In Situ Measurement of Nanoparticle-Blood Protein Adsorption and Its Heterogeneity with Single-Nanoparticle Resolution via Dual Fluorescence Quantification.

The formation of a protein corona gives nanomedicines a distinct biological identity, profoundly influencing their fate in the body. Nonspecific nanoparticle-protein interactions are typically highly heterogeneous, which can lead to unique biological behaviors and in vivo fates for individual nanoparticles that remain underexplored. To address this, we have established an in situ approach that allows quantitative examination of nanoparticle-protein adsorption at the individual nanoparticle level. This method integrates dual fluorescence quantification techniques, wherein the nanoparticles are first individually analyzed via nanoflow cytometry to detect fluorescent signals from adsorbed proteins. The obtained fluorescence intensity is then translated into protein quantities through calibration with microplate reader quantification. Consequently, this approach enables analysis of interparticle heterogeneity of nano-protein interactions, as well as in situ monitoring of protein adsorption kinetics and nanoparticle aggregation status in blood serum, preconditioning for a comprehensive understanding of nano-bio interactions, and predicting in vivo fate of nanomedicines.

ACKR1+ Endothelial Cells Mediate Leukocyte Infiltration and Synergize with SFRP2/ASPN+ Fibroblasts to Promote Skin Fibrosis in Systemic Sclerosis.

BACKGROUND: Skin fibrosis is the most typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS) with unclear etiology and few effective treatments. Though excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, many lines of evidence suggested that vascular damage was the initiating event and various cell types along with fibroblasts worked together to contribute to the pathogenesis of skin fibrosis. OBJECTIVES: We sought to explore the relationships between vascular endothelial cell lesions and immune cell infiltration, along with the cell-cell interactions among various cell types within the fibrotic skin ecosystem. METHODS: Single-cell RNA-seq (10x Genomics) was performed on skin biopsies of 3 healthy donors and 7 SSc patients in Chinese. The additional 3 localized scleroderma patients' data from NCBI database (GSE160536) were integrated by Harmony. CellChat package (v1.5.0) was applied to analyze cell communication network. Transwell assay and subcutaneous bleomycin (BLM) injection in mice were used to explore the role of ACKR1 on immune cell infiltration. Milo single-cell western blot was applied to show the activation of fibroblast subclusters. RESULTS: A total of 62,295 cells were obtained and subpopulations of stromal and immune cells were identified. Interaction network analysis revealed that multiple chemokines secreted by macrophages, pericytes, and pro-inflammatory fibroblasts could bind with Duffy antigen/receptor for chemokines (ACKR1), which is highly expressed on ACKR1+ endothelial cells of lesion skin. Transwell assay revealed that over-expressed ACKR1 in HUVEC facilitated leukocyte infiltration under the treatment of IL8. The BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration, and fibrosis in skin, which could be attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages with TGFB1 or PDGFB high production could activate SFRP2/ASPN+ fibroblasts to contribute to excessive accumulation of extracellular matrix (ECM), and the SOX4-ASPN axis plays an important role in the TGF-ß signaling cascade and the etiology of skin fibrosis. CONCLUSIONS: Our results reveal that highly expressed ACKR1 in endothelial cells of fibrotic skin tissue promotes immune cell infiltration, and SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis.

Preparation of Newly Polymer-Coated Microbial Pellets and Their Adsorption and Degradation Properties for Oil-Containing Wastewater.

