Exploring the anti-skin inflammation substances and mechanism of Paeonia lactiflora Pall. Flower via network pharmacology-HPLC integration.

BACKGROUND: Paeonia lactiflora Pall. (PL) is widely used in China as a homologous plant of medicine and food. PL flower is rich in bioactive substances with anti-inflammatory effects, while the pathogenesis of skin inflammation is complex and the specific mechanism is not clear, the current treatment of skin inflammation is mainly hormonal drugs, and hormonal drugs have obvious toxic side effects. The research on the treatment of skin inflammation by PL flowers is relatively small, so this study provides a basis for the development and utilisation of PL resources. OBJECTIVE: Our study was to investigate the interventional effects of PL flower extracts on skin inflammation and thus to understand its functional role in the treatment of skin inflammation and its molecular mechanisms. METHODS: The major active substances in PL flower extracts were investigated by the HPLC-DAD method, and the potential targets of action were predicted by network pharmacology, which was combined with in vitro experimental validation to explore the mechanism of PL flower extracts on the regulation of skin inflammation. The HPLC-DAD analysis identified seven major active components in PL flower extracts, and in response to the results, combined with the potential mechanism of network pharmacological prediction with skin inflammation, the PL flower extract is closely related to MAPK and NF-κB signaling pathways. In addition, we also investigated the interventional effects of PL flower extract on skin inflammation by western blot detection of MAPK signaling pathway and NF-κB signaling pathway proteins in cells. RESULT: Seven active components were identified and quantified from the extract of PL flowers, including Gallic acid, 1,2,3,4,6-O-Pentagalloylglucose, Oxypaeoniflorin, Paeoniflorin, Albiflorin, Benzoyloxypeoniflorin, and Rutin. It was predicted targets for the treatment of skin inflammation, with PPI showing associations with targets such as TNF, MAPK1, and IL-2. KEGG enrichment analysis revealed that the main signaling pathways involved included MAPK and T cell receptor signaling pathways. Cell experiments showed that the peony flower extract could inhibit the release of NO and inflammatory factors, as well as reduce ROS levels and inhibit cell apoptosis. Furthermore, the extract was found to inhibit the activation of the MAPK and NF-κB signaling pathways in cells. CONCLUSIONS: In this study, we found that PL flower extract can inhibit the production of cell inflammatory substances, suppress the release of inflammatory factors, and deactivate inflammatory signaling pathways, further inhibiting the production of cell inflammation. This indicates that PL flower extract has a therapeutic effect on skin inflammation.

Salivary proteins potentially derived from horizontal gene transfer are critical for salivary sheath formation and other feeding processes.

Herbivorous insects employ an array of salivary proteins to aid feeding. However, the mechanisms behind the recruitment and evolution of these genes to mediate plant-insect interactions remain poorly understood. Here, we report a potential horizontal gene transfer (HGT) event from bacteria to an ancestral bug of Eutrichophora. The acquired genes subsequently underwent duplications and evolved through co-option. We annotated them as horizontal-transferred, Eutrichophora-specific salivary protein (HESPs) according to their origin and function. In Riptortus pedestris (Coreoidea), all nine HESPs are secreted into plants during feeding. The RpHESP4 to RpHESP8 are recently duplicated and found to be indispensable for salivary sheath formation. Silencing of RpHESP4-8 increases the difficulty of R. pedestris in probing the soybean, and the treated insects display a decreased survivability. Although silencing the other RpHESPs does not affect the salivary sheath formation, negative effects are also observed. In Pyrrhocoris apterus (Pyrrhocoroidea), five out of six PaHESPs are secretory salivary proteins, with PaHESP3 being critical for insect survival. The PaHESP5, while important for insects, no longer functions as a salivary protein. Our results provide insight into the potential origin of insect saliva and shed light on the evolution of salivary proteins.

Optimizing electrochemical performance of Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure via preparing concentration-gradient particles for sodium-ion batteries.

