2D materials-based photodetectors combined with ferroelectrics.

Photodetectors are essential optoelectronic devices that play a critical role in modern technology by converting optical signals into electrical signals, which are one of the most important sensors of the informational devices in current "Internet of Things" era. Two-dimensional (2D) material-based photodetectors have excellent performance, simple design and effortless fabrication processes, as well as enormous potential for fabricating highly integrated and efficient optoelectronic devices, which has attracted extensive research attention in recent years. The introduction of spontaneous polarization ferroelectric materials further enhances the performance of 2D photodetectors, moreover, companying with the reduction of power consumption. This article reviews the recent advances of materials, devices in ferroelectric-modulated photodetectors. This review starts with the introduce of the basic terms and concepts of the photodetector and various ferroelectric materials applied in 2D photodetectors, then presents a variety of typical device structures, fundamental mechanisms and potential applications under ferroelectric polarization modulation. Finally, we summarize the leading challenges currently confronting ferroelectric-modulated photodetectors and outline their future perspectives.

Huaier granule improves liver inflammation and fibrosis and prevents recurrence in hepatitis B virus related hepatocellular carcinoma.

Background: There is basic research suggesting that Huaier granule can inhibit liver cirrhosis and hepatocellular carcinoma (HCC), but this conclusion has not been clinically verified. We analyzed the distant cancer tissue of two groups of hepatitis B virus (HBV) related HCC with/without Huaier granule, to clarify the effect of Huaier granule on liver inflammation, liver fibrosis, and postoperative recurrence. Methods: We collected clinicopathological data of HCC patients who received two surgery procedures at Mengchao Hepatobiliary Hospital of Fujian Medical University in China from January 2014 to December 2020. Patients according to taking/not taking Huaier granule after the first hepatectomy were divided into two groups, 51 patients with Huaier granule for more than 6 months after operation (Group A); 56 patients without Huaier granule (Group B). The effects on liver inflammation, fibrosis grade, and postoperative recurrence were compared between two groups. Results: The results showed that liver inflammation improved significantly in the Group A [19 (37.3%) cases improved, 31 (60.8%) cases remained unchanged, and 1 (2.0%) case deteriorated] was significantly more than that in the Group B [7 (12.5%) cases improved, 32 (57.1%) cases remained unchanged, and 17 (30.4%) cases deteriorated] (P<0.001). The liver fibrosis in the Group A [17 (33.3%) cases improved, 32 (62.7%) cases remained unchanged, and 2 (3.9%) cases deteriorated] was significantly improved in the Group B [5 (8.9%) cases improved, 45 (80.4%) cases remained unchanged, and 6 (10.7%) cases deteriorated] (P=0.005). The recurrence interval (27.0±21.2 months) in the Group A was significantly longer than that in the Group B (19.0±14.2 months) (P=0.026). Conclusions: Huaier granule can improve liver inflammation, fibrosis, and liver function and prolong the time to recurrence in HBV-related HCC. Given the high rate of postoperative recurrence and poor prognosis of HBV-related HCC, our findings may have useful clinical significance in the prevention of tumor recurrence in these patients.

NMI Functions as Immuno-regulatory Molecule in Sepsis by Regulating Multiple Signaling Pathways.

Sepsis-induced tissue and organ damage is caused by an overactive inflammatory response, immune dysfunction, and coagulation dysfunction. Danger-associated molecular pattern (DAMP) molecules play a critical role in the excessive inflammation observed in sepsis. In our previous research, we identified NMI as a new type of DAMP molecule that promotes inflammation in sepsis by binding to toll-like receptor 4 (TLR4) on macrophage surfaces, activating the NF-κB pathway, and releasing pro-inflammatory cytokines. However, it is still unknown whether NMI plays a significant role in other pathways. Our analysis of bulk and single-cell transcriptome data from the GEO database revealed a significant increase in NMI expression in neutrophils and monocytes in sepsis patients. It is likely that NMI functions through multiple receptors in sepsis, including IFNAR1, IFNAR2, TNFR1, TLR3, TLR1, IL9R, IL10RB, and TLR4. Furthermore, the correlation between NMI expression and the activation of NF-κB, MAPK, and JAK pathways, as well as the up-regulation of their downstream pro-inflammatory factors, demonstrates that NMI may exacerbate the inflammatory response through these signaling pathways. Finally, we demonstrated that STAT1 phosphorylation was enhanced in RAW cells upon stimulation with NMI, supporting the activation of JAK signaling pathway by NMI. Collectively, these findings shed new light on the functional mechanism of NMI in sepsis.

