Identification of concurrent infection with Jaagsiekte sheep retrovirus and maedi-visna virus in China.

IMPORTANCE: Ovine pulmonary adenomatosis (OPA) and maedi-visna disease (MVD) are chronic and progressive infectious diseases in sheep caused by Jaagsiekte sheep retrovirus (JSRV) and maedi-visna virus (MVV), respectively. OBJECTIVE: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China. METHODS: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022. RESULTS: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464). CONCLUSIONS AND RELEVANCE: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.

Lesion Localization and Pathological Diagnosis of Ovine Pulmonary Adenocarcinoma Based on MASK R-CNN.

Ovine pulmonary adenocarcinoma (OPA) is a contagious lung tumour caused by the Jaagsiekte Sheep Retrovirus (JSRV). Histopathological diagnosis is the gold standard for OPA diagnosis. However, interpretation of traditional pathology images is complex and operator dependent. The mask regional convolutional neural network (Mask R-CNN) has emerged as a valuable tool in pathological diagnosis. This study utilized 54 typical OPA whole slide images (WSI) to extract 7167 typical lesion images containing OPA to construct a Common Objects in Context (COCO) dataset for OPA pathological images. The dataset was categorized into training and test sets (8:2 ratio) for model training and validation. Mean average specificity (mASp) and average sensitivity (ASe) were used to evaluate model performance. Six WSI-level pathological images (three OPA and three non-OPA images), not included in the dataset, were used for anti-peeking model validation. A random selection of 500 images, not included in the dataset establishment, was used to compare the performance of the model with assessment by pathologists. Accuracy, sensitivity, specificity, and concordance rate were evaluated. The model achieved a mASp of 0.573 and an ASe of 0.745, demonstrating effective lesion detection and alignment with expert annotation. In Anti-Peeking verification, the model showed good performance in locating OPA lesions and distinguished OPA from non-OPA pathological images. In the random 500-image diagnosis, the model achieved 92.8% accuracy, 100% sensitivity, and 88% specificity. The agreement rates between junior and senior pathologists were 100% and 96.5%, respectively. In conclusion, the Mask R-CNN-based OPA diagnostic model developed for OPA facilitates rapid and accurate diagnosis in practical applications.

Bmi-1 alleviates alveolar bone resorption through the regulation of autophagy.

BACKGROUND: B-cell­specific Moloney MLV insertion site-1(Bmi-1)is a crucial osteopenic target molecule. The aim of this study is to explore the effects of Bmi-1 on alveolar bone resorption and the underlying mechanisms in vitro and vivo. METHODS: A Bmi-1-knockout (Bmi-1-/-) mouse model was used to investigate the effect of Bmi-1 on alveolar bone metabolism, with micro-computed tomography imaging, histology, and immunohistochemistry staining. Furthermore, we utilized a ligature-induced experimental periodontitis model to examine the impact of Bmi-1-knockdown (Bmi-1±) on inflammatory alveolar bone resorption. Finally, we stimulated human periodontal ligament stem cells (hPDLSCs) with lipopolysaccharide (LPS) to explore the potential mechanism of Bmi-1 overexpression in the process of osteogenesis. RESULTS: Compared with wild-type mice, Bmi-1-/- mice demonstrated more alveolar bone resorption by inhibiting osteogenesis, which was characterized by decreases in Runt-related transcription factor 2 and type 1 collagen formation. In addition, Bmi-1-/- mice had lower levels of autophagy markers such as Parkin and LC3, but higher levels of inflammation-related factors such as interleukin (IL)-6 and IL-1ß in periodontal tissues. In addition, Bmi-1-knockdown aggravated ligature-induced alveolar bone loss. Under in vitro inflammatory conditions, Bmi-1 overexpression stimulated osteoblast differentiation and inhibited the production of inflammatory factors, as well as the autophagy and apoptosis in hPDLSCs stimulated with LPS. When 3-methyladenine (3-MA), an autophagy inhibitor, was added, the osteogenic effect of Bmi-1 was further enhanced. CONCLUSIONS: Bmi-1 alleviates alveolar bone resorption by regulating autophagy, indicating that it could be a potential target for periodontitis prevention and treatment. PLAIN LANGUAGE SUMMARY: Periodontitis is a chronic inflammatory disease, which leads to progressive destruction of periodontal tissues, manifested as periodontal pocket formation, loss of periodontal attachment and alveolar bone resorption. Currently, there is a lack of effective treatments to regenerate damaged periodontal tissues. Therefore, it is of great clinical significance to explore new mechanisms of periodontitis and effective intervention targets. B-cell­specific Moloney MLV insertion site-1 (Bmi-1) is involved in the regulation of the cell cycle, DNA damage repair, autophagy, bone metabolism, tumor, and other physiopathological processes. Autophagy, as an important mechanism of intracellular self-regulation, plays an indispensable role in the destruction and repair of periodontal tissues. The aim of this study was to investigate the role of Bmi-1 on periodontal tissues and its intrinsic mechanism. The results revealed that Bmi-1 regulates autophagy to protect periodontal tissues, suggesting that it may be a potential target for the prevention and treatment of periodontitis.