P2-type layered oxides for rechargeable sodium-ion batteries have drawn a lot of attention because of their excellent electrochemical performance. However, these types of cathodes usually suffer from poor cyclic stability. To overcome this disadvantage, in this work, novel ball-shaped concentration-gradient oxide Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure modified by Mn-rich surface is successfully prepared using co-precipitation method. The concentration of Mn increased from the inner core to the surface, endowing the material with an excellent cyclic stability. The cathode exhibits enhanced electrochemical properties than that of the sample synthesized by solid-state method and concentration-constant material. It shows 143.2 mAh/g initial discharge capacity and retains 131 mAh/g between 2 V and 4.5 V after 100 rounds. The significant improvement in the electrochemical properties of the sample benefits from the unique concentration-gradient structure, and the Mn-rich surface that effectively stabilizes the basic P2 structure. The relatively higher Ni content in the core leads to a slight improvement in the discharge capacity of the sample. This strategy may provide new insights for preparing layered cathodes for sodium-ion batteries with high electrochemical performance.

Co-option of a non-retroviral endogenous viral element in planthoppers.

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.

Conformation Dependent Architectures of Assembled Antimicrobial Peptides with Enhanced Antimicrobial Ability.

Antimicrobial peptides (AMPs) are a developing class of natural and synthetic oligopeptides with host defense mechanisms against a broad spectrum of microorganisms. With in-depth research on the structural conformations of AMPs, synthesis or modification of peptides has shown great potential in effectively obtaining new therapeutic agents with improved physicochemical and biological properties. Notably, AMPs with self-assembled properties have gradually become a hot research topic for various biomedical applications. Compared to monomeric peptides, these peptides can exist in diverse forms (e.g., nanoparticles, nanorods, and nanofibers) and possess several advantages, such as high stability, good biocompatibility, and potent biological functions, after forming aggregates under specific conditions. In particular, the stability and antibacterial property of these AMPs can be modulated by rationally regulating the peptide sequences to promote self-assembly, leading to the reconstruction of molecular structure and spatial orientation while introducing some peptide fragments into the scaffolds. In this work, four self-assembled AMPs are developed, and the relationship between their chemical structures and antibacterial activity is explored extensively through different experiments. Importantly, the evaluation of antibacterial performance in both in vitro and in vivo studies has provided a general guide for using self-assembled AMPs in subsequent treatments for combating bacterial infections.

Safety of prone emergence from general endotracheal anesthesia in patients undergoing ERCP: a randomized controlled trial.

BACKGROUND: Conventional supine emergence and prone extubation from general endotracheal anesthesia (GEA) are associated with extubation-related adverse events (ERAEs). Given the minimally invasive nature of endoscopic retrograde cholangiopancreatography (ERCP) as well as the improved ventilation/perfusion matching and easier airway opening in the prone position, we aimed to assess the safety of prone emergence and extubation in patients undergoing ERCP under GEA. METHODS: Totally, 242 eligible patients were recruited and randomized into the supine extubation group (n = 121; supine group) and the prone extubation group (n = 121; prone group). The primary endpoint was the incidence of ERAEs during emergence, including hemodynamic fluctuations, coughing, stridor, and hypoxemia requiring airway maneuvers. The secondary endpoints included the incidence of monitoring disconnections, extubation time, recovery time, room exit time, and post-procedure sore throat. RESULTS: The incidence of ERAEs was significantly lower in the prone group compared with the supine group (8.3% vs 34.7%, OR = 0.17, 95% CI 0.18-0.56; P < 0.001). Moreover, the prone group demonstrated no monitoring disconnections, shorter extubation time and room exit time, faster recovery, and, lower frequency and milder sore throat after the procedure. CONCLUSIONS: For patients undergoing ERCP under GEA, compared with supine, prone emergence, and extubation had remarkably lower rates of EAREs and better recovery, and can maintain continuous monitoring and improve efficiency.

Functional analysis of neutral lipases in bug feeding and reproduction.

BACKGROUND: The bean bug, Riptortus pedestris, is known to cause significant economic losses in soybean crops due to its seed-sucking behavior, but the mechanism of its adaptation to lipid-rich seeds remains poorly understood. To exploit potential target genes for controlling this pest, neutral lipases are functionally characterized in this study. RESULTS: In this study, a total of 69 lipases were identified in R. pedestris, including 35 neutral lipases that underwent significant expansion. The phylogeny, expression patterns, and catalytic capacity of neutral lipases were investigated and we selected six salivary gland-specific, eight gut-specific, and three ovary-specific genes for functional analysis. All three ovary-specific neutral lipases (Chr1.3195, Chr1.0994, and Chr5.0087) are critical for insect reproduction, while a few gut-specific neutral lipases (Chr4.0221 and Chr1.3207) influence insect survivorship or weight gain. In contrast, no significant phenotype change is observed when silencing salivary gland-specific neutral lipases. CONCLUSION: The lipases Chr1.3195, Chr1.0994, Chr5.0087, Chr4.0221, and Chr1.3207 are essential for R. pedestris feeding and reproduction, and the insect is highly sensitive to their deficiency, suggesting that neutral lipases are promising candidates for application in RNAi-based control of this destructive pest. © 2023 Society of Chemical Industry.

