Angstrom-Level Tuning in Confined Space of Metal-Organic Framework for Ultra-High Resolution in Gas Chromatographic Separation.

Optimizing the balance between thermodynamic interaction and kinetic diffusion is pivotal to obtaining high-performance gas chromatographic stationary phases. Here, three aluminum-based metal-organic frameworks featuring fym topology were chosen to achieve such balance by refined controlling the thermodynamic interactions toward analytes at angstrom level in a confined space. The CAU-10-H with the middle-sized channels (5.4 Å) provided weak interactions with xylenes because of the benzene ring around the channel, leading to the fastest diffusion. While the MIL-160 provided stronger interactions toward the analytes due to the abundance of O-heterocyclic sites of 2,5-furandicarboxylic acid ligands, resulting in slightly higher diffusion barriers. Thereby, although MIL-160 had a larger channel (5.9 Å) than CAU-10-H, the xylenes still diffused more slowly in MIL-160 than in CAU-10-H. The CAU-10-NH2 with the channel of 4.7 Å provided overstrong thermodynamic interactions and significant stereospecific blockade to the analytes because of the NH2 sites in the confined channels. These factors collectively contributed to achieving the lowest diffusion kinetics. The confined interactions were also proved by molecular dynamics simulation. Furthermore, the application indicated that MIL-160 exhibited the highest separation ability as a GC stationary phase among all reported materials. This strategy offers an approach for developing high-performance MOF stationary phases.

A green extraction technology of lignocellulose from cassava residue by mechanical activation-assisted ternary deep eutectic solvent.

Lignocellulose (LC) is a natural polymer material that holds immense potential for various applications. However, extracting LC from biomass wastes with high-starch content has been challenging due to low selectivity and yield. In this study, LC was prepared from cassava residue (CR) via a combination of mechanical activation pretreatment and a citric acid (CA)-enhanced ternary deep eutectic solvent (TDES) consisting of choline chloride (ChCl), lactic acid (LA), and CA. The mechanical activation reduces the size of CR, greatly promoting the removal ability for starch, lignin and hemicellulose using TDES, and thus improving yield and selectivity of LC through this method. The CA esterified LC to prevent its excessive hydrolysis and increased a significantly higher LC content (82.52 wt%) compared to mechanical activation only and DES without CA, increasing by 6.97 times and 1.26 times, respectively. The extraction temperature significantly affected the structure, composition, thermal stability of LC and the properties of recovered TDES. The LC extracted at 90 °C (LC-90) had the highest cellulose content (82.52 wt%), crystallinity index (44.82 %), and higher degradation temperature (339.7 °C). The properties of the recovered TDES and extraction mechanism were analyzed. This study provides a strategy for the high-value utilization of biomass waste.

Stretch-induced hepatic endothelial mechanocrine promotes hepatocyte proliferation.

BACKGROUND AIMS: Partial hepatectomy (PHx)-induced liver regeneration causes the increase in relative blood flow rate within the liver, which dilates hepatic sinusoids and applies mechanical stretch on liver sinusoidal endothelial cells (LSECs). Heparin-binding EGF-like growth factor (HB-EGF) is a crucial growth factor during liver regeneration. We aimed to investigate whether this sinusoidal dilation-induced stretch promotes HB-EGF secretion in LSECs and what the related molecular mechanism is. APPROACH RESULTS: In vivo PHx, ex vivo liver perfusion and in vitro LSEC mechanical stretch were applied to detect HB-EGF expression in LSECs and hepatocyte proliferation. Knockdown or inhibition of mechanosensitive proteins were used to unravel the molecular mechanism in response to stretch. This stretch triggers amplitude- and duration-dependent HB-EGF up-regulation in LSECs, which is mediated by Yes-associated protein (YAP) nuclear translocation and binding to TEAD. This YAP translocation is achieved in two ways: On one hand, F-actin polymerization-mediated expansion of nuclear pores promotes YAP entry into nucleus passively. On the other hand, F-actin polymerization up-regulates the expression of BAG family molecular chaperone regulator 3 (BAG-3), which binds with YAP to enter nucleus cooperatively. In this process, ß1-integrin serves as a target mechanosensory in stretch-induced signaling pathways. This HB-EGF secretion-promoted liver regeneration after 2/3 PHx is attenuated in endothelial cell-specific Yap1-deficient mice. CONCLUSIONS: Our findings indicate that mechanical stretch-induced HB-EGF up-regulation in LSECs via YAP translocation can promote the hepatocyte proliferation during liver regeneration through a mechanocrine manner, which deepens the understanding of the mechanical-biological coupling in liver regeneration.

