[Baicalin induces ferroptosis in HepG2 cells by inhibiting ROS-mediated PI3K/Akt/FoxO3a signaling pathway].

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.

Robotic versus laparoscopic liver resection for liver malignancy: a systematic review and meta-analysis of propensity score-matched studies.

OBJECTIVE: How different surgical procedures, including the robotic-assisted liver resection (RLR) and laparoscopic liver resection (LLR), can affect the prognosis of patients with liver malignancies is unclear. Thus, in this study, we compared the effects of RLR and LLR on the surgical and oncological outcomes in patients with liver malignancies through propensity score-matched cohort studies. METHODS: The PubMed, Embase, and Cochrane databases were searched using Medical Subject Headings terms and keywords from inception until May 31, 2023. The quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale. The mean difference with 95% confidence interval (95% CI) was used for analysis of continuous variables; the risk ratio with 95% CI was used for dichotomous variables; and the hazard ratio with 95% CI was used for survival-related variables. Meta-analysis was performed using a random-effects model. RESULTS: Five high-quality cohort studies with 986 patients were included (370 and 616 cases for RLR and LLR, respectively). In terms of surgical outcomes, there were no significant differences in the operation time, conversion rate to open surgery, overall complication rate, major complication rate, and length of hospital stay between the RLR and LLR groups. In terms of oncological outcomes, there were no significant differences in the 5-year overall survival and disease-free survival between the two groups. CONCLUSION: Surgical and oncological outcomes are comparable between RLR and LLR on patients with liver malignancies. Therefore, the benefits of applying RLR in patients with liver malignancies need to be further explored.

Expression profiles of lncRNAs, miRNAs, and mRNAs during the proliferative phase of liver regeneration in mice with liver fibrosis.

The role of lncRNAs in the regeneration of fibrotic liver is unclear. To address this issue, we established a 70% hepatectomy model of liver fibrosis in mice, used high-throughput sequencing technology to obtain the expression profiles of lncRNAs, miRNAs, and mRNAs, and constructed a lncRNA-miRNA-mRNA regulatory network. A total of 1329 lncRNAs, 167 miRNAs, and 6458 mRNAs were differentially expressed. On this basis, a lncRNA-miRNA-mRNA ceRNA regulatory network consisting of 38 DE lncRNAs, 24 DE miRNAs, and 299 DE mRNAs was constructed, and a transcription factor (TF) - mRNA regulatory network composed of 20 TFs and 98 DE mRNAs was built. Through the protein network analysis, a core protein interaction network composed of 20 hub genes was derived. Furthermore, Xist/miR-144-3p/Cdc14b and Snhg3/miR-365-3p/Map3k14 axes in the ceRNA regulatory network were verified by Real-Time quantitative PCR. Therefore, we concluded that these new insights may further our understanding of liver regeneration.

Strategies for enhancing low-frequency performances of triboelectric, electrochemical, piezoelectric, and dielectric elastomer energy harvesting: recent progress and challenges.

Mechanical energy harvesting transforms various forms of mechanical energy, including ocean waves, wind, and human motions, into electrical energy, providing a viable solution to address the depletion of fossil fuels and environmental problems. However, one major obstacle for the direct conversion of mechanical energy into electricity is the low frequency of the majority of mechanical energy sources (≤5 Hz), resulting in low energy conversion efficiency, output power and output current. Over recent years, a numerous innovative technologies have been reported to enable improved energy harvesting utilizing various mechanisms. This review aims to present an in-depth analysis of the research progress in low-frequency energy harvesting technologies that rely on triboelectric, electrochemical, piezoelectric, and dielectric elastomer effects. The discussion commences with an overview of the difficulties associated with low-frequency energy harvesting. The critical aspects that impact the low-frequency performance of mechanical energy harvesters, including working mechanisms, environmental factors, and device compositions, are elucidated, while the advantages and disadvantages of different mechanisms in low-frequency operation are compared and summarized. Moreover, this review expounds on the strategies that can improve the low-frequency energy harvesting performance through the modulations of material compositions, structures, and devices. It also showcases the applications of mechanical energy harvesters in energy harvesting via waves, wind, and human motions. Finally, the recommended choices of mechanical energy harvesters with different mechanisms for various applications are offered, which can assist in the design and fabrication process.

