Multi-omics analysis of macrophage-associated receptor and ligand reveals a strong prognostic signature and subtypes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of intercellular signaling and plays a vital role in the progression of HCC. This study aimed to identify the macrophage-related receptor ligand marker genes associated with HCC and further explored the molecular immune mechanisms attributed to altered biomarkers. Single-cell RNA sequencing data containing primary and recurrent samples were downloaded from the China National GeneBank. Cell types were first identified to explore differences between immune cells from different sample sources. CellChat analysis was used to infer and analyze intercellular communication networks quantitatively. Three molecular subtypes were constructed based on the screened twenty macrophage-associated receptor ligand genes. Bulk RNA-Seq data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the screening, the minor absolute shrinkage and selection operator (LASSO) regression model was employed to identify key markers. After collecting peripheral blood and clinical information from patients, an enzyme-linked immunosorbent assay (ELISA) was used to detect the correlation between key markers and IL-10, one of the macrophage markers. After developing a new HCC risk adjustment model and conducting analysis, it was found that there were significant differences in immune status and gene mutations between the high-risk and low-risk groups of patients based on macrophage-associated receptor and ligand genes. This study identified SPP1, ANGPT2, and NCL as key biological targets for HCC. The drug-gene interaction network analysis identified wortmannin, ribavirin, and tarnafloxin as potential therapeutic drugs for the three key markers. In a clinical cohort study, patients with immune checkpoint inhibitor (ICI) resistance had significantly higher expression levels of OPN, ANGPT2, NCL, and IL-10 than patients with ICI-responsiveness. These three key markers were positively correlated with the expression level of IL-10. The signature based on macrophage-associated receptor and ligand genes can accurately predict the prognosis of patients with HCC and the sensitivity to immunotherapy. These results may help guide the development of targeted prevention and personalized treatment of HCC.

Dihydrotanshinone I inhibits gallbladder cancer growth by targeting the Keap1-Nrf2 signaling pathway and Nrf2 phosphorylation.

BACKGROUND: Gallbladder cancer (GBC) poses a significant risk to human health. Its development is influenced by numerous factors, particularly the homeostasis of reactive oxygen species (ROS) within cells. This homeostasis is crucial for tumor cell survival, and abnormal regulation of ROS is associated with the occurrence and progression of many cancers. Dihydrotanshinone I (DHT I), a biologically effective ingredient isolated from Salvia miltiorrhiza, has exhibited cytotoxic properties against various tumor cells by inducing apoptosis. However, the precise molecular mechanisms by which dht I exerts its cytotoxic effects remain unclear. PURPOSE: To explore the anti-tumor impact of dht I on GBC and elucidate the potential molecular mechanisms. METHODS: The proliferation of GBC cells, NOZ and SGC-996, was assessed using various assays, including CCK-8 assay, colony formation assay and EdU staining. We also examined cell apoptosis, cell cycle progression, ROS levels, and alterations in mitochondrial membrane potential to delve into the intricate molecular mechanism. Quantitative PCR (qPCR), immunofluorescence staining, and Western blotting were performed to evaluate target gene expression at both the mRNA and protein levels. The correlation between nuclear factor erythroid 2-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1) were examined using co-immunoprecipitation. Finally, the in vivo effect of dht I was investigated using a xenograft model of gallbladder cancer in mice. RESULTS: Our research findings indicated that dht I exerted cytotoxic effects on GBC cells, including inhibiting proliferation, disrupting mitochondrial membrane potential, inducing oxidative stress and apoptosis. Our in vivo studies substantiated the inhibition of dht I on tumor growth in xenograft nude mice. Mechanistically, dht I primarily targeted Nrf2 by promoting Keap1 mediated Nrf2 degradation and inhibiting protein kinase C (PKC) induced Nrf2 phosphorylation. This leads to the suppression of Nrf2 nuclear translocation and reduction of its target gene expression. Moreover, Nrf2 overexpression effectively counteracted the anti-tumor effects of dht I, while Nrf2 knockdown significantly enhanced the inhibitory effect of dht I on GBC. Meanwhile, PKC inhibitors and nuclear import inhibitors increased the sensitivity of GBC cells to dht I treatment. Conversely, Nrf2 activators, proteasome inhibitors, antioxidants and PKC activators all antagonized dht I induced apoptosis and ROS generation in NOZ and SGC-996 cells. CONCLUSION: Our findings indicated that dht I inhibited the growth of GBC cells by regulating the Keap1-Nrf2 signaling pathway and Nrf2 phosphorylation. These insights provide a strong rationale for further investigation of dht I as a potential therapeutic agent for GBC treatment.

