenomyosis within a physical examination population in China. DESIGN: A retrospective, nested case-control study; we matched healthy people and those with potential adenomyosis on a 1:2 ratio by age. SETTING: A tertiary hospital health management centre. PARTICIPANTS: We included 15-60 years old women who underwent at least one uterine examination from October 2017 to December 2020, excluding those who had undergone hysterectomy and menopause. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the incidence and prevalence rate of suspected adenomyosis. Conditional logistic regression was used to estimate associations between serum biomarkers and potential adenomyosis. Areas under the receiver-operating characteristic curves (AUC) were used to determine the cut-off point of the cancer antigen 125 (CA125) level for suspected adenomyosis. RESULTS: A total of 30 629 women had uterus-related imaging examinations; 877 had suspected adenomyosis. The standardised incidence and prevalence of suspected adenomyosis was 1.32% and 2.35%, respectively, for all age groups. The conditional logistic regression analysis results showed that total bilirubin≥18.81 µmol/L (HR: 2.129; 95% CI 1.067 to 4.249; p<0.0321) and CA125 levels (HR: 1.014; 95% CI 1.002 to 4.731; p<0.0273) were positively correlated with onset of suspected adenomyosis; body mass index>24 kg/m2 (HR: 1.262; 95% CI 1.055 to 1.511; p<0.0109), CA125 levels (HR: 1.007; 95% CI 1.006 to 1.009; p<0.0001), and blood platelet levels (HR: 1.002; 95% CI 1 to 1.003; p<0.0141) were positively correlated with potential adenomyosis. The optimal cut-off of CA125 for new suspected adenomyosis was 10.714 U/mL, with a sensitivity of 77.42%, specificity of 53.76%, and AUC of 0.7841 (95% CI 0.7276 to 0.8407). CONCLUSIONS: The disease burden of suspected adenomyosis remains huge and can be informed by biomarkers. The disease-specific threshold of CA125 will support further preventive strategy development in population. TRIAL REGISTRATION NUMBER: ChiCTR2100049520, 2021/8/2.

Variability of rare earth and heavy metal elements in a representative alluvial depositional system.

Heavy metals (Ni, Cr, W, Cd, and Pb) and rare earth elements (REE) were investigated in the flood plain sediments of an island of the lower Yangtze River near Nanjing to determine how the vertical distribution of heavy metals could be affected by natural sedimentation processes and anthropogenic contamination. Stratigraphic analyses of magnetic susceptibility and the mean grain size distribution of the deposits enabled us to identify layers associated with a relatively high influx of suspended sediments that resulted in sudden changes in the concentrations of heavy metals. The results show that layers associated with high sediment influx (0.8 m depth) displayed low concentrations of Cr, Ni, W, and Cd that were mainly lithogenic in origin. The Post Archean Australian Shale (PAAS) normalized REE patterns in the flood plain cores were enrichment in Ce and Eu relative to PAAS, indicating that the sediments were most likely derived from a mixture of sediments and not from an anthropogenic source. Sharp increases in Y/Ho ratios, as well as heavy metal (Cd, Cr, Ni, and W) and Y concentrations were observed in the uppermost layer that could have been deposited from the rapid transport of sediment-laden, contaminated waters. The temporal (vertical) trends in Pb concentrations may be strongly influenced by coal burning. Elevated Pb concentrations (350 ppm and 1000 ppm) correlate with high magnetic susceptibility (> 200 m3 × kg-1) and the history of thermal power plant (1910-2002) activity. The anthropogenic inputs of Pb were, however, not diluted by high suspended sediment loads, which supports the argument that Pb was derived from fly ash.

Longitudinal patterns of patient-reported sleep disturbances after surgery for lung cancer.