Simultaneous Response of Mitochondrial MicroRNAs to Identify Cell Apoptosis with Multiple Responsive Intelligent DNA Biocomputing Nanodevices.

Challenges remained in precisely real-time monitoring of apoptotic molecular events at the subcellular level. Herein, we developed a new type of intelligent DNA biocomputing nanodevices (iDBNs) that responded to mitochondrial microRNA-21 (miR-21) and microRNA-10b (miR-10b) simultaneously which were produced during cell apoptosis. By hybridizing two hairpins (H1 and H2) onto DNA nanospheres (DNSs) that had been previously modified with mitochondria-targeted triphenylphosphine (TPP) motifs, iDBNs were assembled in which two localized catalytic hairpins self-assembly (CHA) reactions occurred upon the co-stimulation of mitochondrial miR-21 and miR-10b to perform AND logic operations, outputting fluorescence resonance energy transfer (FRET) signals for sensitive intracellular imaging during cell apoptosis. Owing to the spatial confinement effects of DNSs, it was discovered that iDBNs had a high efficiency and speed of logic operations by high local concentrations of H1 and H2, making the simultaneous real-time responses of mitochondrial miR-21 and miR-10b reliable and sensitive during cell apoptosis. These results demonstrated that iDBNs were simultaneously responsive to multiple biomarkers, which greatly improved the detection accuracy to identify the cell apoptosis, demonstrating that iDBNs are highly effective and reliable for the diagnosis of major disease and screening of anticancer drugs.

Embryonic and adult synaptic proteome perturbations after maternal immune activation: Identification of persistent changes relevant for early intervention.

Maternal infections during pregnancy pose an increased risk for neurodevelopmental psychiatric disorders (NPDs) in the offspring. Here, we examined age- and sex-dependent dynamic changes of the hippocampal synaptic proteome after maternal immune activation (MIA) in embryonic and adult mice. Adult male and female MIA offspring exhibited social deficits and sex-specific depression-like behaviours, among others, validating the model. Furthermore, we observed dose-, age-, and sex-dependent synaptic proteome differences. Analysis of the embryonic synaptic proteome implicates sphingolipid and ketoacid metabolism pathway disruptions during neurodevelopment for NPD-pertinent sequelae. In the embryonic hippocampus, prenatal immune activation also led to changes in neuronal guidance, glycosphingolipid metabolism important for signalling and myelination, and post-translational modification of proteins that regulate intercellular interaction and developmental timing. In adulthood, the observed changes in synaptoneurosomes revealed a dynamic shift toward transmembrane trafficking, intracellular signalling cascades, and hormone-mediated metabolism. Importantly, 68 of the proteins with differential abundance in the embryonic brains of MIA offspring were also altered in adulthood, 75% of which retained their directionality. These proteins are involved in synaptic organisation, neurotransmitter receptor regulation, and the vesicle cycle. A cluster of persistently upregulated proteins, including AKT3, PAK1/3, PPP3CA, formed a functional network enriched in the embryonic brain that is involved in cellular responses to environmental stimuli. To infer a link between the overlapping protein alterations and cognitive and psychiatric traits, we probed human phenome-wise association study data for cognitive and psychiatric phenotypes and all, but PORCN were significantly associated with the investigated domains. Our data provide insights into the dynamic effects of an early prenatal immune activation on developing and mature hippocampi and highlights targets for early intervention in individuals exposed to such immune challenges.

Amelioratory effects of astragaloside IV on hepatocarcinogenesis via Nrf2-mediated pSmad3C/3L transformation.