Renal abscess complicating acute pyelonephritis in children: Two cases report and literature review.

RATIONALE: To describe the diagnostic and treatment approaches of renal abscesses complicated with acute pyelonephritis in children. PATIENT CONCERNS: Two children presented with fever, vomiting, and abdominal pain with no typical manifestations, like frequent urination, urgency, dysuria, hematuria, foam urine, and lumbago. Renal abscess complicating acute pyelonephritis was diagnosed by B-ultrasound and computed tomography enhancement. Moreover, inflammatory markers were elevated significantly, but routine blood and urine cultures were repeatedly negative. The empirical anti-infection therapy had no obvious effect. A pathogenic diagnosis was confirmed in case two, and macro gene detection in blood and urine guided the follow-up treatment. DIAGNOSES: Both children were diagnosed with acute gastroenteritis on admission, but renal abscess complicating acute pyelonephritis were diagnosed by imaging examination. INTERVENTIONS: Both children were given anti-infection therapy of third-generation cephalosporin, which had no obvious effect. Routine blood and urine cultures were repeatedly negative. Case one was changed to piperacillin sodium tazobactam. We further carried out blood and urinary metagenomic next-generation sequencing detection for case two. Meanwhile, meropenem and linezolid anti-infection treatment was given. The results showed overlapping infection with Escherichia coli and Enterococcus faecalis. According to the genetic test results, amoxicillin clavulanate potassium combined with nitrofurantoin were prescribed after discharge. OUTCOMES: Clinical symptoms of the 2 children disappeared, the infection was controlled, and imaging showed that renal abscess complicated with acute pyelonephritis disappeared. LESSONS: The clinical spectrum of renal abscess complicating acute pyelonephritis is vague, with no specific manifestations, and can be easily misdiagnosed. B-ultrasound and computed tomography enhancement are helpful in making a definite diagnosis. Moreover, the sensitivity of routine culture is low, and metagenomic next-generation sequencing might be helpful to detect pathogenic microorganisms and guided treatment. Early treatment with broad-spectrum antibiotics might have favorable outcomes.

Ferroelectric-defined reconfigurable homojunctions for in-memory sensing and computing.

Recently, the increasing demand for data-centric applications is driving the elimination of image sensing, memory and computing unit interface, thus promising for latency- and energy-strict applications. Although dedicated electronic hardware has inspired the development of in-memory computing and in-sensor computing, folding the entire signal chain into one device remains challenging. Here an in-memory sensing and computing architecture is demonstrated using ferroelectric-defined reconfigurable two-dimensional photodiode arrays. High-level cognitive computing is realized based on the multiplications of light power and photoresponsivity through the photocurrent generation process and Kirchhoff's law. The weight is stored and programmed locally by the ferroelectric domains, enabling 51 (>5 bit) distinguishable weight states with linear, symmetric and reversible manipulation characteristics. Image recognition can be performed without any external memory and computing units. The three-in-one paradigm, integrating high-level computing, weight memorization and high-performance sensing, paves the way for a computing architecture with low energy consumption, low latency and reduced hardware overhead.

The effects of face mask on speech production and its implication for forensic speaker identification-A cross-linguistic study.

