Search

Low molecular aromatic compounds are detrimental to the enzymatic hydrolysis of lignocellulose. However, the specific role of their functional groups remains unclear. Here, a series of nine aromatic compounds as additives were tested to understand their effect on the hydrolysis yield of microcrystalline cellulose (MCC) and alkaline pretreated wheat straw. Based on the results, the inhibition of aldehyde groups on MCC was greater than that of carboxyl groups, whereas for the alkaline pretreated wheat straw case, the inhibitory effect of aldehyde groups was lower than that of carboxyl groups. Increased methoxyl groups of aromatic compounds reduced the inhibitory effect on enzymatic hydrolysis of both substrates. Stronger inhibition of aromatic compounds on MCC hydrolysis was detected in comparison with the alkaline pretreated wheat straw, indicating that the substrate lignin can offset the inhibition to a certain extent. Among all aromatic compounds, syringaldehyde with one aldehyde group and two methoxyl groups improved the glucan conversion of the alkaline pretreated wheat straw.

Abstract Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non‐invasive diagnosis method based on serum markers, such as α‐fetoprotein (AFP), and des‐γ‐carboxy‐prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere‐coated three‐dimensional (3D) hierarchical porous chip, named a SiO2‐chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non‐HCC and HCC subjects are enriched using an SiO2‐chip and performed RNA sequencing to identify HCC‐related long non‐coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT‐1 and EGFR‐AS‐1 are two HCC‐related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT‐PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy‐based approach for noninvasive and reliable HCC detection is developed.

Abstract Obese people with acute pancreatitis (AP) have an increased risk of developing severe acute pancreatitis (SAP), which prolongs the length of hospital stay and increases mortality. Thus, elucidation of the mechanisms through which SAP occurs in obese individuals will provide clues for possible treatment targets. Differences in early events in obese or lean patients with AP have not been conclusively reported. We selected C57BL/6 mice as lean mice models, ob/ob mice or diet induced obese (DIO) mice as obese mice models and then induced experimental AP in mice via injections of caerulein. There were suppressed p-AMPK expressions in the pancreas of obese mice, compared with same-age lean C57BL/6 mice, which were further reduced in AP mice models. Obese AP mice were treated using AICAR, a direct AMPK agonist, which prevented pancreatic damage and cell death, suppressed pancreatic enzyme levels in serum, reduced the areas of fat saponification in the peritoneal cavity, prevented injury in other organs and decreased mice mortality rate. Further assays showed that AICAR activates p-AMPK to stabilize pro-caspase-8. Pro-caspase-8 enhances RIPK3 degradation, inhibits pancreatic acinar cell necroptosis, and downregulates the release of pancreatic enzymes. Thus, activation of AMPK by AICAR alleviates pancreatic acinar cell necroptosis and converts SAP to mild acute pancreatitis in obese mice.

Introduction and Objectives: Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. Materials and Methods: Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. Results: Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished β-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. Conclusions: Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/β-catenin axis activation.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world, with a high likelihood of metastasis and a dismal prognosis. The reprogramming of glucose metabolism is critical in the development of HCC. The Warburg effect has recently been confirmed to occur in a variety of cancers, including HCC. However, little is known about the molecular biological mechanisms underlying the Warburg effect in HCC cells. In this study, we sought to better understand how methyltransferase 5, N6‐adenosine (METTL5) controls the development of HCC and the Warburg effect. Methods In the current study, quantitative real‐time polymerase chain reaction and Western blotting were used to detect the expression of METTL5 in HCC tissues and cell lines. Several different cell models and animal models were established to determine the role of METTL5 in glucose metabolism reprogramming and the underlying molecular mechanism of HCC. Glutathione‐S‐transferase pulldown, coimmunoprecipitation, RNA sequencing, non‐targeted metabolomics, polysome profiling, and luciferase reporter assays were performed to investigate the molecular mechanisms of METTL5 in HCC cells. Results We discovered that METTL5 drove glucose metabolic reprogramming to promote the proliferation and metastasis of HCC. Mechanistically, upregulation of METTL5 promoted c‐Myc stability and thus activated its downstream glycolytic genes lactate dehydrogenase A (LDHA), enolase 1 (ENO1), triosephosphate isomerase 1 (TPI1), solute carrier family 2 member 1 (SLC2A1), and pyruvate kinase M2 (PKM2). The c‐Box and ubiquitin binding domain (UBA) regions of ubiquitin specific peptidase 5 (USP5) binded to c‐Myc protein and inhibited K48‐linked polyubiquitination of c‐Myc. Further study revealed that METTL5 controled the USP5 translation process, which in turn regulated the ubiquitination of c‐Myc. Furthermore, we identified cAMP responsive element binding protein 1 (CREB1)/P300 as a critical transcriptional regulator of METTL5 that promoted the transcription of METTL5 in HCC. In patient‐derived tumor xenograft (PDX) models, adenovirus‐mediated knockout of METTL5 had a good antitumor effect and prolonged the survival of PDX‐bearing mice. Conclusions These findings point to a novel mechanism by which CREB1/P300‐METTL5‐USP5‐c‐Myc controls abnormal glucose metabolism and promotes tumor growth, suggesting that METTL5 is a potential therapeutic target and prognostic biomarker for HCC.

