Smartphone as an alternative to measure chlorophyll-a concentration in small waterbodies.

Monitoring chlorophyll-a concentrations (Chl-a, µg·L-1) in aquatic ecosystems has attracted much attention due to its direct link to harmful algal blooms. However, there has been a lack of a cost-effective method for measuring Chl-a in small waterbodies. Inspired by the increase of smartphone photography, a Smartphone-based convolutional neural networks (CNN) framework (SCCA) was developed to estimate Chl-a in Aquatic ecosystem. To evaluate the performance of SCCA, 238 paired records (a smartphone image with a 12-color background and a measured Chl-a value) were collected from diverse aquatic ecosystems (e.g., rivers, lakes and ponds) across China in 2023. Our performance-evaluation results revealed a NS and R2 value of 0.90 and 0.94 in Chl-a estimation, demonstrating a satisfactory (NS = 0.84, R2 = 0.86) model fit in lower Chl-a (<30 µg L-1) conditions. SCCA had involved a realtime-update method with hyperparameter optimization technology. In comparison with the existing methods of measuring Chl-a, SCCA provides a useful screening tool for cost-effective measurement of Chl-a and has the potential for being an algal bloom screening means in small waterbodies, using Huajin River as a case study, especially under limited resources for water measurement. Overall, we highlight that the SCCA can be potentially integrated into a smartphone application in the future to diverse waterbodies in environmental management.

The application of real-time indocyanine green fluorescence cholangiography in laparoscopic living donor left lateral sectionectomy.

Background: The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy (LLLS). The purpose of this study was to assess the effects of indocyanine green (ICG) fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and recipients. The optimal dose and injection time of ICG were also investigated. Methods: This is a retrospective cohort study. From October 2016 to December 2022, the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively analyzed. According to whether ICG fluorescence cholangiography was used, they were divided into a non-ICG group (n=46) and an ICG group (n=57). Biliary complications were observed and the optimal dose and injection time of ICG were explored. Results: Three donors in the non-ICG group suffered from bile leakage. Four grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG group. Two recipients had bile leakage, and the other two had biliary stenosis. There was no biliary complications both in donors and recipients in the ICG group. The fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection, significantly weaker than that at 0.05 mg/kg 30 minutes (200.3±17.6, P=0.001) and 90 minutes after injection (140.2±15.4, P=0.001). The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg, both measured 90 minutes after injection (0.098±0.032 vs. 0.078±0.022, P=0.021). Conclusions: ICG fluorescence cholangiography is safe and feasible in LLLS. It reduces biliary complications in both donors and recipients. The optimal ICG dose was 0.004 mg/kg, and 90 minutes after injection was the best observation time. ICG fluorescence cholangiography is recommended for routine use in LLLS.

How Can Anomalous-Diffusion Neural Networks Under Connectomics Generate Optimized Spatiotemporal Dynamics.

Spatiotemporal dynamics in the brain have been recognized as strongly related to the formation of perceived and cognitive diseases, such as delusions and hallucinations in Alzheimer's disease. However, two practical considerations are rarely mentioned in related mechanism research: the connectomics networking and the anomalous diffusion generated by the complex medium between neurons and the complex topology of neural networks, respectively. Furthermore, how to optimize the corresponding dynamics behaviors has excellent implications for treating brain diseases. This article first realizes the networking under connectomics for an anomalous-diffusion single-neuron model and applies a nonlinear state feedback control to generate optimized dynamic behaviors, which provides a paradigm of nonequilibrium self-organization driven by anomalous diffusion. Then, by tracing the root distribution of the characteristic equation, some controlled conditions causing or inhibiting Turing instability and Hopf bifurcation are deduced, and the effects of self-diffusion and cross diffusion on Turing instability range are also revealed. At last, thorough numerical simulations are updated to illustrate the results. It is emphasized that delay, self-diffusion, cross diffusion, and fractional order occupy dominant positions in determining the network's spatiotemporal dynamics, and utilizing the control strategy can efficiently reduce Turing instability and delay Hopf bifurcation.

Immune- and metabolism-related gene signature analysis uncovers the prognostic and immune microenvironments of hepatocellular carcinoma.