PURPOSE: The purpose of this study was to identify longitudinal heterogeneous trajectories of sleep status, adjusted for the effect of pain over time, among patients who had surgery for lung cancer and to quantify how disturbed sleep in the hospital affects functional recovery after discharge. METHODS: We included patients from a surgical cohort (CN-PRO-Lung 1). All patients reported symptoms using the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) daily during postoperative hospitalization. Group-based dual trajectory modeling was used to investigate trajectories of disturbed sleep and pain during the first 7 days of postoperative hospitalization. Cox regression was used to compare the recovery of walking ability between the different sleep trajectories. RESULTS: Among 421 patients, disturbed sleep trajectories comprised low (31%), moderate (52%), and high (17%) groups. The surgical approach and number of chest tubes were associated with pain, and the number of chest tubes was also associated with sleep disturbances (OR = 1.99; 95% CI: 1.08-3.67). Recovery of walking ability after discharge was significantly slower in the high (median days = 16; 95% CI: 5-NA) and moderate disturbed sleep trajectory groups (median days = 5; 95%CI: 4-6) than in the low group (median days = 3; 95% CI: 3-4). CONCLUSION: Changes in disturbed sleep among patients with lung cancer followed three distinct trajectories over the first 7 days of hospitalization after surgery. Dual trajectory analyses highlighted the high concordance between specific trajectories of disturbed sleep and pain. Patients at high sleep disturbance and high levels of pain may benefit from appropriate interventions for both symptoms in combination with the patient's surgical approach and the number of chest tubes.

Longitudinal relationship between quality of life and negative life events among adolescents during COVID-19 pandemic: a cross-lagged panel analysis.

BACKGROUND: The negative association of quality of life (QoL) and negative life evens (NLEs) among adolescents has been proved by cross-sectional studies, without exploring sex differences. This study aimed to explore the longitudinal associations between QoL and NLEs among adolescents during novel coronavirus disease 2019 (COVID-19) pandemic and whether there are sex or age differences. METHODS: A stratified cluster sampling was used to select 1421 students in primary school and middle school in Chongqing, China. From November 2020 (T0) to December 2021 (T2), the Adolescent Self-Rating Life Events Checklist and the Adolescent Quality of Life Scale were used to collect 3 waves of data. The correlations between study variables were conducted by the Pearson correlation analyses. The direction and strength of the longitudinal associations were analyzed using cross-lagged panel analyses. RESULTS: Results showed significant changes in both variables during COVID-19 pandemic (P < 0.001). Cross-sectional analyses showed stable negative correlations between NLEs and QoL stratified by sex or by age (P < 0.001). Sex and age differences in longitudinal relationships were shown by cross-lagged panel analyses. For males, NLEs had a short-term bi-directional association with QoL [ßA-D = -(0.091-0.340), P < 0.05]; for females, QoL had a short-term correlation with NLEs [ßA = -0.119), ßC = -0.109), P < 0.001]. In the youngest age group, NLEs had a short-term bi-directional correlation with QoL [ßA-D = -(0.098-0.428), P < 0.05]. There was a short-term association between total QoL and NLEs among students except the 14∼15 year group [ßA = -(0.071-0.149), ßC = -(0.086-0.119), P < 0.05], the long-term association between total QoL and NLEs was only significant in adolescents aged 14∼15 years (ßE = -0.132, P < 0.05). The strength of NLEs was slightly higher than that of total QoL, but lower than that of QoL in each dimension. CONCLUSION: There were negative longitudinal relationships between NLEs and QoL during COVID-19 pandemic, and the strength of the associations varied across sex or age. Strengthening QoL in different dimensions may be a promising way to reduce NLEs during the pandemic among adolescents, and interventions should be tailored according different sex and ages.

Total Ionizing Dose Effects on the Threshold Voltage of GaN Cascode Devices.