Sequence-Dependent Single-Molecule DNA Sensing Using Covalent Organic Framework Nanopores.

Enzyme-free single-molecule sequencing has the potential to significantly expand the application of nanopore technology to DNA, proteins, and saccharides. Despite their advantages over biological nanopores and natural suitability for enzyme-free single-molecule sequencing, conventional solid-state nanopores have not yet achieved single-molecule DNA sequencing. The biggest challenge for the accuracy of single-molecule sequencing using solid-state nanopores lies in the precise control of the pore size and conformity. In this study, we fabricated nanopore devices by covering the tip of a quartz nanopipette with ultrathin two-dimensional (2D) covalent organic framework (COF) nanosheets (pore size ≈ 1.1 nm). The size of the periodically arranged nanopores in COF is comparable to that of protein nanopores, and the structure of each COF nanopore is consistent at the atomic scale. The COF nanopore device could roughly distinguish dAMP, dCMP, dGMP, and dTMP. Furthermore, a certain percentage of the current blockades originating from 150 nucleotides model DNA molecules (13.5% for dA50dC50dA50 and 11.1% for dC50dA50dC50) show distinct DNA sequence-specific concave and convex resistive current patterns. The finite element simulation confirmed that the current blockade pattern of a DNA molecule passing through a COF nanopore is dependent on the relative location of the nanopore with respect to the wall of the nanopipette. Our study is a significant step toward single-molecule DNA sequencing by solid-state nanopores.

Synergistic Performance of Thermoelectric and Mechanical in Nanotwinned High-Entropy Semiconductors AgMnGePbSbTe5.

Introducing nanotwins in thermoelectric materials represents a promising approach to achieving such a synergistic combination of thermoelectric properties and mechanical properties. By increasing configurational entropy, a sharply reduced stacking fault energy in a new nanotwinned high-entropy semiconductor AgMnGePbSbTe5 is reached. Dense coherent nanotwin boundaries in this system provide an efficient phonon scattering barrier, leading to a high figure of merit ZT of ≈2.46 at 750 K and a high average ZT of ≈1.54 (300-823 K) with the presence of Ag2Te nanoprecipitate in the sample. More importantly, owing to the dislocation pinning caused by coherent nanotwin boundaries and the chemical short-range disorder caused by the high configurational entropy effect, AgMnGePbSbTe5 also exhibits robust mechanical properties, with flexural strength of 82 MPa and Vickers hardness of 210 HV.

Mapping Spatial Strain Distribution and Its Effects on Optoelectronic Properties in Wrinkled Perovskite Films.

Organic-inorganic halide perovskite films, fabricated by using the antisolvent method, have garnered intense attention for their application in high-efficiency and stable solar cells. These films characteristically develop periodic wrinkled microstructures. Previous research has indicated that macroscopic residual strain significantly influences the optoelectronic behaviors of these films. However, the detailed interplay between the wrinkled morphology, strain distribution, and local photophysical properties at the micro- and nanoscale has not been fully elucidated. Here, we explore the microscopic morphology-strain-property relationship within wrinkled perovskite films employing correlative micro-optical and nanoelectrical microscopy techniques. Microphotoluminescence (PL) mapping supplemented by in situ strain PL measurements identifies a heterogeneous spatial strain distribution across the microstructural hills and valleys. Additionally, light-intensity-dependent photoconductive atomic force microscopy reveals that valleys experiencing less compressive strain exhibit a lower conductivity and a higher propensity for ion migration. The findings underscore the potential of targeted strain engineering to optimize the performance and longevity of perovskite solar cells.

Case report: Second report of neuromuscular syndrome caused by biallelic variants in ASCC3.

