Hepatic arterial infusion chemotherapy combined with toripalimab and surufatinib for the treatment of advanced intrahepatic cholangiocarcinoma.

PURPOSE: The aim of the present study is to report the clinical results of patients with advanced intrahepatic cholangiocarcinoma (ICC) who received combination therapy of hepatic arterial infusion chemotherapy (HAIC), toripalimab and surufatinib. METHODS: The study cohort consisted of 28 patients with advanced ICC who were treated with HAIC (mFOLFOX6 regimen, Q3W) in combination with intravenous toripalimab (240 mg, Q3W) and oral surufatinib (150 mg, once daily). The cohort had 14 male and 14 female patients. The baseline characteristics of the study cohort were obtained. The tumor response and drug-associated toxicity were assessed and reported. RESULTS: During the follow-up period (median follow-up time: 11.3 months; range: 4-19 months), four patients died of tumor progression. The objective response rate and disease control rate were 58% and 79%, respectively. The mPFS was 9.5 months, and the overall survival rate was 83.3%. The most frequent adverse events were nausea and vomiting (100%) and abdominal pain (85.7%). Serious complications related to death were not observed. CONCLUSION: The combination treatment schedule for advanced ICC demonstrated positive efficacy and safety profiles. CLINICAL SIGNIFICANCE: This study provides promising clinical guidance for the treatment of advanced cholangiocarcinoma and is expected to modify the treatment strategy for this disease.

Electro-stimulation modulates syntrophic interactions in methanogenic toluene-degrading microbiota for enhanced functionality.

Syntrophy achieved via microbial cooperation is vital for anaerobic hydrocarbon degradation and methanogenesis. However, limited understanding of the metabolic division of labor and electronic interactions in electro-stimulated microbiota has impeded the development of enhanced biotechnologies for degrading hydrocarbons to methane. Here, compared to the non-electro-stimulated methanogenic toluene-degrading microbiota, electro-stimulation at 800 mV promoted toluene degradation and methane production efficiencies by 11.49 %-14.76 % and 75.58 %-290.11 %, respectively. Hydrocarbon-degrading gene bamA amplification and metagenomic sequencing analyses revealed that f_Syntrophobacteraceae MAG116 may act as a toluene degrader in the non-electro-stimulated microbiota, which was proposed to establish electron syntrophy with the acetoclastic methanogen Methanosarcina spp. (or Methanothrix sp.) through e-pili or shared acetate. In the electro-stimulated microbiota, 37.22 ± 4.33 % of Desulfoprunum sp. (affiliated f_Desulfurivibrionaceae MAG10) and 58.82 ± 3.74 % of the hydrogenotrophic methanogen Methanobacterium sp. MAG74 were specifically recruited to the anode and cathode, respectively. The potential electrogen f_Desulfurivibrionaceae MAG10 engaged in interspecies electron transfer with both syntroph f_Syntrophobacteraceae MAG116 and the anode, which might be facilitated by c-type cytochromes (e.g., ImcH, OmcT, and PilZ). Moreover, upon capturing electrons from the external circuit, the hydrogen-producing electrotroph Aminidesulfovibrio sp. MAG60 could share electrons and hydrogen with the methanogen Methanobacterium sp. MAG74, which uniquely harbored hydrogenase genes ehaA-R and ehbA-P. This study elucidates the microbial interaction mechanisms underlying the enhanced metabolic efficiency of the electro-stimulated methanogenic toluene-degrading microbiota, and emphasizes the significance of metabolic and electron syntrophic interactions in maintaining the stability of microbial community functionality.

[Spatiotemporal Response of Ecosystem Service Value to Land Use Change in the Lanzhou-Xining Urban Agglomeration over the Past 20 Years].

