Six undescribed 23-norursane triterpenoids from the biotransformation of ilexgenin a by endophytic fungi and their vascular protective activity.

Biotransformation of ursane-type triterpenoid ilexgenin A by endophytic fungi Lasiodiplodia sp. MQD-4 and Pestalotiopsis sp. ZZ-1, isolated from Ilex pubescences and Callicarpa kwangtungensis respectively, was investigated for the first time. Six previously undescribed metabolites (1-6) with 23-norursane triterpenoids skeleton were isolated and their structures were unambiguously established by the analysis of spectroscopic data and single-crystal X-ray crystallographic experiments. Decarboxylation, oxidation, and hydroxylation reactions were observed on the triterpenoid skeleton. Especially, the decarboxylation of C-23 provided definite evidence to understand the biogenetic process of 23-norursane triterpenoids. Moreover, the qualitative analysis of the extract of I. pubescences showed metabolites 1, 3, 4, and 6 could be detected in the originated plant, indicating biotransformation by endophytic fungi is a practical strategy for the isolation of novel natural products. Finally, all isolates were evaluated for the protective activities against H2O2-induced HUVECs dysfunction in vitro. Compound 5 could improve the viability of endothelial cells and decrease the level of intracellular ROS.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.

Association between napping and cognitive impairment: A systematic review and meta-analysis.

STUDY OBJECTIVES: Increasing evidence suggests that napping is associated with cognitive impairment and dementia, but the conclusions are inconsistent. Moreover, the extent of the risk is uncertain. We therefore conducted a systematic review and meta-analysis to quantify the connection between napping and cognitive impairment. METHODS: We performed a systematic search of PubMed, EMBASE, Web of Science, and Cochrane Library for studies that were published up to June 2023, and assessed associations between napping and cognitive impairment. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as the effect sizes for all studies. Heterogeneity and potential publication biases were assessed. RESULTS: A total of 4535 papers were retrieved, with 20 reports assessing the relationships between napping and cognitive impairment. Pooled analysis indicated that napping was associated with dementia (OR = 1.14; 95% CI: 1.07-1.21). Importantly, we found that those napping longer than 30, 45, and 60 min/day were 35%, 41%, and 40%, respectively, more likely to have an increased risk of cognitive impairment (30 min: OR = 1.35; 95% CI: 1.24-1.48; 45 min: OR = 1.41; 95% CI: 1.27-1.58; 60 min: OR = 1.40; 95% CI: 1.26-1.56). North America and Europe showed that associations existed between napping and cognitive impairment (North America: OR = 1.15; 95% CI: 1.04-1.27; Europe: OR = 1.13; 95% CI: 1.08-1.18). CONCLUSIONS: This meta-analysis indicated associations between long napping durations and cognitive impairment or dementia, suggesting that longer napping might be a potential risk factor of adverse cognitive outcomes.

Genetic Diversity and Evolution of Viruses Infecting Felis catus: A Global Perspective.

Cats harbor many important viral pathogens, and the knowledge of their diversity has been greatly expanded thanks to increasingly popular molecular sequencing techniques. While the diversity is mostly described in numerous regionally defined studies, there lacks a global overview of the diversity for the majority of cat viruses, and therefore our understanding of the evolution and epidemiology of these viruses was generally inadequate. In this study, we analyzed 12,377 genetic sequences from 25 cat virus species and conducted comprehensive phylodynamic analyses. It revealed, for the first time, the global diversity for all cat viruses known to date, taking into account highly virulent strains and vaccine strains. From there, we further characterized and compared the geographic expansion patterns, temporal dynamics and recombination frequencies of these viruses. While respiratory pathogens such as feline calicivirus showed some degree of geographical panmixes, the other viral species are more geographically defined. Furthermore, recombination rates were much higher in feline parvovirus, feline coronavirus, feline calicivirus and feline foamy virus than the other feline virus species. Collectively, our findings deepen the understanding of the evolutionary and epidemiological features of cat viruses, which in turn provide important insight into the prevention and control of cat pathogens.

Water-Gas Shift Catalyzed by Iridium-Vanadium Oxide Clusters IrVO2- with Iridium in a Rare Oxidation State of -II.

The discovery of compounds containing transition metals with an unusual and well-established oxidation state is vital to enrich our horizon on formal oxidation state. Herein, benefiting from the study of the water-gas shift reaction (CO + H2O → CO2 + H2) mediated with the iridium-vanadium oxide cluster IrVO2-, the missing -II oxidation state of iridium was identified. The reactions were performed by using our newly developed double ion trap reactors that can spatially separate the addition of reactants and are characterized by mass spectrometry and quantum-chemical calculations. This finding makes an important step that all the proposed 13 oxidation states of iridium (+IX to -III) have been known. The iridium atom in the IrVO2- cluster features the Ir═V double bond and resembles chemically the coordinated oxygen atom. A reactivity study demonstrated that the flexible role switch of iridium between an oxygen-atom like (Ir-IIVO2-) and a transition-metal-atom like behavior (Ir+IIVO3-) in different species can drive the water-gas shift reaction in the gas phase under ambient conditions. This result parallels and well rationalizes the extraordinary reactivity of oxide-supported iridium single-atom catalysts in related condensed-phase reactions.

