A Passive-Active Anti/Deicing Coating Integrating Superhydrophobicity, Thermal Insulation, and Photo/Electrothermal Conversion Effects.

Anti/deicing coatings that combine active and passive methods can utilize various energy sources to achieve anti/deicing effects. However, poor photothermal or electrothermal performance and inevitable heat loss often reduce their anti/deicing efficiency. Herein, copper sulfide loaded activated biochar (AC@CuS) as photo/electric material, polydimethylsiloxane as hydrophobic component, thermally expandable microspheres as foaming agent, and an anti/deicing coating integrating thermal insulation, superhydrophobicity, photo/electrothermal effects was successfully constructed. Benefiting from the synergistic effect of superhydrophobicity and thermal insulation, the freezing time of water droplets on the coating surface is extended from 150 to 2140 s, showing excellent passive anti-icing performance. AC@CuS exhibits photo/electrothermal effects, and porous expanded microspheres reduce heat loss, which endows the coating with desirable photo/electrothermal conversion performance. Under the conditions of 0.2 W/cm2 electric power density (EPD) and 0.1 W/cm2 optical power density (OPD), the temperature of the coating increases from 24 to 96.4 and 113 °C, respectively. Interestingly, with a coheating of 0.05 W/cm2 weaker OPD and 0.05 W/cm2 lower EPD, the ice on the coating surface can be quickly melted in 2.5 min, showing synergistic deicing performance. In addition, the WCA of the prepared coating remains above 150° after mechanical damage, rain impact, UV irradiation, chemical corrosion, and high-temperature treatment, and good superhydrophobic durability ensures the anti/deicing durability of the coating.

Pancreatic STAT5 activation promotes KrasG12D-induced and inflammation-induced acinar-to-ductal metaplasia and pancreatic cancer.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.

Dynamic changes in the aroma profiles and volatiles of Enshi Yulu tea throughout its industrial processing.

Although Enshi Yulu tea (ESYL) possesses a distinctive fragrance, there is a scarcity of studies focusing on its primary volatiles or aroma genesis. This study aims to elucidate the dynamics in the profiles of aromas and volatiles through aroma profiling analysis and headspace solid-phase microextraction/gas chromatography-mass spectrometry. A total of 10 aroma attributes and 128 volatiles were identified in ESYL, with geraniol and linalool exhibiting the highest levels, and alcohols constituting the predominant proportion. Besides, a relative odor activity value (ROAV) based molecular aroma wheel was constructed, revealing 12 key odorants with ROAVs >1, wherein linalool, ß-ionone, and nonanal ranked highest. Notably, steaming and final drying emerged as critical steps for ESYL aroma development, while the non-enzymatic degradation of fatty acids likely contributed to the formation of its fresh aroma. These findings significantly enhance our comprehension of ESYL aroma formation.

Which factors are associated with adverse prognosis in multiple myeloma patients after surgery? - preliminary establishment and validation of the nomogram.

BACKGROUND: To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram. METHODS: Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated. RESULTS: Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%. CONCLUSION: This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.

[Characterization of carbon and oxygen isotopes of plant on climate and plant physiology at the southeastern margin of Qinghai-Tibet Plateau, China]. / é’è—é«˜åŽŸä¸œå—ç¼˜æ¤ç‰©ç¢³æ°§åŒä½ç´ å¯¹æ°”å€™åŠæ¤ç‰©ç”Ÿç†çš„è¡¨å¾.