Water is the lifeblood of everything on earth, nourishing and nurturing all forms of life, while also contributing to the development of civilization. However, with the rapid development of economic construction, especially the accelerated process of modern industrialization, the pollution of oily sewage is becoming increasingly serious, affecting the ecological balance and human health. The efficient elimination of pollutants in sewage is, therefore, particularly urgent. In this paper, a core-shell microbial reactor (MPFA@CNF-SA-AM) was fabricated by using nanocellulose and sodium alginate (SA) particles embedded with microorganisms as the core and lipophilic and hydrophobic fly ash as the outer shell layer. Compared with that of free microorganisms and cellulose and SA aerogel pellets loading with microorganisms (CNF-SA-AM), which has a degradation efficiency of 60.69 and 82.89%, respectively, the MPFA@CNF-SA-AM possesses a highest degradation efficiency of 90.60% within 240 h. So that this self-floating microbial reactor has selective adsorption properties to achieve oil-water separation in oily wastewater and high effective degradation of organic pollutants with low cost. The adsorption curves of MPFA@CNF-SA-AM for diesel and n-hexadecane were studied. The results showed that the adsorption follows the Freundlich model and is a multimolecular layer of physical adsorption. In addition, the degradation mechanism of diesel oil was studied by gas chromatography-mass spectrometry. The results showed that diesel oil was selectively adsorbed to the interior of MPFA@CNF-SA-AM, and it was degraded by enzymes in microorganisms into n-hexadecanol, n-hexadecaldehyde, and n-hexadecanoic acid in turn, and finally converted to water and carbon dioxide. Compared with existing oily wastewater treatment methods, this green and pollution-free dual-functional core-shell microbial reactor has the characteristics of easy preparation, high efficiency, flexibility, and large-scale degradation. It provides a new, effective green choice for oily wastewater purification and on-site oil spill accidents.

Renal anatomical classification systems cannot predict the occurrence of vascular complications after partial nephrectomy.

OBJECTIVES: To determine the relationship between renal tumor complexity and vascular complications after partial nephrectomy using PADUA, RENAL, and ZS scores. METHODS: Between January 2007 and December 2018, a total of 1917 patients with available cross-sectional imaging were enrolled in the study. Logistic regressions were used to identify independent predictors of vascular complications. RESULTS: Of 1917 patients, 31 (1.6%) developed vascular complications, including 10 females and 21 males. The high-complexity category was significantly associated with a decreased risk of vascular complication in PADUA (OR = 0.256; 95%CI = 0.086-0.762; P = 0.014) and ZS score (OR = 0.279; 95%CI = 0.083-0.946; P = 0.040). Laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were independent risk factors for vascular complications. Meanwhile, the incidence was significantly reduced in the recent 4 years in the high score tumor group alone in PADUA (0.2% [1/474] vs. 2.2% [3/139], P = 0.038) and ZS score (0.2% [1/469] vs. 2.7% [3/112], P = 0.024). In the first 8 years, laparoscopic partial nephrectomy and robot-assisted laparoscopic partial nephrectomy were the only two independent risk factors for vascular complications. In the recent 4 years, only the high-complexity category was significantly associated with a decreased risk of vascular complication in the PADUA score (OR = 0.110; 95%CI = 0.013-0.938; P = 0.044). CONCLUSION: The renal anatomic classification system cannot predict the occurrence of vascular complications after partial nephrectomy.

Dual Inhibition of Factor XIIa and Factor XIa Produces a Synergistic Anticoagulant Effect.

ABSTRACT: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.

The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?

OBJECTIVE: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. METHODS: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). RESULTS: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. CONCLUSION: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Spectroscopic characterization of carbon monoxide activation by neutral chromium carbides.

Spectroscopic characterization of carbon monoxide activation by neutral metal carbides is of essential importance for understanding the structure-reactivity relationships of catalytic sites, but has been proven to be very challenging owing to the difficulty in size selection. Here, we report a size-specific infrared-vacuum ultraviolet spectroscopic study of the reactions between carbon monoxide with neutral chromium carbides. Quantum chemical calculations were carried out to identify the low-lying structures and to interpret the experimental features. The results reveal that the most stable structure of CrC3(CO)2 consists of a CCO ketenylidene unit and that of CrC4(CO)2 has a semi-bridging CO with a very low CO stretching vibrational frequency at 1821 cm-1. The electron structure analyses show that this semi-bridging CO is highly activated through the delocalized Cr-C-C three-center two-electron (3c-2e) interaction between the antibonding orbitals of CO and the metal carbide skeleton. The formation of these metal carbide carbonyls is found to be both thermodynamically exothermic and kinetically facile in the gas phase. The present findings have important implications for the mechanical understanding of the catalytic processes with isolated metal atoms/clusters dispersed on supports.