BACKGROUND: Phosphorylated Smad3 isoforms are reversible and antagonistic, and the tumour-suppressive pSmad3C can shift to an oncogenic pSmad3L signal. In addition, Nrf2 has a two-way regulatory effect on tumours, protecting normal cells from carcinogens and promoting tumour cell survival in chemotherapeutics. Accordingly, we hypothesised that the transformation of pSmad3C/3L is the basis for Nrf2 to produce both pro- and/or anti-tumourigenic effects in hepatocarcinogenesis. Astragaloside IV (AS-IV), the major component of Astragalus membranaceus, exerts anti-fibrogenic and carcinogenic actions. Lately, AS-IV administration could delay the occurrence of primary liver cancer by persistently inhibiting the fibrogenesis and regulating pSmad3C/3 L and Nrf2/HO-1 pathways synchronously. However, effect of AS-IV on hepatocarcinogenesis implicated in the bidirectional cross-talking of pSmad3C/3 L and Nrf2/HO-1 signalling, especially which one contributes palpably than the other still remains unclear. PURPOSE: This study aims to settle the above questions by using in vivo (pSmad3C+/- and Nrf2-/- mice) and in vitro (plasmid- or lentivirus- transfected HepG2 cells) models of HCC. STUDY DESIGN AND METHODS: The correlation of Nrf2 to pSmad3C/pSmad3L in HepG2 cells was analysed by Co-immunoprecipitation and dual-luciferase reporter assay. Pathological changes of Nrf2, pSmad3C, and pSmad3L in human HCC patients, pSmad3C+/- mice, and Nrf2-/- mice were gauged by immunohistochemical, haematoxylin and eosin staining, Masson, and immunofluorescence assays. Finally, western blot and qPCR were used to verify the bidirectional cross-talking of pSmad3C/3L and Nrf2/HO-1 signalling protein and mRNA in vivo and in vitro models of HCC. RESULTS: Histopathological manifestations and biochemical indicators revealed that pSmad3C+/- could abate the ameliorative effects of AS-IV on fibrogenic/carcinogenic mice with Nrf2/HO-1 deactivation and pSmad3C/p21 transform to pSmad3L/PAI-1//c-Myc. As expected, cell experiments confirmed that upregulating pSmad3C boosts the inhibitory activity of AS-IV on phenotypes (cell proliferation, migration and invasion), followed by a shift of pSmad3L to pSmad3C and activation of Nrf2/HO-1. Synchronously, experiments in Nrf2-/- mice and lentivirus-carried Nrf2shRNA cell echoed the results of pSmad3C knockdown. Complementarily, Nrf2 overexpression resulted in the opposite result. Furthermore, Nrf2/HO-1 contributes to AS-IV's anti-HCC effect palpably compared with pSmad3C/3L. CONCLUSION: These studies highlight that harnessing the bidirectional crosstalk pSmad3C/3 L and Nrf2/HO-1, especially Nrf2/HO-1 signalling, acts more effectively in AS-IV's anti-hepatocarcinogenesis, which may provide an important theoretical foundation for the use of AS-IV against HCC.

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients treated with immune checkpoint inhibitors: A meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in patients with gastric cancer (GC) treated with immune checkpoint inhibitors (ICIs), although the results are controversial. Therefore, we performed the present meta-analysis to systematically assess the correlation between NLR and prognosis and clinicopathological factors in GC patients undergoing treatment with ICIs. Among the electronic databases, PubMed, Web of Science, Embase, and Cochrane Library were thoroughly searched. To estimate the prognostic value of NLR for progression-free survival (PFS) and overall survival (OS), hazard ratios (HRs) were calculated, and their 95% confidence intervals were calculated. This meta-analysis included 10 studies with 830 patients. Based on the pooled data, a high NLR was associated with poor OS in GC patients receiving ICIs (HR = 2.13, 95% confidence interval [CI] = 1.70-2.66, p < 0.001). Elevated NLR was a significant biomarker for worse PFS in GC patients treated with ICIs (HR = 1.74, 95% CI = 1.22-2.48, p = 0.002). There was, however, no significant correlation between NLR and sex, age, and Eastern Cooperative Oncology Group Performance Status (PS) of the ECOG, differentiation, human epidermal growth factor receptor 2 (HER2) status, or PD-L1 status in GC patients treated with ICIs. High NLR before treatment was associated with poor OS and PFS in GC patients treated with ICIs, according to our meta-analysis. NLR is an effective biomarker for evaluating the prognosis of GC patients receiving ICIs and provide more valuable information for treatment decisions in the era of immunotherapy for GC.