Abstract Background Enhanced de novo lipogenesis is essential for hepatocellular carcinoma (HCC). Abnormally high cullin‐associated and neddylation‐dissociated 1 (CAND1) expression is associated with poor clinical prognosis in HCC. The SKP1‐Cullin‐1‐F‐box (SCF) complex consists of the SKP1, Cullin‐1 and F‐box proteins (FBPs) and performs multiple functions including adipogenesis. SCF complex was modulated by CAND1, but Whether and how the CAND1 promotes HCC by regulating SCF complex and lipogenesis are unknown. Methods HCC samples were used to analyze the correlations between CAND1 expression and clinicopathological characteristics such as survival and prognosis. The in vitro functions of CAND1, FBXO11 and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) were measured by cell proliferation, colony formation and migration assays. The in vivo functions were tested in multiple mouse liver cancer models including patient‐derived xenograft (PDX), cell line‐derived xenograft and AKT/NRASV12‐induced primary liver cancer models. Injections of adeno‐associated virus targeting CAND1 (AAV‐shCAND1) were performed to evaluate the therapeutic efficacy of targeting CAND1. RNA‐Seq and lipidomic assays followed by serial biochemical experiments including mass spectrometry, immunoprecipitation and GST pull‐down were performed to dissect the underlying mechanisms. Results CAND1 promoted the expression of lipid synthesis genes by disrupting SCF complex assembly and lipid accumulation. Furthermore, we identified hnRNPA2B1 as a novel F‐box protein 11 (FBXO11)‐binding partner. FBXO11 directly bound to hnRNPA2B1 and promoted hnRNPA2B1 ubiquitination and subsequent degradation. Our evaluations of the therapeutic efficacy of AAV‐shCAND1 injections confirmed that targeting the CAND1‐SCFFBXO11‐hnRNPA2B1A signalling axis was therapeutically effective. CAND1 downregulation significantly reduced the tumour burden in a primary mouse liver cancer model and a PDX model. Conclusions Our results highlight that CAND1 is associated with poor prognosis in HCC and regulates lipid metabolic reprogramming by dissociating the SCF complex. Targeting the CAND1‐SCFFBXO11‐hnRNPA2B1 axis may be a novel strategy for HCC treatment.

Abstract Background Despite the understanding of the COP9 signalosome subunit 5 (CSN5) in tumor genesis, there is no conclusive evidence on its value to predict the survival and prognosis of digestive system tumor patients. Hence this study aimed to evaluate the impact of CSN5 levels on the survival and clinicopathological parameters of digestive system neoplasm patients. Methods First, a comprehensive search was conducted in four databases. We utilized the Hazard Ratio (HR) with a 95% confidence interval (CI) to evaluate the prognostic value of CSN5 for the overall survival (OS) and recurrence-free survival (RFS) of patients. Then, we estimated the connection between CSN5 and the clinicopathological parameters based on the Odds Ratio (OR) with the corresponding 95% CI. Results This meta-analysis included 22 studies and 2193 patients diagnosed with digestive system tumors. High expression of CSN5 was correlated to poorer OS (HR = 2.28, 95% CI: 1.71–3.03; p

Abstract Despite of advances in treatment options, hepatocellular carcinoma (HCC) remains nearly incurable and has been recognized as the third leading cause of cancer-related deaths worldwide. As a deubiquitinating enzyme, the antitumor effect of ubiquitin-specific peptidase 53 (USP53) has been demonstrated on few malignancies. In this study, we investigated the potential antitumor role of USP53 in HCC. The results showed that USP53 was downregulated in HCC tissues as well as in HCC cell lines using both in silico data as well as patient samples. Furthermore, the ectopic expression of USP53 inhibited the proliferation, migration and invasion, and induced the apoptosis of HCC cells. Co-immunoprecipitation (CO-IP) assay and mass spectrometry (MS) combined with the gene set enrichment analysis (GSEA) identified cytochrome c (CYCS) as an interacting partner of USP53. USP53 overexpression increased the stability of CYCS in HCC cells following cycloheximide treatment. Finally, the overexpression of CYCS compensated for the decreased apoptotic rates in cells with USP53 knocked down, suggesting that USP53 induced the apoptosis in HCC cells through the deubiquitination of CYCS. To summarize, we identified USP53 as a tumor suppressor as well as a therapeutic target in HCC, providing novel insights into its pivotal role in cell apoptosis.

Abstract Objective Pancreatic ductal adenocarcinoma (PDAC) has high mortality and poor prognosis. Pyroptosis can influence the prognosis of patients by regulating the proliferation, invasion, and metastasis of cancer cells. However, the role of pyroptosis-related genes (PRGs) in PDAC remains unclear. Methods In this study, based on the Cancer Genome Atlas (TCGA) cohort of PDAC samples, univariate Cox analysis and LASSO regression analysis were used to screen the prognostic PRGs and establish the gene signature. To further evaluate the functional significance of CASP4 and NLRP1 in PDAC, we also conducted an in vitro study to explore the mechanism of CASP4 and NLRP1 regulating the occurrence and development of PDAC. Finally, we investigated the relationship between CASP4 and NLRP1 expression levels and drug sensitivity in pancreatic cancer cells. Results A risk prediction model based on CASP4 and NLRP1 was established, which can distinguish high-risk patients from low-risk patients (P

Introduction: Dysregulation of iron metabolism is closely associated with the development of obesity and obstructive sleep apnea (OSA), but little is known about the relationship between serum transferrin (TF) level and OSA severity. We aimed to verify this relationship and fit into account for obesity-related confounders among bariatric candidates. Methods: We compared data retrospectively collected in 270 bariatric candidates. A propensity score-matched (PSM) analysis was used to determine the impact of iron metabolism on OSA severity independently of obesity. Univariate analysis was used to evaluate the relationship between serum TF level and the severity of OSA reflected by hypoxia and night awakenings parameters. Serum TF level to predict the severity of OSA was assessed by using univariate and multiple logistic regression model. Results: The preliminary analysis showed that serum ferritin (113 ng/mL [50–203] vs. 79 ng/mL [40–130], p = 0.009) and TF (2.72 g/L [2.46–3.09] vs. 2.65 g/L [2.34–2.93], p = 0.039) level was significantly higher in the moderate/severe OSA group than the no/mild OSA group. After PSM analysis, there were 75 patients in each group and only serum TF level remained significant (p = 0.014). The proportion of patients with combined T2D and hyperlipidemia also remained higher in moderate/severe OSA groups. Univariate analysis showed that the group with higher degree of hypoxia had higher serum TF levels no matter the severity of OSA was grouped by oxygen desaturation index (ODI; 2.79 g/L [2.56–3.06] vs. 2.55 g/L [2.22–2.84], p < 0.001) or minimum oxygen saturation (SpO2nadir; 2.75 g/L [2.50–3.03] vs. 2.56 g/L [2.24–2.92], p = 0.009). Univariate and multiple logistic regression analysis further showed that serum TF level emerged as a significant and independent factor associated with OSA severity especially grouped by ODI (odds ratio: 2.91, 95% CI: 1.36–6.23, p = 0.006). Conclusion: The existence of OSA exacerbates obesity comorbidities, particularly type 2 diabetes and hyperlipidemia. Serum TF level is associated with the severity of OSA independently of obesity and might be a potential identification and therapeutic targets.