To investigate the correlation between carbon and oxygen isotope compositions of plant cellulose and climatic factors as well as plant physiological indices on the southeastern margin of the Qinghai-Tibet Plateau, we examined plant species in eight sampling sites with similar latitudes and different longitudes in this region. Through the characteristics of δ13C and δ18O values, fractionation values (Δ13C and Δ18O) in leaf cellulose, we discussed water use efficiency (WUE) and the environmental factors, the variation of carbon and oxygen isotopes in the southeastern margin of the Qinghai-Tibet Plateau with elevation and longitude, and revealed the indication degrees of isotopic signals to different environments and vegetation physiology. By using the semi-quantitative model of carbon and oxygen dual isotopes, we investigated the physiological adaptation mechanisms of plants to varying environmental conditions. The results demonstrated that both Δ13C and Δ18O of cellulose decreased with increasing elevation and longitude, and Δ13C was more influenced by longitude, while Δ18O was more susceptible to elevation variation. Additionally, Δ13C and Δ18O were significantly and positively correlated with temperature (TEM), precipitation (PRE), potential evapotranspiration (PET), and relative humidity (RH). PRE was the dominant meteorological factor driving the variation of Δ13C, while RH was the dominant meteorological factor influencing Δ18O variation. In contrast to Δ13C, WUE showed a stronger correlation with elevation than with longitude, which increased as elevation and longitude increased. According to the carbon-oxygen model, plant stomatal conductance (gs) and photosynthetic capacity (Amax) decreased with increasing precipitation and relative humidity, while the values increased with increasing elevation and longitude. The combined analysis of carbon and oxygen isotopes of organic matters would yield additional environmental and gas exchange information for studies on climate tracing and vegetation physiology studies on the southeastern margin of the Qinghai-Tibet Plateau.

DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells.

Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.

Deep convolutional neural network model ResNeSt for discrimination of papillary thyroid carcinomas and benign nodules in thyroid nodules diagnosed as atypia of undetermined significance.

Background: A deep convolutional neural network (DCNN) model was employed for the differentiation of thyroid nodules diagnosed as atypia of undetermined significance (AUS) according to the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of this study was to investigate the efficiency of ResNeSt in improving the diagnostic accuracy of fine-needle aspiration (FNA) biopsy. Methods: Fragmented images were used to train and test DCNN models. A training dataset was built from 1,330 samples diagnosed as papillary thyroid carcinoma (PTC) or benign nodules, and a test dataset was built from 173 samples diagnosed as AUS. ResNeSt was trained and tested to provide a differentiation. With regard to AUS samples, the characteristics of the cell nuclei were compared using the Wilcoxon test. Results: The ResNeSt model achieved an accuracy of 92.49% (160/173) on fragmented images and 84.78% (39/46) from a patient wise viewpoint in discrimination of PTC and benign nodules in AUS nodules. The sensitivity and specificity of ResNeSt model were 95.79% and 88.46%. The κ value between ResNeSt and the pathological results was 0.847 (P<0.001). With regard to the cell nuclei of AUS nodules, both area and perimeter of malignant nodules were larger than those of benign ones, which were 2,340.00 (1,769.00, 2,807.00) vs. 1,941.00 (1,567.50, 2,455.75), P<0.001 and 190.46 (167.64, 208.46) vs. 171.71 (154.95, 193.65), P<0.001, respectively. The grayscale (0 for black, 255 for white) of malignant lesions was lower than that of benign ones, which was 37.52 (31.41, 46.67) vs. 45.84 (31.88, 57.36), P <0.001, indicating nuclear staining of malignant lesions were deeper than benign ones. Conclusions: In summary, the DCNN model ResNeSt showed great potential in discriminating thyroid nodules diagnosed as AUS. Among those nodules, malignant nodules showed larger and more deeply stained nuclei than benign nodules.

Long-term survivors after curative-intent resection for intrahepatic cholangiocarcinoma.

OBJECTIVES: The objective of the current study was to characterize prognostic factors related to long-term recurrence-free survival after curative-intent resection of intrahepatic cholangiocarcinoma (ICC). METHODS: Data on patients who underwent curative-intent resection for ICC between 2000 and 2020 were collected from an international multi-institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long-term survivors who survived more than 5 years with no recurrence. RESULTS: Among 635 patients who underwent curative-intent resection for ICC, 104 (16.4%) patients were long-term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254-1.879), satellite lesions (HR: 1.253, 95% CI: 1.003-1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349-2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2-5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post-recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087-2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081-2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years. CONCLUSION: Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative-intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long-term survival.

Effect of heat-reinforcing needling on hypoxia-inducible factor 1α and glycolysis activity in rabbits with cold syndrome of rheumatoid arthritis. / çƒ­è¡¥é’ˆæ³•å¯¹ç±»é£Žæ¹¿å ³èŠ‚ç‚Žå¯’è¯å®¶å ”è†å ³èŠ‚æ»‘è†œç»„ç»‡ç¼ºæ°§è¯±å¯¼å› å­1αå’Œç³–é µè§£æ´»æ€§çš„å½±å“.

