Molecular characterization of PANoptosis-related genes in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by fibrosis and inflammation in renal tissues. Several types of cell death have been implicated in CKD onset and progression. Unlike traditional forms of cell death, PANoptosis is characterized by the crosstalk among programmed cell death pathways. However, the interaction between PANoptosis and CKD remains unclear. Here, we used bioinformatics methods to identify differentially expressed genes and differentially expressed PANoptosis-related genes (DE-PRGs) using data from the GSE37171 dataset. Following this, we further performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and gene set enrichment analysis using the data. We adopted a combined approach to select hub genes, using the STRING database and CytoHubba plug-in, and we used the GSE66494 as a validation dataset. In addition, we constructed ceRNA, transcription factor (TF)-gene, and drug-gene networks using Cytoscape. Lastly, we conducted immunohistochemical analysis and western blotting to validate the hub genes. We identified 57 PANoptosis-associated genes as DE-PRGs. We screened nine hub genes from the 57 DE-PRGs. We identified two hub genes (FOS and PTGS2) using the GSE66494 database, Nephroseq, immunohistochemistry, and western blotting. A common miRNA (Hsa-miR-101-3p) and three TFs (CREB1, E2F1, and RELA) may play a crucial role in the onset and progression of PANoptosis-related CKD. In our analysis of the drug-gene network, we identified eight drugs targeting FOS and 52 drugs targeting PTGS2.

Characteristics of ear fullness and synaptic loss in ear fullness revealed by SV2A positron emission tomographycortical.

Objective: Studies on feeling of ear fullness (FEF) related to sudden sensorineural hearing loss(SSNHL) are limited. The mechanisms of FEF are unclear. This study aimed to explore the characteristics and related brain activation of SSNHL with FEF. Methods: A total of 269 SSNHL patients were prospectively observed and divided into two groups, with FEF and without FEF. Fifteen SSNHL patients with FEF and 20 healthy controls (HCs) were recruited and underwent 18F-SynVesT-1 static PET. Standardized uptake values ratios (SUVr) of 18F-SynVesT-1 were computed between regions of interest. Results: The occurrence of FEF was not related to the audiogram type or severity of hearing loss. There was a positive correlation between the degree of FEF and the degree of hearing loss. Recovery from FEF was not related to the audiogram shape, the degree of hearing loss or recovery. Fifteen SSNHL patients with FEF had relatively low 18F-SynVesT-1 uptake in the right middle frontal gyrus, right inferior frontal gyrus, right middle temporal gyrus, bilateral parietal lobe sub-gyral and left medial frontal gyrus, as compared with HCs. There was no relatively high 18F-SynVesT-1 uptake in the cerebral cortex. Conclusion: The occurrence and recovery of FEF in SSNHL patients are not related to the classification, degree and recovery of hearing loss. The 18F-SynVesT-1 uptake in the cerebral cortex of patients experiencing SSNHL and FEF has shown alterations. This indicates that FEF may be related to cortical reorganization after the sudden impairment of unilateral auditory input.

Evaluation of novel synthetic peptides of avian hepatitis E virus ORF2 as vaccine candidate in chickens.

Avian hepatitis E virus (HEV) has resulted in significant economic losses in the poultry industry. There is currently no commercial vaccination available to prevent avian HEV infection. Previously, a novel epitope (601TFPS604) was discovered in the ORF2 protein of avian HEV. In this study, peptides were synthesized and assessed for their ability to provide immunoprotecting against avian HEV infection in poultry. Twenty-five Hy-Line Variety Brown laying hens were randomly divided into five groups; groups 1 to 3 respectively immunized with RLLDRLSRTFPS, PETRRLLDRLSR (irrelevant peptide control), or truncated avian HEV ORF2 protein (aa 339-606), while group 4 (negative control) was mock-immunized with PBS and group 5 (normal control) was not immunized or challenged. After the challenge, all hens in groups 2 and 4 showed seroconversion, fecal virus shedding, viremia, alanine aminotransferase (ALT) level increasing, liver lesions and HEV antigen in the liver. There were no pathogenic effects in other groups. Collectively, all of these findings showed that hens were completely protected against avian HEV infection when they were immunized with the peptide containing TFPS of the avian HEV ORF2 protein.

