[Medicinal plant biodiversity in Jilin province based on big data of the fourth national survey of traditional Chinese medicine resources].

Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera. There were 1 901 species of medicinal plants(belonging to 778 genera of 227 families) in the eastern mountainous region, 1 503 species(belonging to 690 genera of 225 families) in the mid-mountainous areas of the central mountainous region, and 811 species(belonging to 436 genera of 136 families) in the western plain region. The biodiversity of medicinal plants in Jilin province was high and presented a trend of high in the east and low in the west. The medicinal plant resources were mainly concentrated in the eastern mountainous region, and the number of medicinal plant groups had significant diffe-rences between regions, following the trend of western region > central region > eastern region. The species richness was in the order of eastern region > western region > central region. The species diversity structure in the central region was similar to that in the eastern and western regions, while it was significantly different between the western and eastern regions. Compared with the third national survey of traditional Chinese medicine resources, the fourth survey showed an increase of 1 417 species, a decrease of 580 species, and 824 common species, indicating significant changes in the biodiversity of medicinal plants in Jilin province. The reasons for these changes need to be further explored. This article elucidates the background and biodiversity changes of medicinal plant resources in Jilin province, laying a foundation for the protection, utilization, and industrial development of traditional Chinese medicine resources in Jilin province.

Primary intraspinal neuroendocrine tumor: A case report and literature review.

RATIONALE: Neuroendocrine tumors (NET) refer to a group of uncommon tumors arising in the neuroendocrine system. Most NETs occur in the digestive tract and bronchi but are rare in the central nervous system, especially in the spinal canal. NET in the central nervous system mainly metastasize from other systems, with non-specific clinical symptoms. In this study, we report the diagnosis and treatment of intraspinal NET to provide clinical guidance as well as to avoid misdiagnosis and missed diagnosis. PATIENT CONCERNS: A 59-year-old male patient, presented with recurrent right lower limb pain for half a year, accompanied by numbness and weakness for 4 months and aggravation for 2 months. Lumbar spine magnetic resonance imaging (MRI) revealed a space-occupying lesion in the spinal canal. The diagnosis of primary intraspinal NET was confirmed by topathological examination. DIAGNOSIS: Primary intraspinal NET tumor. INTERVENTIONS: Surgical resection. OUTCOMES: Significant improvements in right lower limb pain, numbness, and weakness were observed, and lumbar spine MRI was performed again to dynamically observe the changes in intraspinal NET. CONCLUSIONS: Surgical resection may be an effective treatment for intraspinal NETs. LESSONS: Intraspinal NETs are relatively rare and mostly manifest as limb numbness, weakness, and pain. Due to its nonspecific clinical symptoms, intraspinal NETs are easily misdiagnosed as lumbar disc herniation with radiculopathy and lumbar spondylolisthesis. Therefore, in patients with long-term symptoms, in addition to common lumbar neuromuscular diseases, lumbar MRI should be performed promptly to exclude the possibility of lumbar NETs.

High prevalence and transmission of blaNDM-positive Escherichia coli between farmed ducks and slaughtered meats: An increasing threat to food safety.