Background: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49–75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. Methods: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. Results: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00–56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. Conclusions: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.

Abstract Recent studies show that small nucleolar RNAs (snoRNAs) play an important role in tumorigenesis. SNORA42 is a potential therapeutic target and prognostic biomarker for various cancers, and the aim of the present study was to investigate the function and clinical relevance of SNORA42 in hepatocellular carcinoma (HCC). We detected the expression levels of SNORA42 in HCC and normal liver tissue samples, as well as in tumor and hepatocyte-derived cell lines. SNORA42 was significantly upregulated in the HCC tissues and cells compared to the adjacent liver tissues and normal hepatocytes. Furthermore, overexpression of SNORA42 correlated with poor prognosis in the HCC patients. Knocking down SNORA42 in HCC cell lines decreased their proliferation, migration and invasion in vitro, and inhibited tumor growth and metastasis in vivo. In contrast, ectopic expression of SNORA42 promoted HCC cell proliferation and inhibited apoptosis. Mechanistically, SNORA42 exerted its oncogenic effects by targeting the p53 signaling pathway and cell cycle transition. In conclusion, SNORA42 acted as an oncogene in HCC and was a potential prognostic biomarker and therapeutic target.

Abstract Enzymatic hydrolysis of lignocellulose for bioethanol production shows a great potential to remit the rapid consumption of fossil fuels, given the fact that lignocellulose feedstocks are abundant, cost-efficient, and renewable. Lignin results in low enzymatic saccharification by forming the steric hindrance, non-productive adsorption of cellulase onto lignin, and deactivating the cellulase. In general, the non-productive binding of cellulase on lignin is widely known as the major cause for inhibiting the enzymatic hydrolysis. Pretreatment is an effective way to remove lignin and improve the enzymatic digestibility of lignocellulose. Along with removing lignin, the pretreatment can modify the lignin structure, which significantly affects the non-productive adsorption of cellulase onto lignin. To relieve the inhibitory effect of lignin on enzymatic hydrolysis, enormous efforts have been made to elucidate the correlation of lignin structure with lignin–enzyme interactions but with different views. In addition, contrary to the traditional belief that lignin inhibits enzymatic hydrolysis, in recent years, the addition of water-soluble lignin such as lignosulfonate or low molecular-weight lignin exerts a positive effect on enzymatic hydrolysis, which gives a new insight into the lignin–enzyme interactions. For throwing light on their structure–interaction relationship during enzymatic hydrolysis, the effect of residual lignin in substrate and introduced lignin in hydrolysate on enzymatic hydrolysis are critically reviewed, aiming at realizing the targeted regulation of lignin structure for improving the saccharification of lignocellulose. The review is also focused on exploring the lignin–enzyme interactions to mitigate the negative impact of lignin and reducing the cost of enzymatic hydrolysis of lignocellulose.

Abstract SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants—alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 μg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a “spike protein-CD147-CyPA signaling axis”: Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

Objective: Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in hepatocellular carcinoma (HCC). A rapidly increasing number of studies have shown that metabolic changes including lipid metabolic reprogramming play a significant role in the progression of HCC. But it remains to be elucidated how lncRNAs affect tumor cell metabolism. Methods: Through analysis and screening of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset, we found a novel lncRNA RP11-386G11.10 was overexpressed, related to prognosis, conserved and non-protein-coding in HCC and related to poor prognosis. Then, CCK-8, colony formation, Transwell invasion, wound healing assays were performed and nude mouse subcutaneous tumour formation and lung metastasis models were established to explore the effect of RP11-386G11.10 on HCC tumour growth and metastasis. Chromatography-mass spectrometry (GC-MS) and Nile red staining detected the effect of RP11-386G11.10 on lipid metabolism in HCC. Mechanistically, we clarified the RP11-386G11.10/miR-345-3p/HNRNPU signalling pathway through dual luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays and identified ZBTB7A as a transcription factor of RP11-386G11.10. Results: RP11-386G11.10 was overexpressed in HCC and positively correlated with tumour size, TNM stage, and poor prognosis in HCC patients. RP11-386G11.10 promoted the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RP11-386G11.10 acted as a competing endogenous RNA (ceRNA) for miR-345-3p to regulate the expression of HNRNPU and its downstream lipogenic enzymes, leading to lipid accumulation in HCC cells and promoting their growth and metastasis. In addition, we identified ZBTB7A as a transcription factor of RP11-386G11.10. Moreover, HNRNPU promoted the expression of ZBTB7A in HCC cells, thereby increasing the transcriptional activity of RP11-386G11.10, and forming a positive feedback loop, ultimately leading continuous lipid accumulation, growth and metastasis in HCC cells. Conclusions: Our results indicated that the lncRNA RP11-386G11.10 was a novel oncogenic lncRNA that was strongly correlated with the poor prognosis of HCC. The ZBTB7A-RP11-386G11.10-HNRNPU positive feedback loop promoted the progression of HCC by regulating lipid anabolism. RP11-386G11.10 may become a new diagnostic and prognostic biomarker and therapy target for HCC.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there still remains a lack of effective diagnostic and therapeutic targets for this disease. Increasing evidence demonstrates that RNA modifications play an important role in the progression of HCC, but the role of the N7-methylguanosine (m7G) methylation modification in HCC has not been properly evaluated. Thus, the goal of the present study was to investigate the function and mechanism of the m7G methyltransferase WD repeat domain 4 (WDR4) in HCC as well as its clinical relevance and potential value. We first verified the high expression of WDR4 in HCC and observed that upregulated WDR4 expression increased the m7G methylation level in HCC. WDR4 promoted HCC cell proliferation by inducing the G2/M cell cycle transition and inhibiting apoptosis in addition to enhancing metastasis and sorafenib resistance through epithelial-mesenchymal transition (EMT). Furthermore, we observed that c-MYC (MYC) can activate WDR4 transcription and that WDR4 promotes CCNB1 mRNA stability and translation to enhance HCC progression. Mechanistically, we determined that WDR4 enhances CCNB1 translation by promoting the binding of EIF2A to CCNB1 mRNA. Furthermore, CCNB1 was observed to promote PI3K and AKT phosphorylation in HCC and reduce P53 protein expression by promoting P53 ubiquitination. In summary, we elucidated the MYC/WDR4/CCNB1 signalling pathway and its impact on PI3K/AKT and P53. Furthermore, the result showed that the m7G methyltransferase WDR4 is a tumour promoter in the development and progression of HCC and may act as a candidate therapeutic target in HCC treatment.