OBJECTIVES: To observe the effect of heat-reinforcing needling (HRN) on synovial inflammation, hypoxia-inducible factor-1α (HIF-1α) and glycolytic activity in serum and synovial tissue in rabbits with cold syndrome of rheumatoid arthritis (RA), so as to explore its mechanisms underlying improvement of RA. METHODS: A total of 32 rabbits were randomly divided into normal, model, inhibitor and HRN groups, with 8 rabbits in each group. The RA with cold syndrome model was induced by injecting ovalbumin dry powder and Freund's complete adjuvant combined with cold freezing. Rabbits in the inhibitor group were intraperitoneally injected with 2-methoxyestradiol (2.5 mg/kg), rabbits in the HRN group were received HRN at bilateral "Zusanli" (ST36) for 30 min. The treatments were conducted once daily for 14 consecutive days. After the interventions, the knee circumference and pain threshold were measured. The contents of nicotinamide adenine dinucleotide phosphoric (NADPH), Hexokinase II (HK2) and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) in serum of rabbits were detected by ELISA. The pathological morphology of synovial tissue of the knee joints were observed by HE staining. The positive expressions of tumor necrosis factor (TNF-α), interleukin (IL)-1ß, IL-6 and IL-17 in synovial tissue of knee joint were detected by immunohistochemistry. The content of lactic acid in synovial tissue of rabbit knee joint was detected by spectrophotometry. The expression levels of HIF-1α, pyruvate kinase 2 (PKM2) and lactate dehydrogenase (LDHA) in synovial tissue of knee joint were detected by Western blot. RESULTS: After intervention, compared with the normal group, the knee circumference was significantly enlarged (P<0.05), the pain threshold was significantly decreased (P<0.05)；the synovial tissue of knee joints showed significant cell proliferation and inflammatory infiltration, the pathological score was significantly increased (P<0.05)；positive expressions of TNF-α, IL-1ß, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P<0.05) in the model group. Compared with model group, the circumference of knee joint was significantly decreased (P<0.05), the pain threshold was significantly increased (P<0.05)；in synovial tissue, the pathological score was decreased (P<0.05)；the positive expressions of TNF-α, IL-1ß, IL-6 and IL-17 in synovial tissue were decreased (P<0.05), the lactic acid content in synovial tissue was decreased (P<0.05)；the contents of NADPH, HK2 and PFKFB3 in serum and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were decreased (P<0.05) in inhibitor group and HRN group. Compared with the inhibitor group, the synovial pathological score was significantly increased (P<0.05), positive expressions of TNF-α, IL-1ß, IL-6 and IL-17, the content of lactic acid in synovial tissue, the contents of NADPH, HK2 and PFKFB3 in serum, and the protein expression levels of HIF-1α, PKM2 and LDHA in synovial tissue were increased (all P<0.05) in HRN group. CONCLUSIONS: HRN can increase the pain threshold, reduce the knee circumference and inhibit the inflammatory response in rabbits with cold syndrome of RA. The possible mechanism is related to the down-regulation of HIF-1α and glycolysis activity.

The fungal protease BbAorsin contributes to growth, conidiation, germination, virulence, and antiphytopathogenic activities in Beauveria bassiana (Hypocreales: Cordycipitaceae).

The fall armyworm, Spodoptera frugiperda (Lepidoptera: Noctuidae), is one of the most destructive agricultural pests. The entomopathogenic fungus Beauveria bassiana (Hypocreales: Clavicipitaceae) is a biopesticide widely used for biocontrol of various pests. Secreted fungal proteases are critical for insect cuticle destruction and successful infection. We have previously shown that the serine protease BbAorsin in B. bassiana has entomopathogenic and antiphytopathogenic activities. However, the contribution of BbAorsin to fungal growth, conidiation, germination, virulence and antiphytopathogenic activities remains unclear. In this study, the deletion (ΔBbAorsin), complementation (Comp), and overexpression (BbAorsinOE) strains of B. bassiana were generated for comparative studies. The results showed that ΔBbAorsin exhibited slower growth, reduced conidiation, lower germination rate, and longer germination time compared to WT and Comp. In contrast, BbAorsinOE showed higher growth rate, increased conidiation, higher germination rate and shorter germination time. Injection of BbAorsinOE showed the highest virulence against S. frugiperda larvae, while injection of ΔBbAorsin showed the lowest virulence. Feeding BbAorsinOE resulted in lower pupation and adult eclosion rates and malformed adults. 16S rRNA sequencing revealed no changes in the gut microbiota after feeding either WT or BbAorsinOE. However, BbAorsinOE caused a disrupted midgut, leakage of gut microbiota into the hemolymph, and upregulation of apoptosis and immunity-related genes. BbAorsin can disrupt the cell wall of the phytopathogen Fusarium graminearum and alleviate symptoms in wheat seedlings and cherry tomatoes infected with F. graminearum. These results highlight the importance of BbAorsin for B. bassiana and its potential as a multifunctional biopesticide.