The emergence of carbapenem-resistant bacteria especially carbapenem-resistant Escherichia coli (CREC) in food animals poses a serious threat to food safety and public health. Reports about the dissemination of carbapenem-resistant bacteria along the food animal production chain are scattered and mainly focus on swine and chicken. Abuse of antibiotics in duck farms is common especially in China which has the largest duck production industry, however, the CREC transmission between farmed ducks and slaughtered meats remains unclear and the role of slaughterhouse in disseminating CREC among duck meats remains largely unknown. Herein, we collected 251 fecal samples from five typical duck farms along with 125 slaughtered meat samples (25 from each farm) in the corresponding slaughterhouse in Anhui Province, China, in December 2018. All samples were screened for CREC isolates which were analyzed for the presence of carbapenemase genes and colistin resistance gene mcr. The resistance profiles, transferability, pulsed-field gel electrophoresis (PFGE), whole-genome sequencing and phylogenetic analysis of the CREC isolates from both ducks and meats were further characterized. This is the first report presenting the high prevalence of blaNDM-positive CREC isolates in ducks from duck farms (57.8 %) and slaughtered meats (33.6 %) in the corresponding slaughterhouse. Among the 203 blaNDM-positive CREC isolates obtained in this study, 19.2 % harbored mcr-1 and all CREC isolates showed resistance to nearly all currently available antibiotics (except tigecycline). Of note, mcr-1 was found in 17.8 % of the meat-derived CREC carrying blaNDM. Based on the PFGE analysis, clonal spread of blaNDM-positive CREC including some also carrying mcr-1 was found between farmed ducks and slaughtered duck meats even from different farms. Special attention should be paid to the clonal dissemination of meat-derived CREC within the slaughterhouse, which contributed to the high prevalence of blaNDM in slaughtered meats. Additionally, horizontal transmission mainly mediated by transferable blaNDM-5-bearing IncX3 plasmids, untypable blaNDM-1-bearing plasmids and mcr-1-bearing IncHI2 plasmids further facilitated the rapid spread of such multidrug-resistant strains. Notably, the blaNDM-bearing plasmids and mcr-1-bearing plasmids in CREC from meats were highly similar to those from animals and humans. More worryingly, the phylogenomic analysis showed that CREC isolates from both ducks and corresponding meats clustered with previously reported human CREC isolates carrying mcr-1 in different geographical areas including China. These findings further prove that the CREC and resistance plasmids in farmed ducks could transmit to meats even from different farms via the slaughterhouse and then trigger infections in humans. The high prevalence and clonal transmission of CREC isolates including those also carrying mcr-1 between ducks and meats are alarming, and urgent control measures are required to reduce the dissemination of such organisms.

Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation.

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis.

Stroke leads to persistently high risk for recurrent vascular events caused by systemic atheroprogression that is driven by endothelial cell (EC) activation. However, whether and how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterations in systemic vessels remain poorly understood. We showed that brain ischemia induces persistent activation, the upregulation of adhesion molecule VCAM1, and increased senescence in peripheral ECs until 4 weeks after stroke onset. This aberrant EC activity resulted from sustained Notch1 signaling, which was triggered by increased circulating Notch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, this led to increased myeloid cell adhesion and atheroprogression by generating a senescent, pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the genetic ablation of endothelial Notch1 reduced atheroprogression after stroke. Our findings revealed a systemic machinery that induces the persistent activation of peripheral ECs after stroke, which paves the way for therapeutic interventions or the prevention of recurrent vascular events following stroke.

Inflammatory biomarkers may be associated with poor outcomes after mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become the mainstay of treatment for acute ischemic stroke (AIS) recently. This case-control study aimed to identify the pivotal role of inflammation in the prognosis of AIS patients after MT. METHODS: Altogether, 70 AIS patients who underwent MT were retrospectively recruited for this study. Receiver operating characteristic analysis was performed to demonstrate the sensitivity and specificity of the inflammatory variables for predicting prognosis. A meta-analysis was performed to pool the published results together. Stata software was used for analysis. RESULTS: There was no differences in pre-MT inflammatory biomarkers between patients who survived and those who died, as well as patients with modified Rankin Scale (mRS) 0-2 and mRS ≥ 3. In contrast, post-MT C-reactive protein (CRP) levels might be a potential parameter to predict death after thrombectomy [area under the curve (AUC), 95%confidence interval (CI), 0.737, 0.587-0.887; p = 0.005; optimal cutoff value = 4.565]. Moreover, post-MT monocyte count might be an appropriate parameter to predict poor long-term prognosis after thrombectomy (AUC, 95%CI, 0.704, 0.575-0.833; p = 0.017; optimal cutoff value = 0.345). A meta-analysis revealed that the pre-MT inflammatory indices, including white blood cell count (weighted mean difference, 95%CI, 1.32, 1.01-1.63), neutrophil count (1.23, 0.95-1.51), monocyte count (0.05, 0.02-0.09), neuthrophil-to-lymphocyte ratio (2.42, 1.98-2.87) and platelet-to-lymphocyte ratio (24.65, 7.99-41.32), were higher in patients with 3-month mRS ≥ 3, and the lymphocyte count (-0.31,-0.43 to -0.18) was lower in this cohort. CONCLUSIONS: Inflammatory indices were significantly associated with the prognosis of patients undergoing MT, especially post-MT CRP and monocyte count, which can predict long-term outcomes.