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, accounting for over 700,000 deaths each year. The lack of predictive and prognostic biomarkers for HCC, with effective therapy, remains a significant challenge for HCC management. Long non-coding RNAs (lncRNAs) play a key role in tumorigenesis and have clinical value as potential biomarkers in the early diagnosis and prediction of HCC. Jun activation domain-binding protein 1 (Jab1, also known as COP9 signalosome subunit 5, CSN5) is a potential oncogene that plays a critical role in the occurrence of HCC. Here, we performed a comprehensive analysis for Jab1/CSN5-associated lncRNAs to predict the prognosis of HCC. The differentially expressed (DE) lncRNAs between in HCC were analyzed based on the TCGA RNA-seq data. We detected 1031 upregulated lncRNAs in 371 HCC tissues and identified a seven-lncRNA signature strongly correlated with Jab1/CSN5 (SNHG6, CTD3065J16.9, LINC01604, CTD3025N20.3, KB-1460A1.5, RP13-582O9.7, and RP11-29520.2). We further evaluated the prognostic significance of these lncRNAs by GEPIA ( http://gepia.cancer-pku.cn/ ). The expression data in 364 liver tumors indicated that this seven-lncRNA signature could better predict worse survival in HCC patients. Moreover, 35 clinical HCC samples were evaluated to assess the validity and reproducibility of the bioinformatic analysis. We found that the targeted lncRNAs were upregulated, with a strong association with Jab1/CSN5 and prognostic value in HCC. Functional enrichment analysis by Gene Ontology (GO) showed that these seven prognostic lncRNAs exhibit oncogenic properties and are associated with prominent hallmarks of cancer. Overall, our findings demonstrate the clinical implication of Jab1/CSN5 with the seven‐lncRNAs in predicting survival for patients with HCC.

Abstract Advanced hepatocellular carcinoma (HCC) results in generally poor clinical outcomes and necessitates better therapeutic strategies. Ivermectin, which is an existing anti‐parasitic drug, has been recently identified as a novel anti‐cancer drug. In line with previous efforts, this work demonstrates the translational potential of ivermectin to treat advanced HCC. We demonstrated that ivermectin at clinically relevant concentrations was active against growth and survival in multiple HCC cell lines. We showed that ivermectin had the potential to inhibit metastasis and target HCC stem cell functions. Mechanism studies correlated well with cellular phenotypes observed in ivermectin‐treated cells, and demonstrated inhibition of mTOR/STAT3 pathway, suppression of epithelial mesenchymal transition (EMT) and reduced expression of stem cell markers. We further demonstrated that ivermectin inhibited tumor formation and growth in HCC xenograft mouse model, without causing significant toxicity in the mice. Using combination index (CI), we showed that ivermectin and sorafenib were synergistic in HCC in vitro, and this was further confirmed in vivo. Our work demonstrates the potent anti‐HCC activities of ivermectin and its multiple targets on essential oncogenic pathways. Our findings provide preclinical evidence to initialize clinical trial using ivermectin and sorafenib for treating advanced HCC.

Abstract Metabolic interventions via targeting intratumoral dysregulated metabolism pathways have shown promise in reinvigorating antitumor immunity. However, approved small molecule immunomodulators often suffer from ineffective response rates and severe off‐target toxicity. ATP occupies a crucial role in energy metabolism of components that form the tumor microenvironment (TME) and influences cancer immunosurveillance. Here, a nanocarrier‐assisted immunometabolic therapy strategy that targets the ATP‐adenosine axis for metabolic reprogramming of TME is reported. An ecto‐enzyme (CD39) antagonist POM1 and AMP‐activated protein kinase (AMPK) agonist metformin are both encapsulated into cancer cell‐derived exosomes and used as nanocarriers for tumor targeting delivery. This method increases the level of pro‐inflammatory extracellular ATP (eATP) while preventing the accumulation of immunosuppressive adenosine and alleviating hypoxia. Elevated eATP triggers the activation of P2X7‐NLRP3‐inflammasome to drive macrophage pyroptosis, potentiates the maturation and antigen capacity of dendritic cells (DCs) to enhance the cytotoxic function of T cells and natural killer (NK) cells. As a result, synergistic antitumor immune responses are initiated to suppress tumor progress, inhibit tumor distant metastases, provide long‐term immune memory that offers protection against tumor recurrence and overcome anti‐PD1 resistance. Overall, this study provides an innovative strategy to advance eATP‐driven antitumor immunity in cancer therapy.