Quality and Flavor Difference in Dry-Cured Meat Treated with Low-Sodium Salts: An Emphasis on Magnesium.

The present study aimed to develop low-sodium curing agents for dry-cured meat products. Four low-sodium formulations (SPMA, SPM, SP, and SM) were used for dry-curing meat. The physicochemical properties and flavor of the dry-cured meat were investigated. The presence of Mg2+ ions hindered the penetration of Na+ into the meat. The weight loss, moisture content, and pH of all low-sodium salt groups were lower than those of S. Mg2+ addition increased the water activity (Aw) of SPMA, SPM, and SM. Dry-curing meat with low-sodium salts promoted the production of volatile flavor compounds, with Mg2+ playing a more prominent role. Furthermore, low-sodium salts also promoted protein degradation and increased the content of free amino acids in dry-cured meat, especially in SM. Principal component analysis (PCA) showed that the low-sodium salts containing Mg2+ were conducive to improving the quality of dry-cured meat products. Therefore, low-sodium salts enriched with Mg2+ become a desirable low-sodium curing agent for achieving salt reduction in dry-cured meat products.

Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: A mediation analysis.

BACKGROUND: POCD is a common complication among patients who underwent coronary artery bypass graft (CABG), it is linked to loss of independence and reduced quality of life. AIMS AND OBJECTIVES: To examine the association between postoperative cognitive dysfunction (POCD), postoperative delirium (POD) and interleukin-6 (IL-6). DESIGN: A prospective cohort study. METHODS: Patients who underwent elective isolated CABG were enrolled. POCD was assessed by a set of cognitive function tools. Delirium was assessed using the CAM-ICU. The logistic regression analyses were used to identify the predictive value of POD or IL-6 on POCD. The path analysis was used to analyse the relationship among POD, IL-6 and POCD. RESULTS: A total of 212 patients were enrolled, with 25.0% of patients developing POD and 32.5% developing POCD. The multiple logistic regression analysis revealed that patients with POD had a four-fold increased hazard of POCD (OR = 3.655), and patients with IL-6 ≥ 830.50 pg/mL at the 6th hours after surgery had a 5-fold increased risk of experiencing POCD (OR = 5.042). However, the mediation effect of POD between IL-6 and POCD was not statistically significant (ß = 0.059, p = .392). CONCLUSIONS: POD and IL-6 at the 6th hour after surgery (≥830.50 pg/mL) are two potent predictors for POCD, while POD did not play a mediation effect between IL-6 and POCD. RELEVANCE TO CLINICAL PRACTICE: Early identification of risk factors (e.g., delirium assessment and testing for serum IL-6 levels) by clinical nurses for POCD may contribute to the clinical practice for the targeted prevention nursing strategies.

Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: An initial cohort study.

BACKGROUND: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. We here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. METHODS: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. RESULTS: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and IVC anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than six months follow-up. CONCLUSION: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.