Two chromosome-level genome assemblies of galling aphids Slavum lentiscoides and Chaetogeoica ovagalla.

Slavum lentiscoides and Chaetogeoica ovagalla are two aphid species from the subtribe Fordina of Fordini within the subfamily Eriosomatinae, and they produce galls on their primary host plants Pistacia. We assembled chromosome-level genomes of these two species using Nanopore long-read sequencing and Hi-C technology. A 332 Mb genome assembly of S. lentiscoides with a scaffold N50 of 19.77 Mb, including 11,747 genes, and a 289 Mb genome assembly of C. ovagalla with a scaffold N50 of 11.85 Mb, containing 14,492 genes, were obtained. The Benchmarking Universal Single-Copy Orthologs (BUSCO) benchmark of the two genome assemblies reached 93.7% (91.9% single-copy) and 97.0% (95.3% single-copy), respectively. The high-quality genome assemblies in our study provide valuable resources for future genomic research of galling aphids.

Naoxintong capsule for treating cardiovascular and cerebrovascular diseases: from bench to bedside.

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy.

Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Corrigendum: Pre-operative evaluation and mid-term outcomes of anomalous origin of the left coronary artery from the pulmonary artery based on left ventricular ejection fraction.

[This corrects the article DOI: 10.3389/fcvm.2022.961491.].

Complex immune microenvironment of chordoma: a road map for future treatment.

BACKGROUND: Chordoma, a rare bone tumor, presents limited treatment options and patients typically exhibit poor survival outcomes. While immunotherapy has shown promising results in treating various tumors, research on the immune microenvironment of chordomas is still in its early stages. Therefore, understanding how the immune microenvironment of chordomas influences the outcomes of immunotherapy is crucial. METHODS: We employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, CellChat, gene set variation analysis, as well as calculation of immune features to further dissect the complex immune microenvironment of chordoma. RESULTS: Previous research by van Oost et al argued that compared with other sarcomas, chordomas typically exhibit an immunologically "hot" microenvironment, a conclusion with which we concur based on their research findings. Additionally, the authors suggest that T cell-mediated immunotherapy is feasible for the majority of chordomas. However, we are inclined to categorize them as an immune-excluded phenotype according to the latest classification methods, rather than persisting with the concepts of "cold" and "hot". Unlike them, we explored immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) using Bulk RNA-seq data from 126 chordoma patients and found that higher IS, TLS, and higher HLA-I expression were associated with poorer patient prognosis. Additionally, CellChat analysis of scRNA-seq results from six chordoma patients revealed no direct interaction between T cells and tumor cells. CONCLUSIONS: These findings suggested that the efficacy of T cell-based immunotherapy may be limited or even ineffective for patients with chordoma.

Single-cell RNA sequencing reveals the MIF/ACKR3 receptor-ligand interaction between neutrophils and nucleus pulposus cells in intervertebral disc degeneration.

OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.

Five-Year Incidence of Nd:YAG Capsulotomy After Cataract Surgery with Different Single-Piece Monofocal Intraocular Lenses: A Follow-Up Study of 3955 Eyes.