Introduction: Activating Signal Cointegrator 1 Complex, Subunit 3 (ASCC3) has been implicated in the pathogenesis of neurodevelopmental disorders and neuromuscular diseases (MIM: 620700). This paper analyzes the clinical manifestations of three patients with developmental delay caused by ASCC3 genetic variation. Additionally, we discuss the previously reported clinical features of these patients along with our own findings, thereby enhancing our understanding of these genetic disorders and providing valuable insights into diagnosis, treatment, and potential interventions for affected individuals. Methods: In this study, we utilized trio-whole-exome sequencing (Trio-WES) and trio-copy number variations sequencing (Trio-CNV-seq) to analyze three unique families diagnosed with developmental delay caused by variation in ASCC3. Additionally, we retrospectively examined eleven previously reported ASCC3 genetic variations exhibiting similar clinical features. Results: Proband I (family 1) and Proband III (family 3) exhibited global developmental delays, characterized by intellectual disability, motor impairment, language retardation, lower muscle strength, and reduced muscle tone in their extremities. Proband II (family 2) presented poor response and dysphagia during feeding within 7 days after birth, clinical examination displayed short limbs, long trunk proportions, and clenched fists frequently observed alongside high muscle tone in his limbs -all indicative signs of developmental delay. Trio-WES revealed compound heterozygous variants in ASCC3 inherited from their parents. Proband I carried c. [489 dup]; [1897C>T], proband II carried c. [2314C>T]; [5002T>A], and proband III carried c. [5113G>T]; [718delG] variations, respectively. Conclusion: This study present the first report of Chinese children carrying compound heterozygous genetic variants in ASCC3 with LOF variants, elucidating the relationship between these variants and various aspects of intellectual disability. This novel finding expands the existing spectrum of ASCC3 variations.

Supportive interventions for preparation for future care of community-dwelling older adults: A scoping review.

AIM: To identify and summarize the content and effectiveness of existing supportive interventions for preparation for future care of community-dwelling older adults. DESIGN: A scoping review. DATA SOURCES: PubMed, Embase, Scopus, Web of Science, Wanfang, China National Knowledge Infrastructure and Chinese medical journal databases were used to identify studies alongside a search for grey literature, from inception to December 1, 2023. RESULTS: In total, 530 records were retrieved. Ten studies met the inclusion criteria, with eight interventions. Two categories of interventions were highlighted: psycho-educational group and web-based decision support. The components included the introduction of preparation for future care, discussing resources, exploration of care preferences and identifying care planning. Outcomes were grouped into four: awareness and attitude towards preparation for future care, participation in preparation for future care, changes in mental health and well-being and feasibility and acceptability of interventions. CONCLUSION: Few studies have investigated interventions that promote preparation for future care in community-dwelling older adults. These interventions, deemed acceptable and feasible, have shown promising results in improving awareness and attitude, and participation in future care preparation. Nevertheless, the impact on mental health appeared mixed. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Supportive interventions should be developed with feasibility and acceptability to improve awareness and participation in future care preparation for community-dwelling older adults. IMPACT: This review lays a foundation for the pre-allocating of care resources, improving the quality of provided care and ultimately promoting healthy ageing. REPORTING METHOD: Reporting was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution. PROTOCOL REGISTRATION: A protocol was registered on the Open Science Framework (https://osf.io/ze8wf).

Robot-assisted vs. laparoscopic right hemicolectomy in octogenarians and nonagenarians: an analysis of the US nationwide inpatient sample 2005-2018.

BACKGROUND: Colorectal cancer (CRC) is a significant health concern, particularly among older adults. Outcomes between laparoscopic and robot-assisted surgeries for right-sided colon cancers in the oldest old population have yet to be evaluated despite increased use of these surgeries. AIM: This study aimed to compare clinical outcomes after robot-assisted right hemicolectomy (RARH) versus laparoscopic right hemicolectomy (LRH) in octogenarian and nonagenarian patients. METHODS: This population-based, retrospective and observational study analyzed the data of adults ≥ 80 years old diagnosed with right-side colon cancer who received RARH or LRH. All data were extracted from the US National Inpatient Sample (NIS) database 2005-2018. Associations between type of surgery and in-hospital outcomes were determined using univariate and multivariable logistic regression and linear regression analysis. RESULTS: Data of 7,550 patients (representing 37,126 hospitalized patients in the U.S.) were analyzed. Mean age of the study population was 84.8 years, 61.4% were females, and 79.1% were non-smokers. After adjusting for relevant confounders, regression analysis showed that patients undergoing RARH had a significantly shorter LOS (adjusted Beta (aBeta), -0.24, 95% CI: -0.32, -0.15) but greater total hospital costs (aBeta, 26.54, 95% CI: 24.64, 28.44) than patients undergoing LRH. No significant differences in mortality, perioperative complications, and risk of unfavorable discharge were observed between the two procedures (p > 0.05). Stratified analyses by frailty status revealed consistent results. CONCLUSIONS: RARH is associated with a significantly shorter LOS but higher total hospital costs than LRH among octogenarians and nonagenarians. Other short-term outcomes for this population are similar between the two procedures, including in-hospital mortality, perioperative complications, and unfavorable discharge. These findings also apply to frail patients.