This study aims to understand the effects of face mask on speech production between Mandarin Chinese and English, and on the automatic classification of mask/no mask speech and individual speakers. A cross-linguistic study on mask speech between Mandarin Chinese and English was then conducted. Continuous speech of the phonetically balanced texts in both Chinese and English versions were recorded from thirty native speakers of Mandarin Chinese (i.e., 15 males and 15 females) with and without wearing a surgical mask. The results of acoustic analyses showed that mask speech exhibited higher F0, intensity, HNR, and lower jitter and shimmer than no mask speech for Mandarin Chinese, whereas higher HNR and lower jitter and shimmer were observed for English mask speech. The results of classification analyses showed that, based on the four supervised learning algorithms (i.e., Linear Discriminant Analysis, Naïve Bayes Classifier, Random Forest, and Support Vector Machine), undesirable performances (i.e., lower than 50%) in classifying the speech with and without a face mask, and highly-variable accuracies (i.e., ranging from 40% to 89.2%) in identifying individual speakers were achieved. These findings imply that the speakers tend to conduct acoustic adjustments to improve their speech intelligibility when wearing surgical mask. However, a cross-linguistic difference in speech strategies to compensate for intelligibility was observed that Mandarin speech was produced with higher F0, intensity, and HNR, while English was produced with higher HNR. Besides, the highly-variable accuracies of speaker identification might suggest that surgical mask would impact the general performance of the accuracy of automatic speaker recognition. In general, therefore, it seems wearing a surgical mask would impact both acoustic-phonetic and automatic speaker recognition approaches to some extent, thus suggesting particular cautions in the real-case practice of forensic speaker identification.

Multiple-phase evolution and electrical transport of Sr4-xYxCo4O12-δ (x = 0-1.0): an ordered phase transition process.

The transition metal oxide (TMO) SrCoO3-δ family with rich structural diversity has been widely studied in the phase transition and energy application fields. We report the multiple-phase structure evolution, phase transitions during sintering, and electrical transport of A-site doped Sr4-xYxCo4O12-δ (x = 0-1.0) ceramics. Sr6Co5O15 (x = 0) adopts a hexagonal structure (H), Sr4-xYxCo4O12-δ (x = 0.2-0.4) ceramics adopts a cubic perovskite (CP) structure, and Sr4-xYxCo4O10.5+δ' (x = 0.8-1.0) ceramics adopts an ordered-tetragonal (OT) structure; moreover, their phase transitions during the sintering processing of samples are systematically investigated. Combining the thermal analysis and X-ray diffraction results, the exothermic peak and weight gain of Sr3YCo4O10.5 (x = 1.0, T) at 1042 °C are considered to correspond to an ordered phase transition (T → OT) occurring. Finally, a systematic phase schema of the Sr4-xYxCo4O12-δ (x = 0-1.0) state dependence on the Y content and sintering temperature is obtained. The high-energy Y-O bond stabilizes the high-temperature CP structure (x = 0.2-0.4) and induces a structural evolution from the CP to OT structure (x = 0.8-1.0). In addition, all Sr4-xYxCo4O12-δ (x = 0-1.0) ceramics show semiconductive electrical transport behavior. Sr6Co5O15 (H) with a one-dimensional chain structure has the highest resistivity, while Sr3.8Y0.2Co4O12-δ (CP) with a three-dimensional corner-sharing structure exhibits the lowest resistivity, and Sr4-xYxCo4O12-δ (x = 0.2-1.0) ceramics show an increasing tendency in resistivity due to the hole carrier Co4+ converting to Co3+. We studied multiple-phase evolution and ordered phase transition in Sr4-xYxCo4O12-δ (x = 0-1.0) ceramics through Y-O bonding.

Inflammation-Related Marker NrLR Predicts Prognosis in AFP-Negative HCC Patients After Curative Resection.