GaN devices are nowadays attracting global attention due to their outstanding performance in high voltage, high frequency, and anti-radiation ability. Research on total ionizing dose and annealing effects on E-mode GaN Cascode devices has been carried out. The Cascode device consists of a low-voltage MOSFET and a high-voltage depletion-mode GaN MISHEMT. Cascode devices of both conventional processed MOSFET and radiation-hardened MOSFET devices are fabricated to observe the TID effects. Experiment results indicate that, for the Cascode device with conventional processed MOSFET, the VTH shifts to negative values at 100 krad(Si). For the Cascode device with radiation-hardened MOSFET, the VTH shifts by -0.5 V at 100 krad(Si), while shifts to negative values are 500 krad(Si). The annealing process, after the TID experiment, shows that it can release trapped charges and help VTH recover. On one hand, the VTH shift and recover trends are similar to those of a single MOSFET device, suggesting that the MOSFET is the vulnerable part in the Cascode which determines the anti-TID ability of the device. On the other hand, the VTH shift amount of the Cascode device is much larger than that of a previously reported p-GaN HEMT device, indicating that GaN material shows a better anti-TID ability than Si.

Using Clinician-Patient WeChat Group Communication Data to Identify Symptom Burdens in Patients With Uterine Fibroids Under Focused Ultrasound Ablation Surgery Treatment: Qualitative Study.

BACKGROUND: Unlike research project-based health data collection (questionnaires and interviews), social media platforms allow patients to freely discuss their health status and obtain peer support. Previous literature has pointed out that both public and private social platforms can serve as data sources for analysis. OBJECTIVE: This study aimed to use natural language processing (NLP) techniques to identify concerns regarding the postoperative quality of life and symptom burdens in patients with uterine fibroids after focused ultrasound ablation surgery. METHODS: Screenshots taken from clinician-patient WeChat groups were converted into free texts using image text recognition technology and used as the research object of this study. From 408 patients diagnosed with uterine fibroids in Chongqing Haifu Hospital between 2010 and 2020, we searched for symptom burdens in over 900,000 words of WeChat group chats. We first built a corpus of symptoms by manually coding 30% of the WeChat texts and then used regular expressions in Python to crawl symptom information from the remaining texts based on this corpus. We compared the results with a manual review (gold standard) of the same records. Finally, we analyzed the relationship between the population baseline data and conceptual symptoms; quantitative and qualitative results were examined. RESULTS: A total of 408 patients with uterine fibroids were included in the study; 190,000 words of free text were obtained after data cleaning. The mean age of the patients was 39.94 (SD 6.81) years, and their mean BMI was 22.18 (SD 2.78) kg/m2. The median reporting times of the 7 major symptoms were 21, 26, 57, 2, 18, 30, and 49 days. Logistic regression models identified preoperative menstrual duration (odds ratio [OR] 1.14, 95% CI 5.86-6.37; P=.009), age of menophania (OR -1.02 , 95% CI 11.96-13.47; P=.03), and the number (OR 2.34, 95% CI 1.45-1.83; P=.04) and size of fibroids (OR 0.12, 95% CI 2.43-3.51; P=.04) as significant risk factors for postoperative symptoms. CONCLUSIONS: Unstructured free texts from social media platforms extracted by NLP technology can be used for analysis. By extracting the conceptual information about patients' health-related quality of life, we can adopt personalized treatment for patients at different stages of recovery to improve their quality of life. Python-based text mining of free-text data can accurately extract symptom burden and save considerable time compared to manual review, maximizing the utility of the extant information in population-based electronic health records for comparative effectiveness research.

The panda-derived Lactiplantibacillus plantarum BSG201683 improves LPS-induced intestinal inflammation and epithelial barrier disruption in vitro.

