Insights into the discovery and intervention of metalloproteinase in marine hazardous jellyfish.

The proliferation of toxic organisms caused by changes in the marine environment, coupled with the rising human activities along the coastal lines, has resulted in an increasing number of stinging incidents, posing a serious threat to public health. Here, we evaluated the systemic toxicity of the venom in jellyfish Chrysaora quinquecirrha at both cellular and animal levels, and found that jellyfish tentacle extract (TE) has strong lethality accompanied by abnormal elevation of blood biochemical indicators and pathological changes. Joint analysis of transcriptome and proteome indicated that metalloproteinases are the predominant toxins in jellyfish. Specially, two key metalloproteinases DN6695_c0_g3 and DN8184_c0_g7 were identified by mass spectrometry of the red blood cell membrane and tetracycline hydrochloride (Tch) inhibition models. Structurally, molecular docking and kinetic analysis are employed and observed that Tch could inhibit the enzyme activity by binding to the hydrophobic pocket of the catalytic center. In this study, we demonstrated that Tch impedes the metalloproteinase activity thereby reducing the lethal effect of jellyfish, which suggests a potential strategy for combating the health threat of marine toxic jellyfish.

Surface-phonon-polariton-enhanced photoinduced dipole force for nanoscale infrared imaging.

The photoinduced dipole force (PiDF) is an attractive force arising from the Coulombic interaction between the light-induced dipoles on the illuminated tip and the sample. It shows extreme sample-tip distance and refractive index dependence, which is promising for nanoscale infrared (IR) imaging of ultrathin samples. However, the existence of PiDF in the mid-IR region has not been experimentally demonstrated due to the coexistence of photoinduced thermal force (PiTF), typically one to two orders of magnitude higher than PiDF. In this study, we demonstrate that, with the assistance of surface phonon polaritons, the PiDF of c-quartz can be enhanced to surpass its PiTF, enabling a clear observation of PiDF spectra reflecting the properties of the real part of permittivity. Leveraging the detection of the PiDF of phonon polaritonic substrate, we propose a strategy to enhance the sensitivity and contrast of photoinduced force responses in transmission images, facilitating the precise differentiation of the heterogeneous distribution of ultrathin samples.

Paeoniflorin inhibits the inflammation of rheumatoid arthritis fibroblast-like synoviocytes by downregulating hsa_circ_009012.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint damage. Circular RNA (circRNA) can regulate the inflammatory response of fibroblast-like synoviocytes (FLSs) in RA, influencing the disease progression. Paeoniflorin (PF) is the main active ingredient extracted from Paeonia lactiflora and is known for its anti-inflammatory effect. This study aims to explore the potential mechanisms by which hsa_circ_009012 and PF regulate the inflammatory response in RA. Methods: RNA expression of hsa_circ_009012, has-microRNA-1286 (miR-1286), toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting (WB). Cell inflammation markers (TNF-α, IL-1ß, IL-6) were assessed by RT-qPCR and immunofluorescence (IF). Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to test cell viability, cell cycle distribution, and migration. Results: Hsa_circ_009012 was highly expressed in RA-FLS. Hsa_circ_009012 over-expression facilitated the inflammation in RA-FLS and was closely associated with the miR-1286/TLR4 axis. Paeoniflorin inhibited inflammation and the expression of hsa_circ_009012 and TLR4, while upregulating the expression of miR-1286 in RA-FLS. Moreover, the upregulation of hsa_circ_009012 reversed the repressive effect of paeoniflorin on RA-FLS progression. Conclusion: Paeoniflorin inhibits the inflammation of RA-FLS via mediating the hsa_circ_009012/miR-1286/TLR4/NLRP3 axis.

Binder-Free Three-Dimensional Porous Graphene Cathodes via Self-Assembly for High-Capacity Lithium-Oxygen Batteries.