BACKGROUND: Metabolic reprogramming is an emerging hallmark that influences the tumour microenvironment (TME) by regulating the behavior of cancer cells and immune cells. The relationship between metabolism and immunity remains elusive. The purpose of this study was to explore the predictive value of immune- and metabolism-related genes in hepatocellular carcinoma (HCC) and their intricate interplay with TME. METHODS: We established the immune- and metabolism-related signature (IMRPS) based on the LIHC cohort from The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and Cox regression analysis confirmed the prognostic value of IMRPS. We investigated differences in immune cell infiltration, clinical features, and therapeutic response between risk groups. The quantitative real-time PCR (qPCR) was used to confirm the expression of signature genes. Immunohistochemical staining was performed to evaluate immune infiltration features in HCC tissue samples. We conducted cell experiments including gene knockout, cell counting kit-8 (CCK-8), and flow cytometry to explore the role of the IMRPS key gene UCK2 in HCC. RNA-seq was used to further investigate the potential underlying mechanism involved. RESULTS: The IMRPS, composed of four genes, SMS, UCK2, PFKFB4 and MAPT, exhibited significant correlations with survival, immune cell infiltration, clinical features, immune checkpoints and therapeutic response. The IMRPS was shown to be an excellent predictor of HCC prognosis. It could stratify patients appropriately and characterize the TME accurately. The high-risk HCC group exhibited an immunosuppressive microenvironment with abundant M2-like macrophage infiltration, which was confirmed by the immunohistochemistry results. The results of qPCR revealed that the expression of signature genes in 20 HCC tissues was significantly greater than that in adjacent normal tissues. After the key gene UCK2 was knocked out, the proliferation of the Huh7 cell line was significantly inhibited, and monocyte-derived macrophages polarized towards an M1-like phenotype in the coculture system. RNA-seq and GSEA suggested that the phenotypes were closely related to the negative regulation of growth and regulation of macrophage chemotaxis. CONCLUSIONS: This study established a new IMRS for the accurate prediction of patient prognosis and the TME, which is also helpful for identifying new targets for the treatment of HCC.

Distributed Nash equilibrium seeking in noncooperative game with partial decision information of neighbors.

In the real world, individuals may conceal some of their real decision information to their neighbors due to competition. It is a challenge to explore the distributed Nash equilibrium when individuals play the noncooperative game with partial decision information in complex networks. In this paper, we investigate the distributed Nash equilibrium seeking problem with partial decision information of neighbors. Specifically, we construct a two-layer network model, where players in the first layer engage in game interactions and players in the second layer exchange estimations of real actions with each other. We also consider the case where the actions of some players remain unchanged due to the cost of updating or personal reluctance. By means of the Lyapunov function method and LaSalle's invariance principle, we obtain the sufficient conditions in which the consensus of individual actions and estimations can be achieved and the population actions can converge to the Nash equilibrium point. Furthermore, we investigate the case with switched topologies and derive the sufficient conditions for the convergence of individual actions to Nash equilibrium by the average dwell time method. Finally, we give numerical examples for cases of fixed and switched topologies to verify our theoretical results.

A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria.

BACKGROUND: Liver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. METHODS: Retrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. RESULTS: A total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. CONCLUSIONS: The nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

Short-term postoperative bacteriobilia or fungibilia in liver transplantation patients with donation after circulatory death allografts associated with a longer hospital stay: A single-center retrospective observational study in China.

BACKGROUND: Normal bile is sterile. Studies have shown that cholangitis after liver transplantation (LT) was associated with a relatively poor prognosis. It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients, especially with donation after circulatory death (DCD) allografts, which was correlated with a higher risk of allograft failure. METHODS: This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021. All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia. The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes, especially hospital stay were analyzed. RESULTS: Totally 135 and 171 organisms were isolated at weeks 1 and 2, respectively. Among all patients included in this analysis, 83 (59.7%) developed bacteriobilia or fungibilia within 2 weeks post-transplantation. The occurrence of bacteriobilia or fungibilia (ß = 7.43, 95% CI: 0.02 to 14.82, P = 0.049), particularly the detection of Pseudomonas (ß = 18.84, 95% CI: 6.51 to 31.07, P = 0.003) within 2 weeks post-transplantation was associated with a longer hospital stay. However, it did not affect the graft and patient survival. CONCLUSIONS: The occurrence of bacteriobilia or fungibilia, particularly Pseudomonas within 2 weeks post-transplantation, could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges.