Gallbladder cancer: surgical treatment, immunotherapy, and targeted therapy.

Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research.

Construction of a pathological model of skin lesions in acute herpes zoster virus infection and its molecular mechanism.

Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.

Intestinal microbiota and biliary system diseases.

Introduction: The incidence of biliary system diseases has been continuously increasing in the past decade. Biliary system diseases bring a heavy burden to humanity and society. However, the specific etiology and pathogenesis are still unknown. The biliary system, as a bridge between the liver and intestine, plays an indispensable role in maintaining the physiological metabolism of the body. Therefore, prevention and treatment of biliary diseases are crucial. It is worth noting that the microorganisms participate in the lipid metabolism of the bile duct, especially the largest proportion of intestinal bacteria. Methods: We systematically reviewed the intestinal microbiota in patients with gallstones (GS), non-calculous biliary inflammatory, and biliary tract cancer (BTC). And searched Pubmed, Embase and Web of science for research studies published up to November 2023. Results: We found that the abundance of Faecalibacterium genus is decreased in GS, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and BTC. Veillonella, Lactobacillus, Streptococcus and Enterococcus genus were significantly increased in PSC, PBC and BTC. Interestingly, we found that the relative abundance of Clostridium was generally reduced in GS, PBC and BTC. However, Clostridium was generally increased in PSC. Discussion: The existing research mostly focuses on exploring the mechanisms of bacteria targeting a single disease. Lacking comparison of multiple diseases and changes in bacteria during the disease process. We hope to provide biomarkers forearly diagnosis of biliary system diseases and provide new directions for the mechanism of intestinal microbiota in biliary diseases.

Clinical application of indocyanine green fluorescence navigation technique in laparoscopic common bile duct exploration for complex hepatolithiasis.

BACKGROUND: This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. METHODS: Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. RESULTS: Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P < 0.05). Postoperatively, the observation group had lower rates of postoperative bile leakage, abdominal infection, postoperative hemorrhage, and residual stone than the control group. Additionally, the observation group demonstrated significantly shorter times for resuming flatus, removal of the abdominal drainage tube, and hospitalization than the control group, with statistical significance (P < 0.05). CONCLUSION: ICG fluorescence navigation technology effectively visualizes the bile duct, improves its identification rate, shortens the operation time, prevents biliary tract injury, and reduces the occurrence of complications.

A clinical prognostic model of oxidative stress-related genes linked to tumor immune cell infiltration and the prognosis of ovarian cancer patients.

Background: According to statistics, ovarian cancer (OV) is the most prevalent type of gynecologic malignancy and has the highest mortality rate of all gynecologic tumors. Although several studies have shown that oxidative stress (OS) contributes significantly to the onset and progression of cancer, the role of OS in OV needs to be investigated further. Thus, it is critical to comprehend the function of OS-related genes in OV. Methods: In this study, all data related to the transcriptome and clinical status of the patients were retrieved from "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) databases. Using the unsupervised cluster analysis technique, all patients with OV were classified into two different subtypes (categories) based on the OS gene. All hub genes were screened using the weighted gene co-expression network analysis (WGCNA). Since the hub genes and the differentially expressed genes (DEGs) in both categories were found to intersect, the univariate Cox regression analysis was implemented. A multivariate Cox analysis was also performed to construct a novel clinical prognosis model, which was validated using data from the GEO cohort. In addition, the relationship between risk score and immune cell infiltration level was evaluated using CIBERSORT. Finally, qRT-PCR was used to confirm the expression of the genes used to construct the model. Results: Two subtypes of OS were obtained. The findings indicated that OS-C1 had a better survival outcome than OS-C2. The results of WGCNA yielded 112 hub genes. For univariate COX regression analyses, 49 OS-related trait genes were obtained. Finally, a clinical prognostic model containing two genes was constructed. This model could differentiate between patients with OV having varying years of survival in the TCGA and GEO cohorts. The model risk score was verified as an independent prognostic indicator. According to the results of CIBERSORT, many tumor-infiltrating immune cells were found to be significantly related to the risk score. Furthermore, the results revealed that patients with low-risk OV in the CTLA4 treatment group had a high likelihood of benefiting from immunotherapy. qRT-PCR results also showed that the expression of MARVELD1 and VSIG4 was high in the OV samples. Conclusions: Analysis of the results suggested that the newly developed model, which contained two characteristic OS-related genes, could successfully predict the survival outcomes of all patients with OV. The findings of this study could offer valuable information and insights into the refinement of personalized therapy and immunotherapy for OV in the future.