Surgical timing for primary encapsulating peritoneal sclerosis: A case report and review of literature.

BACKGROUND: Primary encapsulating peritoneal sclerosis (EPS) is a rare but devastating disease that causes fibrocollagenous cocoon-like encapsulation of the bowel, resulting in bowel obstruction. The pathogenesis, prevention, and treatment strategies of EPS remain unclear so far. Since most patients are diagnosed during exploratory laparotomy, for the non-surgically diagnosed patients with primary EPS, the surgical timing is also uncertain. CASE SUMMARY: A 44-year-old female patient was referred to our center on September 6, 2021, with complaints of abdominal distention and bilious vomiting for 2 d. Physical examination revealed that the vital signs were stable, and the abdomen was slightly distended. Computerized tomography scan showed a conglomerate of multiple intestinal loops encapsulated in a thick sac-like membrane, which was surrounded by abdominal ascites. The patient was diagnosed with idiopathic EPS. Recovery was observed after abdominal paracentesis, and the patient was discharged on September 13 after the resumption of a normal diet. This case raised a question: When should an exploratory laparotomy be performed on patients who are non-surgically diagnosed with EPS. As a result, we conducted a review of the literature on the clinical manifestations, intraoperative findings, surgical methods, and therapeutic effects of EPS. CONCLUSION: Recurrent intestinal obstructions and abdominal mass combined with the imaging of encapsulated bowel are helpful in diagnosing idiopathic EPS. Small intestinal resection should be avoided.

Feline Calicivirus Virulent Systemic Disease: Clinical Epidemiology, Analysis of Viral Isolates and In Vitro Efficacy of Novel Antivirals in Australian Outbreaks.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2'-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI = 21; 2CMC EC50, 2.7-5.3 µM, TI > 18; NITD-008, 0.5 to 0.9 µM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted.

An IrVO4+ Cluster Catalytically Oxidizes Four CO Molecules: Importance of Ir-V Multiple Bonding.

The generation and characterization of multiple metal-metal (M-M) bonds between early and late transition metals is vital to correlate the nature of multiple M-M bonds with the related reactivity in catalysis, while the examples with multiple M-M bonds have been rarely reported. Herein, we identified that the quadruple bonding interactions were formed in a gas-phase ion IrV+ with a dramatically short Ir-V bond. Oxidation of four CO molecules by IrVO4+ is a highly exothermic process driven by the generation of stable products IrV+ and CO2, and then IrV+ can be oxidized by N2O to regenerate IrVO4+. This finding overturns the general impression that vanadium oxide clusters are unwilling to oxidize multiple CO molecules because of the strong V-O bond and that at most two oxygen atoms can be supplied from a single V-containing cluster in CO oxidation. This study emphasizes the potential importance of heterobimetallic multiple M-M bonds in related heterogeneous catalysis.

LncRNA-LINC00472 contributes to the pathogenesis of atrial fibrillation (Af) by reducing expression of JP2 and RyR2 via miR-24.

BACKGROUND: Dysregulated methylation of the promoter of lncRNA LINC00472 reduces the expression of LINC00472 and subsequently up-regulates the expression of its competing endogenous RNA miR-24. In addition, JP2 can stabilize the expression of RyR2, whereas the deregulation of RyR2 expression may contribute to the pathogenesis of atrial fibrillation (AF). In this study, we aimed to study the role of LINC00472 in the pathogenesis of AF. METHODS: 125 AF patients and 168 healthy controls were enrolled to compare their expression of miR-24, LINC00472, JP2 and RyR2. A dual-luciferase reporter gene assay accompanied by real-time PCR, Western blot and IHC assay was subsequently conducted to evaluate the regulatory relationship among miR-24, LINC00472, JP2 and RyR2 in HCM and H9C2 cells. RESULTS: AF patients were associated with an increased level of miR-24 expression and reduced level of LINC00472 expression. Also, the level of DNA methylation in LINC00472 was increased in AF patients. MiR-24 could negatively regulate the expression of LINC00472 and JP2 by directly binding to them. CONCLUSIONS: LINC00472 could regulate the progression of AF via modulating the LINC00472/miR-24/JP2/RyR2 signaling pathway.

Predicting the weld width from high-speed successive images of the weld zone using different machine learning algorithms during laser welding.