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.

The Absence of Intra-Tumoral Tertiary Lymphoid Structures is Associated with a Worse Prognosis and mTOR Signaling Activation in Hepatocellular Carcinoma with Liver Transplantation: A Multicenter Retrospective Study.

Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC-LT) has not been explored. In this study, it is found that intra-tumoral TLS abundance is significantly correlated with recurrence-free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single-cell RNA-seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S-phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non-invasive manner. The classifier demonstrates remarkable performance in predicting intra-tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra-tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC-LT.

Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma: a multicenter cohort study in China.

OBJECTIVE: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. METHODS: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. RESULTS: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM (P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival (P < 0.05). CONCLUSIONS: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.

A fully Bayesian approach for comprehensive mapping of magnitude and phase brain activation in complex-valued fMRI data.

Functional magnetic resonance imaging (fMRI) plays a crucial role in neuroimaging, enabling the exploration of brain activity through complex-valued signals. These signals, composed of magnitude and phase, offer a rich source of information for understanding brain functions. Traditional fMRI analyses have largely focused on magnitude information, often overlooking the potential insights offered by phase data. In this paper, we propose a novel fully Bayesian model designed for analyzing single-subject complex-valued fMRI (cv-fMRI) data. Our model, which we refer to as the CV-M&P model, is distinctive in its comprehensive utilization of both magnitude and phase information in fMRI signals, allowing for independent prediction of different types of activation maps. We incorporate Gaussian Markov random fields (GMRFs) to capture spatial correlations within the data, and employ image partitioning and parallel computation to enhance computational efficiency. Our model is rigorously tested through simulation studies, and then applied to a real dataset from a unilateral finger-tapping experiment. The results demonstrate the model's effectiveness in accurately identifying brain regions activated in response to specific tasks, distinguishing between magnitude and phase activation.

Super-resolution terahertz imaging based on a meta-waveguide.

A terahertz metamaterial waveguide (meta-waveguide) and a meta-waveguide-based lens-free imaging system are presented. The meta-waveguide not only inherits the low-loss transmission performance of a waveguide but also breaks through the diffraction limit under the action of the metamaterial, achieving subwavelength focusing. The focusing distance is far greater than the Rayleigh length, thus enabling far-field scanning imaging. For verification, a metal ring-based meta-waveguide was fabricated by 3D printing and metal cladding technology. Then, a transmission scanning imaging system working at 0.1 THz was built. High quality terahertz images with a resolution of 1/3 of the wavelength were obtained by placing the imaging targets at the focus and performing two-dimensional scanning. The focusing and transmission of terahertz wave in the meta-waveguide were simulated and analyzed.

Evaluation of Profile Control and Oil Displacement Effect of Starch Gel and Nano-MoS2 Combination System in High-Temperature Heterogeneous Reservoir.

The Henan Oilfield's medium-permeability blocks face challenges such as high temperatures and severe heterogeneity, making conventional flooding systems less effective. The starch gel system is an efficient approach for deep profile control in high-temperature reservoirs, while the nano-MoS2 system is a promising enhanced oil recovery (EOR) technology for high-temperature low-permeability reservoirs. Combining these two may achieve the dual effects of profile control and oil displacement, significantly enhancing oil recovery in high-temperature heterogeneous reservoirs. The basic performance evaluation of the combination system was carried out under reservoir temperature. Displacement experiments were conducted in target blocks under different permeabilities and extreme disparity core flooding to evaluate the combination system's oil displacement effect. Additionally, the displacement effects and mechanisms of the starch gel and nano-MoS2 combination system in heterogeneous reservoirs were evaluated by simulating interlayer and intralayer heterogeneity models. The results show that the single nano-MoS2 system's efficiency decreases with increased core permeability, and its effectiveness is limited in triple and quintuple disparity parallel experiments. After injecting the starch gel-nano-MoS2 combination system, the enhanced oil recovery effect was significant. The interlayer and intralayer heterogeneous models demonstrated that the primary water flooding mainly affected the high-permeability layers, while the starch gel effectively blocked the dominant channels, forcing the nano-MoS2 oil displacement system towards unswept areas. This coordination significantly enhanced oil displacement, with the combination system improving recovery by 15.33 and 12.20 percentage points, respectively. This research indicates that the starch gel and nano-MoS2 combination flooding technique holds promise for enhancing oil recovery in high-temperature heterogeneous reservoirs of Henan Oilfield, providing foundational support for field applications.