Unveiling the Virome of Wild Birds: Exploring CRESS-DNA Viral Dark Matter.

Amid global health concerns and the constant threat of zoonotic diseases, this study delves into the diversity of circular replicase-encoding single-stranded DNA (CRESS-DNA) viruses within Chinese wild bird populations. Employing viral metagenomics to tackle the challenge of "viral dark matter," the research collected and analyzed 3,404 cloacal swab specimens across 26 bird families. Metagenomic analysis uncovered a rich viral landscape, with 67.48% of reads classified as viral dark matter, spanning multiple taxonomic levels. Notably, certain viral families exhibited host-specific abundance patterns, with Galliformes displaying the highest diversity. Diversity analysis categorized samples into distinct groups, revealing significant differences in viral community structure, particularly noting higher diversity in terrestrial birds compared to songbirds and unique diversity in migratory birds versus perching birds. The identification of ten novel Circoviridae viruses, seven Smacoviridae viruses, and 167 Genomoviridae viruses, along with 100 unclassified CRESS-DNA viruses, underscores the expansion of knowledge on avian-associated circular DNA viruses. Phylogenetic and structural analyses of Rep proteins offered insights into evolutionary relationships and potential functional variations among CRESS-DNA viruses. In conclusion, this study significantly enhances our understanding of the avian virome, shedding light on the intricate relationships between viral communities and host characteristics in Chinese wild bird populations. The diverse array of CRESS-DNA viruses discovered opens avenues for future research into viral evolution, spread factors, and potential ecosystem impacts.

Comparison of characteristics of children hospitalized for respiratory syncytial virus infection during the pre- and post-COVID-19 eras: a multicenter retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infection (LRTI) among children, has resurged in the form of endemic or even pandemic in many countries and areas after the easing of COVID-19 containment measures. This study aimed to investigate the differences in epidemiological and clinical characteristics of children hospitalized for RSV infection during pre- and post-COVID-19 eras in Yunnan, China. METHODS: A total of 2553 pediatric RSV inpatients from eight hospitals in Yunnan were retrospectively enrolled in this study, including 1451 patients admitted in 2018-2019 (pre-COVID-19 group) and 1102 patients admitted in 2023 (post-COVID-19 group). According to the presence or absence of severe LRTI (SLRTI), patients in the pre- and post-COVID-19 groups were further divided into the respective severe or non-severe subgroups, thus analyzing the risk factors for RSV-associated SLRTI in the two eras. Demographic, epidemiological, clinical, and laboratory data of the patients were collected for the final analysis. RESULTS: A shift in the seasonal pattern of RSV activity was observed between the pre-and post-COVID-19 groups. The peak period of RSV hospitalizations in the pre-COVID-19 group was during January-April and October-December in both 2018 and 2019, whereas that in the post-COVID-19 group was from April to September in 2023. Older age, more frequent clinical manifestations (fever, acute otitis media, seizures), and elevated laboratory indicators [neutrophil-to-lymphocyte ratio (NLR), c-reactive protein (CRP), interleukin 6 (IL-6), co-infection rate] were identified in the post-COVID-19 group than those in the pre-COVID-19 group (all P < 0.05). Furthermore, compared to the pre-COVID-19 group, the post-COVID-19 group displayed higher rates of SLRTI and mechanical ventilation, with a longer length of hospital stay (all P < 0.05). Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6 were the shared independent risk factors for RSV-related SLRTI in both pre- and post-COVID-19 groups, whereas seizures and co-infection were independently associated with SLRTI only in the post-COVID-19 group. CONCLUSIONS: An off-season RSV endemic was observed in Yunnan during the post-COVID-19 era, with changed clinical features and increased severity. Age, low birthweight, preterm birth, personal history of atopy, underlying condition, NLR, IL-6, seizures, and co-infection were the risk factors for RSV-related SLRTI in the post-COVID-19 era.