Rational Design of Cascade DNA System for Signal Amplification.

System leakage critically confines the development of cascade DNA systems that need to be implemented in a strict order-by-order manner. In principle, ternary DNA reactants, composed of three single-strand DNA (ssDNA) with a strict equimolar ratio (1:1:1), have been indispensable for successfully cascading upstream entropy-driven DNA circuit (EDC) with downstream circuits, and system leakage will occur with any unbalance of the molar ratio. In this work, we proposed "splitting-reconstruction" and "protection-release" strategies on the potential downstream circuit initiator derived from upstream EDC to guide the construction of EDC-involved cascade systems independent of system leakage derived from unpurified reactants. Both the reconstructed and released downstream circuit initiators were in compliance with the principle of the cascade AND logic gate. Using these two strategies, two cascade systems─EDC2-4WJ-TMSDR and EDC3-HCR─were developed to carry out the designed order, which did not require that the ratio of 1:1:1 be maintained. Furthermore, the inherent property of the upstream EDC could transfer into the downstream circuit, endowing the developed cascade systems with a more powerful signal amplification ability for the sensitive detection of the corresponding initiator strand. These two strategies may provide new insights into the process of constructing EDC-like circuit-involved high-order DNA networks.

PKM2 allosteric converter: A self-assembly peptide for suppressing renal cell carcinoma and sensitizing chemotherapy.

Stronger intrinsic Warburg effect and resistance to chemotherapy are the responses to high mortality of renal cell carcinoma (RCC). Pyruvate kinase M2 (PKM2) plays an important role in this process. Promoting PKM2 conversion from dimer to tetramer is a critical strategy to inhibit Warburg effect and reverse chemotherapy resistance. Herein, a PKM2 allosteric converter (PAC) is constructed based on the "in vivo self-assembly" strategy, which is able to continuously stimulate PKM2 tetramerization. The PAC contains three motifs, a serine site that is protected by enzyme cleavable ß-N-acetylglucosamine, a self-assembly peptide and a AIE motif. Once PAC nanoparticles reach tumor site via the EPR effect, the protective and hydrophilic ß-N-acetylglucosamine will be removed by over-expressed O-GlcNAcase (OGA), causing self-assembled peptides to transform into nanofibers with large serine (PKM2 tetramer activator) exposure and long-term retention, which promotes PKM2 tetramerization continuously. Our results show that PAC-induced PKM2 tetramerization inhibits aberrant metabolism mediated by Warburg effect in cytoplasm. In this way, tumor proliferation and metastasis behavior could be effectively inhibited. Meanwhile, PAC induced PKM2 tetramerization impedes the nuclear translocation of PKM2 dimer, which restores the sensitivity of cancer cells to first-line anticancer drugs. Collectively, the innovative PAC effectively promotes PKM2 conversion from dimer to tetramer, and it might provide a novel approach for suppressing RCC and enhancing chemotherapy sensitivity.

Controlled Cascade-Release and High Selective Sterilization by Core-Shell Nanogels for Microenvironment Regulation of Aerobic Vaginitis.

Aerobic vaginitis (AV) is a gynecological disease associated with vaginal flora imbalance. The nonselective bactericidal nature of antibiotics and low customization rate of probiotic supplementation in existing treatments lead to AV recurrence. Here, a drug delivery strategy is proposed that works with the changing dynamics of the bacterial flora. In particular, a core-shell nanogel (CSNG) is designed to encapsulate prebiotic inulin and antimicrobial peptide Cath 30. The proposed strategy allows for the sequential release of both drugs using gelatinase produced by AV pathogenic bacteria, initially selectively killing pathogenic bacteria and subsequently promoting the proliferation of beneficial bacteria in the vagina. In a simulated infection environment in vitro, the outer layer of CSNGs, Cath 30 is rapidly degraded and potently killed the pathogenic bacterium Staphylococcus aureus at 2-6 h. CSNGs enhances proliferation of the beneficial bacterium Lactobacillus crispatus by more than 50% at 24 h. In a rat AV model, the drug delivery strategy precisely regulated the bacterial microenvironment while controlling the inflammatory response of the vaginal microenvironment. This new treatment approach, configured on demand and precisely controlled, offers a new strategy for the treatment of vaginal diseases.