LncRNA PCAT6 is a predictor of poor prognosis of colorectal cancer.

Background: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) has been studied in many cancers, yet its relationship with colorectal cancer (CRC) remains poorly defined. Here, we conducted an analysis of The Cancer Genome Atlas (TCGA) database to better clarify the role of PCAT6 in this cancer type. Methods: Wilcoxon rank-sum tests were utilized to assess relative levels of PCAT6 in CRC tumors and normal tissues, while logistic regression analyses were utilized to compare the relationships between PCAT6 levels and clinicopathological findings. Kaplan-Meier curves and Cox regression analyses were used to gauge correlations between PCAT6 and patient survival outcomes, while the biological roles of this lncRNA were investigated via a gene set enrichment analysis (GSEA) approach. The expression level of PCAT6 in CRC cell lines was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: PCAT6 levels were significantly correlated with CRC patient lymph node metastasis (N) stage [odds ratio (OR) =1.8 for N1 & N2 vs. N0], lymphatic invasion [OR =1.9 for yes vs. no), distant metastasis (M stage) (OR =2.1 for M1 vs. M0), carcinoembryonic antigen (CEA) level (OR =1.9 for >5 vs. ≤5), perineural invasion (OR =1.9 for yes vs. no), pathologic stage (OR =1.9 for stage III/IV vs. stage I/II), and neoplasm type (OR =2.1 for rectal adenocarcinoma vs. colon adenocarcinoma) (all P<0.05). CRC patients expressing higher PCAT6 levels exhibited poorer survival outcomes than those expressing low levels of this lncRNA (P=0.017), and in univariate analyses, higher PCAT6 levels were linked to worse overall survival [hazard ratio (HR) =1.540; 95% confidence interval (CI): 1.079-2.199; P=0.017], with this relationship also being preserved in a multivariate analysis (HR =6.892; 95% CI: 1.713-27.727, P=0.007). GSEA revealed high PCAT6 expression to be linked to differential DNA methylation enrichment, with high PCAT6 levels being associated with changes in base excision repair, cellular senescence, G2/M DNA damage checkpoint, chromatin-modifying enzyme, and gene silencing by RNA activity. The high expression of lncRNA PCAT6 in CRC cell lines was demonstrated by PCR experiments. Conclusions: PCAT6 represents a promising prognostic biomarker of poor CRC patient survival outcomes, with DNA methylation and RNA-mediated gene silencing being potentially promising mechanistic pathways whereby this lncRNA may shape patient outcomes.

Subicular neurons encode concave and convex geometries.

Animals in the natural world constantly encounter geometrically complex landscapes. Successful navigation requires that they understand geometric features of these landscapes, including boundaries, landmarks, corners and curved areas, all of which collectively define the geometry of the environment1-12. Crucial to the reconstruction of the geometric layout of natural environments are concave and convex features, such as corners and protrusions. However, the neural substrates that could underlie the perception of concavity and convexity in the environment remain elusive. Here we show that the dorsal subiculum contains neurons that encode corners across environmental geometries in an allocentric reference frame. Using longitudinal calcium imaging in freely behaving mice, we find that corner cells tune their activity to reflect the geometric properties of corners, including corner angles, wall height and the degree of wall intersection. A separate population of subicular neurons encode convex corners of both larger environments and discrete objects. Both corner cells are non-overlapping with the population of subicular neurons that encode environmental boundaries. Furthermore, corner cells that encode concave or convex corners generalize their activity such that they respond, respectively, to concave or convex curvatures within an environment. Together, our findings suggest that the subiculum contains the geometric information needed to reconstruct the shape and layout of naturalistic spatial environments.