The porous architectures of oxygen cathodes are highly desired for high-capacity lithium-oxygen batteries (LOBs) to support cathodic catalysts and provide accommodation for discharge products. However, controllable porosity is still a challenge for laminated cathodes with cathode materials and binders, since polymer binders usually shield the active sites of catalysts and block the pores of cathodes. In addition, polymer binders such as poly(vinylidene fluoride) (PVDF) are not stable under the nucleophilic attack of intermediate product superoxide radicals in the oxygen electrochemical environment. The parasitic reactions and blocking effect of binders deteriorate and then quickly shut down the operation of LOBs. Herein, the present work proposes a binder-free three-dimensional (3D) porous graphene (PG) cathode for LOBs, which is prepared by the self-assembly and the chemical reduction of GO with triblock copolymer soft templates (Pluronic F127). The interconnected mesoporous architecture of resultant 3D PG cathodes achieved an ultrahigh capacity of 10,300 mAh g-1 for LOBs. Further, the cathodic catalysts ruthenium (Ru) and manganese dioxide (MnO2) were, respectively, loaded onto the inner surface of PG cathodes to lower the polarization and enhance the cycling performance of LOBs. This work provides an effective way to fabricate free-standing 3D porous oxygen cathodes for high-performance LOBs.

The impact of grandparenting on mental health among rural middle-aged and older adults in China: exploring the role of children's support.

Objectives: In the rural regions of China, characterized by a pronounced aging demographic and limited resources, a substantial proportion of middle-aged and older adults engage in grandparenting roles. Yet, the literature lacks consistent evidence regarding the effects of grandparenting on the mental health of this cohort. Accordingly, this study aimed to explore the impact of grandparenting on the mental health of rural middle-aged and older adults, as well as the underlying mechanisms. Methods: This analysis encompassed 10,881 middle-aged and older adults, utilizing data from the 2018 Harmonized China Health and Retirement Longitudinal Study (CHARLS). The mental health of participants was assessed using the Center for Epidemiological Studies Depression-10 (CESD-10) scale, while support from children was categorized into financial and emotional types. The study employed logistic and OLS regression models to identify the mediating role of child support and utilized the Karlson-Holm-Breen (KHB) method for decomposing this mediating effect. Results: The findings demonstrated that grandparenting had a significant negative impact on depression among rural middle-aged and older adults. Furthermore, children's support played a vital role in mediating this relationship, accounting for approximately one-third of the overall influence. Moreover, the decomposition analysis revealed that both emotional and economic support from adult children equally contributed to the declination of depression among rural middle-aged and older adults. Conclusion: Grandparenting significantly enhances mental well-being in rural middle-aged and older adults, with the support from adult children serving as a vital pathway for this positive impact. Both economic and emotional assistance from children hold equal importance in this dynamic. It underscores the necessity of fortifying the family support system to amplify the support provided by children, which in turn could significantly enhance the mental health of rural middle-aged and older adults.

Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.

Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high-energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two-pore-domain K+ channel (K2P) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin-mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.

Renal cell carcinoma in an adult-onset ESRD patient with nephronophthisis harboring NPHP3 deletion: A case report.

Background: Nephronophthisis (NPHP) is a rare autosomal recessive inherited tubulointerstitial nephropathy, the most prevalent genetic cause of end-stage renal disease (ESRD) in children. Convincing evidence indicated that the overall prevalence of NPHP in adult-onset ESRD is very likely to be an underestimation. Therefore, understanding the genetic background and clinicopathologic features of adult-onset NPHP is warranted. Case presentation: we reported one intriguing case with concurrent NPHP3 c.2694-2_2694-1delAG (splicing) variant and c.1082C > G (p.S361C) variant. A 48-year-old male was admitted to our hospital, complained about renal dysfunction for 10 years, and found right renal space-occupying lesion for 1 week. One of the most interesting clinical features is adult-onset ESRD, which differs from previous cases. Another discovery of this study is that the NPHP harboring NPHP3 deletion may be associated with clear cell renal cell carcinoma. Conclusion: In conclusion, we report two mutations in the NPHP3 gene that cause NPHP with adult-onset ESRD and renal clear cell carcinoma in a Chinese family, enriching the clinical features of NPHP.

The association between different physical activity (PA) patterns and cardiometabolic index (CMI) in US adult population from NHANES (2007-2016).