The dynamic behavior of the keyhole and molten pool is associated with the quality of weld seam. In this study, an on-line visual monitoring system is devised to photograph the keyhole and molten pool during external magnetic field assisted laser welding on the AISI 2205 duplex stainless steel plates. Seven features are defined to describe the morphology of the keyhole and molten pool. Then, the principal component analysis (PCA) algorithm is applied to reduce the dimensions of these features to obtain different number of principal components (PCs). Three different machine learning algorithms, i.e. the back propagation neural network (BPNN), the radial based function neural network (RBFNN) and the support vector regression (SVR), are utilized to fit the relationship between the chosen PCs and the weld width. Finally, the global and local prediction accuracy of these three machine learning algorithms are compared under different number of PCs. Results illustrated that data dimensionality reduction is helpful to improve the modeling efficiency. Machine learning algorithms can be exploited to predict the weld quality during laser welding with high accuracy. Among them, the BPNN model performs best and SVR model performs better than RBFNN model in this research. This work aims to model the relation between the features in weld zone and the weld quality with different machine learning algorithms, and provides a guideline of model selection for laser welding on-line monitoring and a necessary foundation for realizing intelligent welding with advanced algorithm.

MXene-supported Co3O4 quantum dots for superior lithium storage and oxygen evolution activities.

A novel hybrid, composed of Co3O4 quantum dots supported on Ti3C2Tx (MXene) nanosheets, exhibits a strong synergetic effect, and shows superior lithium storage (capacity = 766.5 mA h g-1 at 2 A g-1 after 400 cycles) and oxygen evolution (overpotential = 340 mV at 10 mA cm-2) activities.

[Gardner syndrome with chronic osteomyelitis of the jaw: a case report].

Gardner syndrome is a rare autosomal dominant disease. Its symptoms include multiple intestinal polyps, soft tissue tumors, dental disorders, osteoma, and congenital hypertrophy of the retinal pigment epithelium. Here, we present a patient with Gardner syndrome and chronic osteomyelitis of the jaw to highlight the serious damage that can be caused by Gardner syndrome.

Creating a synergistic interplay between tubular MoS2 and particulate Fe3O4 for improved lithium storage.

A novel three-dimensional MoS2@Fe3O4 nanohybrid, composed of tubular MoS2 uniformly and densely decorated with particulate Fe3O4, is constructed, which exhibits significantly improved lithium storage performances through an impressive synergistic interplay between the two active materials.

Efficacy and safety of celecoxib in chinese patients with ankylosing spondylitis: a 6-week randomized, double-blinded study with 6-week open-label extension treatment.

BACKGROUND: Nonsteroidal anti-inflammatory drugs are the first-line option for treating ankylosing spondylitis (AS) in China. However, no large-scale controlled trials have been conducted in this ethnic population. OBJECTIVE: To evaluate the efficacy and safety of 6 weeks' treatment with celecoxib in patients with AS in China. METHODS: This Phase 3, double-blind, parallel-group study randomized patients with AS aged ≥18 to 65 years 1:1 to receive celecoxib 200 mg once daily or diclofenac sustained release 75 mg once daily. After 6 weeks, patients could use celecoxib 400 mg once daily or maintain blinded therapy. The primary efficacy end point was mean change from baseline at Week 6 for Patient's Global Assessment of Pain Intensity score (100-mm visual analog scale). Noninferiority was established if the upper bound of the CI was <10 mm. Secondary objectives included patients' and physicians' assessments of disease activity, change from baseline in C-reactive protein level, and safety. RESULTS: In the per-protocol analysis set the least squares mean change from baseline in the Patient's Global Assessment of Pain Intensity score at Week 6 was -23.8 mm and -27.1 mm in patients receiving celecoxib (n = 111) and diclofenac (n = 108), respectively. The 2-sided 95% CI for the treatment difference (celecoxib - diclofenac) was -2.2 to 8.8. Overall, 4.2% and 6.7% of patients in the celecoxib and diclofenac groups, respectively, reported treatment-related adverse events. All were mild to moderate in severity. CONCLUSIONS: Celecoxib 200 mg once daily is noninferior to diclofenac sustained release 75 mg once daily for pain treatment in Chinese patients with AS. ClinicalTrials.gov identifier: NCT00762463.

Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury.

Long-term potentiation (LTP) is the key cellular mechanism for physiological learning and pathological chronic pain. In the anterior cingulate cortex (ACC), postsynaptic recruitment or modification of AMPA receptor (AMPAR) GluA1 contribute to the expression of LTP. Here we report that pyramidal cells in the deep layers of the ACC send direct descending projecting terminals to the dorsal horn of the spinal cord (lamina I-III). After peripheral nerve injury, these projection cells are activated, and postsynaptic excitatory responses of these descending projecting neurons were significantly enhanced. Newly recruited AMPARs contribute to the potentiated synaptic transmission of cingulate neurons. PKA-dependent phosphorylation of GluA1 is important, since enhanced synaptic transmission was abolished in GluA1 phosphorylation site serine-845 mutant mice. Our findings provide strong evidence that peripheral nerve injury induce long-term enhancement of cortical-spinal projecting cells in the ACC. Direct top-down projection system provides rapid and profound modulation of spinal sensory transmission, including painful information. Inhibiting cortical top-down descending facilitation may serve as a novel target for treating neuropathic pain.