Abstract Serum deprivation-response protein (SDPR), a phosphatidylserine-binding protein, which is known to have a promising role in caveolar biogenesis and morphology. However, its function in hepatocellular carcinoma (HCC) was still largely unknown. In this study, we discussed the characterization and identification of SDPR, and to present it as a novel apoptosis candidate in the incidence of HCC. We identified 81 HCC cases with lower SDPR expression in the tumor tissues with the help of qRT-PCR assay, and lower SDPR expression was potentially associated with poor prognostication. The phenotypic assays revealed that cell proliferation, invasion, and migration were profoundly connected with SDPR, both in vivo and in vitro. The data obtained from the gene set enrichment analysis (GSEA) carried out on the liver hepatocellular carcinoma (LIHC), and also The Cancer Genome Atlas (TCGA) findings indicated that SDPR was involved in apoptosis and flow cytometry experiments further confirmed this. Furthermore, we identified the interaction between SDPR and apoptosis signal-regulating kinase 1 (ASK1), which facilitated the ASK1 N-terminus-mediated dimerization and increased ASK1-mediated signaling, thereby activating the JNK/p38 mitogen-activated protein kinases (MAPKs) and finally enhanced cell apoptosis. Overall, this work identified SDPR as a tumor suppressor, because it promoted apoptosis by activating ASK1-JNK/p38 MAPK pathways in HCC.

AbstractHeinrich (H) events are significant millennial climatic events that occurred during the last glacial period. Their footprints exited most parts of the global world, including the Asian monsoon (AM) region. However, the internal hydroclimatic characteristics of the AM system and their link to the external forcing during the H stadials are not fully understood. This study reconstructed monsoon precipitation changes during 33,000-12,500 a BP using grain size characteristics, elementary ratios, and pollen percentages from sediments of a crater lake (Tianchi Lake) in northeastern China. The H1 ~ H3 events are identified by high values of median grain size (MGS) and low values of Fe/Mn ratios and pollen percentages. By comparison with other records in the AM region, we found that H events in monsoon precipitation records were more obvious in the relatively higher-latitude region than in the lower-latitude sites. These inconsistent responses within the AM region during the H stadials might be attributed to both the high- and low-latitude climate processes.

PurposeWe aimed to investigate the restoration of CD8+PD-1+ T cells through adoptive T-cell therapy (ACT) in relation to the prognosis and the therapeutic response to anti-PD-1 in patients with advanced pancreatic cancer (APC).MethodsA total of 177 adult patients who underwent tumor resection as initial treatment for pancreatic ductal adenocarcinoma (PDAC) from February 2013 to July 2019 at Zhongnan Hospital of Wuhan University were enrolled in this study. Another cohort of 32 patients with APC was prospectively enrolled from Capital Medical University Cancer Center between June 1, 2013, and May 30, 2019.ResultsOf the 177 patients who received tumor resection, 67 tumor samples showed overexpression of PD-L1 and 110 patients with low expression of PD-L1. We found that overexpressed PD-L1 was a significant prognostic factor related to overall survival (OS). Furthermore, we tested the percentage of peripheral CD8+PD-1+ T cells in all patients and found that it was significantly correlated with the PD-L1 expression and the prognosis of patients with PDAC. The peripheral blood T lymphocyte subtypes were tracked for 30 months, and CD8+PD-1+ cells were shown to decrease. After that, we performed ACT for patients with APC in another cancer center. We found that the ratios of posttreatment of ACT/pre-ACT CD8+PD-1+ T cells were significantly related to the prognosis of patients with APC. Moreover, patients with combined treatment of ACT with anti-PD-1 had significantly favorable OS.ConclusionsThis study showed that the CD8+PD-1+ T-cell level was related to the expression of PD-L1. Restoring CD8+PD-1+ T cells in patients with APC by treatment of ACT significantly benefits the prognosis and facilitates the response to anti-PD-1.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galβ1-3/β1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC.

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies today. Patients suffer from HCC since its high malignancy and limited treatment means. With the development of genetic research, new therapeutic strategy comes up in the way of gene editing. Clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) was discovered as an immune sequence in bacteria and archaea. After artificial transformation and follow-up research, it is widely used as a gene editing tool. In this review, the development of CRISPR/Cas9 is summarized in retrospect. Through the evaluation of novel research in HCC, it is concluded that CRISPR/Cas9 would promote cancer research and provide a new tool for genetic treatment in prospect.

Objective. To investigate the association of weight loss daily of term infants with hospitalization in the first week after birth. Methods. This prospective cohort study was conducted among 1865 infants from May 2020 to June 2021, born in the Department of Obstetrics, Kunshan’s First People’s Hospital Affiliated to Jiangsu University and Huai’an Maternal and Child Health Care Center. The infants’ weight was collected daily in the hospital, and the weight loss was calculated daily. According to the weight loss daily, the infants were divided into 3 groups. Group A: the weight loss per day was less than 2% of birth weight, and the total weight loss was less than 10%. Group B: the weight loss per day was between 2 and 4% of the birth weight, and the total weight loss was less than 10%. Group C: the weight loss per day was more than 4% of the birth weight, or the total weight was more than 10%. The infants in group C were monitored carefully in the hospital or Outpatient Department (OPD) daily. The primary outcome was the incidence of hospitalization. Results. Of the 1865 term infants enrolled, 1052 were completed on the 7th day (356 in group A, 513 in group B, and 183 in group C). There was no significant difference among the three groups of subjects in terms of infant data, including birth weight, gender, Apgar scores, and gestational age. The number of C-sections and primiparas was substantially higher in groups C and B than in group A. The incidence of hospitalization in group C was significantly higher than that in group A and group B (30.6%, 12.1%, and 12.5%, respectively). The incidence of exclusive breastfeeding in group C was significantly lower than that in group A and group B (28.4%, 41%, and 38.4%, respectively). There was no significant difference between group A and group B in the incidence of hospitalization and exclusive breastfeeding. Most of the hospitalization was because of hyperbilirubinemia, and in group C, there were 2 babies because of dehydration fever and 3 because of hypoglycemia. Conclusions. The neonates whose weight loss daily after birth was more than 4% of the total weight loss of more than 10% had higher hospitalization rates.