With rapid urbanization and human activities exacerbating threats to the degradation of various ecosystem services in modern urban agglomerations, the exploration of the state of ecological security at the scale of urban agglomerations is of great significance. This study considered the Lanzhou-Xining Urban Agglomeration as the research area, based on the land use data in 2000, 2005, 2010, 2015, and 2020. At the same time, the landscape ecological risk index was introduced. The land use change characteristics of the Lanzhou-Xining Urban Agglomeration were analyzed by using the land use transfer matrix, the value per unit area equivalent factor method, and the bivariate spatial autocorrelation analysis method to elucidate the impacts of the changes in the ecological risk index induced by the land use transition on the value of ecosystem services. This study analyzed the land use change characteristics of the Lanzhou-Xining Urban Agglomeration and elucidated the impacts of changes in the ecological risk index on the value of ecosystem services caused by land use transformation. The results showed that:① During the period from 2000 to 2020, the land use types of the Lanzhou-Xining Urban Agglomeration were mainly dominated by grassland, cropland, and forest land. The construction land area had expanded significantly mainly from cropland and grassland, and the six land use types had strong cross-transformation. The total area of land use change was 6 646.05 km2. ② In terms of spatial changes, the spatial pattern of ecosystem service value in the Lanzhou-Xining Urban Agglomeration had not undergone obvious transformation. However, the regional variability was significant, generally showing the distribution characteristics of high in the northwest and low in the southeast. ③From the perspective of temporal change, the value of ecosystem services in the Lanzhou-Xining Urban Agglomeration showed an upward trend, with the total flow of value increasing from 186.459 billion yuan to 192.156 billion yuan, with a total value-added of 5.697 billion yuan. ④ There was a rising trend in the overall ecological risk index of the Lanzhou-Xining Urban Agglomeration over the past 20 years. Low ecological risk areas and lower ecological risk areas dominated the ecological risk areas. There was a significant positive correlation between the value of ecosystem services and the ecological risk index. This study aimed to reveal the understanding of the impacts of land-use practices on ecosystem service values and ecological risks, to provide important references for regional ecological risk management and land-use policy formulation, and thus to promote the high-quality development of the ecological environment in the Yellow River Basin.

H2O2/acid self-supplying double-layer electrospun nanofibers based on ZnO2 and Fe3O4 nanoparticles for efficient catalytic therapy of wound infection.

Catalytic therapy based on nanozymes is promising for the treatment of bacterial infections. However, its therapeutic efficacy is usually restricted by the limited amount of hydrogen peroxide and the weak acidic environment in infected tissues. To solve these issues, we prepared polyvinyl alcohol (PVA)-polyacrylic acid (PAA)-iron oxide (Fe3O4)/polyvinyl alcohol (PVA)-zinc peroxide (ZnO2) double-layer electrospun nanofibers (PPF/PZ NFs). In this design, PVA serves as the carrier for ZnO2 nanoparticles (NPs), Fe3O4 NPs, and PAA. The double-layer structure of nanofibers can spatially separate the PAA and ZnO2 to avoid their reaction with each other during preparation and storage, while in the wet wound bed, PVA can dissolve and PAA can provide H+ ions to promote the generation of hydrogen peroxide and subsequent conversion to hydroxyl radicals for bacteria killing. In vitro experimental results demonstrated that PPF/PZ NFs can reduce the methicillin-resistant Staphylococcus aureus by 3.1 log (99.92%). Moreover, PPF/PZ NFs can efficiently treat the bacterial infection in a mouse wound model and promote wound healing with negligible toxicity to animals, indicating their potential use as "plug-and-play" antibacterial wound dressings. This work provides a novel strategy for the construction of double-layer electrospun nanofibers as catalytic wound dressings with hydrogen peroxide/acid self-supplying properties for the efficient treatment of bacterial infections.

"Isolation by Gentes with Asymmetric Migration" shapes the genetic structure of the common cuckoo in China.

Amid coevolutionary arms races between brood parasitic birds and their diverse host species, the formation of host-specific races, or gentes, has drawn significant research focus. Nevertheless, numerous questions about gentes evolutionary patterns persist. Here, we investigated the potential for gentes evolution across multiple common cuckoo (Cuculus canorus) populations parasitizing diverse host species in China. Using maternal (mitochondrial and W-linked DNA) and biparental (autosomal and Z-linked DNA) markers, we found consistent clustering of cuckoo gentes (rather than geographical populations) into distinct clades in matrilineal gene trees, indicating robust differentiation. In contrast, biparental markers indicated intermixing of all gentes, suggesting asymmetric gene flow regardless of geography. Unlike the mitonuclear discordance commonly resulting from incomplete lineage sorting, adaptive introgression, or demographic disparities, the observed pattern in brood parasitic cuckoos might reflect biased host preferences between sexes. We hereby present the "Isolation by Gentes with Asymmetric Migration" model. According to this model, the maternal line differentiation of the common cuckoo in China is potentially driven by host preferences in females, whereas males maintained the integrity of the cuckoo species through random mating. To achieve this, cuckoo males could perform flexible migration among gentes or engage in early copulation with females before reaching the breeding sites, allowing female cuckoos to store sperm from various gentes. Future studies collecting additional samples from diverse cuckoo gentes with overlapping distribution and investigating the migratory and copulation patterns of each sex would enhance our understanding of sex-biased differentiation among cuckoo populations in China.