Numerous studies have revealed that the ATP-gated ion channel purinergic 2X7 receptor (P2X7R) plays an important role in tumor progression and the pathogenesis of cancer pain. P2X7R requires activation by extracellular ATP to perform its regulatory role functions. During tumor development or cancer-induced pain, ATP is released from tumor cells or other cells in the tumor microenvironment (such as tumor-associated immune cells), which activates P2X7R, opens ion channels on the cell membrane, affects intracellular molecular metabolism, and regulates the activity of tumor cells. Furthermore, peripheral organs and receptors can be damaged during tumor progression, and P2X7R expression in nerve cells (such as microglia) is significantly upregulated, enhancing sensory afferent information, sensitizing the central nervous system, and inducing or exacerbating pain. These findings reveal that the ATP-P2X7R signaling axis plays a key regulatory role in the pathogenesis of tumors and cancer pain and also has a therapeutic role. Accordingly, in this study, we explored the role of P2X7R in tumors and cancer pain, discussed the pharmacological properties of inhibiting P2X7R activity (such as the use of antagonists) or blocking its expression in the treatment of tumor and cancer pain, and provided an important evidence for the treatment of both in the future.

Integrating transcriptomics and machine learning for immunotherapy assessment in colorectal cancer.

Colorectal cancer (CRC) is a highly prevalent and lethal malignancy worldwide. Although immunotherapy has substantially improved CRC outcomes, intolerance remains a major concern among most patients. Considering the pivotal role of the tumor microenvironment (TME) in tumor progression and treatment outcomes, profiling the TME at the transcriptomic level can provide novel insights for developing CRC treatment strategies. Seventy-seven TME-associated signatures were acquired from previous studies. To elucidate variations in prognosis, clinical features, genomic alterations, and responses to immunotherapy in CRC, we employed a non-negative matrix factorization algorithm to categorize 2595 CRC samples of 27 microarrays from the Gene Expression Omnibus database. Three machine learning techniques were employed to identify a signature specific to immunotherapy. Subsequently, the mechanisms by which this signature interacts with TME subtypes and immunotherapy were investigated. Our findings revealed five distinct TME subtypes (TMESs; TMES1-TMES5) in CRC, each exhibiting a unique pattern of immunotherapy response. TMES1, TMES4, and TMES5 had relatively inferior outcomes, TMES2 was associated with the poorest prognosis, and TMES3 had a superior outcome. Subsequent investigations revealed that activated dendritic cells could enhance the immunotherapy response rate, with their augmentation effect closely associated with the activation of CD8+T cells. We successfully classified CRC into five TMESs, each demonstrating varying response rates to immunotherapy. Notably, the application of machine learning to identify activated dendritic cells helped elucidate the underlying mechanisms contributing to these differences. We posit that these TMESs hold promising clinical implications for prognostic evaluation and guidance of immunotherapy strategies, thereby providing valuable insights to inform clinical decision-making.

Molecular mechanism analyses of post-traumatic epilepsy and hereditary epilepsy based on 10× single-cell transcriptome sequencing technology.

BACKGROUND: Single-cell RNA sequencing analysis has been usually conducted on post-traumatic epilepsy (PET) and hereditary epilepsy (HE) patients; however, the transcriptome of patients with traumatic temporal lobe epilepsy has rarely been studied. MATERIALS AND METHODS: Hippocampus tissues isolated from one patient with PTE and one patient with HE were used in the present study. Single cell isolates were prepared and captured using a 10× Genomics Chromium Single-Cell 3' kit (V3) according to the manufacturer's instructions. The libraries were sequenced on an Illumina NovaSeq 6000 sequencing system. Raw data were processed, and the cells were filtered and classified using the Seurat R package. Uniform Manifold Approximation and Projection was used for visualization. Differentially expressed genes (DEGs) were identified based on a p-value ≤0.01 and log fold change (FC) ≥0.25. Gene Ontology (GO, http://geneontology.org/) and KEGG (Kyoto Encyclopedia of Genes and Genomes, www.genome.jp/kegg) analyses were performed on the DEGs for enrichment analysis. RESULTS: The reads obtained from the 10× genomic platform for PTE and HE were 39.56 M and 30.08 M, respectively. The Q30 score of the RNA reads was >91.6%. After filtering, 7479 PTE cells and 9357 HE cells remained for further study. More than 96.4% of the reads were mapped to GRCh38/GRCm38. The cells were differentially distributed in two groups, with higher numbers of oligodendrocytes (6522 vs. 2532) and astrocytes (133 vs. 52), and lower numbers of microglial cells (2242 vs. 3811), and neurons (3 vs. 203) present in the HE group than in the PTE group. The DEGs in four cell clusters were identified, with 25 being in oligodendrocytes (13 upregulated and 12 downregulated), 87 in microglia cells (42 upregulated and 45 downregulated), 222 in astrocytes (115 upregulated and 107 downregulated), and 393 in neurons (305 upregulated and 88 downregulated). The genes MTND1P23 (downregulated), XIST (downregulated), and RPS4Y1 (upregulated) were commonly expressed in all four cell clusters. The DEGs in microglial cells and astrocytes were enriched in the IL-17 signaling pathway. CONCLUSION: Our study explored differences in cells found in a patient with PE compared to a patient with HE, and the transcriptome in the different cells was analyzed for the first time. Studying inflammatory and immune functions might be the best approach for investigating traumatic temporal lobe epilepsy in neurons.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Structure-based prediction and characterization of photo-crosslinking in native protein-RNA complexes.