Integrated analysis of lncRNA/circRNA-miRNA-mRNA in the proliferative phase of liver regeneration in mice with liver fibrosis.

BACKGROUND: Non-coding RNAs play important roles in liver regeneration; however, their functions and mechanisms of action in the regeneration of fibrotic liver have not been elucidated. We aimed to clarify the expression patterns and regulatory functions of lncRNAs, circRNAs, miRNAs, and mRNAs in the proliferative phase of fibrotic liver regeneration. METHODS: Based on a mouse model of liver fibrosis with 70% hepatectomy, whole-transcriptome profiling was performed using high-throughput sequencing on samples collected at 0, 12, 24, 48, and 72 h after hepatectomy. Hub genes were selected by weighted gene co-expression network analysis and subjected to enrichment analysis. Integrated analysis was performed to reveal the interactions of differentially expressed (DE) lncRNAs, circRNAs, miRNAs, and mRNAs, and to construct lncRNA-mRNA cis- and trans-regulatory networks and lncRNA/circRNA-miRNA-mRNA ceRNA regulatory networks. Real-Time quantitative PCR was used to validate part of the ceRNA network. RESULTS: A total of 1,329 lncRNAs, 48 circRNAs, 167 miRNAs, and 6,458 mRNAs were differentially expressed, including 812 hub genes. Based on these DE RNAs, we examined several mechanisms of ncRNA regulatory networks, including lncRNA cis and trans interactions, circRNA parental genes, and ceRNA pathways. We constructed a cis-regulatory core network consisting of 64 lncRNA-mRNA pairs (53 DE lncRNAs and 58 hub genes), a trans-regulatory core network consisting of 103 lncRNA-mRNA pairs (18 DE lncRNAs and 85 hub genes), a lncRNA-miRNA-mRNA ceRNA core regulatory network (20 DE lncRNAs, 12 DE miRNAs, and 33 mRNAs), and a circRNA-miRNA-mRNA ceRNA core regulatory network (5 DE circRNAs, 5 DE miRNAs, and 39 mRNAs). CONCLUSIONS: These results reveal the expression patterns of lncRNAs, circRNAs, miRNAs, and mRNAs in the proliferative phase of fibrotic liver regeneration, as well as core regulatory networks of mRNAs and non-coding RNAs underlying liver regeneration. The findings provide insights into molecular mechanisms that may be useful in developing new therapeutic approaches to ameliorate diseases that are characterized by liver fibrosis, which would be beneficial for the prevention of liver failure and treatment of liver cancer.

Laparoscopic versus open repeat hepatectomy for recurrent hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched cohort studies.

OBJECTIVE: The effectiveness of laparoscopic repeat hepatectomy (LRH) versus open repeat hepatectomy (ORH) on recurrent hepatocellular carcinoma (RHCC) is unclear. We compared the surgical and oncological outcomes of LRH and ORH in patients with RHCC with a meta-analysis of studies based on propensity score-matched cohorts. METHODS: A literature search was conducted on PubMed, Embase, and Cochrane Library with Medical Subject Headings terms and keywords until 30 September 2022. The quality of eligible studies was evaluated with the Newcastle-Ottawa Scale. Mean difference (MD) with a 95% CI was used for the analysis of continuous variables; odds ratio (OR) with 95% CI was used for binary variables; and hazard ratio with 95% CI was used for survival analysis. A random-effects model was used for meta-analysis. RESULTS: Five high-quality retrospective studies with 818 patients were included; 409 patients (50%) were treated with LRH and 409 (50%) with ORH. In most surgical outcomes, LRH was superior to ORH: less estimated blood loss, shorter operation time, lower major complication rate, and shorter length of hospital stay (MD=-225.9, 95% CI=[-360.8 to -91.06], P =0.001; MD=66.2, 95% CI=[5.28-127.1], P =0.03; OR=0.18, 95% CI=[0.05-0.57], P =0.004; MD=-6.22, 95% CI=[-9.78 to -2.67], P =0.0006). There were no significant differences in the remaining surgical outcomes: blood transfusion rate and overall complication rate. In oncological outcomes, LRH and ORH were not significantly different in 1-year, 3-year, and 5-year overall survival and disease-free survival. CONCLUSIONS: For patients with RHCC, most surgical outcomes with LRH were superior to those of ORH, but oncological outcomes with the two operations were similar. LRH may be a preferable option for the treatment of RHCC.