Extraction and immunomodulatory effects of acid Lagenaria siceraria (Molina) Standl. Polysaccharide on chickens.

Herbal polysaccharides are extensively studied as vaccine adjuvants due to their safety and potent immunoenhancing activity. This study aimed to analyze the structure of Lagenaria siceraria (Molina) Standl polysaccharide (LSP50) and investigate its adjuvant activity for the H9N2 vaccine in broiler chickens. Structural analysis revealed that LSP50 primarily consisted of rhamnose, arabinose, xylose, mannose, glucose, and galactose with molar ratios of 23.12: 12.28: 10.87: 8.26: 2.64: 22.82 respectively. The adjuvant activity of LSP50 was evaluated, which showing significant enhancements compared to the H9N2 group. Parameters including the immune organ index, H9N2 specific IgG level, cytokines contents (IFN-γ, IL-2, IL-4, and IL-5), and the proportion of CD3e+CD8aT+cells were significantly increased in the LSP50 group (P < 0.05). Additionally, sequencing results showed that LSP50 modulates the immune response by regulating PLA2G12B and PTGDS genes involved in the arachidonic acid pathway. These findings were further validated through qPCR analysis to affirm the reliability of the sequencing data. In conclusion, our results demonstrate that LSP50 exhibits potent adjuvant activity, enhancing both cellular and humoral immunity.

Origins of Severe Structural Changes during Alloying-Dealloying Reactions in Black Phosphorus.

Li-alloying reactions facilitate the incorporation of a large number of Li atoms into the crystalline structures of electrodes, such as black phosphorus (BP). However, the reactions inevitably induce multistep phase transitions characterized by drastic atomic rearrangements and lattice collapse. Despite many theoretical and experimental studies on alloying mechanisms, long-term debates persist regarding the structures of the intermediate phases, the accurate pathways of phase transitions, the formation of specific configurations, and alloying/dealloying reversibility. Here, through a combination of operando electron diffraction measurements and ab initio simulations at the atomic and electronic scales, we identify key factors that govern the severe structural changes during alloying-dealloying reactions in BP. P-P bonds of three-bond P atoms are continuously broken during lithiation, generating two-bond P atoms with a high ability to accept inserted electrons and Li ions. Consequently, the pristine layered structure in BP is transformed to P7 cages in Li3P7, which then evolve to chain configurations in LiP and finally to isolated P atoms in Li3P. Specifically, the preferential formation of the P7 cage results from its lowest binding energy with three Li ions compared to other cage isomers. Furthermore, only LiP can be reversibly transformed to the crystalline structure of Li3P7 during charge, but it is thermodynamically favorable for Li3P7 and Li3P intermediates to be delithiated to amorphous structures. Our findings offer unique insights into the alloying mechanisms and deepen the fundamental understanding of alloying anode systems.

Potential applications of single-incision laparoscopic totally preperitoneal hernioplasty.