A rare case report of endobronchial neurofibroma treated with transbronchial endoscopic resection and literature review.

RATIONALE: Endobronchial neurofibroma is an extremely rare neoplastic disease. The majority of endobronchial neurofibroma are symptomatic, but nonspecific. The treatment of endobronchial neurofibroma is controversial that surgery is previously considered to be the main option. With the development of bronchoscopic intervention, most endobronchial neurofibroma can be treated with transbronchial endoscopic resection with few complications. Here we reported a case of diagnosed endobronchial neurofibroma that was successfully resected with transbronchial electrical snaring and laser coagulation. Moreover, the relevant literature was reviewed to raise awareness of this disease. PATIENT CONCERNS: A 57-year-old man presented to our hospital with cough, sputum, and shortness of breath for 2 days. Physical examination was normal. Laboratory tests revealed moderately increased C-reactive protein. Chest computed tomography showed a 10 × 8 mm round, polypoid-shaped nodule located in the left main bronchus, which was heterogeneous after contrast enhancement. It demonstrated a smooth, round, hypervascularized neoplasma obstructing most of the lumen of the upper left main bronchus under bronchoscopy. INTERVENTIONS AND OUTCOMES: The tumor was removed with electrical snaring and laser coagulation completely instead of surgical resection, without any complications. Pathologically, it was confirmed of endobronchial neurofibroma. Repeated bronchoscopy showed no recurrence of the tumor, and the procedure site healed with a little of fibrotic scar formation. LESSONS: Endobronchial neurofibroma is rare. Although the standard treatment for endobronchial neurofibroma is surgery, transbronchial endoscopic resection (electrical snaring and laser coagulation) is an applicable option, especially for those lesions strictly in the lumen.

Data-Driven Subtypes of Multiple System Atrophy and Their Implications for Prognosis.

Background: While multiple system atrophy (MSA) presents with high heterogeneous motor and nonmotor symptoms, the associations between clinical phenotypes and prognosis are unclear. Objective: We aimed to evaluate clinical phenotypes of MSA using data-driven approach and measure the impact of phenotypes on survival and bedbound status. Methods: 193 MSA patients were recruited from Xuanwu Hospital Capital Medical University, whose history, motor and non-motor symptoms were examined using cluster analysis. Ninety-five participants were followed-up via telephone after a mean of 31.87 months. We employed Kaplan- Meier analysis to examine survival and performed Cox and logistic regression analyses to identify factors associated with survival and bedbound status. Results: We identified four clinical profiles of MSA: cerebellar symptom-dominant, sleep and mood disorder-dominant, rigid akinetic-dominant, and malignant diffuse. The overall median survival was 7.75 years (95% CI 7.19-8.31). After adjusting for years from symptom onset to diagnosis, age and sex, patients in the malignant diffuse and rigid akinetic-dominant clusters had greater risk of death than sleep and mood disorder-dominant cluster. Furthermore, patients in the malignant diffuse and rigid akinetic-dominant clusters had higher risk of being bedbound than cerebellar symptom-dominant cluster. Conclusions: The malignant diffuse and sleep and mood disorder-dominant were identified besides the two classical subtypes, parkinsonism, and cerebellar symptom-variant. Patients with rigid-akinetic motor profiles have a worse prognosis than cerebellar symptom-dominant profiles in general. Diffuse symptoms, especially postural instability, and cognitive alterations at diagnosis, indicate rapid functional loss and disease progression. The different profiles and prognoses might indicate varied underlying pathological mechanisms.