Background: Physical activity (PA) is widely recommended for preventing and combating obesity, but the most effective PA pattern for treating obesity remains unclear. Cardiometabolic index (CMI), derived from waist height ratio and triglycerides to high-density lipoprotein-cholesterol ratio, is a novel indicator for evaluating obesity. However, the relationship between different PA patterns and CMI remains unelucidated. Objective: This study aimed to explore the association between different PA patterns and CMI in U.S. adults. Methods: Participants with complete information in CMI, PA patterns, and other covariates in the National Health and Nutrition Examination Survey database (2007-2016) were included in this study. Multivariate linear regression models were utilized to explore the relationship between PA patterns and CMI. Moreover, stratified analyses, interaction tests and restricted cubic spline (RCS) regression analysis were used to investigate the stability and nonlinearity of the association, respectively. Results: A total of 16,442 adults were included in this study. After adjusting for all potential covariates, only the regularly active group was significantly associated with CMI reduction (ß = -0.13, 95% CI: 0.19 to -0.07, P < 0.0001), while the weekend warriors group did not achieve equivalent CMI reduction (ß = -0.09, 95% CI: 0.32 to 0.14, P = 0.4204). Subgroup analyses and interaction tests revealed that the CMI-PA association was more pronounced in the subgroup with age≤45 or >60, with higher education level, and who are current drinkers. Furthermore, RCS analysis indicated that total PA in a week was significantly, nonlinearly associated with CMI in non-inactive adults, and that a total of PA more than 330 min can reap favorable CMI reduction. Conclusion: Being regularly active is associated with significant CMI reduction, while being weekend warriors and insufficiently active do not achieve equivalent benefits. For non-inactive individuals, engaging in PA for more than 330 min weekly helps to reduce CMI effectively.

Prediction of acute toxicity for Chlorella vulgaris caused by tire wear particle-derived compounds using quantitative structure-activity relationship models.

Tire wear particles (TWPs) enter aquatic ecosystems through various pathways, such as rainwater and urban runoff. Additives in TWPs can harm aquatic organisms in these ecosystems. Therefore, it is essential to investigate their toxicity to aquatic organisms. In our study, we initially recorded the median effective concentrations of 21 TWP-derived compounds on Chlorella vulgaris growth, ranging from 0.04 to 8.60 mg/L. Subsequently, through an extensive review of the literature, we incorporated 112 compounds with specific toxicity endpoints to construct the QSAR model using genetic algorithm and multiple linear regression techniques, followed by the construction of the consensus model and the quantitative read-across structure-activity relationship (q-RASAR) model. Meanwhile, we employed rigorous internal and external validation measures to assess the performance of the model. The results indicated that the developed q-RASAR model exhibited strong adaptation, robustness, and reliable prediction, with q-RASAR indicators of Q2LOO = 0.7673, R2tr = 0.8079, R2test = 0.8610, Q2Fn = 0.8285-0.8614, and CCCtest = 0.9222. Based on an external dataset containing 128 emerging TWP-derived compounds, the model's applicability domain coverage was 90.6 %. The q-RASAR model predicted that the structure of diphenylamine was associated with higher toxicity, possibly liked to the SpMax2_Bhm and LogBCF descriptors. The established model reliably provides prediction and fills a critical data gap. These findings highlight the potential risks posed by emerging TWP-derived compounds to aquatic organisms.

[Efficacy analysis of OLIF combined with posterior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots].