Background: The role of inflammation-related markers in alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) is not well known. This study aimed to investigate the clinical significance of inflammation-related markers in AFP-negative HCC patients after curative resection. Methods: One thousand one hundred and seventy-nine AFP-negative HCC patients after curative resection were included. Survival rate and prognostic analysis were performed using Kaplan-Meier and Cox regression analysis. Propensity score matching (PSM) was used for patient selection. Results: Multivariate Cox regression showed that neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NrLR) was the independent risk factor associated with OS (p = 0.002) and RFS (p = 0.017). Low NrLR groups (n = 628) had lower rates of albumin-bilirubin (ALBI) grade 2 (p < 0.001), lower rates of bleeding and blood transfusion (p < 0.001) than high NrLR groups. Considering tumor features, low NrLR groups had lower AFP levels (p < 0.001), smaller tumor size (p < 0.001), and lower rates of Edmondson grade III-IV (p = 0.024) than high NrLR groups. After PSM, the 1-year, 3 year-, and 5-year OS rates in the low NrLR and high NrLR groups were 96.3%, 86.9%, 64.9%, and 91.4%, 76.7%, 59.5% (p < 0.001), respectively. The 1-year, 3-year, and 5-year RFS rates in the low NrLR and high NrLR groups were 80.0%, 62.9%, 47.5%, and 71.7%, 52.6%, 39.5% (p < 0.001), respectively. Conclusion: NrLR was a poor prognostic factor for mortality and tumor recurrence in AFP-negative HCC patients after curative resection. The simple and low-cost marker could help physician to determine patients at high risk of tumor recurrence for frequent clinical surveillance.

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification.

BACKGROUND: There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma (HCC) recurrence. Recent studies suggest that postoperative adjuvant transarterial chemoembolization (PA-TACE) is beneficial for patients at high risk of tumor recurrence. However, it is difficult to select the patients. The present study aimed to develop an easy-to-use score to identify these patients. METHODS: A total of 4530 patients undergoing liver resection were recruited. Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization (PDTE) scoring system was established. RESULTS: The scoring system was composed of ten risk factors including alpha-fetoprotein (AFP), albumin-bilirubin (ALBI) grade, operative bleeding loss, resection margin, tumor capsular, satellite nodules, tumor size and number, and microvascular and macrovascular invasion. Using 5 points as risk stratification, the patients with PA-TACE had higher recurrence-free survival (RFS) compared with non-TACE in > 5 points group (P < 0.001), whereas PA-TACE patients had lower RFS compared with non-TACE in ≤ 5 points group (P = 0.013). In the training and validation cohorts, the C-indexes of PDTE scoring system were 0.714 [standard errors (SE) = 0.010] and 0.716 (SE = 0.018), respectively. CONCLUSIONS: The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance. Patients with > 5 points may benefit from PA-TACE.

Efficacy of Adjuvant Transarterial Chemoembolization Combined Antiviral Therapy for HBV-Related HCC with MVI after Hepatic Resection: A Multicenter Study.

BACKGROUND: Efficacy of transarterial chemoembolization (TACE) combined antiviral therapy (AVT) on long-term outcome in hepatitis B virus-related HCC with microvascular invasion (MVI) after hepatic resection is unclear. METHODS: A multicenter retrospective study was conducted. All patients were divided into four groups according to postoperative adjuvant therapy (control group, AVT group, TACE group, and combined group). The overall survival (OS) and recurrence-free survival (RFS) were analyzed. RESULTS: A total of 1090 patients were enrolled in this study, including control group (n=319), TACE group (n=152), AVT group (n=335) and combined group (n=284). Multivariate Cox analysis showed that postoperative adjuvant AVT and TACE were the independent protective factors for OS and RFS. The median OS among the control group, TACE group, AVT group, and the combined group were 16.44, 18.36 months, 38.88 months, and 48.24 months respectively(p<0.01). The median RFS among 4 group were 4.68, 5.40 months, 8.64 months and 10.32 months respectively(p<0.01). CONCLUSIONS: Postoperative adjuvant TACE and AVT were the independent protective factors associated with mortality and tumor recurrence in HBV-related HCC with MVI after resection. This combined treatment strategy may provide useful clinical significance in the prevention of tumor recurrence in these patients.