Multiple system atrophy (MSA) is a complex disease that can affect both movement and non-movement functions of patients. However, we do not know much about how these different symptoms relate to how the patient's health might change over time. In this study, we looked at 193 MSA patients to learn more about if the patients can be distinguished into different subgroups at diagnosis and if the subgroups might be associated with their survival and ability to move in the future. We found four main subgroups of patients: group 1 characterized by the dysfunction of cerebellum (a part of the brain), group 2 characterized by sleep and mood problems, group 3 characterized by rigidity and slow movements, and group 4 with diffuse symptoms mentioned above. After tracking 95 patients for nearly 32 months, we found that those characterized by rigidity and slow movements, and those with diffuse symptoms had a higher chance of dying compared to those characterized by sleep and mood problems. Group 3 and 4 also had a higher chance of becoming unable to move out of bed. This suggests that patients with severe symptoms of rigidity and slowness at diagnosis tend to have a worse outlook than those without. And if multiple MSA symptoms are found when the patient is diagnosed, especially trouble with thinking, are also signs that the disease is getting worse quickly. By understanding these disease patterns, we can better tailor treatments and provide better support for people with MSA.

Exploration of GmDof11-lncRNA13082 Module Regulating Oil Synthesis in Plants.

Soybean (Glycine max [Linn.] Merr.) is an important oilseed crop. Although transcription factors (TFs) can coordinate the expression of mRNA and lncRNA, their coordination in the soybean oil synthesis pathway remains unclear. This study examined the interaction between the TF GmDof11 and lncRNA13082 and found that overexpression of GmDof11 led to an increase in the number of Arabidopsis seeds, thousand seed weight, crude protein, hydrolysis amino acid, and soluble sugar. Additionally, it reduced the triglyceride and starch contents and affected the proportion of fatty acids, increasing the contents of palmitic acid, stearic acid, and linolenic acid. The yeast two-hybrid experiments revealed that GmDof11 interacts with GmBCCP1, GmLEC1b, and GmFAB2 proteins. In the RT-qPCR analysis of transgenic soybean roots, it was found that GmDof11 can activate the production of lncRNA13082 and work in conjunction with lncRNA13082 to oversee oil synthesis and nutrient storage. Our research provides robust theoretical evidence for a comprehensive resolution of TF-lncRNA regulation in the soybean oil synthesis network.

Methanol-involved heterogeneous transformation of ginsenoside Rb1 to rare ginsenosides using heteropolyacids embedded in mesoporous silica with HPLC-MS investigation.

Background: The biological activity and pharmacological effects of rare ginsenosides have been proven to be superior to those of the major ginsenosides, but they are rarely found in ginseng. Methods: Ginsenoside Rb1 was chemically transformed with the involvement of methanol molecules by a synthesized heterogeneous catalyst 12-HPW@MeSi, which was obtained by the immobilization of 12-phosphotungstic acid on a mesoporous silica framework. High-performance liquid chromatography coupled with mass spectrometry was used to identify the transformation products. Results: A total of 18 transformation products were obtained and identified. Methanol was found to be involved in the formation of 8 products formed by the addition of methanol molecules to the C-24 (25), C-20 (21) or C-20 (22) double bonds of the aglycone. The transformation pathways of ginsenoside Rb1 involved deglycosylation, addition, elimination, cycloaddition, and epimerization reactions. These pathways could be elucidated in terms of the stability of the generated carbenium ion. In addition, 12-HPW@MeSi was able to maintain a 60.5% conversion rate of Rb1 after 5 cycles. Conclusion: Tandem and high-resolution mass spectrometry analysis allowed rapid and accurate identification of the transformation products through the characteristic fragment ions and neutral loss. Rare ginsenosides with methoxyl groups grafted at the C-25 and C-20 positions were obtained for the first time by chemical transformation using the composite catalyst 12-HPW@MeSi, which also enabled cyclic heterogeneous transformation and facile centrifugal separation of ginsenosides. This work provides an efficient and recyclable strategy for the preparation of rare ginsenosides with the involvement of organic molecules.