Captive pandas are suffering from intestinal infection due to intestinal microbiota characterized by a high abundance of Enterobacteriaceae induced by long-term captivity. Probiotic supplements showed improvement in intestinal barrier function and inflammation. However, the effects of panda-derived probiotics on the intestinal epithelium and inflammation have not been elucidated. In the present study, lipopolysaccharide (LPS) impaired Caco-2 and RAW264.7 inflammatory models were applied to assess the protection of Lactiplantibacillus plantarum BSG201683 (L. plantarum G83) on barrier disruption and inflammation. The results showed that treatment with L. plantarum G83 significantly decreased the paracellular permeability to fluorescein isothiocyanate conjugated dextran (MW 4000, FITC-D4) after LPS induction. Meanwhile, L. plantarum G83 alleviated the reduction in tight junction (TJ) proteins and downregulated proinflammatory cytokines caused by LPS in Caco-2 cells. L. plantarum G83 also significantly decreased the expression and secretion of pro-inflammatory cytokines in LPS-induced RAW264.7 cells. In addition, the IL-10 increased in both Caco-2 and RAW264.7 cells after L. plantarum G83 treatment. The phagocytosis activity of RAW264.7 cells was significantly increased after L. plantarum G83 treatment. Toll-like receptor 4/ nuclear factor kappa-B (TLR4/NF-κB) signaling pathways were significantly down-regulated after L. plantarum G83 intervention, and the phosphorylation of NF-κB/p65 was consistent with this result. Our findings suggest that L. plantarum G83 improves intestinal inflammation and epithelial barrier disruption in vitro.

[Mechanism of Gardeniae Fructus in ameliorating rheumatoid arthritis based on metabolomics and intestinal microbiota].

Rheumatoid arthritis(RA), a chronic autoimmune disease, is featured by persistent joint inflammation. The development of RA is associated with the disturbance of endogenous metabolites and intestinal microbiota. Gardeniae Fructus(GF), one of the commonly used medicinal food in China, is usually prescribed for the prevention and treatment of jaundice, inflammation, ache, fever, and skin ulcers. GF exerts an effect on ameliorating RA, the mechanism of which remains to be studied. In this study, ultra-perfor-mance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)-based serum non-target metabolomics and 16S rDNA high-throughput sequencing were employed to elucidate the mechanism of GF in ameliorating RA induced by complete Freund's adjuvant in rats. The results showed that GF alleviated the pathological conditions in adjuvant arthritis(AA) rats. The low-and high-dose GF lo-wered the serum levels of interleukin(IL)-6, tumor necrosis factor-α(TNF-α), IL-1ß, and prostaglandin E2 in the rats(P<0.05, P<0.01). Pathways involved in metabolomics were mainly α-linolenic acid metabolism and glycerophospholipid metabolism. The results of 16S rDNA sequencing showed that the Streptococcus, Facklamia, Klebsiella, Enterococcus, and Kosakonia were the critical gut microorganisms for GF to treat AA in rats. Spearman correlation analysis showed that the three differential metabolites PE-NMe[18:1(9Z)/20:0], PC[20:1(11Z)/18:3(6Z,9Z,12Z)], and PC[20:0/18:4(6Z,9Z,12Z,15Z)] were correlated with the differential bacteria. In conclusion, GF may ameliorate RA by regulating the composition of intestinal microbiota, α-linolenic acid metabolism, and glycerophospholipid metabolism. The findings provide new ideas and data for elucidating the mechanism of GF in relieving RA.

Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-ß and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits.

Deficiencies in the clearance of peripheral amyloid ß (Aß) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aß is decreased in AD. However, the exact mechanism of Aß clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aß. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aß in vivo and in vitro. Moreover, enhancing blood monocyte Aß phagocytosis by improving energy metabolism alleviated brain Aß deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aß phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

The paleolacustrine significance of sedimentary nitrogen isotopes: A comparative study of late Holocene records in two lakes on the eastern Qinghai-Tibet Plateau.