Nanoscale phase management of the 2D/3D heterostructure toward efficient perovskite solar cells.

The stabilization of the formamidinium lead iodide (FAPbI3) structure is pivotal for the development of efficient photovoltaic devices. Employing two-dimensional (2D) layers to passivate the three-dimensional (3D) perovskite is essential for maintaining the α-phase of FAPbI3 and enhancing the power conversion efficiency (PCE) of perovskite solar cells (PSCs). However, the role of bulky ligands in the phase management of 2D perovskites, crucial for the stabilization of FAPbI3, has not yet been elucidated. In this study, we synthesized nanoscale 2D perovskite capping crusts with  = 1 and 2 Ruddlesden-Popper (RP) perovskite layers, respectively, which form a type-II 2D/3D heterostructure. This heterostructure stabilizes the α-phase of FAPbI3, and facilitates ultrafast carrier extraction from the 3D perovskite network to transport contact layer. We introduced tri-fluorinated ligands to mitigate defects caused by the halide vacancies and uncoordinated Pb2+ ions, thereby reducing nonradiative carrier recombination and extending carrier lifetime. The films produced were incorporated into PSCs that not only achieved a PCE of 25.39% but also maintained 95% of their initial efficiency after 2000 h of continuous light exposure without encapsulation. These findings underscore the effectiveness of a phase-pure 2D/3D heterostructure-terminated film in inhibiting phase transitions passivating the iodide anion vacancy defects, facilitating the charge carrier extraction, and boosting the performance of optoelectronic devices.

Phage-induced "one-to-many" FRET sensor for highly sensitive detection of Escherichia coli O157:H7.

As a foodborne pathogen capable of causing severe illnesses, early detection of Escherichia coli O157:H7 (E. coli O157:H7) is crucial for ensuring food safety. While Förster resonance energy transfer (FRET) is an efficient and precise detection technique, there remains a need for amplification strategies to detect low concentrations of E. coli O157:H7. In this study, we presented a phage (M13)-induced "one to many" FRET platform for sensitively detecting E. coli O157:H7. The aptamers, which specifically recognize E. coli O157:H7 were attached to magnetic beads as capture probes for separating E. coli O157:H7 from food samples. The peptide O157S, which specifically targets E. coli O157:H7, and streptavidin binding peptide (SBP), which binds to streptavidin (SA), were displayed on the P3 and P8 proteins of M13, respectively, to construct the O157S-M13K07-SBP phage as a detection probe for signal output. Due to the precise distance (≈3.2 nm) between two neighboring N-terminus of P8 protein, the SA-labeled FRET donor and acceptor can be fixed at the Förster distance on the surface of O157S-M13K07-SBP via the binding of SA and SBP, inducing FRET. Moreover, the P8 protein, with ≈2700 copies, enabled multiple FRET (≈605) occurrences, amplifying FRET in each E. coli O157:H7 recognition event. The O157S-M13K07-SBP-based FRET sensor can detect E. coli O157:H7 at concentration as low as 6 CFU/mL and demonstrates excellent performance in terms of selectivity, detection time (≈3 h), accuracy, precision, practical application, and storage stability. In summary, we have developed a powerful tool for detecting various targets in food safety, environmental monitoring, and medical diagnosis.

Enhancing Thermoelectric and Cooling Performance of Bi0.5Sb1.5Te3 through Ferroelectric Polarization in Flexible Ag/PZT/PVDF/Bi0.5Sb1.5Te3 Film.

Bi2Te3-based thin films are gaining recognition for their remarkable room temperature thermoelectric performance. Beyond the conventional "process-composition-performance" paradigm, it is highly desirable to explore new methods to enhance their performance further. Here, we designed a sandwich-structured Ag/PZT/PVDF/Bi0.5Sb1.5Te3(BST) thin film device and effectively regulated the performance of the BST film by controlling the polarization state of the PZT/PVDF layers. Results indicate that polarization induces interlayer charge redistribution and charge transfer between PZT/PVDF and BST, thereby achieving the continuous modulation of the electrical transport characteristics of BST films. Finally, following polarization at a saturation voltage of 3 kV, the power factor of the BST film increased by 13% compared to the unpolarized condition, reaching 20.8 µW cm-1 K-2. Furthermore, a device with 7 pairs of P-N legs was fabricated, achieving a cooling temperature difference of 11.0 K and a net cooling temperature difference of 2.4 K at a current of 10 mA after the saturation polarization of the PZT/PVDF layer. This work reveals the critical effect of introducing ferroelectric layer polarization to achieve excellent thermoelectric performance of the BST film.