Exploring the role of endogenous retroviruses in seasonal reproductive cycles: a case study of the ERV-V envelope gene in mink.

Introduction: Endogenous retroviruses (ERVs), which originated from exogenous retroviral infections of germline cells millions of years ago and were inherited by subsequent generations as per Mendelian inheritance patterns, predominantly comprise non-protein-coding sequences due to the accumulation of mutations, insertions, deletions, and truncations. Nevertheless, recent studies have revealed that ERVs play a crucial role in diverse biological processes by encoding various proteins. Methods: In this study, we successfully identified an ERV envelope (env) gene in a mink species. A phylogenetic tree of mink ERV-V env and reference sequences was constructed using Bayesian methods and maximum-likelihood inference. Results: Phylogenetic analyses indicated a significant degree of sequence conservation and positive selection within the env-surface open reading frame. Additionally, qRT-PCR revealed diverse patterns of mink ERV-V env expression in various tissues. The expression of mink ERV-V env gene in testicular tissue strongly correlated with the seasonal reproductive cycles of minks. Discussion: Our study suggests that the ERV-V env gene in mink may have been repurposed for host functions.

Update on functional analysis of long non-coding RNAs in common crops.

With the rapid advances in next-generation sequencing technology, numerous non-protein-coding transcripts have been identified, including long noncoding RNAs (lncRNAs), which are functional RNAs comprising more than 200 nucleotides. Although lncRNA-mediated regulatory processes have been extensively investigated in animals, there has been considerably less research on plant lncRNAs. Nevertheless, multiple studies on major crops showed lncRNAs are involved in crucial processes, including growth and development, reproduction, and stress responses. This review summarizes the progress in the research on lncRNA roles in several major crops, presents key strategies for exploring lncRNAs in crops, and discusses current challenges and future prospects. The insights provided in this review will enhance our comprehension of lncRNA functions in crops, with potential implications for improving crop genetics and breeding.

Gait Analysis with Wearable Sensors in Isolated REM Sleep Behavior Disorder Associated with Phenoconversion: An Explorative Study.

Background: Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038). Conclusions: Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

Differential gene expression and immune cell infiltration in maedi-visna virus-infected lung tissues.

BACKGROUND: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology. RESULT: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs. CONCLUSION: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts.

Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains.

The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.

UHPLC-HRMS based saponins profiling of three morphological regions in American ginseng (Panax quinquefolium L.) and their correlation with the antioxidant activity.

American ginseng (Panax quinquefolium L.) is used as tonic plant and high-grade nourishment. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was established for identifying the chemical constituent in three morphological regions of American ginseng, including main root (MR), rhizome (RH) and lateral root (LR). The 63 saponins was identified in different morphological regions of 10 American ginseng samples. The chemical maker compounds in corresponding morphological region, while the major compounds of MR (malonyl-ginsenoside Rb1, ginsenoside Rd, Rs2 and pseudo-RC1), LR (stipuleanoside R2, ginsenoside Re and malonyl-ginsenoside Rc), and RH (malonyl-ginsenoside Rd, Rb3, and chikusetsu saponin II) were discovered. Correlation analysis showed that 11 compounds were positively correlated with the antioxidant activity of American ginseng. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01453-4.

Striatal and Extrastriatal Monoaminergic Disruption in Progressive Supranuclear Palsy.

BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18F-9-fluoropropyldihydrotetrabenazine (18F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.

Modulation of autophagy affected tumorigenesis induced by the envelope glycoprotein of JSRV.