AIM2 inflammasome regulated by the IFN-γ/JAK2/STAT1 pathway promotes activation and pyroptosis of monocytes in Coronary Artery Disease.

BACKGROUND: Numerous studies have demonstrated that Absent in Melanoma 2 (AIM2) is upregulated in aortic plaques, especially in Vascular Smooth Muscle Cells in Coronary Artery Disease (CAD), and is related to inflammasome-induced inflammation. However, the underlying mechanism of this phenomenon and the role of AIM2 in atherosclerosis remained unclear. METHODS: This study enrolled 133 CAD patients and 123 controls. We isolated Peripheral Blood Leukocytes (PBLs) and the mRNA expression of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1ß, and IL-18) were detected by real-time quantitative PCR (qPCR). We assessed correlations between AIM2 expressions and clinical characteristics by multiple linear regression and spearman's correlation. The THP-1 cells cultured in poly(dA:dT), A151, interferon-gamma (IFN-γ), AG490, or JC2-11. And then the mRNA and protein levels of AIM2, ASC, Caspase-1, IL-1ß, IL-18, GSDMD, and STAT1 were analyzed by qPCR and Western blot analysis, respectively. The migration and adhesive capacity of THP-1 cells was assessed using an inverted microscope and an inverted fluorescence microscope, respectively. RESULTS: In this study, we found that expressions of components of AIM2 inflammasome and its downstream genes (ASC, Caspase-1, IL-1ß, and IL-18), were all increased in PBLs of CAD patients, which indicated the inflammasome activation. AIM2 inflammasome activation further induced pyroptosis, and stimulated migration and adhesion in monocyte cell lines, which was regulated by IFN-γ probably through JAK2/STAT1 pathway. In addition, AIM2 expressions were positively correlated with systemic inflammatory indicators as an independent risk factor for CAD. CONCLUSIONS: In conclusion, increased AIM2 expression, induced by the IFN-γ/JAK2/STAT1 signal, orientates monocytes to inflammatory status or even pyroptosis through AIM2 inflammasome activation, which is involved in the development of CAD.

Efficacy and Safety of Transarterial Chemoembolization and Repeated Partial Splenic Embolization for Hepatocellular Carcinoma with Hypersplenism and Thrombocytopenia.

Aim: Partial splenic embolization (PSE) combined with transarterial chemoembolization (TACE) has been reported in treatment of hepatocellular carcinoma (HCC) with cirrhotic hypersplenism and thrombocytopenia. However, efficacy and safety of repeated PSE when required are unclear. This study aims to investigate post-procedural changes in peripheral blood cell and hepatic function, progression-free survival (PFS), and safety of HCC patients with hypersplenism received TACE and repeated PSE compared to those received TACE alone. Methods: This retrospective study included 102 HCC patients with hypersplenism who received TACE (n = 73) or TACE+PSE (n = 29) from January 2014 to December 2021. Changes in peripheral blood cell and hepatic function were investigated at 1 week, 2, 6, 12, 18, and 24 months. TACE procedure sessions and adverse events were recorded. PFS and prognostic factors were analyzed. Results: Despite response to initial PSE being limited, repeated PSE increased platelet (PLT) again, which peaked at 18 months. It also continued to improve red blood cell (RBC) and hemoglobin, which showed significant differences in changes from baseline between two groups until 24 months, as well as Child-Pugh scores at 12 and 18 months. Mean TACE procedure sessions were significantly higher in TACE+PSE group than that in TACE alone group (4.55 vs 3.26, P = 0.019). TACE+PSE group had longer median PFS (19.4 vs 9.5 months, P = 0.023) than TACE alone group, where PSE was an independent protective factor (HR, 0.508; P = 0.014). Initial and repeated PSE showed no significant differences in safety. Conclusion: Repeated PSE is effective in increasing PLT again and improving RBC, hemoglobin and liver function. It contributed to performing serial TACE procedures thereafter. TACE combined with repeated PSE has significantly longer PFS than TACE alone, where PSE was an independent protective factor. Moreover, the safety of repeated PSE was comparable to initial PSE.

Mechanisms linking triclocarban biotransformation to functional response and antimicrobial resistome evolution in wastewater treatment systems.