Planthopper salivary sheath protein LsSP1 contributes to manipulation of rice plant defenses.

Salivary elicitors secreted by herbivorous insects can be perceived by host plants to trigger plant immunity. However, how insects secrete other salivary components to subsequently attenuate the elicitor-induced plant immunity remains poorly understood. Here, we study the small brown planthopper, Laodelphax striatellus salivary sheath protein LsSP1. Using Y2H, BiFC and LUC assays, we show that LsSP1 is secreted into host plants and binds to salivary sheath via mucin-like protein (LsMLP). Rice plants pre-infested with dsLsSP1-treated L. striatellus are less attractive to L. striatellus nymphs than those pre-infected with dsGFP-treated controls. Transgenic rice plants with LsSP1 overexpression rescue the insect feeding defects caused by a deficiency of LsSP1 secretion, consistent with the potential role of LsSP1 in manipulating plant defenses. Our results illustrate the importance of salivary sheath proteins in mediating the interactions between plants and herbivorous insects.

Superior thermoelectric properties through triangular triple quantum dots (TTQD) attached to one metallic and one superconducting lead.

We theoretically investigate the thermoelectric transport properties of triangular triple quantum dots (TTQD) with the central quantum dot coupled to one metallic and one superconducting lead. The system shows significantly superior thermoelectric performance over parallel coupled triple quantum dots and those coupled to two conventional metallic leads. The thermoelectric coefficients strongly depend on the ratio of superconducting gap to interdot coupling, as well as asymmetry and interference effects. The thermopower exhibits single-platform and double-platform structures for different ratios of superconducting gap to interdot coupling. The thermopower and figure of merit achieve quite remarkable values near the superconducting gap edges where the single-particle tunnelling occurs. For symmetric coupling, the maximal figure of merit might reach the order of 102 when the superconducting gap is about half that of the interdot coupling. Moreover, the figure of merit can be further greatly enhanced by appropriately matching the electrode coupling asymmetry and interdot coupling asymmetry.

[Advances in Research on the Mechanism of Association Between Periodontitis and Diabetes Mellitus].

Periodontitis and diabetes mellitus are both chronic diseases with a rather high prevalence and they are closely associated with each other. On one hand, diabetes mellitus poses as a risk factor for periodontitis. On the other hand, periodontitis has a negative impact on glucose control in diabetic patients. The two-way relationship has aroused a lot of research interest in recent years. Herein, approaching the issue by looking at the effect of periodontitis on diabetes, we summarized the mechanism of the traditional periodontal pocket-blood circulation pathway and reviewed the role of the oral-gut axis in the mechanism, which has been proposed in recent years. In addition, regarding the impact of diabetes on periodontitis, we summarized new findings concerning changes in oral microbiota, abnormal levels of cytokines and adipokines, oxidative stress, unbalanced osteogenic and osteoclastic activities, and the accumulation of advanced glycation end-products. We hope this paper will be helpful for further studies on the mechanism of association between periodontitis and diabetes.

Noval ceRNA axis-mediated high expression of TOP2A correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options, suboptimal efficacy, and poor prognosis, resulting in an economic burden to countries worldwide. TOP2A is a mammalian protein that plays a vital role in DNA replication. Previous studies have shown that upregulation of TOP2A expression is associated with tumorigenesis and progression in various cancers, but the exact mechanism of upregulation remains unclear. Methods: We first conducted a pan-cancer analysis using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to study the oncogenicity of TOP2A through the cBioPortal database. Next, using The Encyclopedia of RNA Interactomes (ENCORI) database, we identified microRNAs (miRNAs) that are associated with the downregulation of TOP2A and investigated potential long non-coding RNAs (lncRNAs) that may act as competing endogenous RNAs (ceRNAs) by binding to candidate miRNAs. We then analyzed immune cell infiltration and immune checkpoints using the TIMER database. Finally, we performed a multivariate regression analysis using lncRNAs and clinical pathological characteristics, constructed a nomogram to predict the prognosis of HCC based on the analysis results, and evaluated its diagnostic efficiency. Results: TOP2A was highly expressed in HCC and was associated with poor patient prognosis. TOP2A was subject to post-transcriptional regulation in HCC, with the ceRNA mechanism being a significant pathway. miR-139-5p was an important miRNA that suppressed the upregulation of TOP2A in HCC, and patients with low expression of miR-139-5p had worse overall survival (OS). After screening and analysis, three lncRNAs, AC078846.1, AC124798.1 and SNHG3, were found to inhibit the activity of miR-139-5p through the ceRNA mechanism, and patients with high expression of these three lncRNAs had worse prognosis. In addition, TOP2A was found to be closely related to tumor-infiltrating immune cells (TIICs) and immune checkpoints. A nomogram constructed using the three lncRNAs and selected clinicopathological features showed good predictive value for the prognosis of liver cancer. Conclusions: The TOP2A-miR-139-5p-AC078846.1/AC124798.1/SNHG3 axis plays a significant role in the progression of HCC and leads to poor patient outcomes. Additionally, TOP2A influences the development of HCC by affecting TIICs and immune checkpoints. A nomogram constructed using the three lncRNAs and clinicopathological features has good clinical utility.