Spectroscopic Characterization of Highly Excited Neutral Chromium Tricarbonyl.

Spectroscopic characterization of highly excited neutral transition-metal complexes is important for understanding the multifaceted reaction mechanisms between metals and ligands. In this work, the reactions of neutral chromium atoms with carbon monoxide were probed by size-specific infrared spectroscopy. Interestingly, Cr(CO)3 was found to have an unprecedented 7A2″ septet excited state rather than the singlet ground state. A combination of experiment and theory shows that the gas-phase formation of this highly excited Cr(CO)3 is facile both thermodynamically and kinetically. Electronic structure and bonding analyses indicate that the valence electrons of Cr atoms in the septet Cr(CO)3 are in a relatively stable configuration, which facilitate the highly excited structure and the planar geometric shape (D3h symmetry). The observed septet Cr(CO)3 affords a paradigm for exploring the structure, properties, and formation mechanism of a large variety of excited neutral compounds.

Casuattimines A-N, fourteen new Lycopodium alkaloids from Lycopodiastrum casuarinoides with Cav3.1 channel inhibitory activity.

Two new dimeric Lycopodium alkaloids, casuattimines A and B (1 and 2), along with twelve previously undescribed Lycopodium alkaloids, casuattimines C-N (3-14), and eight known Lycopodium alkaloids, were isolated from Lycopodiastrum casuarinoides. Casuattimines A and B (1 and 2) are the first two ether-linked Lycopodium alkaloid dimers. Casuattimines C and D (3 and 4) are unique Lycopodium alkaloids characterized by a long fatty acid chain. Structural elucidation was achieved through HRESIMS, NMR, and electronic circular dichroism (ECD) calculations. In addition, the absolute configurations of compounds 7, 13, and 14 were determined by single crystal X-ray diffraction. Compounds 1, 2, and 4 demonstrated notable Cav3.1 channel inhibitory activities presenting IC50 values of 10.75 ± 1.02 µM, 9.33 ± 0.79 µM, and 7.14 ± 0.86 µM, respectively. The dynamics of compound 4 against the Cav3.1 channel and preliminary structure-activity relationships of these active Lycopodium alkaloids were also discussed.

Trends in parkinson's disease mortality in China from 2004 to 2021: a joinpoint analysis.

BACKGROUND: This study aimed to analyze the trends of Parkinson's disease (PD) mortality rates among Chinese residents from 2004 to 2021, provide evidence for the formulation of PD prevention and control strategies to improve the quality of life among PD residents. METHODS: Demographic and sociological data such as gender, urban or rural residency and age were obtained from the National Cause of Death Surveillance Dataset from 2004 to 2021. We then analyzed the trends of PD mortality rates by Joinpoint regression. RESULTS: The PD mortality and standardized mortality rates in China showed an overall increasing trend during 2004-2021 (average annual percentage change [AAPC] = 7.14%, AAPCASMR=3.21%, P < 0.001). The mortality and standardized mortality rate in male (AAPC = 7.65%, AAPCASMR=3.18%, P < 0.001) were higher than that of female (AAPC = 7.03%, AAPCASMR=3.09%, P < 0.001). The PD standardized mortality rates of urban (AAPC = 5.13%, AAPCASMR=1.76%, P < 0.001) and rural (AAPC = 8.40%, AAPCASMR=4.29%, P < 0.001) residents both increased gradually. In the age analysis, the mortality rate increased with age. And the mortality rates of those aged > 85 years was the highest. Considering gender, female aged > 85 years had the fastest mortality trend (annual percentage change [APC] = 5.69%, P < 0.001). Considering urban/rural, rural aged 80-84 years had the fastest mortality trend (APC = 6.68%, P < 0.001). CONCLUSIONS: The mortality rate of PD among Chinese residents increased from 2004 to 2021. Male sex, urban residence and age > 85 years were risk factors for PD-related death and should be the primary focus for PD prevention.