UV-crosslinking of protein and RNA in direct contacts has been widely used to study protein-RNA complexes while our understanding of the photo-crosslinking mechanisms remains poor. This knowledge gap is due to the challenge of precisely mapping the crosslink sites in protein and RNA simultaneously in their native sequence and structural contexts. Here we systematically analyze protein-RNA interactions and photo-crosslinking by bridging crosslinked nucleotides and amino acids mapped using different assays with protein-RNA complex structures. We developed a computational method PxR3D-map which reliably predicts crosslink sites using structural information characterizing protein-RNA interaction interfaces. Analysis of the informative features revealed that photo-crosslinking is facilitated by base stacking with not only aromatic residues, but also dipeptide bonds that involve glycine, and distinct mechanisms are utilized by different RNA-binding domains. Our work suggests protein-RNA photo-crosslinking is highly selective in the cellular environment, which can guide data interpretation and further technology development for UV-crosslinking-based assays.

Preoperative anemia: impact on short- and long-term outcomes following curative-intent resection of gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: The effect of preoperative anemia on clinical outcomes of patients undergoing resection of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been previously investigated. This study aimed to characterize how preoperative anemia affected short- and long-term outcomes of patients undergoing curative-intent resection of GEP-NETs. METHODS: Patients who underwent curative-intent resection for GEP-NETs between January 1990 and December 2020 were identified from 8 major institutions. The last preoperative hemoglobin level was recorded; anemia was defined as <13.5 g/dL in males or <12.0 g/dL in females based on the guides of the American Society of Hematology. The effect of anemia on postoperative outcomes was assessed on uni- and multivariate analyses. RESULTS: Among 1559 patients, the median age was 58 years (IQR, 48-66), and roughly one-half of the cohort was male (796 [51.1%]). Most patients had a pancreatic tumor (1040 [66.7%]), followed by small bowel (259 [16.6%]), duodenum (103 [6.6%]), stomach (66 [4.2%]), appendix (53 [3.4%]), and other locations (38 [2.6%]). The median preoperative hemoglobin level was 13.4 g/dL (IQR, 12.2-14.5). Overall, 101 (6.7%) and 119 (8.5%) patients received an intra- or postoperative packed red blood cell (pRBC) transfusion, respectively. A total of 972 patients (44.5%) experienced a postoperative complication. Although the overall incidence of complications was no different among patients who did (anemic: 48.7%) vs patients who did not (nonanemic: 47.3%) have anemia (P = .597), patients with preoperative anemia were more likely to develop a major (Clavien-Dindo grade ≥IIIa: 48.9% [anemic] vs 38.0% [nonanemic]; P = .006) and multiple (≥3 types of complications: 32.2% [anemic] vs 19.7% [anemic]; P < .001) complications. Of note, 1-, 3-, and 5-year overall survival (OS) rates were 96.7%, 90.5%, and 86.6%, respectively. On multivariable analysis, anemia (hazard ratio, 2.0; 95% CI, 1.2-3.2; P = .006) remained associated with worse OS; postoperative pRBC transfusion was associated with an OS (5-year OS: 75.0% vs 87.7%; P = .017) and recurrence-free survival (RFS; 5-year RFS: 66.9% vs 76.5%; P = .047). CONCLUSION: Preoperative anemia was commonly identified in roughly 1 in 3 patients who underwent curative-intent resection for GEP-NETs. Preoperative anemia was strongly associated with a higher risk of postoperative morbidity and worse long-term outcomes.