Intrahepatic cholangiocarcinoma (ICC) is one of the most commonly diagnosed malignancies worldwide, and the second most common primary liver tumor. The lack of effective diagnostic and treatment methods results in poor patient prognosis and high mortality rate. Atypical protein kinase C-ι (aPKC-ι) is highly expressed in primary and metastatic ICC tissues, and regulates epithelial mesenchymal transition (EMT) through the aPKC-ι/P-Sp1/Snail signaling pathway. Recent studies have correlated aberrant glucose metabolism with EMT. Given the vital role of FBP1 in regulating glucose metabolism in cancer cells, we hypothesized that aPKC-ι downregulates FBP1 in ICC cells through the Snai1 pathway, and enhances glycolysis and metastasis. We confirmed the ability of aPKC-ι promotes glycolysis, invasion and metastasis of cancer cells, and further demonstrated that FBP1 inhibits the malignant properties of ICC cells by antagonizing aPKC-ι. Our findings provide novel insights into the molecular mechanisms of ICC progression and metastasis, as well as a theoretical basis for exploring new treatment strategies.

This study provided a theoretical insight for designing novel plasmonic biosensors using bismuth selenide (Bi2Se3)-Graphene heterostructures. It was a van der Waals (vdWs) stacked configuration composed of gold (Au) film, few quintuple layer (QL) Bi2Se3 and few-layered graphene. In particular, the proposed biosensor was created by Goos-Hänchen (GH) shift rather than phase, resulting in a more sensitive biosensing response. Under the excitation of 632.8 nm, significant sensitivity enhancement performance was obtained via varying the thickness of Bi2Se3-Graphene heterostructures. The best configuration was 32 nm Au film−2-QL Bi2Se3-3-layer graphene, generating the largest GH shift, as high as −1.0202 × 104 µm. Moreover, the highest detection sensitivity was determined to be 8.5017 × 106 µm/RIU, responding to a tiny refractive index (RI) change of 0.0012 RIU (RIU, refractive index unit). More importantly, our proposed biosensor has shown a theoretical feasibility of monitoring virus samples. For example, there was an efficient linear detection range for severe acute respiratory syndrome coronavirus 2 (SARS-CoV−2, 0~13.44 nanomole (nM)) and its Spike (S) glycoprotein (0~59.74 nM), respectively. It is expected that our proposed plasmonic biosensor has a potential application in performing sensitive detection of SARS-CoV−2.

Objective: This study aimed to determine the association between prognosis of COVID-19 patients with and without cancer. Moreover, we compared the prognosis of cancer patients subjected to anti-tumor therapy with those who have not undergone anti-tumor therapy in the past 6 months.Methods and Results: A total of 7,926 adult patients with COVID-19 were retrospectively enrolled in Hubei Province,China between December 31, 2019 and February 20, 2020. Two hundred and seventy seven cancer patients (cancer group, median age 64 [IQR 56–70] years; 50.90% male) and 7,649 non-cancer patients were identified (non-cancer group, median age 55 [IQR 42–64] years; 48.19% male). The mortality rate was lower in the non-cancer group compared to the cancer group (4.50 vs. 9.03%; P < 0.001). The duration between onset and admission shorter in the cancer group (Days, 9 [IQR 5–18]) compared to the non-cancer group (Days, 10; [IQR 6–19]; P = 0.036). ICU occupancy was higher in the cancer group (n[%], 30[10.83%]) than in the non-cancer group (n[%], 314[4.11%]). In reviewing the anti-tumor therapy, data from 277 selected cancer patients were obtained out of which 74 patients had undergone anti-tumor therapy (mean age 65 [IQR 51–67] years; 45.95% male), 203 had not undergone anti-tumor therapy (non-anti-tumor therapy group, mean age 63 [IQR 53–75] years; 49.75% male) in the past 6 months. The mortality rate for the anti-tumor therapy group and the non-anti-tumor therapy group was similar (9.46 vs. 8.87%; P = 0.879).Conclusion: The mortality rate was higher in COVID-19 patients with cancer compared to those without cancer. Moreover, anti-tumor therapy in the past 6 months did not worsen the prognosis of cancer patients with COVID-19.

BackgroundHigh glycolysis efficiency in tumor cells can promote tumor growth. lncRNAs play an important role in the proliferation, metabolism and migration of cancer cells, but their regulation of tumor glycolysis is currently not well researched.MethodsWe analyzed the co-expression of glycolysis-related genes and lncRNAs in The Cancer Genome Atlas (TCGA) database to screen glycolysis-related lncRNAs. Further prognostic analysis and differential expression analysis were performed. We further analyzed the relationship between lncRNAs and tumor immune infiltration. Since WAC antisense RNA 1 (WAC-AS1) had the greatest effect on the prognosis among all screened lncRNAs and had a larger coefficient in the prognostic model, we chose WAC-AS1 for further verification experiments and investigated the function and mechanism of action of WAC-AS1 in hepatocellular carcinoma.ResultsWe screened 502 lncRNAs that have co-expression relationships with glycolytic genes based on co-expression analysis. Among them, 112 lncRNAs were abnormally expressed in liver cancer, and 40 lncRNAs were related to the prognosis of patients. Eight lncRNAs (WAC-AS1, SNHG3, SNHG12, MSC-AS1, MIR210HG, PTOV1-AS1, AC145207.5 and AL031985.3) were used to established a prognostic model. Independent prognostic analysis (P

Abstract Since the coronavirus disease 2019 (COVID-19) identified in Wuhan, Hubei, China in December 2019, it has been characterized as a pandemic by World Health Organization (WHO). It was reported that asymptomatic persons are potential sources of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We present an outbreak among health-care workers incited by a doctor who cared a patient with COVID-19 in a Hospital in Wuhan, Hubei, China, which indicates existence of super-spreader even during incubation period.