Purpose: To estimate the incidence of neodymium-doped yttrium aluminum garnet laser (Nd:YAG) capsulotomy up to five years after cataract surgery with different single-piece acrylic monofocal IOLs in a Spanish cohort. Patients and Methods: Data were extracted from electronic medical records. Eligible participants were aged ≥65, had cataract surgery with one of five different acrylic monofocal IOLs (Alcon AcrySof, AJL LLASY60, Medicontur Bi-flex, IOL Tech Stabibag and Zeiss Asphina), and more than six months baseline data. Participants were followed up to five years from surgery and up to six months from Nd:YAG. The incidence of Nd:YAG was compared between the IOLs and multivariate analyses were conducted to identify predictors of Nd:YAG incidence at five-years after cataract surgery. Results: The initial cohort included 9545 patients with 14,519 eyes (53% female, average age 75 years). Of those, 3955 eyes were available for analysis five years after cataract surgery. Throughout the five years post-surgery, Nd:YAG incidence was consistently lower with Alcon Acrysof IOLs than the other IOLs. At five years the Nd:YAG incidence rate for Alcon Acrysof was 8.8%. In comparison, the incidence was 47.4% for AJL LLASY60 (OR = 9.54, 95% CI [6.57, 13.84]), 44.3% for Zeiss Asphina (OR = 8.35, 95% CI [5.85, 11.94]) and 44.0% for IOL Tech Stabibag (OR = 8.02, 95% CI [4.60, 13.84]). Conclusion: Alcon AcrySof IOLs have a consistently lower risk of Nd:YAG incidence over a long follow-up period after cataract surgery, highlighting the importance of IOL choice for patients' long-term outcomes.

The importance of mother-child interaction on smart device usage and behavior outcomes among toddlers: a longitudinal study.

BACKGROUND: In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers' smart device usage and behavioral outcomes, are limited. Understanding the impact of parent-child interactions on this relationship is crucial for enhancing toddlers' developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers' behaviors, as well as the positive effects of mother-child interactions on this influence. METHODS: We used relevant data related to 277 children born between November 2016 and July 2020 and who were part of an ongoing prospective follow-up study conducted across five hospitals in Taipei City, Taiwan. We analyzed (1) data from maternal reports regarding children's behavior by using the Child Behavior Checklist (for ages 11/2-5 years), (2) assessments of mother-child interactions by using the Brigance Parent-Child Interactions Scale, and (3) self-reported parental data covering the first 3 postpartum years. Statistical analyses involved group-based trajectory modeling and multiple linear regression. RESULTS: A considerable increase in screen time between the ages of 1 and 3 years was associated with less favorable behavioral outcomes at age 3. These outcomes included somatic complaints [adjusted beta coefficient (aß) = 2.17, 95% confidence interval (CI) = 0.39-3.95, p-value = 0.01], withdrawal (aß = 2.42, 95% CI = 0.15-4.69, p-value = 0.04), and aggressive behavior (aß = 6.53, 95% CI = 0.25-12.81, p-value = 0.04). This association was particularly evident among children with lower levels of mother-child interaction. Nevertheless, positive mother-child interactions mitigated most of the adverse effects. Additionally, increased exposure to games and cartoons was associated with poorer behavioral outcomes in all children except for those experiencing positive mother-child interactions. CONCLUSION: Early mother-child interactions play a crucial role in mitigating the risk of behavioral problems in toddlers who spend prolonged periods looking at screens and who are frequently exposed to game and cartoon content.

[Correlation between serum HDL/LDL and t-PINP /ß-CTX and osteoporotic vertebral fractures in elderly women].