OBJECTIVE: To investigate the clinical efficacy of oblique lumbar interbody fusion(OLIF) combined with posterior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots(RNRs). METHODS: A retrospective analysis of 92 patients with lumbar spinal stenosis treated by oblique lateral lumbar interbody fusion combined with posterior percutaneous internal fixation from June 2019 to June 2022 was performed. There were 32 males and 60 females, aged from 44 to 82 years old with an average of (63.67±9.93) years old. All patients were divided into RNRs positive group and RNRs negative group according to redundancy or not before operation. There were 38 patients in RNRs positive group, including 15 males and 23 females. The age ranged from 45 to 82 years old with an average of (65.45±10.37) years old. The disease duration was 24.00(12.00, 72.00) months. There were 54 patients in RNRs negative group, including 17 males and 37 females. The age ranged from 44 to 77 years old with an average of (62.42±9.51) years old. The disease duration was 13.50(9.00, 36.00) months. The general data of patients were recorded, including operation time, intraoperative blood loss and complications. The imaging parameters before and after operation were observed, including the number of stenosis segments, intervertebral space height, lumbar lordosis angle and dural sac area. The visual analogue scale (VAS) was used to evaluate the back and lower extremity pain, and the Oswestry disability index (ODI) was used to evaluate the activities of daily living. RESULTS: All patients were followed up for 8 to 18 months with an average of (11.04±3.61) months, and no complications were found during the follow-up period.The number of stenosis segments in RNRs positive group (1.71±0.46) was more than that in RNRs negative group(1.17±0.38). In RNRs positive group, intervertebral space height, dural sac area, low back pain VAS, lower extremity pain VAS, ODI score were (1.11±0.19) cm, (0.46±0.17) cm2, (5.39±1.00) scores, (5.05±1.01) points, (55.74±4.05) points, respectively. RNRs negative groups respectively (0.97±0.23) cm, (0.69±0.26) cm2, (4.50±0.77) scores, (4.00±0.58) scores, (47.33±3.43) %. In RNRs positive group, intervertebral space height, dural sac area, low back pain VAS, leg pain VAS, ODI score were (1.60±0.19) cm, (0.74±0.36) cm2, (3.39±0.72) scores, (3.05±1.01) scores, (46.74±4.82) scores, respectively. RNRs negative groups respectively (1.48±0.25) cm, (1.12±0.35) cm2, (3.00±0.82) scores, (3.00±0.82) scores, (37.67±3.58) %. The postoperative intervertebral space height, dural sac area, low back pain VAS score, lower extremity pain VAS and ODI score of the patients in the RNRs positive group and the negative group were significantly improved compared with those before operation, and the differences were statistically significant (P<0.05). There were statistically significant differences in the number of stenosed segments, preoperative intervertebral space height, dural sac area, low back pain VAS, lower extremity pain VAS, and ODI between the two groups(P<0.05). There were significant differences in postoperative intervertebral space height and postoperative ODI between the two groups(P<0.05), but there was no significant difference in intervertebral space height before and after operation and ODI score before and after operation(P>0.05). There were significant differences in operation time, intraoperative blood loss, postoperative dural sac area, difference of dural sac area before and after operation, postoperative low back pain VAS, difference of low back pain VAS score before and after operation, difference of lower extremity pain VAS before and after operation between the two groups(P<0.05). CONCLUSION: OLIF combined with posterior percutaneous internal fixation has a good effect on patients with or without RNRs. Multi-segmental lumbar spinal stenosis and decreased dural sac area may lead to the occurrence of RNRs, and LSS patients with RNRs have more severe symptoms. LSS patients with RNRs have worse surgical outcomes than those without RNRs.

Consistent signatures in the human gut microbiome of old- and young-onset colorectal cancer.

The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

Absolute Configuration of Oxabornyl Polyenes Prugosenes A1-A3 and Structural Revision of Prugosene A2.

Oxabornyl polyenes represent a unique group of polyketides characterized by a central polyene core flanked by a conserved oxabornyl moiety and a structurally diverse oxygen heterocyclic ring. They are widely distributed in fungi and possess a variety of biological activities. Due to the significant spatial separation between the two stereogenic ring systems, it is difficult to establish their overall relative configurations. Here, we isolated three oxabornyl polyenes, prugosenes A1-A3 (1-3), from Talaromyces sp. JNU18266-01. Although these compounds were first reported from Penicillium rugulosum, their overall relative and absolute configurations remained unassigned. By employing ozonolysis in combination with ECD calculations, we were able to establish their absolute configurations, and additionally obtained seven new chemical derivatives (4-10). Notably, through NMR data analysis and quantum chemical calculations, we achieved the structural revision of prugosene A2. Furthermore, prugosenes A1-A3 exhibited potent antiviral activity against the respiratory syncytial virus, with compound 1 displaying an IC50 value of 6.3 µM. Our study thus provides a valuable reference for absolute configuration assignment of oxabornyl polyene compounds.