BACKGROUND: The totally preperitoneal (TPP) approach is a new concept that was recently introduced. Although the TPP approach combined with single-incision laparoscopic hernia repair has its own advantages, there is little evidence reflecting the characteristics and feasibility of either approach. AIM: To analyze the potential applications of single-incision laparoscopic TPP (SIL-TPP) inguinal hernia hernioplasty for the treatment of inguinal hernias. METHODS: A total of 152 SIL-TPP surgeries were performed at the First Affiliated Hospital of Ningbo University from February 2019 to November 2022. A single-port, named Iconport, and standard laparoscopic instruments were used during the operation. Demographic data, intraoperative parameters and short-term postoperative outcomes were collected and retrospectively analyzed. RESULTS: The demographic data of 152 patients underwent SIL-TPP were shown in Table 1. The average age was 49.5 years (range from 21 to 81 years). The average body mass index was 27.7 kg/m2 (range from 17.7 kg/m2 to 35.6 kg/m2). SIL-TPP were conducted successfully in 147 patients. Three patients were converted to the SIL-transabdominal preperitoneal laparoscopic herniorrhaphy at the initial stage of the study due to a lack of experience. In 2 patients with incisional hernias, an auxiliary operation hole was added during the SIL-TPP procedure, as required for surgery. The mean operative time was 64.5 minutes (range: 36.0-110.0 minutes) for unilateral direct and femoral hernias and 81.6 minutes for indirect hernias (range: 40.0-150.0 minutes). The mean postoperative hospital stay was 3.4 days. CONCLUSION: SIL-TPP is feasible and has advantages for inguinal hernia repair. SIL-TPP has potential benefits for patients with various abdominal wall hernias. Consequently, doctors should be encouraged to actively apply the TPP approach combined with a single incision in their daily work.

Solid-State Electrocatalysis in Heteroatom-Doped Alloy Anode Enables Ultrafast Charge Lithium-Ion Batteries.

Electrocatalysis is generally confined to dynamic liquid-solid and gas-solid interfaces and is rarely applicable in solid-state reactions. Here, we report a paradigm shift strategy to exploit electrocatalysis to accelerate solid-state reactions in the context of lithium-ion batteries (LIBs). We employ heteroatom doping, specifically boron for silicon and sulfur for phosphorus, to catalyze electrochemical Li-alloying reactions in solid-state electrode materials. The preferential cleavage of polar dopant-host chemical bonds upon lithiation triggers chemical bond breaking of the host material. This solid-state catalysis, distinct from liquid and gas phases, requires a critical doping concentration for optimal performance. Beyond a critical concentration of ∼1 atom %, boron and sulfur doping drastically reduces activation energies and accelerates redox kinetics during lithiation/delithiation processes, leading to markedly enhanced rate performance in boron-doped silicon and sulfur-doped black/red phosphorus anode. Notably, a sulfur-doped black phosphorus anode coupled with a lithium cobalt oxide cathode achieves an ultrafast-charging battery, recharging 80% energy of a battery in 302 Wh kg-1 in 9 min, surpassing the thus far reported LIBs.

Modeling and biological evaluation of pegmolesatide, a novel and potent erythropoiesis-stimulating agent.

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

Pathogenicity of two different genotypes avian hepatitis E strains in laying hens and silkie fowl.

To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls.

A Broad-specificity Neutralizing Nanobody against Hepatitis E Virus Capsid Protein.

Hepatitis E virus (HEV) is a worldwide zoonotic and public health concern. The study of HEV biology is helpful for designing viral vaccines and drugs. Nanobodies have recently been considered appealing materials for viral biological research. In this study, a Bactrian camel was immunized with capsid proteins from different genotypes (1, 3, 4, and avian) of HEV. Then, a phage library (6.3 × 108 individual clones) was constructed using peripheral blood lymphocytes from the immunized camel, and 12 nanobodies against the truncated capsid protein of genotype 3 HEV (g3-p239) were screened. g3-p239-Nb55 can cross-react with different genotypes of HEV and block Kernow-C1/P6 HEV from infecting HepG2/C3A cells. To our knowledge, the epitope recognized by g3-p239-Nb55 was determined to be a novel conformational epitope located on the surface of viral particles and highly conserved among different mammalian HEV isolates. Next, to increase the affinity and half-life of the nanobody, it was displayed on the surface of ferritin, which can self-assemble into a 24-subunit nanocage, namely, fenobody-55. The affinities of fenobody-55 to g3-p239 were ∼20 times greater than those of g3-p239-Nb55. In addition, the half-life of fenobody-55 was nine times greater than that of g3-p239-Nb55. G3-p239-Nb55 and fenobody-55 can block p239 attachment and Kernow-C1/P6 infection of HepG2/C3A cells. Fenobody-55 can completely neutralize HEV infection in rabbits when it is preincubated with nonenveloped HEV particles. Our study reported a case in which a nanobody neutralized HEV infection by preincubation, identified a (to our knowledge) novel and conserved conformational epitope of HEV, and provided new material for researching HEV biology.