What Breast Cancer Screening Program do Rural Women Prefer? A Discrete Choice Experiment in Jiangsu, China.

BACKGROUND: Chinese rural women aged 35-64 years are encouraged to complete breast cancer screening (BCS) free of charge. However, it is challenging to reach a satisfying BCS uptake rate. In this study, rural women's preferences and preferences heterogeneity were measured for the development of strategies to enhance participation in BCS. METHODS: A cross-sectional survey with a discrete choice experiment (DCE) was conducted via convenience sampling via face-to-face interviews in Jiangsu, China. Six DCE attributes were identified through a systematic literature review; our previous study of Chinese rural women's BCS intentions; a qualitative work involving in-depth interviews with rural women (n = 13), medical staff (n = 4), and health care managers (n = 2); and knowledge of realistic and actionable policy. The D-efficient design was generated using Ngene 1.3.0. A mixed logit model (MXL) in Stata 18.0 was used to estimate the main effect of attribute levels on rural women's preferences. The relative importance and willingness to utilize BCS services (WTU) were also estimated. The heterogeneous preferences were analyzed by a latent class model (LCM). Sociodemographic status was used to predict the characteristics of class membership. The WTU for different classes was also calculated. RESULTS: A total of 451 rural women, aged 35-64 years, were recruited. The MXL results revealed that the screening interval (SI) was the most important attribute for rural women with regard to utilizing BCS services, followed by the level of screening, the attitude of medical staff, ways to get knowledge and information, people who recommend screening, and time spent on screening (TSS). Rural women preferred a BCS service with a shorter TSS; access to knowledge and information through multiple approaches; a shorter SI; a recommendation from medical staff or workers from the village or community, and others; the enthusiasm of medical staff; and medical staff with longer tenures in the field. Two classes named "process driven" and "efficiency driven" were identified by the preference heterogeneity analysis of the LCM. CONCLUSION: There is a higher uptake of breast cancer screening when services are tailored to women's preferences. The screening interval was the most important attribute for rural women in China with a preference for a yearly screening interval versus longer intervals.

Comprehensive analysis of EML2 as a prognostic biomarker in colon cancer.

BACKGROUND: Echinoderm microtubule-associated protein-like 2 (EML2), a gene located on 19q13.32, is overexpressed in various cancers and has been identified as a prognostic factor. However, the function and carcinogenic mechanism of EML2 in colon cancer is yet to be explored. METHODS: This study aimed to demonstrate the relationship between EML2 expression and colon cancer using The Cancer Genome Atlas (TCGA) database. The EML2 expression, including GSE33113 and GSE39923, was validated in colon cancer in the Gene Expression Omnibus (GEO) database. The Receiver Operating Characteristic (ROC) curves were used to assess the feasibility of EML2 as a distinguishing factor from the area under the curve (AUC) scores. In addition, Cox regression and logistic regression analyses were conducted to evaluate the factors linked to the prognosis of colon cancer. Moreover, the STRING tool was used to establish the EML2 binding protein network. The enrichment analysis cluster Profiler of the R package was utilized to investigate the function of EML2. The relationship between the immune infiltration and EML2 expression level in colon cancer was investigated by the R package Gene Set Variation Analysis (GSVA) and the single sample Gene Set Enrichment Analysis (ssGSEA) method in the Tumor Immune Estimation Resource (TIMER) database. RESULTS: Pan-cancer data analysis revealed that EML2 expression was higher in most cancers, including colon cancer. This outcome was in line with the findings of the GEO database. The ROC curve demonstrated that EML2 can serve as a diagnostic biomarker for colon cancer (AUC = 0.738). High EML2 expression was associated with poorer overall survival (OS; P = 0.004). Moreover, the results of the enrichment and immune infiltration analysis revealed that high EML2 expression correlated with regulation of the infiltration level of GTPase binding and some immune cell types like NK cells and NK CD56 bright cells. CONCLUSION: The findings revealed that colon cancer tissues had a higher EML2 expression than normal colon epithelial tissues. This phenomenon was significantly associated with poor prognosis and altered immune cell infiltration. Consequently, EML2 has shown the capacity to serve as a prognostic biomarker for patients diagnosed with colon cancer.