Microplastics are effective carriers of bisphenol A and facilitate its escape from wastewater treatment systems.

Microplastics (MPs) pollution is a major issue in aquatic environments. Wastewater treatment plants are significant point sources of MPs, which may also be carriers of organic pollutants. We analyzed MP number, shape, color, and polymer type distribution in sewage wastewater treatment plants. The potential of MPs to act as carriers for typical organic pollutants in sewage, such as bisphenol A (BPA), was also assessed. The predominant MPs in the influent were fibers, primarily transparent and black in color, and composed of polyethylene, polypropylene, and polystyrene. During wastewater treatment, the concentration of MPs decreased from 10.89 items per L in the influent to 0.89 items per L in the treated effluent, with significant differences in treatment efficiency at different stages. In the simulated wastewater, the three predominant MPs exhibited certain adsorption capacities for bisphenol A. Changing the temperature and pH within the range expected for wastewater could interfere with the interactions between MPs and bisphenol A, with a limited impact on adsorption. The results show that although wastewater treatment plants intercept a significant amount of MP, a considerable number of them enter the aquatic environment daily because of the high volume of wastewater discharge. These MPs, which carry pollutants such as bisphenol A, may threaten the health of fish and other aquatic organisms. However, by scientifically adjusting operational parameters, wastewater treatment plants could become "controllable sources" of MP compound pollutants.

Effect of thumbtack needle on functional constipation: A pragmatic randomized controlled trial.

OBJECTIVE: Thumbtack Needling (TN) has been employed in the treatment of functional constipation (FC), although the existing evidence supporting its effectiveness is limited. This study is to evaluate the efficacy of TN in ameliorating FC. METHOD: A total of 482 eligible patients were recruited and randomly assigned to the TN group or the Mosapride Citrate (MC) group. The TN was buried once for three days, rest for one day after two consecutive burials, followed by a 4-week follow-up. The primary outcome measure was the score for Complete and spontaneous bowel movement score (CSBMs). Secondary outcome measures included the Bristol Stool Form Scale (BSFS), Cleveland Clinic Score (CCS), and the Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL). RESULTS: Out of the 482 patients randomized, 241 were allocated to each group. Of these, 216 patients (89.6 %) in both groups completed the intervention and follow-up. Compared with the baseline, the differences of CSBMs in TN group [1.76(95 % CI, 1.61 to 1.91)] and MC group [1.35(95 % CI, 1.20 to 1.50)] at week 4 meet the threshold for minimal clinically important difference (MCID). However, there were no clinical difference from baseline at week 2 and week 8 in both groups. Mean CSBMs at week 4 was 3.35 ± 0.99 in the TN group and 3 ± 1.03 in the MC group (adjusted difference between groups, 0.37 points [95 % CI, 0.18 to 0.55]; P < 0.001), although differences between the two groups did not meet the MCID threshold. CONCLUSION: Compared with mosapride citrate, thumbtack needling produced a greater improvement in CSBMs, although the difference from control was not clinically significant. GOV IDENTIFIER: ChiCTR2100043684.