Background: Accumulating evidence has revealed that coronavirus disease 2019 (COVID-19) patients may be complicated with myocardial injury during hospitalization. However, data regarding persistent cardiac involvement in patients who recovered from COVID-19 are limited. Our goal is to further explore the sustained impact of COVID-19 during follow-up, focusing on the cardiac involvement in the recovered patients.Methods: In this prospective observational follow-up study, we enrolled a total of 40 COVID-19 patients (20 with and 20 without cardiac injury during hospitalization) who were discharged from Zhongnan Hospital of Wuhan University for more than 6 months, and 27 patients (13 with and 14 without cardiac injury during hospitalization) were finally included in the analysis. Clinical information including self-reported symptoms, medications, laboratory findings, Short Form 36-item scores, 6-min walk test, clinical events, electrocardiogram assessment, echocardiography measurement, and cardiac magnetic resonance imaging was collected and analyzed.Results: Among 27 patients finally included, none of patients reported any obvious cardiopulmonary symptoms at the 6-month follow-up. There were no statistically significant differences in terms of the quality of life and exercise capacity between the patients with and without cardiac injury. No significant abnormalities were detected in electrocardiogram manifestations in both groups, except for nonspecific ST-T changes, premature beats, sinus tachycardia/bradycardia, PR interval prolongation, and bundle-branch block. All patients showed normal cardiac structure and function, without any statistical differences between patients with and without cardiac injury by echocardiography. Compared with patients without cardiac injury, patients with cardiac injury exhibited a significantly higher positive proportion in late gadolinium enhancement sequences [7/13 (53.8%) vs. 1/14 (7.1%), p = 0.013], accompanied by the elevation of circulating ST2 level [median (interquartile range) = 16.6 (12.1, 22.5) vs. 12.5 (9.5, 16.7); p = 0.044]. Patients with cardiac injury presented higher levels of aspartate aminotransferase, creatinine, high-sensitivity troponin I, lactate dehydrogenase, and N-terminal pro–B-type natriuretic peptide than those without cardiac injury, although these indexes were within the normal range for all recovered patients at the 6-month follow-up. Among patients with cardiac injury, patients with positive late gadolinium enhancement presented higher cardiac biomarker (high-sensitivity troponin I) and inflammatory factor (high-sensitivity C-reactive protein) on admission than the late gadolinium enhancement–negative subgroup.Conclusions: Our preliminary 6-month follow-up study with a limited number of patients revealed persistent cardiac involvement in 29.6% (8/27) of recovered patients from COVID-19 after discharge. Patients with cardiac injury during hospitalization were more prone to develop cardiac fibrosis during their recovery. Among patients with cardiac injury, those with relatively higher cardiac biomarkers and inflammatory factors on admission appeared more likely to have cardiac involvement in the convalescence phase.

Photothermal therapy (PTT) has become an important therapeutic strategy in the treatment of cancer. However, exploring novel photothermal nanomaterials with satisfactory biocompatibility, high photothermal conversion efficiency, and efficient theranostic outcomes, remains a major challenge for satisfying clinical application. In this study, poly-ethylene glycol modified rhenium disulfide (PEG-ReS2) nanosheets are constructed by a simple-liquid phase exfoliation method. The PEG-ReS2 nanosheets were demonstrated to have good solubility, good biocompatibility, low toxicity, and strong capability of accumulating near-infrared (NIR) photons. Under 808 nm laser irradiation, the PEG-ReS2 nanosheets were found to have an excellent photothermal conversion efficiency (PTCE) of 42%. Moreover, the PEG-ReS2 nanosheets were demonstrated to be ideal photothermal transduction agents (PTAs), which promoted rapid cancer cell death in vitro and efficiently ablated tumors in vivo. Interestingly, the potential utility of up-regulation or down-regulation of miRNAs was proposed to evaluate the therapeutic outcomes of PEG-ReS2 nanosheets. The expression levels of a set of miRNAs in tumor-bearing mice were restored to normal levels after PTT therapy with PEG-ReS2 nanosheets. Both down-regulation miRNAs (miR-125a-5p, miR-34a-5p, miR-132-3p, and miR-148b-3p) and up-regulation miRNAs (miR-133a-3p, miR-200c-5p, miR-9-3p, and miR-150-3p) were suggested to be important clinical biomarkers for evaluating therapeutic outcomes of breast cancer-related PTT. This work highlights the great significance of PEG-ReS2 nanosheets as therapeutic nanoagents for cancer therapy.

Functionalized black phosphorus (BP) nanosheets have been considered as promising nanoagents in cancer therapy due to their excellent photothermal conversion efficiency. However, it is still difficult to visually monitor the dynamic localization of BP nanoagents in cancer cells. In this paper, we systematically studied the second-harmonic generation (SHG) signals originating from exfoliated BP nanosheets. Interestingly, under the excitation of a high frequency pulsed laser at 950 nm, the SHG signals of BP nanosheets in vitro are almost undetectable because of their poor stability. However, the intracellular SHG signals from BP nanosheets could be measured by in vivo optical imaging due to the efficient enrichment of living HeLa cells. Moreover, the SHG signal intensity from BP nanosheets increases with the prolonged incubation time. It can be expected that the BP nanosheets could be a promising intracellular SHG nanoprobe employed for visually in vivo biomedical imaging in practical cancer photothermal therapy (PIT).

Objectives To assess the knowledge, attitude and practice (KAP) concerning healthcare-associated infections (HAIs) among healthcare givers and to identify the factors influencing KAP.Design This was a hospital-based, cross-sectional study.Setting Two public hospitals in Wuhan, central China.Participants Participants were recruited among healthcare workers (HCWs) of one general hospital and one children’s hospital in Wuhan city between 1 June and 30 September 2019.Primary and secondary outcome measures The outcomes were KAPs concerning HAIs.Results Data from 455 HCWs were included in the final data analysis. The mean scores of KAP and total KAP were 15.67±3.32, 25.00±2.75, 43.44±5.15 and 84.76±6.72, respectively. The following factors were significantly associated with the total KAP score concerning HAIs, explaining 61% of the variance (p

Summary: The outbreak of SARS-CoV-2 in China, attracted a large number of medical staff to help in the city's hospitals and this put them at a high risk of infection. We describe twenty medical staff who were diagnosed with COVID-19 within one week in the department of surgery in a Wuhan hospital. Epidemiological investigation of these cases identified misdiagnosed patients (source of infection), an inappropriate clinical meeting and working without wearing face masks to be the causes of the outbreaks. This report emphasizes the importance of wearing a facemask and applying other standard infection control precautions to protect medical personnel from infection with the virus.