Preoperative and follow-up variations of psoas major muscle are related to S1 screw loosening in patients with degenerative lumbar spinal stenosis.

BACKGROUND: It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS. METHODS: 212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening. RESULTS: The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2-S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3-S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening. CONCLUSIONS: Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2-3 to L5-S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.

Key Factors Influencing the Operationalization and Effectiveness of Telemedicine Services in Henan Province, China: Cross-Sectional Analysis.

BACKGROUND: Telemedicine has demonstrated its potential in alleviating the unbalanced distribution of medical resources across different regions. Henan, a province in China with a population of approximately 100 million, is especially affected by a health care divide. The province has taken a proactive step by establishing a regional collaborative platform for telemedicine services provided by top-tier provincial hospitals. OBJECTIVE: We aim to identify the key factors that influence the current operationalization and effectiveness of telemedicine services in Henan province. The insights gained from this study will serve as valuable references for enhancing the efficient operation of telemedicine platforms in low- and middle-income regions. METHODS: We analyzed service reports from the performance management system of telemedicine services in Henan province throughout 2020. Using descriptive statistics and graphical methods, we examined key influencing factors, such as management competency; device configuration; and hospital capability, capacity, and service efficacy, across hospitals at 2 different tiers. In addition, we used generalized linear models and multiple linear regression models to identify key operational factors that significantly affect the service volume and efficacy of 2 major telemedicine services, namely teleconsultation and tele-education. RESULTS: Among the 89 tier 3 hospitals and 97 tier 2 hospitals connected to the collaborative telemedicine platform, 65 (73%) and 55 (57%), respectively, have established standardized management procedures for telemedicine services. As the primary delivery method for telemedicine services, 90% (80/89) of the tier 3 hospitals and 94% (91/97) of the tier 2 hospitals host videoconferencing consultations through professional hardware terminals rather than generic computers. Teleconsultation is the dominant service type, with an average annual service volume per institution of 173 (IQR 37-372) and 60 (IQR 14-271) teleconsultations for tier 3 and tier 2 hospitals, respectively. Key factors influencing the service volume at each hospital include available funding, management competency, the number of connected upper tiers, and the number of professional staff. After receiving teleconsultations from tier 3 (65/89, 73%) and tier 2 (61/97, 63%) hospitals, patients reported significant improvements in their medical conditions. In addition, we observed that service efficacy is positively influenced by management competency, financial incentives, the number of connected upper or lower tiers, and the involvement of participating medical professionals. CONCLUSIONS: Telemedicine has become increasingly popular in Henan province, with a notable focus on teleconsultation and tele-education services. Despite its popularity, many medical institutions, especially tier 2 hospitals, face challenges related to management competency. In addition to enhancing the effectiveness of existing telemedicine services, health care decision-makers in Henan province and other low- and middle-income regions should consider expanding the service categories, such as including remote emergency care and telesurgery, which have promise in addressing crucial health care needs in these regions.

Association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease with comorbidity: evidence in 17 cities of Henan, Central China.