Incidence and risk factors of systemic lupus erythematosus in patients with primary immune thrombocytopenia: a systematic review and meta-analysis.

Background: Immune disorders and autoantibodies has been noted in both primary immune thrombocytopenia (ITP) and systemic lupus erythematosus (SLE). Whether the two disorders are correlated is unclear. The lack of evidence on the incidence of and risk factors for SLE in primary ITP patients poses a challenge for prediction in clinical practice. Therefore, we conducted this study. Methods: The protocol was registered with PROSPERO (CRD42023403665). Web of Science, Cochrane, PubMed, and EMBASE were searched for articles published from inception to 30 September 2023 on patients who were first diagnosed with primary ITP and subsequently developed into SLE. Furthermore, the risk factors were analyzed. Study quality was estimated using the Newcastle-Ottawa Scale. The statistical process was implemented using the R language. Results: This systematic review included eight articles. The incidence of SLE during the follow-up after ITP diagnosis was 2.7% (95% CI [1.3-4.4%]), with an incidence of 4.6% (95% CI [1.6-8.6%]) in females and 0 (95% CI [0.00-0.4%]) in males. Older age (OR = 6.31; 95% CI [1.11-34.91]), positive antinuclear antibody (ANA) (OR = 6.64; 95% CI [1.40-31.50]), hypocomplementemia (OR = 8.33; 95% CI [1.62-42.91]), chronic ITP (OR = 24.67; 95% CI [3.14-100.00]), organ bleeding (OR = 13.67; 95% CI [2.44-76.69]), and female (OR = 20.50; 95% CI [4.94-84.90]) were risk factors for subsequent SLE in ITP patients. Conclusion: Patients with primary ITP are at higher risk of SLE. Specific follow-up and prevention strategies should be tailored especially for older females with positive ANA, hypocomplementemia, or chronic ITP. In subsequent studies, we need to further investigate the risk factors and try to construct corresponding risk prediction models to develop specific prediction strategies for SLE.

Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide, responsible for approximately 20 million infections annually. Among the three open reading frames (ORFs) of the HEV genome, the ORF3 protein is involved in virus release. However, the host proteins involved in HEV release need to be clarified. In this study, a host protein, thioredoxin domain-containing protein 5 (TXNDC5), interacted with the non-palmitoylated ORF3 protein by co-immunoprecipitation analysis. We determined that the overexpression or knockdown of TXNDC5 positively regulated HEV release from the host cells. The 17FCL19 mutation of the ORF3 protein lost the ability to interact with TXNDC5. The releasing amounts of HEV with the ORF3 mutation (FCL17-19SSP) were decreased compared with wild-type HEV. The overexpression of TXNDC5 can stabilize and increase ORF3 protein amounts, but not the TXNDC5 mutant with amino acids 1-88 deletion. Meanwhile, we determined that the function of TXNDC5 on the stabilization of ORF3 protein is independent of the Trx-like domains. Knockdown of TXNDC5 could lead to the degradation of ORF3 protein by the endoplasmic reticulum (ER)-associated protein degradation-proteasome system. However, the ORF3 protein cannot be degraded in the knockout-TXNDC5 stable cells, suggesting that it may hijack other proteins for its stabilization. Subsequently, we found that the other members of protein disulfide isomerase (PDI), including PDIA1, PDIA3, PDIA4, and PDIA6, can increase ORF3 protein amounts, and PDIA3 and PDIA6 interact with ORF3 protein. Collectively, our study suggested that HEV ORF3 protein can utilize TXNDC5 for its stability in ER to facilitate viral release. IMPORTANCE: Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. After the synthesis and modification in the cells, the mature ORF3 protein is essential for HEV release. However, the host protein involved in this process has yet to be determined. Here, we reported a novel host protein, thioredoxin domain-containing protein 5 (TXNDC5), as a chaperone, contributing to HEV release by facilitating ORF3 protein stability in the endoplasmic reticulum through interacting with non-palmitoylated ORF3 protein. However, we also found that in the knockout-TXNDC5 stable cell lines, the HEV ORF3 protein may hijack other proteins for its stabilization. For the first time, our study demonstrated the involvement of TXNDC5 in viral particle release. These findings provide some new insights into the process of the HEV life cycle, the interaction between HEV and host factors, and a new direction for antiviral design.