Evaluating the role of antimicrobials biotransformation in the regulation of metabolic functions and antimicrobial resistance evolution in wastewater biotreatment systems is crucial to ensuring water security. However, the associated mechanisms remain poorly understood. Here, we investigate triclocarban (TCC, one of the typical antimicrobials) biotransformation mechanisms and the dynamic evolution of systemic function disturbance and antimicrobial resistance risk in a complex anaerobic hydrolytic acidification (HA)-anoxic (ANO)/oxic (O) process. We mined key functional genes involved in the TCC upstream (reductive dechlorination and amide bonds hydrolysis) and downstream (chloroanilines catabolism) biotransformation pathways by metagenomic sequencing. Acute and chronic stress of TCC inhibit the production of volatile fatty acids (VFAs), NH4+ assimilation, and nitrification. The biotransformation of TCC via a single pathway cannot effectively relieve the inhibition of metabolic functions (e.g., carbon and nitrogen transformation and cycling) and enrichment of antimicrobial resistance genes (ARGs). Importantly, the coexistence of TCC reductive dechlorination and hydrolysis pathways and subsequent ring-opening catabolism play a critical role for stabilization of systemic metabolic functions and partial control of antimicrobial resistance risk. This study provides new insights into the mechanisms linking TCC biotransformation to the dynamic evolution of systemic functions and risks, and highlights critical regulatory information for enhanced control of TCC risks in complex biotreatment systems.

Formation and retention of aroma compounds in pigeons roasted by circulating non-fried roast technique by means of UHPLC-HRMS and GC-O-MS.

Lipids are key aroma contributors in meat products. However, the role of different lipids in the presence of aroma compounds in roasted pigeons has not been studied. The formation of aroma compounds and lipids during the circulating non-fried roasting of pigeons was investigated. The results presented that 18 aroma compounds, including 5-methy-2,3-diethylpyrazine, were identified as key aroma compounds. A total of 6324 lipids were classed into 47 categories, such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triglyceride (TG). Nine lipids, containing PA(P-20:0/22:4(7Z,10Z,13Z,16Z)) and LPC 16:0-SN1, showed promise as potential biomarkers for discriminating differential pigeons using OPLS-DA. PC (13.76%), TG (13.58%), and their products were major lipids, among which TG 16:0 16:0 18:2, LPC 18:2-SN1, and PC 18:1_18:1 played a crucial role in the presence of aroma compounds. Interestingly, the linoleic acid, an important aroma contributor, was predominantly bonded to the sn-2 position of phospholipid and sn-3 position of neutral lipids.

Thymol Induces Fenton-Reaction-Dependent Ferroptosis in Vibrio parahemolyticus.

Thymol has efficient bactericidal activity against a variety of pathogenic bacteria, but the bactericidal mechanism against Vibrio parahemolyticus (V. parahemolyticus) has rarely been reported. In the current study, we investigated the bactericidal mechanism of thymol against V. parahemolyticus. The Results revealed that 150 µg/mL of thymol had 99.9% bactericidal activity on V. parahemolyticus. Intracellular bursts of reactive oxygen species (ROS), Fe2+accumulation, lipid peroxidation, and DNA breakage were checked by cell staining. The exogenous addition of H2O2 and catalase promoted and alleviated thymol-induced cell death to a certain extent, respectively, and the addition of the ferroptosis inhibitor Liproxstatin-1 also alleviated thymol-induced cell death, confirming that thymol induced Fenton-reaction-dependent ferroptosis in V. parahemolyticus. Proteomic analysis revealed that relevant proteins involved in ROS production, lipid peroxidation accumulation, and DNA repair were significantly upregulated after thymol treatment. Molecular docking revealed two potential binding sites (amino acids 46H and 42F) between thymol and ferritin, and thymol could promote the release of Fe2+ from ferritin proteins through in vitro interactions analyzed. Therefore, we hypothesized that ferritin as a potential target may mediate thymol-induced ferroptosis in V. parahemolyticus. This study provides new ideas for the development of natural inhibitors for controlling V. parahemolyticus in aquatic products.

LncRNA MIR181A2HG negatively regulates human keratinocytes proliferation by binding SRSF1.