OBJECTIVE: To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of typeⅠcollagen ß special sequence(ß-CTX)and risk of osteoporosis vertebral fractures (OPVFs) in elderly women. METHODS: The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed. According to whether or not fracture, patients were divided into non-fracture group (186 patients) and fracture group(260 patients). Univariate analysis was performed to analysis age, body mass index(BMI), N-terminal mioldle molecular fragment of osteocalcin, N-MID OC), t-PINP, ß-CTX, 25-hydroxyvitamin D[25-(OH) VitD], blood sugar (Glu), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Ca, P, Mg, urea (UREA), creatinine (Cr) and Cystatin C(CysC), and correlation between OPVFs and the above indexes and lipid, bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL, t-PINP/ß-CTX. Logistic regression was used to analyze risk factors and stratification relationship between OPVFs and HDL/LDL, t-PINP/ß-CTX. RESULTS: There were no significant difference in age and BMI between non-fracture group and fracture group (P>0.05). Compared with non-fracture group, contents of HDL, t-PINP/ß-CTX and HDL/LDL in fracture group were decreased, and contents of ß-CTX were increased (P<0.05). OPVFs was positively correlated with ß-CTX (r=0.110, P<0.05), and negatively correlated with HDL, HDL/LDL and t-PINP/ß-CTX (r=-0.157, -0.175, -0.181, P<0.05). HDL and HDL/LDL were negatively correlated with ß-CTX (r=-0.22, -0.12, P<0.05) and t-PINP (r=-0.13, -0.10, P<0.05). 25-(OH) VitD was positively correlated with TC and HDL (r=0.11, 0.18, P<0.05). HDL/LDL was positively correlated with t-PINP/ß-CTX(r=0.11, P=0.02). t-PINP/ß-CTX[OR=0.998, 95%CI(0.997, 1.000), P<0.05], HDL/LDL[OR=0.228, 95%CI(0.104, 0.499), P<0.01] were risk factors for vertebral fracture. The lower levels between two tristratified indicators, the higher the vertebral fracture rate. The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum, with an adjusted OR was[2.112, 95%CI(1.310, 3.404)] and [2.331, 95%CI(1.453, 3.739)], respectively. CONCLUSION: Serum low HDL/LDL and t-PINP /ß-CTX are independent risk factors for OPVF in elderly women, and have good predictive value for OPVF risk.

Combined ROS Sensitive Folate Receptor Targeted Micellar Formulations of Curcumin Effective Against Rheumatoid Arthritis in Rat Model.

Introduction: Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs. Methods: We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo. Results: TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo. Conclusion: The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.

Genomic signatures associated with recurrent scale loss in cyprinid fish.

Scale morphology represents a fundamental feature of fish and a key evolutionary trait underlying fish diversification. Despite frequent and recurrent scale loss throughout fish diversification, comprehensive genome-wide analyses of the genomic signatures associated with scale loss in divergent fish lineages remain scarce. In the current study, we investigated genome-wide signatures, specifically convergent protein-coding gene loss, amino acid substitutions, and cis-regulatory sequence changes, associated with recurrent scale loss in two divergent Cypriniformes lineages based on large-scale genomic, transcriptomic, and epigenetic data. Results demonstrated convergent changes in many genes related to scale formation in divergent scaleless fish lineages, including loss of P/Q-rich scpp genes (e.g. scpp6 and scpp7), accelerated evolution of non-coding elements adjacent to the fgf and fgfr genes, and convergent amino acid changes in genes (e.g. snap29) under relaxed selection. Collectively, these findings highlight the existence of a shared genetic architecture underlying recurrent scale loss in divergent fish lineages, suggesting that evolutionary outcomes may be genetically repeatable and predictable in the convergence of scale loss in fish.

Dehydration in cerebral venous sinus thrombosis.

AIMS: This study aimed to unravel the dehydration status of patients with cerebral venous sinus thrombosis (CVST) to facilitate the understanding of dehydration in CVST. METHODS: This was a multicenter retrospective study and three populations were recruited, namely, patients with CVST, CVST mimics, and healthy subjects. Blood samples were obtained 1-2 days after admission to assess dehydration status. Stata 15.1 was performed for statistical analysis. RESULTS: A total of 208 patients were diagnosed with CVST, 237 with CVST mimics, and 200 healthy individuals were enrolled. The urine specific gravity (USG, 1.020 [1.014, 1.029] vs. 1.017 [1.011, 1.021]) was higher in patients with CVST than in those with mimics (all p < 0.001). The percentage of USG >1.03 was also higher in CVST (22.6%) than in its mimics (6.3%, p < 0.001). With the development of CVST, USG (acute vs. sub-acute vs. chronic, 1.022 [1.015, 1.033] vs. 1.021 [1.015, 1.031] vs. 1.019 [1.014, 1.025]) decreased. All dehydration-related markers could not differentiate CVST from its mimics and healthy populations, and they were not associated with CVST severity and prognosis (p > 0.05). CONCLUSION: High levels of USG, especially USG >1.013, were more common in patients with CVST. Dehydration-related indices could not characterize CVST and were not associated with CVST severity and prognosis.