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Hirudo nipponia is an important medicinal animal in China. Its salivary gland secretions contain a variety of protein bioactive substances. Investigations of its salivary glands are of great significance in the study of the medicinal value and mechanism of leech secretions. Illumina RNA-Seq technology was used to perform transcriptome sequencing of salivary gland tissue of H . nipponia under starvation (D30) and fed (D0) states. A total of 2,650 differentially expressed genes (DEGs) were screened. Using the label-free protein quantification technique and bioinformatics analysis, the expression of differentially expressed proteins (DEPs) in the salivary gland tissue of H . nipponia was compared. A total of 2,021 proteins were identified, among which 181 proteins were differentially expressed between the starvation and fed states, with 72 significantly upregulated and 109 significantly downregulated. The salivary glands of H . nipponia synthesized protein-based active substances after 30 days of starvation and adapted to the starvation environment by weakening respiratory activity and reducing metabolic activity to reduce energy expenditure. Energy was produced by glycolysis and the tricarboxylic acid cycle for the synthesis of substances such as antibiotics. This study combined transcriptome and proteome sequencing data to provide a data reference for an in-depth study of the regulatory mechanism of salivary gland secretions of H . nipponia under starvation stress by analyzing DEGs and DEPs.

Postoperative nutritional support in gastrointestinal cancer, including enteral nutrition (EN), parenteral nutrition (PN), and combined nutrition strategies, is vital for enhancing recovery and patient outcomes. We aimed to comprehensively evaluate the impact of postoperative EN, PN, and EN + PN in patients with gastrointestinal cancer. PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wan Fang, and VIP were searched from conception until January 2, 2024. Randomized controlled trials (RCTs) that compared different postoperative nutritional support (EN, PN, or EN + PN) in patients with gastrointestinal cancer were included. The Cochrane Risk of Bias Assessment tool was used to assess the quality of the RCTs. Fixed- and random-effects models were chosen according to the heterogeneity of variables for the synthesis of results. Continuous and categorical variables were analyzed using the weighted mean difference or relative risk (RR) and 95% confidence interval (CI). In this meta-analysis, 11 RCTs were included. The PN + EN group exhibited significantly improved postoperative recovery, nutritional function, and immune indicators than the PN and EN groups ( < 0.05). Additionally, a higher incidence of postoperative complications such as abdominal distension (RR: 2.53; 95% CI: 1.17-5.49), nausea/vomiting (RR: 2.01; 95% CI: 1.09-3.71), and diarrhea (RR: 3.17; 95% CI: 1.41-7.10) was observed in the EN group than in the PN + EN group. Combining supplemental PN with enteral support improves energy intake and prognosis in gastrointestinal cancer, though limited studies restrict publication bias evaluation.

The complex dynamics of generalizedHénon map with nonconstant Jacobian determinant areinvestigated. The conditions of existence for fold bifurcation,flip bifurcation, and Hopf bifurcation are derived by using centermanifold theorem and bifurcation theory and checked up bynumerical simulations. Chaos in the sense of Marotto's definitionis proved by analytical and numerical methods. The numericalsimulations show the consistence with the theoretical analysis andreveal some new complex phenomena which can not be given bytheoretical analysis, such as the invariant cycles which areirregular closed graphics, the six and forty-one coexistinginvariant cycles, and the two, six, seven, nine, ten, and thirteencoexisting chaotic attractors, andsome kinds of strange chaotic attractors.

To investigate the effect of feeding on hibernating Hirudo nipponia, metagenomic sequencing was performed on the microorganisms collected from the digestive tract of H. nipponia individuals that were fed (FW) or starving (SW) before hibernation. In addition, the salivary gland tissues were obtained from these individuals to conduct transcriptome sequencing. Results showed that feeding before hibernation increased the relative abundance of Bacteroidetes and Proteobacteria at the phylum level and that of Aeromonas, Mucinivorans, Bacteroides, and Desulfovibrio at the genus level. Functional prediction results indicated that feeding before hibernation not only improved metabolic capacity but also increased the susceptibility of H. nipponia to pathogens. Among the 133,082 unigenes obtained by transcriptome sequencing, a total of 2801 differentially expressed genes (DEGs) were found, of which 355 were up-regulated and 2446 were down-regulated; the expression patterns of 15 selected DEGs were validated by qRT-PCR. Results from the GO and KEGG enrichment analyses showed that a majority of these DEGs were involved in the signal transduction pathways. This study established a basis for H. nipponia breeding during hibernation through analyses of the abundance of microorganisms in the digestive tract and the gene expression pattern of salivary glands by high-throughput sequencing. The findings also revealed the effect of feeding on the expression of both gastrointestinal microorganisms and salivary gland genes of hibernating H. nipponia.

To investigate the effect of feeding on hibernating Hirudo nipponia, metagenomic sequencing was performed on the microorganisms collected from the digestive tract of H. nipponia individuals that were fed (FW) or starving (SW) before hibernation. In addition, the salivary gland tissues were obtained from these individuals to conduct transcriptome sequencing. Results showed that feeding before hibernation increased the relative abundance of Bacteroidetes and Proteobacteria at the phylum level and that of Aeromonas, Mucinivorans, Bacteroides, and Desulfovibrio at the genus level. Functional prediction results indicated that feeding before hibernation not only improved metabolic capacity but also increased the susceptibility of H. nipponia to pathogens. Among the 133,082 unigenes obtained by transcriptome sequencing, a total of 2801 differentially expressed genes (DEGs) were found, of which 355 were up-regulated and 2446 were down-regulated; the expression patterns of 15 selected DEGs were validated by qRT-PCR. Results from the GO and KEGG enrichment analyses showed that a majority of these DEGs were involved in the signal transduction pathways. This study established a basis for H. nipponia breeding during hibernation through analyses of the abundance of microorganisms in the digestive tract and the gene expression pattern of salivary glands by high-throughput sequencing. The findings also revealed the effect of feeding on the expression of both gastrointestinal microorganisms and salivary gland genes of hibernating H. nipponia.