Dissecting the genome sequence of a clinical isolated Cunninghamella bertholletiae Z2 strain with rich cytochrome P450 enzymes (Article).

Mucormycosis is receiving much more attention because of its high morbidity and extremely high mortality rate in immunosuppressed populations. In this study, we isolated a Cunnignhamella bertholletiae Z2 strain from a skin lesion of a 14 year, 9 months old girl with acute lymphoblastic leukemia who die of infection from the Z2 strain. Genome sequencing was performed after isolation and amplification of the Z2 strain to reveal potential virulence factors and pathogenic mechanisms. The results showed that the genome size of the Z2 strain is 30.9 Mb with 9213 genes. Mucoral specific virulence factor genes found are ARF, CalN, and CoTH, while no gliotoxin biosynthesis gene cluster was found, which is a known virulence factor in Aspergillus fumigatus adapted to the environment. The Z2 strain was found to have 69 cytochrome P450 enzymes, which are potential drug resistant targets. Sensitivity testing of Z2 showed it was only inhibited by amphotericin B and posaconazole. Detailed genomic information of the C. bertholletiae Z2 strain may provide useful data for treatment.

Breaking Low-Strain and Deep-Potassiation Trade-Off in Alloy Anodes via Bonding Modulation for High-Performance K-Ion Batteries.

Alloy anode materials have garnered unprecedented attention for potassium storage due to their high theoretical capacity. However, the substantial structural strain associated with deep potassiation results in serious electrode fragmentation and inadequate K-alloying reactions. Effectively reconciling the trade-off between low-strain and deep-potassiation in alloy anodes poses a considerable challenge due to the larger size of K-ions compared to Li/Na-ions. In this study, we propose a chemical bonding modulation strategy through single-atom modification to address the volume expansion of alloy anodes during potassiation. Using black phosphorus (BP) as a representative and generalizing to other alloy anodes, we established a robust P-S covalent bonding network via sulfur doping. This network exhibits sustained stability across discharge-charge cycles, elevating the modulus of K-P compounds by 74%, effectively withstanding the high strain induced by the potassiation process. Additionally, the bonding modulation reduces the formation energies of potassium phosphides, facilitating a deeper potassiation of the BP anode. As a result, the modified BP anode exhibits a high reversible capacity and extended operational lifespan, coupled with a high areal capacity. This work introduces a new perspective on overcoming the trade-off between low-strain and deep-potassiation in alloy anodes for the development of high-energy and stable potassium-ion batteries.

Hepatitis E virus causes apoptosis of ovarian cells in hens and resulting in a decrease in egg production.

Previous studies have shown that avian hepatitis E virus (HEV) decreases egg production by 10-40% in laying hens, but have not fully elucidated the mechanism of there. In this study, we evaluated the replication of avian HEV in the ovaries of laying hens and the mechanism underlying the decrease in egg production. Forty 150-days-old commercial laying hens were randomly divided into 2 groups of 20 hens each. A total of 1 mL (104GE) of avian HEV stock was inoculated intravenously into each chicken in the experimental group, with 20 chickens in the other group serving as negative controls. Five chickens from each group were necropsied weekly for histopathological examination. The pathogenicity of avian HEV has been characterized by seroconversion, viremia, fecal virus shedding, ovarian lesions, and decreased egg production. Both positive and negative-strand avian HEV RNA, and ORF2 antigens can be detected in the ovaries, suggesting that avian HEV can replicate in the ovaries and serve as an important extrahepatic replication site. The ovaries of laying hens underwent apoptosis after avian HEV infection. These results indicate that avian HEV infection and replication in ovarian tissues cause structural damage to the cells, leading to decreased egg production.