Ovine pulmonary adenocarcinoma (OPA), caused by the jaagsiekte sheep retrovirus (JSRV), is a chronic, progressive, and contagious lung tumor that seriously affects sheep production. It also represents a valuable animal model for several human lung adenocarcinomas. However, little is known about the role of autophagy in OPA tumorigenesis. Here, Western blotting combined with transmission electron microscopy examination and Cyto-ID dye staining was employed for evaluation of changes of autophagic levels. The results of the present study showed that expression of the autophagy marker proteins Beclin-1 and LC3 was decreased in OPA lung tissues, as well as in cells overexpressing the envelope glycoprotein of JSRV (JSRV Env). Reduced numbers of autophagosomes were also observed in cells overexpressing JSRV Env, although assessment of autophagic flux showed that JSRV Env overexpression did not block the formation of autophagosomes, suggesting increased degradation of autolysosomes. Last, mouse xenograft experiments indicated that inhibition of autophagy by 3-methyladenine suppressed both tumor growth and the epithelial-to-mesenchymal transition. In conclusion, JSRV, through JSRV Env, takes advantage of the autophagy process, leading to the development of OPA.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

BACKGROUND: Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. OBJECTIVE: This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. METHOD: 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum ß-isomer of C-terminal telopeptides of type I collagen (ß-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. RESULTS: Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. CONCLUSION: All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

18F-FP-DTBZ PET/CT detectable associations between monoaminergic depletion in the putamen with rigidity and the pallidus with tremor in Parkinson's disease.

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.

Prediction of molecular mechanism of processed ginseng in the treatment of heart failure based on network pharmacology and molecular docking technology.

BACKGROUND: Heart failure (HF) is the most common cardiovascular disease in clinics. Processed Panax ginseng C.A. Mey. Products have significant therapeutic effects on HF. Therefore, it is of great significance to explore the mechanism of action of Processed Panax ginseng C.A. Mey. Products in the treatment of HF. METHODS: The saponin-like constituents of 3 different ginseng preparations were characterized by UPLC/QE-MS and the identified saponin constituents were subjected to network pharmacological analysis. Protein-protein interaction analyses of the targets of different ginseng preparations for the treatment of heart failure (HF) were performed using the STRING database, Gene Ontology enrichment analyses and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the DAVID database, and the results of the network pharmacological analyses were validated using the Autodock software. Finally, the relative quantitative content of 5 major ginsenosides in 3 processed ginseng products was evaluated. RESULTS: A total of 40 saponin compounds were identified based on mass spectrometry data. Network pharmacology and molecular docking analyses were used to predict the major targets of these sapions compounds and the key pathways mediating their anti-HF effects. After conducting a thorough screening, the study identified 5 primary ingredients of ginseng products ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rk1, ginsenoside Rg5, and ginsenoside CK that can potentially target 22 essential proteins: EGFR, AKT1, ERBB2, STAT3, TNF, ESR1, MTOR, HRAS, MMP9, and PIK3CA, etc. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that ginseng products can be beneficial in treating HF by interacting with pathways such as the PI3K-Akt signaling pathway, the TNF signaling pathway, the mTOR signaling pathway, and others. CONCLUSION: The present study revealed that the treatment of HF with different processed ginseng products may be related to the regulation of the PI3K-Akt signaling pathway, TNF signaling pathway, apoptosis pathway, mTOR signaling pathway, etc, and that the key active ingredients may be concentrated in black ginseng, which provides a theoretical basis and direction for the further study of the mechanism of action of ginseng. This provides a theoretical basis and research direction for further in-depth study of its mechanism of action.

Heterogeneous Transformation of Ginsenoside Rb1 with Ethanol Using Heteropolyacid-Loaded Mesoporous Silica and Identification by HPLC-MS.

Rare ginsenosides with major pharmacological effects are barely present in natural ginseng and are required to be obtained by transformation. In the current study, ginsenoside Rb1 was chemically transformed with the involvement of ethanol molecules to prepare rare ginsenosides using the synthesized heterogeneous catalyst 12-HPW@MeSi. A total of 16 transformation products were obtained and identified using high-performance liquid chromatography coupled with multistage tandem mass spectrometry and high-resolution mass spectrometry. Ethanol molecules were involved in the production of 6 transformation products by adding to the C-20(21), C-20(22), or C-24(25) double bonds on the aglycone to produce ethoxyl groups at the C-25 and C-20 positions. Transformation pathways of ginsenoside Rb1 are summarized, which involve deglycosylation, elimination, cycloaddition, epimerization, and addition reactions. In addition, 12-HPW@MeSi was recyclable through a simple centrifugation, maintaining an 85.1% conversion rate of Rb1 after 3 cycles. This work opens up an efficient and recycled process for the preparation of rare ginsenosides with the involvement of organic molecules.