Camrelizumab, apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib (TRIPLET protocol) is promising for advanced hepatocellular carcinoma (Ad-HCC). However, the usefulness of microwave ablation (MWA) after TRIPLET is still controversial. AIM: To compare the efficacy and safety of TRIPLET alone (T-A) vs TRIPLET-MWA (T-M) for Ad-HCC. METHODS: From January 2018 to March 2022, 217 Ad-HCC patients were retrospectively enrolled. Among them, 122 were included in the T-A group, and 95 were included in the T-M group. A propensity score matching (PSM) was applied to balance bias. Overall survival (OS) was compared using the Kaplan-Meier curve with the log-rank test. The overall objective response rate (ORR) and major complications were also assessed. RESULTS: After PSM, 82 patients were included both the T-A group and the T-M group. The ORR (85.4%) in the T-M group was significantly higher than that (65.9%) in the T-A group (P < 0.001). The cumulative 1-, 2-, and 3-year OS rates were 98.7%, 93.4%, and 82.0% in the T-M group and 85.1%, 63.1%, and 55.0% in the T-A group (hazard ratio = 0.22; 95% confidence interval: 0.10-0.49; P < 0.001). The incidence of major complications was 4.9% (6/122) in the T-A group and 5.3% (5/95) in the T-M group, which were not significantly different (P = 1.000). CONCLUSION: T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Identification of pivotal genes and crucial pathways in liver fibrosis through WGCNA analysis.

BACKGROUND: Liver fibrosis is a progressive liver disease with increasing incidence, yet its underlying pathogenic mechanisms remain incompletely understood. OBJECTIVE: : This study aims to explore potential therapeutic targets for liver fibrosis using weighted gene co-expression network analysis (WGCNA) and experimental validation. METHODS: We retrieved the microarray data (GSE174099) from the GEO database and performed differential expression analysis and WGCNA to identify co-expression modules associated with liver fibrosis. A module with the highest correlation to liver fibrosis was selected for further analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions and signaling pathways of the identified genes. Protein-protein interaction (PPI) networks were constructed using the STRING database. The correlation between core genes and immune cells was analyzed with the CIBERSORT algorithm. Additionally, pathological and molecular biology experiments were performed to validate the expression levels of core genes in liver tissue, including HE and Masson staining, immunohistochemistry, RT-qPCR, and Western blotting. RESULTS: We identified a total of 86 intersecting genes from the differential expression analysis and WGCNA. GO enrichment analysis revealed that these genes were involved in processes such as cellular response to cAMP, collagen-containing extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis highlighted the involvement of these genes in pathways like Cell Adhesion Molecules and the PI3K-Akt signaling pathway. Using Cytoscape software, we identified four core genes: Cftr, Cldn4, Map2, and Spp1. Pathological examinations showed that the experimental group exhibited significant fibrous tissue proliferation compared to the control group. Immunohistochemistry, RT-qPCR, and Western blotting analyses confirmed that these core genes were significantly upregulated in the experimental group (P< 0.05). CONCLUSION: This study identified four key genes (Cftr, Cldn4, Map2, Spp1) that are significantly associated with liver fibrosis. These genes are upregulated in liver fibrosis and could potentially as biomarkers for diagnosis and targets for therapeutic interventions.

Dihydroartemisinin inhibits ATP6 activity, reduces energy metabolism of hepatocellular carcinoma cells, promotes apoptosis and inhibits metastasis via CANX.

Dihydroartemisinin (DHA) may inhibit the migration and invasion of liver cancer cells by reducing ATP synthase production (specifically ATP1A1 and ATP5H) through the calcium/calmodulin dependent protein kinase kinase 2/solute carrier family 8 member B1 signaling pathway. However, it is unclear whether DHA regulates ATP synthase activity by modulating other calcium ion signals to inhibit the energy metabolism and the transfer of hepatocellular carcinoma (HCC) cells. Using the Gene Expression Profiling Interactive Analysis database, a search for specific expression genes in liver cancer tissues was performed. Human HCC HuH-7 and Li-7 cells were used to produce CANX overexpression and small interfering RNA cell models. The study assessed changes in cell proliferation, apoptosis, migration and invasion. Reactive oxygen species production, ATP production, mitochondrial membrane potential (JC-1), NAD+/NADH ratio and mitochondrial fluorescence were also evaluated. Western blotting was used to assess changes in CANX, ATP6V1 domain (ATP6V1F) and V0 domain (ATP6V0B) protein expression levels. The results demonstrated that CANX is highly expressed in liver cancer tissues. Furthermore, CANX regulated malignant biological behavior, mediated mitochondrial function and energy metabolism. However, these effects were inhibited by DHA, which decreased the expression of CANX, ATP6V0B and ATP6V1F. The findings of the present study underscore the central role of CANX in affecting the malignant biological behavior of liver cancer cells by regulating mitochondrial function and energy metabolism. Additionally, they indicate that DHA serves an anticancer role by inhibiting CANX expression.