The danger signal interferon-induced protein 35 (IFP35) mediates acetaminophen-induced liver injury.

Acute liver injury caused by overdose usage of acetaminophen (APAP) is an intractable clinical problem. Necrotic hepatocytes release large amounts of intracellular components including damage-associated molecular patterns (DAMPs) which contribute to liver failure and may serve as therapeutic targets. However, the pathogenic mechanisms of DAMPs in APAP-induced liver injury (AILI) are remain largely uncovered. Here, we found that a recently identified DAMP, interferon-induced protein 35 (IFP35), is involved in the early phase of AILI. Our data demonstrated that although the expression level of IFP35 is not significantly increased in either patients or mice with AILI, it is released from necrotic hepatocytes. Within 24 h post APAP injection, mice lacking Ifp35 are resistant to APAP-induced toxicity, and induce less inflammatory response than that of wild-type mice, including reduced AST/ALT level, pro-inflammatory cytokines production and neutrophils infiltration. More importantly, antibody of IFP35 reduces the expression level of inflammatory factors and chemokines. This study brings new knowledge into the pathogenic mechanism of AILI.

Deubiquitinating enzyme JOSD2 promotes hepatocellular carcinoma progression through interacting with and inhibiting CTNNB1 degradation.

Although a variety of molecular targets have been identified, hepatocellular carcinoma (HCC) remains among the leading causes of death. As functions of they deubiquitinating enzyme Josephin domain containing 2 (JOSD2) in cancers are still poorly understood, we investigated its function and molecular mechanism in the regulation of HCC progression. Here, we indicated that JOSD2 expression is elevated in patient samples with HCC and positively associated with poor prognosis. Moreover, the promoting roles of JOSD2 in HCC cell survival, migration, and invasion were determined using in vitro models. Importantly, a mechanistic study revealed that JOSD2 binds to and decreases the ubiquitination level of catenin beta 1 (CTNNB1), a key component of Wnt signaling, thereby augmenting Wnt pathway transduction. Furthermore, a series of rescue experiments confirmed the significance of CTNNB1 in the modulation of HCC progression by JOSD2. Our study uncovered JOSD2 as a novel prognostic marker for patients with HCC and identified CTNNB1 as a pivotal partner and downstream target protein of JOSD2, which may aid in the development of JOSD2 as a promising molecular target for HCC treatment.

Development of a machine learning model to predict early recurrence for hepatocellular carcinoma after curative resection.

Background: Early recurrence is common for hepatocellular carcinoma (HCC) after surgical resection, being the leading cause of death. Traditionally, the COX proportional hazard (CPH) models based on linearity assumption have been used to predict early recurrence, but predictive performance is limited. Machine learning models offer a novel methodology and have several advantages over CPH models. Hence, the purpose of this study was to compare random survival forests (RSF) model with CPH models in prediction of early recurrence for HCC patients after curative resection. Methods: A total of 4,758 patients undergoing curative resection from two medical centers were included. Fifteen features including age, gender, etiology, platelet count, albumin, total bilirubin, AFP, tumor size, tumor number, microvascular invasion, macrovascular invasion, Edmondson-Steiner grade, tumor capsular, satellite nodules and liver cirrhosis were used to construct the RSF model in training cohort. Discrimination, calibration, clinical usefulness and overall performance were assessed and compared with other models. Results: Five hundred survival trees were used to generate the RFS model. The five highest Variable Importance (VIMP) were tumor size, macrovascular invasion, microvascular invasion, tumor number and AFP. In training, internal and external validation cohort, the C-index of RSF model were 0.725 [standard errors (SE) =0.005], 0.762 (SE =0.011) and 0.747 (SE =0.016), respectively; the Gönen & Heller's K of RSF model were 0.684 (SE =0.005), 0.711 (SE =0.008) and 0.697 (SE =0.014), respectively; the time-dependent AUC (2 years) of RSF model were 0.818 (SE =0.008), 0.823 (SE =0.014) and 0.785 (SE =0.025), respectively. The RSF model outperformed early recurrence after surgery for liver tumor (ERASL) model, Korean model, American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) stage, Barcelona Clinic Liver Cancer (BCLC) stage and Chinese stage. The RSF model is capable of stratifying patients into three different risk groups (low-risk, intermediate-risk, high-risk groups) in the training and two validation cohorts (all P<0.0001). A web-based prediction tool was built to facilitate clinical application (https://recurrenceprediction.shinyapps.io/surgery_predict/). Conclusions: The RSF model is a reliable tool to predict early recurrence for patients with HCC after curative resection because it exhibited superior performance compared with other models. This novel model will be helpful to guide postoperative follow-up and adjuvant therapy.