Laparoscopic versus open hepatectomy for intrahepatic cholangiocarcinoma: Systematic review and meta-analysis of propensity score-matched studies.

OBJECTIVE: To compare the effects of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) on the short-term and long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) through a meta-analysis of studies using propensity score-matched cohorts. METHODS: The literature search was conducted in PubMed, Embase, and Cochrane Library databases until August 31, 2022. Meta-analysis of surgical (major morbidity, the length of hospital stay, 90-day postoperative mortality), oncological (R0 resection rate, lymph node dissection rate) and survival outcomes (1-, 3-, and 5-year overall survival and disease-free survival) was performed using a random effects model. Data were summarized as relative risks (RR), mean difference (MD) and hazard ratio (HR) with 95% confidence intervals (95% CI). RESULTS: Six case-matched studies with 1054 patients were included (LH 518; OH 536). Major morbidity was significantly lower (RR = 0.57, 95% CI = 0.37-0.88, P = 0.01) and the length of hospital stay was significantly shorter (MD = -2.44, 95% CI = -4.19 to -0.69, P = 0.006) in the LH group than in the OH group, but there was no significant difference in 90-day postoperative mortality between the 2 groups. There were no significant differences in R0 resection rate, lymph node dissection rate, 1-, 3-, and 5-year overall survival or disease-free survival between the LH and OH groups. CONCLUSIONS: LH has better surgical outcomes and comparable oncological outcomes and survival outcomes than does OH on ICC. Therefore, laparoscopy is at least not inferior to open surgery for intrahepatic cholangiocarcinoma.

Comprehensive Study of In vivo and In vitro Metabolites of Cycloastragenol Based on UHPLC-Q-Exactive Orbitrap Mass Spectrometer.

BACKGROUND: Cycloastragenol (CAG) is a sapogenin derived from the main bioactive constituents of Astragali Radix (AR). However, the current research on CAG metabolism in vivo and in vitro is still inadequate, and the metabolite cluster is incomplete due to incomplete analysis strategy. OBJECTIVE: The objective of this study was to screen and identify the metabolic behavior of CAG in vivo and in vitro. METHODS: A simple and rapid analysis strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry combined with data-mining processing technology was developed and used to screen and identify CAG metabolites in rat body fluids and tissues after oral administration. RESULTS: As a result, a total of 82 metabolites were fully or partially characterized based on their accurate mass, characteristic fragment ions, retention times, corresponding Clog P values, and so on. Among the metabolites, 61 were not been reported in previous reports. These metabolites (6 metabolites in vitro and 91 in vivo) were generated through reactions of hydroxylation, glucuronidation, sulfation, hydrogenation, hydroxylation, demethylation, deisopropylation, dehydroxylation, ring cleavage, and carboxyl substitution and their composite reactions, and the hydroxylation might be the main metabolic reaction of CAG. In addition, the characteristic fragmentation pathways of CAG were summarized for the subsequent metabolite identification. CONCLUSION: The current study not only clarifies the metabolite cluster-based and metabolic regularity of CAG in vivo and in vitro, but also provides ideas for metabolism of other saponin compounds.

Characterization of active peptides derived from three leeches and comparison of their anti-thrombotic mechanisms using the tail vein thrombosis model in mice and metabonomics.