Serine-arginine protein kinase 1 is associated with breast cancer progression and poor patient survival.

Breast cancer is the most common cancer and the second leading cause of mortality for women worldwide. It is necessary to identify valuable molecular markers to predict breast cancer progression in patients and treatment effect. Serine-arginine protein kinase 1 (SRPK1), a member of SR kinase family, phosphorylates the SR splicing factors which plays essential roles in normal cell development and multiple human diseases. In the current study, we wanted to explore if there are any relationships between SRPK1 expression in breast cancer and its clinical characteristics. The results showed that SRPK1 is upregulated in breast cancer cell lines and tissues at both mRNA and protein levels, measured by quantitative reverse transcriptase PCR and Western blotting. Immunohistochemical analysis showed a high expression of SRPK1 in 132 paraffin samples of patients with breast cancer; statistical analyses demonstrated that high expression of SRPK1 significantly correlated with clinical staging of patients with breast cancer (P < 0.001), TNM classification (P < 0.05). Low expression of SRPK1 leads to longer survival time, while high expression of SRPK1 leads to shorter survival time of patients. Multivariate analysis revealed that upregulation of SRPK1 might be an independent prognostic marker for the outcomes of patients with breast cancer. In conclusion, upregulation of SRPK1 might play an important role in the progression of breast cancer and might be considered as the potential diagnostic and therapeutic target to this malignancy.

[Mesenchymal stem cells for treatment of steroid-resistant chronic graft-versus-host disease].

OBJECTIVE: To assess whether treatment with mesenchymal stem cells (MSCs) is an effective adjunct therapy for refractory extensive chronic graft-versus-host disease (GVHD) resistant to conventional therapy. METHODS: 12 patients with steroid-resistant extensive chronic GVHD were treated with MSCs. One patient received one dose, 10 received two doses, and the remaining three doses. The MSCs were obtained from HLA-identical sibling donors (n = 14), haploidentical donors (n = 2), unrelated mismatched donor (n = 1) and third-party HLA-mismatched donors (n = 7). Of the 11 patients treated with multiple infusions, 5 received cells derived from two donors. The median first dose of MSCs was 1.0 (0.4-2.1) x 10(6)/kg, the median second dose was 1.2 (0.8-1.9) x 10(6)/kg , and the third dose in one patient was 1.1 x 10(6)/kg. Meanwhile the proportion of CD3+, CD4+, CD8+, CD19+, CD4+, CD25+, FOXP3+, FOXP3+ CD4+ and FOXP3 + CD25+ was determined with double fluorescent-labeled antibodies and flow cytometry before and 4 weeks after the MSCs infusion. RESULTS: No patients had side-effects during or immediately after the infusions of MSCs. After a treatment course of one to three doses, 3 patients had complete response( CR), 6 showed partial response (PR) and 3 did not respond; the total effective rate was 75% (9/12). Complete resolution was seen in the involvement of skin (3/12), lung (1/3), joints (1/5), liver (3/10), oral cavity (4/12) and eye (2/7). Response rate was not related to donor HLA-match. 3 CR patients discontinued all of the immunosuppressive agents without relapse 100 to 292 days after the MSC infusion and 6 PR patients taped all immunosuppressive agents after 60 to 79 days. Mean follow-up period was 1152 (795-1914) days, leukemia free survival rate was 91.7% (11/12) and the overall survival rate was 75% (9/12). The ratio of CD4/CD8 and the proportion of regulatory T cells were significantly higher than that before MSCs treatment. CONCLUSION: Third-party MSCs were as effective as HLA-identical or haploidentical cells. This finding has practical implications and suggests that third-party cells can be prepared and stored frozen to be used for steroid-resistant extensive chronic GVHD therapy. It is concluded that MSCs may prevent the lethal cGVHD after allogeneic hematopoietic stem cell transplantation and raise the survival rate by increasing the ratio of CD4/CD8 and proportion of regulatory T cells in vivo.

[Identification of acute lymphoctic leukemia extramedullary relapse and PTLD after allo-HSCT by monitoring sex chromosome chimeric status with FISH].

OBJECTIVE: To explore the role of monitoring sex chromosome chimeric status by fluorescence in situ hybridization (FISH) in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Six ALL patients who received sex-mismatched allo-HSCT and manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrows (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH). RESULTS: The sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. The other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and were diagnosed PTLD. EBV-RNA and latent membrane protein (LMP-1) were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy. CONCLUSION: Monitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.