Psoriasis is a common chronic inflammatory skin disease. Abnormal proliferation of keratinocytes plays an important role in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) are involved in the regulation of a variety of cell biological processes. The purpose of this study was to investigate the potential role of lncRNA MIR181A2HG in the proliferation of human keratinocytes. qRT-PCR and Western blotting were performed to measure the expression levels of MIR181A2HG, SRSF1, KRT6, and KRT16 in tissue specimens and HaCaT keratinocytes. The effects of MIR181A2HG on HaCaT keratinocytes proliferation were evaluated using Cell Counting Kit-8 (CCK-8) assays, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation, and cell-cycle assays. RNA pulldown-mass spectrometry (MS) was applied to identify the proteins interacting with MIR181A2HG. RNA pull-down-Western blotting and RNA immunoprecipitation coupled with real-time quantitative reverse transcription-PCR (RIP-qRT-PCR) assays were used to determine the interactions between MIR181A2HG and its RNA-binding proteins (RBPs). MIR181A2HG was down-regulated in psoriasis tissues. MIR181A2HG overexpression induced G0/G1 and G2/M phase cell cycle arrest and decreased the protein levels of KRT6, KRT16, Cyclin D1, CDK4, and Cyclin A2 in HaCaT keratinocytes. MIR181A2HG knockdown showed the opposite effect. By using RNA pulldown-MS, 356 proteins were identified to interact with MIR181A2HG potentially. Bioinformatics analysis showed that NOP56 and SRSF1 may be RNA binding proteins (RBPs) that may be interact with MIR181A2HG. Furthermore, by using RNA pull-down-Western blotting and RIP-qRT-PCR, SRSF1 was determined to interact with MIR181A2HG. Moreover, silencing of SRSF1 inhibited keratinocytes proliferation, which could be reversed with the knockdown of MIR181A2HG. Our findings indicated that MIR181A2HG can negatively regulate HaCaT keratinocytes proliferation by binding SRSF1, suggesting that MIR181A2HG and SRSF1 may serve as potential targets for the treatment of psoriasis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-024-00621-6.

Mineralization, degradation and osteogenic property of polylactide multicomponent porous composites for bone repair: In vitro and in vivo study.

Gelatin and hydroxyapatite were assembled into polylactide porous matrix to prepare multicomponent porous composites for bone repair (PLA-gH). PLA-gH possessed a superior ability of mineralization. During simulated body fluids (SBF), the spherical Ca-P depositions on surface of PLA-gH became bulk as Ca/P decreased, while they locally turned into the rod with different variation in Ca/P during SBF containing bovine serum albumin (SBF-BSA), indicating that the mineralization of PLA-gH could be regulated by BSA. Meanwhile, PLA-gH possessed good degradation behaviour, especially in SBF-BSA, the degradation of PLA porous matrix was higher than that in SBF after 14-day immersion, whose crystallinity (Xc) decreased to a slightly lower level. Gelatin and hydroxyapatite endowed PLA-gH with good osteogenic property, characterized by obvious osteogenic differentiation and bone regeneration. In terms of predicting the cytocompatibility, osteogenic differentiation and new bone mineralization of PLA-gH by in vitro methods, applying SBF-BSA may be more reliable than SBF.

Antitumor effects of Cypaliuruside F from Cyclocarya paliurus on HepG2 cells.

An undescribed dammarane triterpenoid saponin Cypaliuruside F was isolated from the leaves of Cyclocarya paliurus in our preliminary study. The MTT assay, flow cytometry, cell scratch, and DAPI staining were used to detect the antitumor effects of Cypaliuruside F on HepG2 cells. Subsequently, network pharmacology and molecular docking analysis were used to analyse the key targets of Cypaliuruside F against HCC. In addition, a Western blot was performed to determine the effects of Cypaliuruside F on the expression of key proteins in HepG2 cells. The experimental results indicated that the damarane triterpenoid saponin Cypaliuruside F from Cyclocarya paliurus inhibits the proliferation of HepG2 cells by inducing apoptosis and cell cycle arrest. These changes may promote the apoptosis of HepG2 cells by inhibiting the expression of mTOR, STAT3, and Bcl-2 while activating Bax.

Hepatitis B virus reactivation in hepatocellular carcinoma patients after hepatic arterial infusion chemotherapy combined with and without immunotherapy.