Background and aims: The increasing incidence of cardiovascular diseases has created an urgent need for safe and effective anti-thrombotic agents. Leech, as a traditional Chinese medicine, has the effect of promoting blood circulation and removing blood stasis, but its real material basis and mechanism of action for the treatment of diseases such as blood stasis and thrombosis have not been reported. Methods: In this study, Whitmania Pigra Whitman (WPW), Hirudo nipponica Whitman (HNW) and Whitmania acranutata Whitman (WAW) were hydrolyzed by biomimetic enzymatic hydrolysis to obtain the active peptides of WPW (APP), the active peptides of HNW (APH) and the active peptides of WAW (APA), respectively. Then their structures were characterized by sykam amino acid analyzer, fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectrometer and LC-MS. Next, the anti-thrombotic activities of APP, APH and APA were determined by carrageenan-induced tail vein thrombosis model in mice, and the anti-thrombotic mechanisms of high-dose APP group (HAPP), high-dose APH group (HAPH) and high-dose APA group (HAPA) were explored based on UHPLC-Q-Exactive Orbitrap mass spectrometry. Results: The results showed that the amino acid composition of APP, APH and APA was consistent, and the proportion of each amino acid was few different. The results of FT-IR and CD showed that there were no significant differences in the proportion of secondary structures (such as ß-sheet and random coil) and infrared absorption peaks between APP, APH and APA. Mass spectrometry data showed that there were 43 common peptides in APP, APH and APA, indicating that the three have common material basis. APP, APH and APA could significantly inhibit platelet aggregation, reduce black-tail length, whole blood viscosity (WBV), plasma viscosity (PV), and Fibrinogen (FIB), and prolong coagulation time, including activated partial thrombin time (APTT), prothrombin time (PT) and thrombin time (TT). In addition, 24 metabolites were identified as potential biomarkers associated with thrombosis development. Among these, 19, 23, and 20 metabolites were significantly normalized after administration of HAPP, HAPH, and HAPA in the mice, respectively. Furthermore, the intervention mechanism of HAPP, HAPH and HAPA on tail vein thrombosis mainly involved in linoleic acid metabolism, primary bile acid biosynthesis and ether lipid metabolism. Conclusion: Our findings suggest that APP, APH and APA can exert their anti-blood stasis and anti-thrombotic activities by interfering with disordered metabolic pathways in vivo, and there is no significant difference in their efficacies.

Comprehensive Analysis of Pterostilbene Metabolites In Vivo and In Vitro Using a UHPLC-Q-Exactive Plus Mass Spectrometer with Multiple Data-Mining Methods.

Pterostilbene, a stilbene phytoalexin, is mainly obtained from blueberries and grape vines; however, its metabolic mechanisms were unclear in vivo. In the present study, three different methods were used to prepare biological samples, and then, an efficient strategy based on ultrahigh-performance liquid chromatography coupled with mass spectrometry was developed to screen and identify pterostilbene metabolites in rat urine, plasma, liver, and feces. In order to elucidate pterostilbene or its metabolites involved in vitro, this study was assessed by the liver microsome system. As a result, a total of 88 pterostilbene metabolites were characterized. Among them, 77 metabolites in vivo and 14 metabolites in vitro were found; 50 and 38 metabolites were observed in rat plasma and urine, while only 4 and 12 metabolites were detected in rat feces and liver, inferring that plasma and urine possessed more diverse types of pterostilbene metabolites; 41 metabolic products were obtained by solid-phase extraction, and 9 and 10 metabolites were screened by methanol precipitation and acetonitrile precipitation, respectively, indicating that solid-phase extraction could be adopted as the most acceptable method for pterostilbene metabolism. The results also demonstrated that pterostilbene mainly underwent glucosylation, dehydrogenation, hydrogenation, demethoxylation, sulfation, NAC binding, methylene ketogenic, acetylation, and methylation. In summary, this research provides an idea for the further study of drug metabolism.

Active Peptide AR-9 From Eupolyphaga sinensis Reduces Blood Lipid and Hepatic Lipid Accumulation by Restoring Gut Flora and Its Metabolites in a High Fat Diet-Induced Hyperlipidemia Rat.