The bulk nitrogen isotope composition of lacustrine sediments can be a useful proxy of past climatic and environmental changes. We previously reconstructed paleoenvironmental histories recorded in sediments of Lake Ximencuo and Lake Ngoring, both located on the eastern Qinghai-Tibetan Plateau (QTP), using a suite of biogeochemical paleoclimate proxies that included the sedimentary δ15Ntot values. We have revisited the different patterns of δ15Ntot variations in the two lakes and now conclude that their isotopic trends over the last millennium have been controlled by multiple factors. Regional temperature evidently is one potential factor affecting the sedimentary δ15Ntot values, indicating that the lake ecosystems respond to regional temperature changes on a sub-millennial timescale but in indirect and lake-specific ways. The processes involved in the sedimentary δ15Ntot changes appear to be more strongly influenced by the shapes of lake basins and associated hydrologic characteristics that control the origins of nitrogen-containing compounds in the lakes. To help understand the dynamics of nitrogen cycling and nitrogen isotope records in the QTP lakes, we identified two patterns - a terrestrial nitrogen-controlled pattern (TNCP) that is observed in deeper, steep-walled glacial-basin lakes and an aquatic nitrogen-controlled pattern (ANCP) that is observed in shallower, tectonic-basin lakes. We also considered the influences of the "amount effect" and the "temperature effect" on sedimentary δ15Ntot values and their possible operative mechanisms in these montane lakes. We postulate that both patterns are applicable to the QTP lakes, including both glacial and tectonic lakes, and probably to lakes in other regions that have also not experienced significant human disturbance.

Diterpenoid alkaloids from Delphinium trichophorum.

Three new hetisine type C20-diterpenoid alkaloids, named as trichophorines A-C (1-3), were isolated from Delphinium trichophorum, together with nine known alkaloids (4-12). Their structures were elucidated on the basis of spectroscopic data (1D, 2D NMR, single-crystal X-ray, and HR-ESI-MS). All compounds were evaluated for the inhibitory activities against LPS induced NO production in RAW 264.7 macrophage cells, and none of them showed considerable inhibitory activity.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Analysis of immunotherapeutic response-related signatures in esophageal squamous-cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common and lethal malignant diseases. Immunotherapy has been widely studied and has exhibited potential in ESCC treatment. However, there are only a portion of ESCC patients have benefited from immunotherapy. We herein identified immunotherapeutic response-related signatures (IRRS) and evaluated their performance in ESCC prognosis and immunotherapeutic responsiveness. Methods: We constructed an IRRS using the gene expression data of 274 ESCC patients based on y -30significantly differentially expressed genes, which were compared responders and non-responders from various patient cohorts treated with immunotherapy. Survival analysis was performed in both the GSE53625 and TCGA-ESCC cohorts. We also explored the differences in the tumor microenvironment between the high-IRRS and low-IRRS score groups using single-cell data as a reference. Three immunotherapy cohorts were used to verify the value of the IRRS in predicting immunotherapy response. Results: Twelve immunotherapy-related genes were selected to construct a signature score and were validated as independent prognostic predictors for patients with ESCC. Patients with high IRRS scores exhibited an immunosuppressive phenotype. Therefore, patients with low IRRS scores may benefit from immunotherapy. Conclusions: IRRS score is a biomarker for immunotherapy response and prognosis of ESCC.

Stokes shift spectroscopy and machine learning for label-free human prostate cancer detection.

The Stokes shift spectra (S3) of human cancerous and normal prostate tissues were collected label free at a selected wavelength interval of 40 nm to investigate the efficacy of the approach based on three key molecules-tryptophan, collagen, and reduced nicotinamide adenine dinucleotide (NADH)-as cancer biomarkers. S3 combines both fluorescence and absorption spectra in one scan. The S3 spectra were analyzed using machine learning (ML) algorithms, including principal component analysis (PCA), nonnegative matrix factorization (NMF), and support vector machines (SVMs). The components retrieved from the S3 spectra were considered principal biomarkers. The differences in the weights of the components between the two types of tissues were found to be significant. Sensitivity, specificity, and accuracy were calculated to evaluate the performance of SVM classification. This research demonstrates that S3 spectroscopy is effective for detecting the changes in the relative concentrations of the endogenous fluorophores in tissues due to the development of cancer label free.