Efficacy of Sailuotong on neurovascular unit in amyloid precursor protein/presenilin-1 transgenic mice with Alzheimer's disease.

OBJECTIVE: To discuss the influence of Sailuotong (, SLT) on the Neurovascular Unit (NVUs) of amyloid precursor protein (APP)/presenilin-1(PS1) mice and evaluate the role of gas supplementation in activating blood circulation during the progression of Alzheimer's disease (AD). METHODS: The mice were allocated into the following nine groups: (a) the C57 Black (C57BL) sham-operated group (control group), (b) ischaemic treatment in C57BL mice (the C57 ischaemic group), (c) the APP/PS1 sham surgery group (APP/PS1 model group), (d) ischaemic treatment in APP/PS1 mice (APP/PS1 ischaemic group), (e) C57BL mice treated with aspirin following ischaemic treatment (C57BL ischaemic + aspirin group), (f) C57BL mice treated with SLT following ischaemic treatment (C57BL ischaemic + SLT group), (g) APP/PS1 mice treated with SLT (APP/PS1 + SLT group), (h) APP/PS1 mice treated with donepezil hydrochloride following ischaemic treatment (APP/PS1 ischaemic + donepezil hydrochloride group) and (i) APP/PS1 mice treated with SLT following ischaemic treatment (APP/PS1 ischaemic + SLT group). The ischaemic model was established by operating on the bilateral common carotid arteries and creating a microembolism. The Morris water maze and step-down tests were used to detect the spatial behaviour and memory ability of mice. The hippocampus of each mouse was observed by haematoxylin and eosin (HE) and Congo red staining. The ultrastructure of NVUs in each group was observed by electron microscopy, and various biochemical indicators were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression level was detected by Western blot. The mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The results of the Morris water maze and step-down tests showed that ischemia reduced learning and memory in the mice, which were restored by SLT. The results of HE staining showed that SLT restored the pathological changes of the NVUs. The Congo red staining results revealed that SLT also improved the scattered orange-red sediments in the upper cortex and hippocampus of the APP/PS1 and APP/PS1 ischaemic mice. Furthermore, SLT significantly reduced the content of Aß, improved the vascular endothelium and repaired the mitochondrial structures. The ELISA detection, western blot detection and qRT-PCR showed that SLT significantly increased the vascular endothelial growth factor (VEGF), angiopoietin and basic fibroblast growth factor, as well as the levels of gene and protein expression of low-density lipoprotein receptor-related protein-1 (LRP-1) and VEGF in brain tissue. CONCLUSIONS: By increasing the expression of VEGF, SLT can promote vascular proliferation, up-regulate the expression of LRP-1, promote the clearance of Aß and improve the cognitive impairment of APP/PS1 mice. These results confirm that SLT can improve AD by promoting vascular proliferation and Aß clearance to protect the function of NVUs.

Salt tolerance evaluation and mini-core collection development in Miscanthus sacchariflorus and M. lutarioriparius.

Marginal lands, such as those with saline soils, have potential as alternative resources for cultivating dedicated biomass crops used in the production of renewable energy and chemicals. Optimum utilization of marginal lands can not only alleviate the competition for arable land use with primary food crops, but also contribute to bioenergy products and soil improvement. Miscanthus sacchariflorus and M. lutarioriparius are prominent perennial plants suitable for sustainable bioenergy production in saline soils. However, their responses to salt stress remain largely unexplored. In this study, we utilized 318 genotypes of M. sacchariflorus and M. lutarioriparius to assess their salt tolerance levels under 150 mM NaCl using 14 traits, and subsequently established a mini-core elite collection for salt tolerance. Our results revealed substantial variation in salt tolerance among the evaluated genotypes. Salt-tolerant genotypes exhibited significantly lower Na+ content, and K+ content was positively correlated with Na+ content. Interestingly, a few genotypes with higher Na+ levels in shoots showed improved shoot growth characteristics. This observation suggests that M. sacchariflorus and M. lutarioriparius adapt to salt stress by regulating ion homeostasis, primarily through enhanced K+ uptake, shoot Na+ exclusion, and Na+ sequestration in shoot vacuoles. To evaluate salt tolerance comprehensively, we developed an assessment value (D value) based on the membership function values of the 14 traits. We identified three highly salt-tolerant, 50 salt-tolerant, 127 moderately salt-tolerant, 117 salt-sensitive, and 21 highly salt-sensitive genotypes at the seedling stage by employing the D value. A mathematical evaluation model for salt tolerance was established for M. sacchariflorus and M. lutarioriparius at the seedling stage. Notably, the mini-core collection containing 64 genotypes developed using the Core Hunter algorithm effectively represented the overall variability of the entire collection. This mini-core collection serves as a valuable gene pool for future in-depth investigations of salt tolerance mechanisms in Miscanthus.