The dysbiosis of gut flora and its metabolites plays important roles in the progression of hyperlipidemia (HL), and some bioactive peptides are available for HL treatment. In this study, we aimed to isolate an active peptide (AR-9) from active peptides of E. sinensis (APE) and determine whether AR-9 could improve many symptoms of a HL rat induced by a high-fat diet (HFD) by modulating gut flora and its metabolites. Above all, AR-9 was derived from APE using ion-exchange chromatography, and its structure was deconstructed by Fourier transform infrared spectrometer (FT-IR), circular dichroism (CD) spectroscopy, and UHPLC-Q-Exactive-Orbitrap MS. Then, an HFD-induced HL model in SD rats was established and used to clarify the regulatory effects of AR-9 (dose of 3 mg/kg) on HL. Normal diet-fed rats were taken as the control. The plasma samples and liver were harvested for biochemical and histopathological examinations. 16S rRNA gene sequencing and untargeted metabolomics were sequenced to assess changes in gut flora and its metabolites from rat fecal samples. Finally, Spearman's correlation analysis was used to assess the relationship between lipid-related factors, gut flora, and its metabolites so as to evaluate the mechanism of AR-9 against HL. The results of the separation experiments showed that the amino acid sequence of AR-9 was AVFPSIVGR, which was a fragment of the actin protein from Blattaria insects. Moreover, HFD rats developed exaltation of index factors, liver lipid accumulation, and simple fibrosis for 8 weeks, and the profiles of gut flora and its metabolites were significantly altered. After treatment, AR-9 decreased the levels of lipid factors in plasma and the extent of liver damage. 16S rRNA gene sequencing results indicated that AR-9 significantly increased the relative abundance of beneficial bacteria Bacteroidetes and reduced the relative abundance of the obesity-associated bacteria Firmicutes. Furthermore, AR-9 changed gut microbiota composition and increased the relative abundance of beneficial bacteria: Lactobacillus, Clostridium, Dehalobacterium, and Candidatus arthromitus. Fecal metabolomics showed that the pathway regulated by AR-9 was "arginine biosynthesis", in which the contents were citrulline and ornithine. Spearman's correlation analysis revealed that two metabolites (ornithine and citrulline) showed significantly negative correlations with obesity-related parameters and positive correlations with the gut genera (Clostridium) enriched by AR-9. Overall, our results suggested interactions between gut microbial shifts and fecal amino acid/lipid metabolism and revealed the mechanisms underlying the anti-HL effect of AR-9. The abovementioned results not only reveal the initial anti-HL mechanism of AR-9 but also provide a theoretical basis for the continued development of AR-9.

Oncological outcomes of anatomic versus non-anatomic resections for small hepatocellular carcinoma: systematic review and meta-analysis of propensity-score matched studies.

BACKGROUND: Primary liver cancer is the second-most commonly occurring cancer and has resulted in numerous deaths worldwide. Hepatic resection is of two main types, i.e., anatomic resection (AR) and non-anatomic resection (NAR). The oncological outcomes of hepatocellular carcinoma (HCC) patients after AR and NAR are still considered controversial. Therefore, we aimed to compare the impact of AR and NAR on the oncological outcomes of HCC patients with tumor diameters ≤ 5 cm using the propensity score matching method and research-based evidence. METHOD: A systematic literature search was conducted. The main outcomes were disease-free survival (DFS), overall survival (OS), intrahepatic recurrence rate, and extrahepatic metastasis rate. Relative risk (RR) was calculated from forest plots and outcomes using random-effects model (REM). RESULT: AR significantly improved DFS at 1, 3. and 5 years after surgery, compared to NAR (RR = 1.09, 95% CI = 1.04-1.15, P = 0.0003; RR = 1.16, 95% CI = 1.07-1.27, P = 0.0005; RR = 1.29, 95% CI = 1.07-1.55, P = 0.008). However, both of the difference in DFS at 7 years and OS at 1 and 3 years after AR versus that after NAR were not statistically significant. Nevertheless, the long-term OS associated with AR (5, 7, and 10 years) was superior to that associated with NAR (RR = 1.12, 95% CI = 1.03-1.21, P = 0.01; RR = 1.19, 95% CI = 1.04-1.36, P = 0.01; RR = 1.18, 95% CI = 1.05-1.34, P = 0.008). The difference in the intrahepatic recurrence rate after AR versus that after NAR was not statistically significant, but the extrahepatic metastasis rate after AR was significantly lower than that observed after NAR (RR = 0.61, 95% CI = 0.40-0.94, P = 0.03). CONCLUSION: Therefore, AR should be the preferred surgical approach for HCC patients with tumor diameters ≤ 5 cm. TRIAL REGISTRATION: PROSPERO registration number CRD42022330596.

RNA-seq transcriptome profiling of liver regeneration in mice identifies the miR-34b-5p/phosphoinositide-dependent protein kinase 1 axis as a potential target for hepatocyte proliferation.