Study of Bulk Properties of Strange Particles in Au+Au Collisions at sNN = 54.4 GeV.

We analyzed the transverse momentum pT spectra of various strange hadrons KS0, Λ(Λ¯) and Ξ-(Ξ¯+) at mid-rapidity (y) in different centrality intervals from Au+Au collisions at sNN= 54.4 GeV. The pT spectra of these strange hadrons are investigated by the Tsallis-like distribution, which satisfactorily fits the experimental data. The bulk properties of the medium produced in ultra-relativistic heavy-ion collisions at the kinetic freeze-out are reflected by measuring the hadron spectra. The effective temperature T, transverse flow velocity ßT, and mean pT along with other parameters that are strongly dependent on centrality and particle specie are extracted. The effective temperature of multi-strange particle (Ξ-(Ξ¯+)) is larger as compared to singly-strange particles Λ(Λ¯) and KS0. Furthermore, the kinetic freeze-out temperature T, transverse flow velocity ßT. and mean pT (⟨pT⟩) show a decreasing trend towards lower centrality, while the entropy parameter q increases from central to peripheral collisions. In addition, a positive correlation of ⟨pT⟩ and T and a negative correlation of q and T are also reported.

Effect of electroacupuncture on the repair of stress ulcer injury in neurocritical patients: A randomized clinical trial.

Background: Stress ulcer (SU) is one of the main causes of prolonged hospital stay, poor prognosis, and increased mortality in critically ill patients. This study aimed to investigate the effect of electroacupuncture (EA) on SU in patients with severe neurological diseases and explore its possible mechanisms. Methods: Taking patients with SU in adult neurocritical care as the research object, they were randomly divided into the EA group and the control group. Through the perioperative EA intervention, the following indicators were documented: main observation indicator (the effective rate of SU treatment), secondary observation indicators (gastric juice pH, gastric juice occult blood test, and stool occult blood test), related mechanisms [repair factors trefoil factor family 2 (TFF2), vascular endothelial growth factor (VEGF), and heat shock protein 70 (HSP70)], complications during hospitalization, and intensive care unit (ICU) stay time. Results: Compared with the control treatment, EA increased the effective rate of SU treatment (85.4% for the EA group, 57.5% for the control group, risk difference: 27.9% (95% CI: 8.3%-45.1%); P < 0.01). EA increased the success rate of gastric juice pH treatment on days 1, 2, and 3 (P < 0.01 for day 1, P < 0.05 for days 2 and 3). EA lowered the positive rate of gastric occult blood test on days 1 and 3 (all P-values < 0.05) and the positive rate of fecal occult blood test on day 3 (P < 0.05). EA also reduced the ICU stay time (P < 0.01) and total hospitalization time (P < 0.05). Compared with day 0, all serum repair factors (VEGF, HSP70, and TFF2) of both groups significantly increased on days 1, 3, and 5 (all P-values < 0.01). Compared with the control group, VEGF in the EA group was increased on days 3 and 5 (all P-values < 0.01); HSP70 was increased on days 1, 3, and 5 (P < 0.05 for day 1, P < 0.01 for days 3 and 5); and TFF2 was increased on days 1, 3, and 5 (all P-values < 0.01). Conclusion: Electroacupuncture promoted the repair of SU damage in severe neurological disease, and its effect was related to enhancing the expression of gastric mucosal repair factors. Clinical trial registration: [https://www.chictr.org.cn/showprojen.aspx?proj=127012], identifier [ChiCTR2100046701].