BACKGROUND: Hepatitis B virus (HBV) reactivation (HBVr) is a major concern for hepatocellular carcinoma (HCC) patients undergoing hepatic arterial infusion chemotherapy (HAIC) using mFOLFOX6 regimen. There is insufficient evidence to support the routine use of HAIC combined with immunotherapy in HCC patients with HBVr. The aim of this study was to examine the adverse events (AEs) related to HBVr in HCC patients after HAIC, with or without immunotherapy, and to assess the effectiveness of antiviral prophylaxis for HBVr. METHODS: Medical records of HCC patients receiving HAIC combined with and without immunotherapy between January 2021 and June 2023 were reviewed. The patients were divided into two groups based on whether they received immunotherapy or not. RESULTS: Out of the 106 patients, 32 (30.2%) developed HBVr. Among these, 23 eligible patients with HBVr were included, with 14 patients (61%) receiving immunotherapy and nine patients (39%) not receiving immunotherapy. Prior to HAIC treatment, four patients in each group had detectable HBV DNA with median titre of 3.66 × 102 IU/ml (patients with immunotherapy) and 1.98 × 102 IU/ml (patients without immunotherapy), respectively. Fifteen patients did not show detectable HBV DNA. At HBVr occurrence, the median HBV DNA level was 6.95 × 102 IU/ml for all patients, 4.82 × 102 IU/ml in patients receiving immunotherapy and 1.3 × 103 IU/ml in patients not receiving immunotherapy. Grade 3 hepatitis developed in 12 cases of all patients (12/23, 48%), including five patients with immunotherapy (56%) and seven patients without immunotherapy (78%). At the 3-month follow-up, HBV DNA was detected in 10 patients, with a median HBV DNA level of 2.05 × 102 IU/ml (range, 1.5 × 102- 3.55 × 102 IU/ml) in patients (7/10) with immunotherapy and 4.28 × 102 IU/ml (range, 1.15 × 102- 5.88 × 102 IU/ml) in patients (3/10) without immunotherapy. Intensified antiviral treatment was administered to all patients. No HBVr-related fatal events occurred. CONCLUSION: HBVr can occur after HAIC combined with or without immunotherapy. The degree of liver damage did not differ significantly in patients treated with or without immunotherapy. Intensified antiviral treatment was found to be crucial for HCC patients with HBVr.

A fully autonomous robotic ultrasound system for thyroid scanning.

The current thyroid ultrasound relies heavily on the experience and skills of the sonographer and the expertise of the radiologist, and the process is physically and cognitively exhausting. In this paper, we report a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nod- ules. In this system, human skeleton point recognition, reinforcement learning, and force feedback are used to deal with the difficulties in locating thyroid targets. The orientation of the ultrasound probe is adjusted dynamically via Bayesian optimization. Experimental results on human participants demonstrated that this system can perform high-quality ultrasound scans, close to manual scans obtained by clinicians. Additionally, it has the potential to detect thyroid nodules and provide data on nodule characteristics for American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) calculation.

Caudo-dorsal approach combined with the occlusion of right hepatic vein and Pringle maneuver in laparoscopic anatomical resection of segment 7.

BACKGROUND: Laparoscopic anatomical resection of segment 7 (LARS7) remains a technically challenging procedure due to the deep anatomical location and the potential risk of injury to the right hepatic vein (RHV). Herein, we initiated an innovative technique of caudo-dorsal approach combined with the occlusion of the RHV and Pringle maneuver for LARS7 and presented the outcomes of our initial series. METHOD: Since January 2021, the patients who underwent LARS7 by using this novel technique were enrolled in this study. The critical aspect of this technique was the interruption of communication between the RHV and the inferior vena cava. Meanwhile, the Pringle maneuver was adopted to control the hepatic inflow. RESULT: A total of 11 patients underwent LARS7 by using this novel technique, which included 8 hepatocellular carcinoma, 2 bile duct adenocarcinoma and one focal nodular hyperplasia. The median operative time was 199 min (range of 151-318 min) and the median blood loss was 150 ml (range of 50-200 ml). The main trunk of the RHV was fully exposed on the cutting surface in all cases and no patient received perioperative blood transfusion. No procedure was converted to open surgery. Of note, no indications of CO2 gas embolism were observed in these cases after the introduction of double occlusion. Only one patient suffered from postoperative complications and healed after treatment. The median postoperative stay was 5 days (range of 4-7 days). The 90-day mortality was nil. At a median follow-up period of 19 months, all of the patients were alive without any evidence of tumor recurrence. CONCLUSION: The caudo-dorsal approach combined with the occlusion of RHV and the Pringle maneuver may be a feasible and expected technique for safe exposure of RHV in LARS7. Further validation of the feasibility and efficacy of this technique is needed.