A novel strategy for an anti-idiotype vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2.

Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7's binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens.IMPORTANCEAnti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.

Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis.

BACKGROUND: Xuebijing (XBJ) can alleviate the inflammatory response, improve organ function, and shorten the intensive care unit (ICU) stay in patients with pyogenic liver abscess (PLA) complicated with sepsis, but the molecular mechanisms have not been elucidated. This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach. METHODS: The active ingredients and targets of XBJ were retrieved from the ETCM database. Potential targets related to PLA and sepsis were retrieved from the GeneCards, PharmGKB, DisGeNet, Online Mendelian Inheritance in Man (OMIM), Therapeutic Targets Database (TTD), and DrugBank databases. The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets. Protein-protein interaction networks were analyzed using the STRING database. Potential treatment targets were imported into the Metascape platform for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Molecular docking was performed to validate the interactions between active ingredients and core targets. RESULTS: XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis. Interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor (TNF) were identified as core targets. KEGG enrichment analysis revealed important pathways, including the interleukin-17 (IL-17) signaling pathway, the TNF signaling pathway, the nuclear factor-kappa B (NF-κB) signaling pathway, and the Toll-like receptor (TLR) signaling pathway. Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets. CONCLUSION: XBJ may exert therapeutic effects on PLA complicated with sepsis by modulating signaling pathways, such as the IL-17, TNF, NF-κB, and TLR pathways, and targeting IL-1ß, IL-6, and TNF.

[Finite element analysis of the stability of Mason type â ¢ radial head fracture fixed with three cross-bridge headless compression screw and locking plate].

OBJECTIVE: To compare the biomechanical stability of three cross-bridge headless compression screws and locking plates in the fixation of Mason type Ⅲ radial head fractures by finite element method. METHODS: Using reverse modeling technology, the radial CT data and internal fixation data of a healthy 25-year-old male were imported into the relevant software. Three-dimensional finite element model of 3 cross-bridge headless compression screws and locking plates for MasonⅢ radial head fractures were established, and the radial head was loaded with 100 N axial loading. The maximum displacement, maximum Von Mises stress and stress distribution of the two groups were compared. RESULTS: The maximum displacements of the three cross-bridge screws group and locking plate group were 0.069 mm and 0.087 mm respectively, and the Von Mises stress peaks were 18.59 MPa and 31.85 MPa respectively. The stress distribution of the three screws group was more uniform. CONCLUSION: Both internal fixation methods can provide good fixation effect. CoMPared with the locking plate fixation method, the 3 cross-bridge headless compression screws fixation is more stable and the stress distribution is more uniform.

Who are the receivers and transmitters of volatility spillovers: oil, clean energy, and green and non-green cryptocurrency markets.

In the context of clean energy and green cryptocurrency development, the relationship between energy and cryptocurrency markets deserves further exploration. This study employs a quantile time-frequency connectedness approach to measure the dynamic connectedness and volatility propagation mechanisms between oil, clean energy, green cryptocurrency (GC), and non-green cryptocurrency (NGC) markets. Our findings suggest that, at median and low volatility levels, the oil and clean energy markets act as net receivers, taking on volatility spillovers from cryptocurrency markets. However, at high volatility levels, oil and clean energy markets transform into net transmitters. Most NGCs are volatility transmitters, while most GCs are volatility receivers in the median and extremely high volatility cases. We also observe that the total connectedness index (TCI) is heterogeneous over time and dependent on economic events. At median and low volatility levels, the short-run TCI makes the primary contribution. On the other hand, for high volatility levels, where short-term TCI does not have an absolute advantage, long-term TCI plays a greater role in many periods. Additionally, there is asymmetry in the TCI (including long-term and short-term TCI) at the quantile level. In the median and extreme scenarios, the COVID-19 has caused different levels of shock on oil, clean energy, GC, and NGC markets connectedness.