Characterized by compensatory hyperplasia dependent on hepatocyte proliferation, the liver will initiate regeneration after partial hepatectomy (PH) and acute or chronic injuries. A variety of genes and noncoding RNAs play pivotal roles in these cell proliferation and growth processes. However, it is still unclear how competition endogenous RNAs (ceRNAs) modulate cellular activities during each phase of liver regeneration, and the specific mechanisms of posttranscriptional gene expression regulation in hepatocyte proliferation remain to be elucidated. To investigate the mechanism of liver regeneration through RNA-seq profiling and to determine the role of miR-34b-5p/PDK1 on hepatocyte proliferation, we established a 2/3 PH mouse model for whole transcriptome profiling based on high-throughput sequencing techniques. We subsequently constructed a lncRNA-miRNA-mRNA ceRNA regulatory network through integrative analyses of RNA interactions. Finally, plasmid transfection in NCTC 1469 cells, dual luciferase reporter gene assay, quantitative real-time PCR, western blotting, Cell Counting Kit-8, and EdU-DNA synthesis cell proliferation assay were used to demonstrate the role of the miR-34b-5p/PDK1 axis in hepatocyte proliferation in vitro. A total of 1443 mRNAs (962 up, 481 down), 48 miRNAs (35 up, 13 down), and 1955 lncRNAs (986 up, 969 down) were identified as significantly differentially expressed. We then successfully constructed a ceRNA regulatory network consisting of 7 lncRNAs, 15 miRNAs, and 347 mRNAs based on the predicted inverse interactions among ceRNAs. Additionally, miR-34b-5p/PDK1 was predicted to be closely related to hepatocyte proliferation. We further demonstrated that miR-34b-5p could bind specifically to the 3'-untranslated region (3'-UTR) of PDK1 using the dual luciferase reporter assay. Ectopic overexpression of miR-34b-5p significantly reduced the mRNA and protein expression of PDK1, while it markedly inhibited the proliferation of mouse NCTC 1469 cells in vitro. In contrast, knocking down miR-34b-5p exhibited the inverse effects on PDK1 expression and hepatocyte proliferation. Through analyzing the ceRNA network during mouse liver regeneration, this study reveals that miR-34b-5p can inhibit hepatocyte proliferation through negatively regulating PDK1 and may be a potential pharmacological intervention target.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: Systematic review and meta-analysis of propensity-score matched studies.

BACKGROUND: The outcomes of elderly (≥65 years) patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) vs open liver resection (OLR) are debated. We compared the surgical and oncological outcomes after LLR and OLR in elderly HCC patients based on matched cohort studies that performed propensity score matching (PSM). METHODS: A computer search of the PubMed, Embase, and Cochrane databases until January 31, 2022, was conducted using a combination of Medical Subject Heading (MeSH) terms and other terms. The Newcastle-Ottawa literature evaluation scale was used for quality assessment of the included studies that met the inclusion criteria and none of the exclusion criteria. The postoperative LLR and OLR markers after PSM were summarized. RESULTS: Seven matched cohort studies were included. There were 1346 patients after PSM, of which 673 (50%) underwent LLR and 673 (50%) underwent OLR. All studies were of high quality. For surgical outcomes, the length of surgery was longer in the LLR group than in the OLR group (RR = 29.47, 95% CI = 26.55-32.39, P < 0.00001), but the length of hospitalization was significantly shorter (RR = -1.05,95% CI = -1.24 to -0.86, P < 0.00001), and the incidence of total postoperative complications and severe complications were significantly fewer (RR = 0.69,95% CI = 0.60-0.79, P < 0.00001; RR = 0.49,95% CI = 0.35-0.71, P = 0.0001, respectively). There were no significant differences in overall survival or disease-free survival between the two groups (HR = 0.87, 95% CI = 0.63-1.21, P = 0.41; HR = 0.87, 95% CI = 0.69-1.08, P = 0.20, respectively). CONCLUSIONS: In elderly patients with HCC, LLR was associated with better surgical outcomes than OLR, but there was no significant difference in oncological outcomes. LLR should be the preferred surgical method for elderly patients with HCC.

Structural Design and Fabrication of Multifunctional Nanocarbon Materials for Extreme Environmental Applications.