BATF-mediated regulation of exhausted CD8+ T-cell responses and potential implications for chimeric antigen receptor-T therapy.

Chimeric antigen receptor (CAR) T-cell therapy for malignant tumors has reached a crucial stage, with recent studies underscoring the role of T-cell exhaustion in determining the efficacy of CAR-T therapy. This trailblazing discovery has opened new avenues to augment the potency of CAR-T therapy. Basic leucine zipper ATF-like transcription factor (BATF) is indispensable in alleviating T-cell exhaustion and is pivotal in the early stages of CD8+ T-cell differentiation. In cooperation with other transcription factors, it plays a key role in the differentiation and maturation processes of exhausted T cells. A deeper comprehension of BATF's mechanisms in T-cell biology may yield novel insights into amplifying the efficacy of CAR-T therapy.

Chimeric antigen receptor (CAR) T-cell therapy, a treatment that boosts the body's immune system to fight cancer, has made significant progress. Recent research has shown that T-cell exhaustion, which is when the body's immune cells become less effective, affects how well this therapy works. This finding has opened new possibilities to make CAR-T therapy more effective. There is a specific protein called BATF that plays an important role in reducing T-cell exhaustion and influencing the early development of certain immune cells. This review describes how BATF interacts with exhausted T cells, to improve CAR-T therapy. By understanding how BATF works in the immune system, new ways to enhance CAR-T therapy and its ability to fight cancer may be found.

A novel nomogram for prognosis stratification in salvage liver transplantation: a national-wide study with propensity score matching analysis in China.

Background: Salvage liver transplantation (SLT) has been reported to be an efficient treatment option for patients with recurrent hepatocellular carcinoma (HCC) after liver resection (LR). However, for recipients who underwent liver transplantation (LT) due to recurrent HCC after LR in China, the selection criteria are not well established. Methods: In this study, data from the China Liver Transplant Registry (CLTR) of 4,244 LT performed from January 2015 to December 2019 were examined, including 3,498 primary liver transplantation (PLT) and 746 SLT recipients. Propensity score matching (PSM) analysis was used to minimize between-group imbalances. The overall survival (OS) and disease-free survival (DFS) between PLT and SLT in recipients fulfilling the Milan or Hangzhou criteria were compared based on the multivariate analysis, nomograms were plotted to further classify the SLT group into low- and high-risk groups. Results: In this study, the 1-, 3- and 5-year OS and DFS of SLT recipients fulfilling Milan criteria (OS, P=0.01; DFS, P<0.001) or Hangzhou criteria (OS, P=0.03; DFS, P=0.003) were significantly reduced when compared to that of PLT group after PSM analysis. Independent risk factors, including preoperative transarterial chemoembolization (TACE), alpha fetoprotein (AFP) level, tumor maximum size and tumor total diameter were selected to draw a prognostic nomogram. The low-risk SLT recipients (1-year, 95.34%; 3-year, 84.26%; 5-year, 77.20%) showed a comparable OS with PLT recipients fulfilling Hangzhou criteria (P=0.107). Conclusions: An optimal nomogram model for prognosis stratification and clinical decision guidance of SLT was established. The low-risk SLT recipients based on the nomograms showed comparable survival with those fulfilling Hangzhou criteria in PLT group.

Identification and validation of PCSK9 as a prognostic and immune-related influencing factor in tumorigenesis: a pan-cancer analysis.