The complex behaviors of Duffing equation with periodic damping and external excitations are investigated. The existence conditions and bifurcations of periodic orbits with three different frequencies resonant conditions are concerned by the second-order averaging method and the Melnikov method. The rich dynamical behaviors are so distinct when different periodic damping excitations are added, including more complicated averaged equations, bifurcation curves, bifurcation conditions, and even chaos. The numerical simulations show the consistence with the theoretical analysis and reveal new complex phenomena which cannot be given by theoretical analysis.

Aims Growing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV‐971 in NMOSD. GV‐971 is a drug used for treating mild‐to‐moderate Alzheimer's disease, which targets the gut‐brain axis and reduces neuroinflammation. Methods To evaluate GV‐971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO‐IgG into aged mice (11 months old) or using NMO‐IgG along with complement injection and microbubble‐enhanced low‐frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV‐971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis. Results Our findings indicated that GV‐971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV‐971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders. Conclusions GV‐971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders. The NMOSD model demonstrated substantial neuroinflammation and neural injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that exacerbates disease pathogenesis. Notably, GV‐971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders.

Cathepsin B (CatB) is a cysteine proteolytic enzyme widely expressed in various cells and mainly located in the lysosomes. It contributes to the pathogenesis and development of many diseases. However, the role of CatB in viral myocarditis (VMC) has never been elucidated. Here we generated the VMC model by intraperitoneal injection of coxsackievirus B3 (CVB3) into mice. At day 7 and day 28, we found CatB was significantly activated in hearts from VMC mice. Compared with the wild-type mice receiving equal amount of CVB3, genetic ablation of CatB (Ctsb-/-) significantly improved survival, reduced inflammatory cell infiltration, decreased serum level of cardiac troponin I, and ameliorated cardiac dysfunction, without altering virus titers in hearts. Conversely, genetic deletion of cystatin C (Cstc-/-), which markedly enhanced CatB levels in hearts, distinctly increased the severity of VMC. Furthermore, compared with the control, we found the inflammasome was activated in the hearts of wild-type mice with VMC, which was attenuated in the hearts of Ctsb-/- mice but was further enhanced in Cstc-/- mice. Consistently, the inflammasome-initiated pyroptosis was reduced in Ctsb-/- mice hearts and further increased in Cstc-/- mice. These results suggest that CatB aggravates CVB3-induced VMC probably through activating the inflammasome and promoting pyroptosis. This finding might provide a novel strategy for VMC treatment.

Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s), if any, during postinfarction cardiac remodeling. Acute myocardial infarction (AMI) was induced by ligating left anterior descending (LAD) coronary artery. Autophagy was found to be induced sharply 12-24 hours after surgery by testing LC3 modification and Electron microscopy. P62 degradation in the infarct border zone was increased from day 0.5 to day 3, and however, decreased from day 5 until day 21 after LAD ligation. These results indicated that autophagy was induced in the acute phase of AMI, and however, impaired in the latter phase of AMI. To investigate the significance of the impaired autophagy in the latter phase of AMI, we treated the mice with Rapamycin (an autophagy enhancer, 2.0 mg/kg/day) or 3-methyladenine (3MA, an autophagy inhibitor, 15 mg/kg/day) one day after LAD ligation until the end of experiment. The results showed that Rapamycin attenuated, while 3MA exacerbated, postinfarction cardiac remodeling and dysfunction respectively. In addition, Rapamycin protected the H9C2 cells against oxygen glucose deprivation in vitro. Specifically, we found that Rapamycin attenuated NFκB activation after LAD ligation. And the inflammatory response in the acute stage of AMI was significantly restrained with Rapamycin treatment. In vitro, inhibition of NFκB restored autophagy in a negative reflex. Sustained myocardial ischemia impairs cardiomyocyte autophagy, which is an essential mechanism that protects against adverse cardiac remodeling. Augmenting autophagy could be a therapeutic strategy for acute myocardial infarction.

The three-dimensional finite difference method was used in this study to analyze the deformation and stresses of a passive pile under surcharge load in extensively deep soft soil. A three-dimensional numerical model was proposed and verified by a field test. The horizontal displacements of the pile agreed well with the field results. This study investigated the pile-foundation soil interaction, the load transfer mechanism, the excess pore water pressure (EPWP), and the horizontal resistance of the foundation soil. The results show that the soil in the corner of the loading area developed a large uplift deformation, while the center of the loading area developed a large settlement. The lateral displacement of the pile decreased sharply with the increase of the depth and increased with the surcharge load. The lateral displacement of the soil was negligible when the depth exceeded 30 m. The EPWP increased in a nonlinear way with the increase of the surcharge load and accumulated with the placement of the new lift. The distribution of the lateral earth pressure in the shallow soil layer was complex, and the negative value was observed under a high surcharge load due to the suction effect. The proportion coefficient of the horizontal resistance coefficient showed much smaller value in the situation of large lateral deformation and high surcharge load. The design code overestimated the horizontal resistance of the shallow foundation soil, which should be given attention for the design and analysis of the laterally loaded structures in extensively soft soil.