Research on the electrochemistry synergied cellulase enzymes strengthens the anaerobic fermentation of cow dung.

Lignocellulose degradation (LCD) was the key factor limiting the development of anaerobic fermentation (AF) by the cow dung (CD). In the research, the effects of cellulase pretreatment (CP) and microvoltage (MV) alone and combination on the gas production and LCD during the AF were investigated. The results showed that both CP and MV had an significant effect on the AF, though the synergistic reaction was more pronounced. The total biogas yield (TBY) could reach 11521 mL, and the highest methane production rate was 73% in the synergistic reactions, which was increased by 18.7% and 10.0% compared to CP and MV alone respectively. Meanwhile, the degradation rates of cellulose and lignin could be increased by 33.44% and 22.23%, respectively. The results of SEM, FT-IR and excitation emission matrix demonstrated that CP and MV played an important role in improving the fermentation efficiency. The microbial biomass change results indicated that the synergistic effect of CP and 0.8 V MV on the LCD was achieved by promoting the growth of lignocellulose-degrading bacteria. Moreover, the electricity could not only accelerate the movement of microorganisms and enzymes, but also promoted and enhanced the activity of enzymes, which provided an important reference for further development of the AF technology and the biogas industry.

Antiviral Therapy Improves Survival in Hepatocellular Carcinoma with Microvascular Invasion: A Propensity Score Analysis.

BACKGROUND AND AIMS: To investigate the effect of postoperative adjuvant antiviral therapy (AVT) on hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) with microvascular invasion (MVI) after R0 liver resection. METHODS: A total of 1008 patients with HBV-related HCC with MVI were recruited, which comprises 378 non-AVT groups and 630 AVT groups. Propensity score matching (PSM) was developed to reduce any bias in patient selection. Independent risk factors were identified by Cox regression analysis. RESULTS: After PSM, the 1-, 3-, and 5-year overall survival rates in the AVT group and non-AVT group were 89.2%, 62.4%, 42.1%, and 73.3%, 46.3%, 22.1%, (p < 0.01), respectively. The 1-, 3-, and 5-year recurrence-free survival rates in the AVT group and non-AVT group were 52.5%, 30.4%, 22.1%, and 46.3%, 26.8%, 13.2% (p = 0.02), respectively. Multivariate Cox analysis revealed that postoperative adjuvant AVT was the independent protective factor associated with mortality (HR = 0.55, 95%CI = 0.46-0.67, p < 0.01) and tumor recurrence (HR = 0.81, 95%CI = 0.69-0.96, p = 0.01). CONCLUSIONS: Among patients who underwent curative hepatectomy for HBV-related HCC with MVI, postoperative adjuvant AVT was the independent protective factor associated with mortality and tumor recurrence. Given the high rate of postoperative recurrence and poor prognosis of HBV-related HCC with MVI, our findings may have useful clinical significance in the prevention of tumor recurrence in these patients.