Introduction: Proprotein convertase subtilisin/kexin-9 (PCSK9) has been primarily studied in the cardiovascular field however, its role in cancer pathophysiology remains incompletely defined. Recently, a pivotal role for PCSK9 in cancer immunotherapy was proposed based on the finding that PCSK9 inhibition was associated with enhancing the antigen presentation efficacy of target programmed cell death-1 (PD-1). Herein, we provide results of a comprehensive pan-cancer analysis of PCSK9 that assessed its prognostic and immunological functions in cancer. Methods: Using a variety of available online cancer-related databases including TIMER, cBioPortal, and GEPIA, we identified the abnormal expression of PCSK9 and its potential clinical associations in diverse cancer types including liver, brain and lung. We also validated its role in progression-free survival (PFS) and immune infiltration in neuroblastoma. Results: Overall, the pan-cancer survival analysis revealed an association between dysregulated PCSK9 and poor clinical outcomes in various cancer types. Specifically, PCSK9 was extensively genetically altered across most cancer types and was consistently found in different tumor types and substages when compared with adjacent normal tissues. Thus, aberrant DNA methylation may be responsible for PCSK9 expression in many cancer types. Focusing on liver hepatocellular carcinoma (LIHC), we found that PCSK9 expression correlated with clinicopathological characteristics following stratified prognostic analyses. PCSK9 expression was significantly associated with immune infiltrate since specific markers of CD8+ T cells, macrophage polarization, and exhausted T cells exhibited different PCSK9-related immune infiltration patterns in LIHC and lung squamous cell carcinoma. In addition, PCSK9 was connected with resistance of drugs such as erlotinib and docetaxel. Finally, we validated PCSK9 expression in clinical neuroblastoma samples and concluded that PCSK9 appeared to correlate with a poor PFS and natural killer cell infiltration in neuroblastoma patients. Conclusion: PCSK9 could serve as a robust prognostic pan-cancer biomarker given its correlation with immune infiltrates in different cancer types, thus potentially highlighting a new direction for targeted clinical therapy of cancers.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence.

Objective: Hepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors. Methods: For this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety. Results: In this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib [26.8 months, 95% confidence interval (95% CI): 6.8-NE] and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%). Conclusions: The results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled.

The m6A-related gene signature stratifies poor prognosis patients and characterizes immunosuppressive microenvironment in hepatocellular carcinoma.

Background: N6-methyladenosine (m6A) is the most abundant epitranscriptomic modification of RNA, which can affect RNA metabolism and protein translation. The m6A modification plays a critical role in cancer development, including hepatocellular carcinoma (HCC). Despite several m6A-related signatures in HCC, most of them lack the necessary validation and the reliability is still elusive. Methods: Differentially expressed genes (DEGs) in the Cancer Genome Atlas were comprehensively analyzed to identify m6A signature associated with HCC prognosis. Gene set enrichment analysis, tumor mutation burden (TMB), immune infiltration, and therapeutic response were evaluated. Importantly, mass spectrometry proteomics and multiplex immunofluorescence assays were performed for validation. Results: The m6A-related protein-coding gene signature was established, which can divide HCC into high-/low-risk subgroups with markedly different overall survival (OS) and clinical stages. Furthermore, we validated its reliability and robustness in our 101 independent HCC specimens using proteomic detection and confirmed that our signature readily identified high-risk HCC patients with 3-year survival rates of 44.1% vs. 71.8% in the low-risk group. Functional analysis indicated that the high-risk group might stimulate the cell cycle and activate oncogenic pathways such as MAPK, mTOR, and VEGF, whereas the low-risk group mainly regulated amino acid, fatty acid, and drug metabolism. Additionally, the high-risk group had more TMB, upregulated immune checkpoint molecule expression, including PD-1, CTLA4, TIM3, and LAG3, and preferentially formed an immunosuppressive microenvironment. Accordingly, potential therapeutic responses showed that high-risk patients were potentially sensitive to inhibitors targeting the cell cycle and MAPK signaling, with patients possibly benefiting from immunotherapy. Moreover, multiplex immunofluorescence assays indicated that high-risk HCC samples displayed distinct immunosuppressive features, with abundant M2-polarized macrophages and T-regulatory cell infiltration. Conclusion: The m6A signature had a prominent capacity to evaluate OS and characterize the tumor immune microenvironment of HCC, which may serve as a useful approach for risk stratification management and provide a valuable clue to choosing rational therapeutic strategies.

Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases.

Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.