Terahertz fan-beam computed tomography.

A terahertz (THz) fan-beam computed tomography (CT) system using a 0.3 THz continuous-wave sheet beam is proposed. The diffraction-free sheet beam expands in a fan shape in only one direction and provides propagation-invariant focal lines and extended the depth-of-field. The fan-beam CT based on this beam is the second-generation THz CT. It breaks the conventional 4-f symmetric structure of THz CT using the parallel beam. The fan-beam THz CT allows for use with a linear array detector, which reduces the time required to collect data. To demonstrate its feasibility for three-dimensional (3D) imaging, the 3D structure of a metal rod packed in a carton is reconstructed with the support of the system. The results show that the object's internal structure can be obtained by this new THz CT system while retaining the geometrically magnified features of the cross-sectional structure. The results of our research provide a template for the second-generation THz CT system, which provides an additional method for nondestructive testing.

Novel kinase 1 regulates CD8+T cells as a potential therapeutic mechanism for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and progressively worsening lung disease that poses a significant threat to patient prognosis, with a mortality rate exceeding that of some common malignancies. Effective methods for early diagnosis and treatment remain for this condition are elusive. In our study, we used the GEO database to access second-generation sequencing data and associated clinical information from IPF patients. By utilizing bioinformatics techniques, we identified crucial disease-related genes and their biological functions, and characterized their expression patterns. Furthermore, we mapped out the immune landscape of IPF, which revealed potential roles for novel kinase 1 and CD8+T cells in disease progression and outcome. These findings can aid the development of new strategies for the clinical diagnosis and treatment of IPF.

Fabricating Pea Protein Micro-Gel-Stabilized Pickering Emulsion as Saturated Fat Replacement in Ice Cream.

Unsaturated fat replacement should be used to reduce the use of saturated fat and trans fatty acids in the diet. In this study, pea protein micro-gels (PPMs) with different structures were prepared by microparticulation at pH 4.0-7.0 and named as PPM (pH 4.0), PPM (pH 4.5), PPM (pH 5.0), PPM (pH 5.5), PPM (pH 6.0), PPM (pH 6.5), and PPM (pH 7.0). Pea protein was used as a control to evaluate the structure and interfacial properties of PPMs by particle size distribution, Fourier transform infrared spectroscopy (FTIR), free sulfhydryl group content, and emulsifying property. PPM (pH 7.0) was suitable for application in O/W emulsion stabilization because of its proper particle size, more flexible structure, high emulsifying activity index (EAI) and emulsifying stability index (ESI). The Pickering emulsion stabilized by PPM (pH 7.0) had a uniform oil droplet distribution and similar rheological properties to cream, so it can be used as a saturated fat replacement in the manufacture of ice cream. Saturated fat was partially replaced at different levels of 0%, 20%, 40%, 60%, 80%, and 100%, which were respectively named as PR0, PR20, PR40, PR60, PR80, and PR100. The rheological properties, physicochemical indexes, and sensory properties of low-saturated fat ice cream show that PPM (pH 7.0)-stabilized emulsion can be used to substitute 60% cream to manufacture low-saturated fat ice cream that has high structural stability and similar melting properties, overrun, and sensory properties to PR0. The article shows that it is feasible to prepare low-saturated fat ice cream with PPM (pH 7.0)-stabilized Pickering emulsion, which can not only maintain the fatty acid profile of the corn oil used, but also possess a solid-like structure. Its application is of positive significance for the development of nutritious and healthy foods and the reduction of chronic disease incidence.

An overview of the cholesterol metabolism and its proinflammatory role in the development of MASLD.

Cholesterol is an essential lipid molecule in mammalian cells. It is not only involved in the formation of cell membranes but also serves as a raw material for the synthesis of bile acids, vitamin D, and steroid hormones. Additionally, it acts as a covalent modifier of proteins and plays a crucial role in numerous life processes. Generally, the metabolic processes of cholesterol absorption, synthesis, conversion, and efflux are strictly regulated. Excessive accumulation of cholesterol in the body is a risk factor for metabolic diseases such as cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). In this review, we first provide an overview of the discovery of cholesterol and the fundamental process of cholesterol metabolism. We then summarize the relationship between dietary cholesterol intake and the risk of developing MASLD, and also the animal models of MASLD specifically established with a cholesterol-containing diet. In the end, the role of cholesterol-induced inflammation in the initiation and development of MASLD is discussed.