Forensic human image identification using medical indicators.

Diseases not only bring troubles to people's body functions and mind but also influence the appearances and behaviours of human beings. Similarly, we can analyse the diseases from people's appearances and behaviours and use the personal medical history for human identification. In this article, medical indicators presented in abnormal changes of human appearances and behaviours caused by physiological or psychological diseases were introduced, and were applied in the field of forensic identification of human images, which we called medical forensic identification of human images (mFIHI). The proposed method analysed the people's medical signs by studying the appearance and behaviour characteristics depicted in images or videos, and made a comparative examination between the medical indicators of the questioned human images and the corresponding signs or medical history of suspects. Through a conformity and difference analysis on medical indicators and their indicated diseases, it would provide an important information for human identification from images or videos. A case study was carried out to demonstrate and verify the feasibility of the proposed method of mFIHI, and our results showed that it would be important contents and angles for forensic expert manual examination in forensic human image identification.

Development of pre and post-operative nomograms to predict individual survival for ideal liver resection candidates with hepatocellular carcinoma.

BACKGROUND: Liver resection is currently the only recommended treatment option for solitary hepatocellular carcinoma (HCC) at an early stage, with well-preserved liver function and no clinically significant portal hypertension. However, this population is heterogeneous, rendering it crucial to develop a risk stratification tool. Therefore, this study aimed to develop preoperative and post-operative nomograms to predict individual survival and stratify patient risk in the ideal candidates for liver resection. METHODS: A total of 1405 ideal liver resection candidates were recruited. Independent risk factors were identified by Cox regression model and used to establish two ideal liver resection for overall survival (IROS) nomograms in training cohort. Model performance was assessed by discrimination, calibration, clinical usefulness. The two model also compared with six other prognostic nomograms and six other staging systems. RESULTS: Multivariate COX analysis revealed that ALP, ln(AFP), NrLR, PNI, ln(tumor size), microvascular invasion, Edmondson-Steiner grade and tumour capsular were the independent risk factors associated with mortality. 5 preoperative variables were incorporated to construct IROS-pre model; All eight available variables were used to draw IROS-post model. The C-index, K-index, time-dependent AUC and DCA of the two models showed significantly better predictive performances than other models. The models could stratify patients into three different risk groups. The web-based tools are convenient for clinical practice. CONCLUSIONS: These two nomograms were developed to estimate survival probability and stratify three strata with significantly different outcomes, outperforming other models in training and validation cohorts, as well as different subgroups. Both IROS models will help guide individualized follow-up.

Autophagy Is Required for Hepatic Differentiation of Hepatic Progenitor Cells via Wnt Signaling Pathway.

The molecular mechanisms regulating differentiation of hepatic progenitor cells (HPCs), which play pivotal roles in liver regeneration and development, remain obscure. Autophagy and Wnt signaling pathways regulate the development and differentiation of stem cells in various organs. However, the roles of autophagy and Wnt signaling pathways in hepatic differentiation of HPCs are not well understood. Here, we describe the effects of autophagy and Wnt signaling pathways during hepatic differentiation of HPCs. We used a well-established rat hepatic progenitor cell line called WB-F344, which was treated with differentiation medium to promote differentiation of WB-F344 cells along the hepatic phenotype. Firstly, autophagy was highly activated in HPCs and gradually decreased during hepatic differentiation of HPCs. Induction of autophagy by rapamycin or starvation suppressed hepatic differentiation of HPCs. Secondly, Wnt3a signaling pathway was downregulated, and Wnt5a signaling pathway was upregulated in hepatic differentiation of HPCs. At last, Wnt3a signaling pathway was enhanced, and Wnt5a signaling pathway was inhibited by activation of autophagy during hepatic differentiation of HPCs. In summary, these results demonstrate that autophagy regulates hepatic differentiation of hepatic progenitor cells through Wnt signaling pathway.