Structures, Biosynthesis, and Bioactivity of Oligomycins from the Marine-Derived Streptomyces sp. FXY-T5.

Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycin-producing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure-activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a ß-catenin signaling pathway.

Comparative study of interfacial properties and thermal behaviour of milk fat globules and membrane prepared from ultrasonicated bovine milk.

Milk fat globules or milk fat globule membranes (MFGs/MFGM) have been added to the infant formula to fortify the phospholipids and narrow the nutritional gap from breast milk. The main aim of this study was to profile the interfacial and thermal properties of MFGs/MFGM prepared from ultrasonicated bovine milk. Bovine milk was sonicated at ultrasonic intensities of 20 kHz and 40 kHz independently or synchronously with the duration time of 0 min (control), 5 min, 10 min, and 15 min (work/rest cycles = 5 s: 3 s). Ultrasonic treatments at 20 kHz/ 5 min and 20 + 40 kHz/ 5 min improved the volume density (%) of smaller particles (1-10 µm) while significantly decreasing the surface hydrophobicity (H0) (p < 0.05). 40 kHz/5 min samples showed significantly higher ζ- potential than the other samples (p < 0.05), which might be because more negative charges were detected. In comparison with control samples, ultrasonic treatments decreased the interfacial tension (π) between the air and MFGs/MFGM liquid phase. 20 kHz ultra-sonicated treatments decreased the diffusion rate (k diff) of MFGs/MFGM interfacial compositions significantly as the duration prolonged from 5 min to 15 min (p < 0.05) but did not affect the adsorption or penetration rate (k a) (p > 0.05). X-ray diffraction (XRD) results showed that α-crystal peaks only existed in control and ultrasonicated 5 min samples but disappeared in all 15 min samples. According to the different scanning calorimetry (DSC), one or two new exothermic events (in the range of 17.29 - 18.81 â„ƒ and 22.14 - 25.21 â„ƒ) appeared after ultrasonic treatments, which, however, were not found in control samples. Ultrasonic treatments resulted in the low-melting fractions (LMF) (TM1) peaks undetectable in MFGs/MFGM samples in which only peaks of medium-melting fractions (MMF) (TM2) and high-melting fractions (HMF) (TM3) were detected. Compared with the control, both enthalpies of crystallisation (ΔHC) and melting (ΔHM) decreased in ultrasonicated samples. In conclusion, ultrasonic treatment affects the interfacial and thermal properties of MFGs/MFGM.

Five new biflavonoids with acetylcholinesterase inhibitory activity from Diphylleia sinensis.

Five new biflavonoids, diphybiflavonoids A - E (1-5), were isolated from the roots and rhizomes of Diphylleia sinensis. Their structures were elucidated by extensive spectroscopic data, including UV, IR, HR-ESI-MS and 2D NMR. Their absolute configurations were determined by ECD spectra. All isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activity. Compounds 1-4 exhibited the potent AChE inhibitory activities with IC50 values of 1.62, 2.10, 2.08, and 5.15 µM, respectively. The preliminary structure-activity relationship study indicated that the connection mode (C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''') of biflavonoid subunits, and 3-hydroxy group of flavonol subunit were important structural factors for AChE inhibitory activity. Biflavonoids, containing a C2-O-C4'''/C3-O-C3''' or C2-O-C3'''/C3-O-C4''' linkage, can be a potentially useful platform for development of cholinesterase inhibitors.

Synergistic Effect of Oxygen Vacancy and High Porosity of Nano MIL-125(Ti) for Enhanced Photocatalytic Nitrogen Fixation.

This work reports that a low-temperature thermal calcination strategy was adopted to modulate the electronic structure and attain an abundance of surface-active sites while maintaining the crystal morphology. All the experiments demonstrate that the new photocatalyst nano MIL-125(Ti)-250 obtained by thermal calcination strategy has abundant Ti3+ induced by oxygen vacancies and high specific surface area. This facilitates the adsorption and activation of N2 molecules on the active sites in the photocatalytic nitrogen fixation. The photocatalytic NH3 yield over MIL-125(Ti)-250 is enhanced to 156.9 µmol g-1 h-1 , over twice higher than that of the parent MIL-125(Ti) (76.2 µmol g-1 h-1 ). Combined with density function theory (DFT), it shows that the N2 adsorption pattern on the active sites tends to be from "end-on" to "side-on" mode, which is thermodynamically favourable. Moreover, the electrochemical tests demonstrate that the high atomic ratio of Ti3+ /Ti4+ can enhance carrier separation, which also promotes the efficiency of photocatalytic N2 fixation. This work may offer new insights into the design of innovative photocatalysts for various chemical reduction reactions.