Extreme environments represent numerous harsh environmental conditions, such as temperature, pressure, corrosion, and radiation. The tolerance of applications in extreme environments exemplifies significant challenges to both materials and their structures. Given the superior mechanical strength, electrical conductivity, thermal stability, and chemical stability of nanocarbon materials, such as carbon nanotubes (CNTs) and graphene, they are widely investigated as base materials for extreme environmental applications and have shown numerous breakthroughs in the fields of wide-temperature structural-material construction, low-temperature energy storage, underwater sensing, and electronics operated at high temperatures. Here, the critical aspects of structural design and fabrication of nanocarbon materials for extreme environments are reviewed, including a description of the underlying mechanism supporting the performance of nanocarbon materials against extreme environments, the principles of structural design of nanocarbon materials for the optimization of extreme environmental performances, and the fabrication processes developed for the realization of specific extreme environmental applications. Finally, perspectives on how CNTs and graphene can further contribute to the development of extreme environmental applications are presented.

[UHPLC-Q-Exactive Orbitrap MS/MS-based rapid identification of chemical components in substance benchmark of Kaixin San].

Ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS/MS) was used for rapid identification of the chemical components in Kaixin San substance benchmark. The gradient elution was performed through a Waters ACQUITY~(TM) BEH C_(18) column(2.1 mm×150 mm, 1.7 µm) with water-acetonitrile as mobile phase, a column temperature of 30 ℃, a flow rate of 0.3 mL·min~(-1), and a sample size of 1 µL. The scanning was performed in the negative ion mode. The complex component groups in Kaixin San substance benchmark were quickly and accurately identified and clearly assigned based on the comparison of the retention time and MS data with those of the reference substance as well as the relative molecular weight of the same or similar components in the mass spectrum database and literature. A total of 77 compounds were identified, including 26 saponins, 13 triterpenoid acids, 20 oligosaccharide esters, 5 xanthones, and 13 other compounds. The qualitative method established in this study can systematically, accurately, and quickly identify the chemical components in Kaixin San substance benchmark, which can provide a basis for the further analysis of its active components in vivo and the establishment of its quality control system.

Study of the metabolism of myricetin in rat urine, plasma and feces by ultra-high-performance liquid chromatography.

Myricetin is a common natural flavonoid compound with various pharmacological activities. However, the metabolite characterization of this substance remains inadequate. In this study, a simple and rapid system strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry combining parallel reaction monitoring mode was established to screen and identify myricetin metabolites in rat urine, plasma and feces after oral administration. A total of 38 metabolites were fully or partially characterized based on their accurate mass, characteristic fragment ions, retention times, corresponding cLogP values, etc. These metabolites were presumed to be generated through glucuronidation, glucosylation, sulfation, dihydroxylation, acetylation, hydrogenation, hydroxylation and their composite reactions. In addition, the characteristic fragmentation pathways of flavonoids with more metabolites were summarized for the subsequent metabolite identification. The study provides an overall metabolic profile of myricetin, which would be of great help in predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.

Exosomal 15-LO2 mediates hypoxia-induced pulmonary artery hypertension in vivo and in vitro.

Our previous studies have shown that 15-LO2/15-HETE induced by hypoxia played an important role in pulmonary arterial hypertension (PH). However, the transportations of 15-LO2/15-HETE among the cells remain elusive. In this study, we investigated the specific involvement of 15-LO2-containing exosomes in the overproliferation of pulmonary artery endothelial cells (PAECs) induced by hypoxia and the underlying mechanism. In vitro, 15-LO2 was abundantly expressed and enriched in exosomes secreted from hypoxic PAECs, which subsequently activated the STAT3 signaling pathway, resulting in a robust increase in PAECs proliferation. In vivo treatment with the exosomes inhibitor GW4869 protected the pulmonary vascular homeostasis from dysfunctional and abnormal remodeling. Moreover, 15-LO2 was ubiquitinated under hypoxia, and further inhibition of the ubiquitin-proteasome system significantly suppressed PAECs proliferation, suggesting that ubiquitination of 15-LO2 may contribute to its sorting into exosomes. Overall, these findings indicate a previously unrecognized effect of exosomes and the cargo 15-LO2 in pulmonary vascular homeostasis on the pathogenesis of PH.