Genomic nursing science revealed the prolyl 4-hydroxylase subunit alpha 2 as a significant biomarker involved in osteosarcoma.

Backgrounds: This study aims to explore the clinical value of P4HA2 (prolyl 4-hydroxylase subunit alpha 2) in Osteosarcoma (OSC), and assess its potential to provide directions and clues for the practice of precision nursing. Methods: The GSE73166 and GSE16088 datasets were used to explore the P4HA2 expression in OSC. We then used the clinical data of patients obtaining from TARGET database to assess the prognostic value of P4HA2 in OSC. We also evaluated the predictive value of prognostic model based on P4HA2-related genes. Further, GSEA analysis was performed to explore related pathways. Results: The P4HA2 mRNA expression was higher in OSC than that in normal tissues and other bone cancer samples. Survival analysis found that P4HA2 high expression caused poor overall survival (OS) of patients with OSC and P4HA2 presented a favorable performance for predicting OS. Specifically, P4HA2 high expression statistically influenced the OS of patients with age≥15 years old and those with or without metastasis. Cox regression analysis indicated the independent prognostic value of P4HA2 in OSC, and nomogram analysis revealed its significant contribution to the survival probability of patients. We further established a prognostic model based on P4HA2-related genes, finding that prognostic model had a good prediction ability on OS. These results supported the clinical significance of P4HA2 in OSC. GSEA analysis suggested that P4HA2 was significantly related to the MAPK signaling pathway. In addition, P4HA2-associated natural killer cell-mediated cytotoxicity and T cell receptor signaling pathway were also predicted. Conclusions: This study revealed that P4HA2 can serve as an important prognostic biomarker for OSC patients, and it may become a promising therapeutic target in OSC treatment.

Genomic and functional diversity of cultivated Bifidobacterium from human gut microbiota.

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

Mucin-producing tumors of the ovary--preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Identification of potential molecular mechanism related to craniofacial dysmorphism caused by FOXI3 deficiency.

BACKGROUND: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now. METHOD: In this study, we first constructed a Foxi3 deficiency (Foxi3-/- ) mouse model to verify the craniofacial phenotype of Foxi3-/- mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real-time PCR. RESULTS: By observing the phenotype of Foxi3-/- mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K-Akt signaling pathway. Quantitative real-time PCR results showed that the expression of PI3K-Akt signaling pathway-related gene Akt2 was significantly increased in Foxi3-/- mice. CONCLUSION: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K-Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.

Design, Optimization, and Modeling of a Hydraulic Soft Robot for Chronic Total Occlusions.

Chronic total occlusion (CTO) is one of the most severe and sophisticated vascular stenosis because of complete blockage, greater operation difficulty, and lower procedural success rate. This study proposes a hydraulic-driven soft robot imitating the earthworm's locomotion to assist doctors or operators in actively opening thrombi in coronary or peripheral artery vessels. Firstly, a three-actuator bionic soft robot is developed based on earthworms' physiological structure. The soft robot's locomotion gait inspired by the earthworm's mechanism is designed. Secondly, the influence of structure parameters on actuator deformation, stress, and strain is explored, which can help us determine the soft actuators' optimal structure parameters. Thirdly, the relationship between hydraulic pressure and actuator deformation is investigated by performing finite element analysis using the bidirectional fluid-structure interaction (FSI) method. The kinematic models of the soft actuators are established to provide a valuable reference for the soft actuators' motion control.