Pancreatic index: A prognostic factor of upfront surgery for body or tail pancreatic ductal adenocarcinoma with vascular involvement-A retrospective study.

BACKGROUND: The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. METHOD: All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty-five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. RESULTS: The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301-0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA-PBTC (OR = 0.272, 95% CI: 0.077-0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285-0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206-6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140-0.763, p = 0.010) were independent factors. CONCLUSION: This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long-term prognosis comparable to that of resectable PBTC patients.

The Effect of Random Roughness on the Electromagnetic Flow in a Micropipe.

The features of stationary random processes and the small parameter expansion approach are used in this work to examine the impact of random roughness on the electromagnetic flow in cylindrical micropipes. Utilizing the perturbation method, the analytical solution until second order velocity is achieved. The analytical expression of the roughness function ζ, which is defined as the deviation of the flow rate ratio with roughness to the case having no roughness in a smooth micropipe, is obtained by integrating the spectral density. The roughness function can be taken as the functions of the Hartmann number Ha and the dimensionless wave number λ. Two special corrugated walls of micropipes, i.e., sinusoidal and triangular corrugations, are analyzed in this work. The results reveal that the magnitude of the roughness function rises as the wave number increases for the same Ha. The magnitude of the roughness function decreases as the Ha increases for a prescribed wave number. In the case of sinusoidal corrugation, as the wave number λ increases, the Hartmann number Ha decreases, and the value of ζ increases. We consider the λ ranging from 0 to 15 and the Ha ranging from 0 to 5, with ζ ranging from -2.5 to 27.5. When the λ reaches 15, and the Ha is 0, ζ reaches the maximum value of 27.5. At this point, the impact of the roughness on the flow rate reaches its maximum. Similarly, in the case of triangular corrugation, when the λ reaches 15 and the Ha is 0, ζ reaches the maximum value of 18.7. In addition, the sinusoidal corrugation has a stronger influence on the flow rate under the same values of Ha and λ compared with triangular corrugation.

Ketamine evoked disruption of entorhinal and hippocampal spatial maps.

Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine's impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal's spatial position, as mice navigated virtual reality and real world environments. Ketamine acutely increased firing rates, degraded cell-pair temporal firing-rate relationships, and altered oscillations, leading to longer-term remapping of spatial representations. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings demonstrate ketamine-induced dysfunction of the MEC-hippocampal circuit at the single cell, local-circuit population, and network levels, connecting previously demonstrated physiological effects of ketamine on spatial cognition to alterations in the spatial navigation circuit.

Network pharmacology-based analysis of potential mechanisms of myocardial ischemia-reperfusion injury by total salvianolic acid injection.

In this review, we investigated the potential mechanism of Total Salvianolic Acid Injection (TSI) in protecting against myocardial ischemia reperfusion injury (MI/RI). To achieve this, we predicted the component targets of TSI using Pharmmapper and identified the disease targets of MI/RI through GeneCards, DisGenNET, and OMIM databases. We constructed protein-protein interaction networks by analyzing the overlapping targets and performed functional enrichment analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Our analysis yielded 90 targets, which were implicated in the potential therapeutic effects of TSI on MI/RI. Seven critical signaling pathways significantly contributed to TSI's protective effects, namely, PI3K signaling, JAK-STAT signaling, Calcium signaling, HIF-1 signaling, Nuclear receptor signaling, Cell Cycle, and Apoptosis. Subsequently, we conducted a comprehensive literature review of these seven key signaling pathways to gain further insights into their role in the TSI-mediated treatment of MI/RI. By establishing these connections, our study lays a solid foundation for future research endeavours to elucidate the molecular mechanisms through which TSI exerts its beneficial effects on MI/RI.