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide with limited therapeutic options. Accumulating evidences suggest that immunotherapy could be a promising option for treating HCC. T cell-associated immunotherapy lights up the hope for the improvement of complementary approach to conventional HCC treatments, which needs further research to consummate the clinical consequences. The present work reviewed several T cells associated cellular immunotherapies for HCC, including immune checkpoint blockade, gene–engineered T cells, bispecific T cell engagers, and so on. We also analyzed how these immunotherapies can mediate tumor cell eradication and evaluated their superiority or insufficiency.

Recently, photothermal therapy (PTT) has been proved to have great potential in tumor therapy. In the last several years, MoS2, as one novel member of nanomaterials, has been applied into PTT due to its excellent photothermal conversion efficacy. In this work, we applied fluorescence lifetime imaging microscopy (FLIM) techniques into monitoring the PPT-triggered cell death under MoS2 nanosheet treatment. Two types of MoS2 nanosheets (single layer nanosheets and few layer nanosheets) were obtained, both of which exhibited presentable photothermal conversion efficacy, leading to high cell death rates of 4T1 cells (mouse breast cancer cells) under PTT. Next, live cell images of 4T1 cells were obtained via directly labeling the mitochondria with Rodamine123, which were then continuously observed with FLIM technique. FLIM data showed that the fluorescence lifetimes of mitochondria targeting dye in cells treated with each type of MoS2 nanosheets significantly increased during PTT treatment. By contrast, the fluorescence lifetime of the same dye in control cells (without nanomaterials) remained constant after laser irradiation. These findings suggest that FLIM can be of great value in monitoring cell death process during PTT of cancer cells, which could provide dynamic data of the cellular microenvironment at single cell level in multiple biomedical applications.

An amendment to this paper has been published and can be accessed via the original article.

This study theoretically proposed a novel surface plasmon resonance biosensor by incorporating emerging two dimensional material blue phosphorus and graphene layers with plasmonic gold film. The excellent performances employed for biosensing can be realized by accurately tuning the thickness of gold film and the number of blue phosphorus interlayer. Our proposed plasmonic biosensor architecture designed by phase modulation is much superior to angular modulation, providing 4 orders of magnitude sensitivity enhancement. In addition, the optimized stacked configuration is 42 nm Au film/2-layer blue phosphorus /4-layer graphene, which can produce the sharpest differential phase of 176.7661 degrees and darkest minimum reflectivity as low as 5.3787 × 10−6. For a tiny variation in local refractive index of 0.0012 RIU (RIU, refractive index unit) due to the binding interactions of aromatic biomolecules, our proposed biosensor can provide an ultrahigh detection sensitivity up to 1.4731 × 105 °/RIU, highly promising for performing ultrasensitive biosensing application.

Timely and accurately identification of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can greatly contribute to monitoring and controlling the global pandemic. This study gained theoretical insight into a novel phase-modulation plasmonic biosensor working in the near-infrared (NIR) regime, which can be employed for sensitive detection of SARS-CoV-2 and its spike (S) glycoprotein. The proposed plasmonic biosensor was created by integrating two-dimensional (2D) Van der Waals heterostructures, including tellurene and carboxyl-functionalized molybdenum disulfide (MoS _2 ) layers, with transparent indium tin oxide (ITO) film. Excellent biosensing performance can be achieved under the excitation of 1550 nm by optimizing the thickness of ITO film and tellurene-MoS _2 heterostructures. For a sensing interface refractive index change as low as 0.0012 RIU (RIU, refractive index unit), the optimized plasmonic configuration of 121 nm ITO film/three-layer tellurene/ten-layer MoS _2 -COOH can produce the highest detection sensitivity of 8.4069 × 10 ^4 degree/RIU. More importantly, MoS _2 –COOH layer can capture angiotensin-converting enzyme II, which is an ideal adsorption site for specifically binding SARS-CoV-2 S glycoprotein. Then, an excellent linear detection range for S glycoprotein and SARS-CoV-2 specimens is ∼0–301.67 nM and ∼0–67.8762 nM, respectively. This study thus offers an alternative strategy for rapidly performing novel coronavirus diagnosis in clinical applications.

Hepatocellular carcinoma is third leading cause of cancer-related death globally. Long non-coding RNA plasmacytoma variant translocation 1 has been reported to be dysregulated and plays a crucial role in various cancers. In this study, we investigated the interactions between plasmacytoma variant translocation 1 and miR-186-5p in the progression of hepatocellular carcinoma and explored the functional significance of plasmacytoma variant translocation 1. It was determined that plasmacytoma variant translocation 1 was significantly higher, while miR-186-5p was statistically lower in the hepatocellular carcinoma tissues than that in the adjacent normal tissues. Using gain-of-function and loss-of-function methods, our results revealed that plasmacytoma variant translocation 1 affected hepatocellular carcinoma cells proliferation, invasion, and migration. It was found that there was direct interaction between miR-186-5p and the binding site of plasmacytoma variant translocation 1 by performing dual-luciferase assay and RNA immunoprecipitation assay. Furthermore, it was identified that plasmacytoma variant translocation 1 regulated the expression of the miR-186-5p target gene, yes-associated protein 1. Taken together, plasmacytoma variant translocation 1 served as an endogenous sponge for miR-186-5p to reduce its inhibiting effect on yes-associated protein 1 and thus promoted the tumorigenesis of hepatocellular carcinoma.

Goethite- and hematite-supported highly dispersed gold catalysts for carbon monoxide oxidation were synthesized by gold precursor adsorption onto the support materials in self-generated alkaline solutions. The support materials were prepared by reacting iron nitrate with excess sodium hydroxide. The residual minor alkali incorporated into the support could provide suitable alkaline conditions at approximately pH 8 for the hydrolysis of tetrachloroaurate anions and the subsequent adsorption process. Gold species underwent autoreduction to achieve activation during the synthesis. An increase in pH or temperature to 80 °C decreased the gold loading of the catalysts. The optimal catalysts could achieve complete oxidation of carbon monoxide at −20 °C.