Particulate matter (PM10) changes have been confirmed as one of the contributory factors affecting human health, the association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease (COPD) with comorbidity diseases was rarely reported. The same inpatient more than twice times admissions with COPD illness from January 1, 2016 to December 31, 2021 were identified from hospitals in the 17 cities of Henan, Central China. City-specific associations were firstly estimated using the case time series (CTS) model and then combined to obtain the regional average association. The multivariate meta-analytic model produces pooled estimates of the set of coefficients representing the PM10-COPD hospitalizations association across the 17 cities. Cause-specific hospitalization analyses were performed by COPD patients with different comorbidity combinations. A total of 34,348 elderly (age ≥ 65) subjects were analyzed and with a total of 35,122.35 person-years. These coefficients can be used to compute the linear exposure-response curve expressed as relative risk (RR) in per 10 µg/m3 increase in PM10 at lag03, which was 1.0091 (95% CI 1.0070-1.0112) for COPD with comorbidity, 1.0089 (95% CI 1.0067-1.0110) for COPD with circulatory system diseases, 1.0079 (95% CI 1.0052-1.0105) for COPD with respiratory system diseases, 1.0076 (95% CI 1.0032-1.0121) for COPD with endocrine system diseases, and 1.0087 (95% CI 1.0013-1.0162) for COPD with genitourinary system diseases, respectively. Some heterogeneity was found across cities, with estimates ranging from 1.0227 in the Puyang and Jiaozuo to 1.0053 in Henan Provance, China. The effect of higher PM10, on average, was higher in studies for northern cities, with a steeper raise in risk: per 10 µg/m3 increase in PM10, the RR from 1.0062 (95% CI 1.0030-1.0093) for the 10th percentile of latitude to 1.0124 (95% CI 1.0089-1.0160) for the 90th percentile. Our findings indicated that PM10 exposure may increase the risk of hospitalizations for COPD with comorbidity. Moreover, there might be a higher morbidity risk associated with PM10 in northern latitudes, indicating that stricter air quality standards could potentially reduce PM10-related morbidity among individuals with COPD. These findings have implications for the implementation of effective clean air interventions aligned with national climate policies.

Bioinformatics screening and verification of ischemic stroke-related key genes and drug prediction.

Stroke is one of the major causes of disability and death worldwide. The lack of effective medical treatment for stroke heightens the need for new therapeutic targets. In this study, we obtained two microarray data sets from the Gene Expression Omnibus (GEO) database and identified differential genes (DEGs) between MCAO and control groups. Then, enrichment analysis of the DEGs was performed using DAVID and Metascape. The results show 27 DEGs shared between the two datasets. The functional enrichment analysis showed that these genes are mainly enriched in immune response, complement and coagulation cascades, apoptotic processes. The four hub genes (C1qc, Fcgr2b, C1qb, and Cd14) were screened out using the Cytoscape. Next, real-time PCR and Western blot analysis showed that expression of C1q and CD14 increased at 14 days after tMCAO. Furthermore, we took eight small molecule compounds with the lowest score using Cmap and studied their background characteristics. These results are built on a meta-analysis of data, which are generally accessible from the online space. Finally, we evaluated the protective effect of the rolipram through behavior tests after tMCAO, and results showed that the rolipram significantly attenuated neurobehavioral dysfunction at 14 days after brain ischemia. The present results provide novel insights into the biological process and potential therapeutic drugs involved in stroke.

The Chemistry and Biology of Lycopodium Alkaloids.

Lycopodiales, an order comprising 388 distinct species, is the source of Lycopodium alkaloids (LAs), a group of naturally occurring alkaloids that share a common biosynthesis and structural attributes. These remarkable organisms are considered vestiges of ancient ferns, with fossil evidence dating their existence back to an impressive 300 million years. LAs usually are tricyclic or tetracyclic compounds with C16N or C16N2 skeleton. But then there are also have a few C11N, C15N, C15N2, C22N2, and C27N3 skeleton. LAs have attracted much scientific attention because of their important biological activities related to acetylcholinesterase and unique structural characteristics. From 1881 to December 2023, there are 593 LAs from 49 species of Lycopodiales have been reported. Because the total amount of LAs is nearly five times that of 1994, the classification and group allocation of some newly isolated LAs is often challenging and not unambiguous by Ayer's simple classification. This review makes a more systematic and detailed classification for it and provides extensive coverage of naturally occurring LAs discovered from 1881 to December 2023. Until now, there is no comprehensively summary of biological activity of the LAs. This review is the first time covered the biological activity of the all LAs.

Systematic review of the efficacy and safety of lenvatinib in various solid tumors.

OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. METHOD: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures. RESULTS: A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, p < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, p < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities. CONCLUSIONS: Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.

Lycopodium Alkaloids from Huperzia goebelii.

One new fawcettimine-type Lycopodium alkaloid, hupertimine F (1), together with five known (2-6) Lycopodium alkaloids were isolated from Huperzia goebelii. The structure of 1 was elucidated by 1D and 2D NMR spectra, HRESIMS, and X-ray diffraction. Structurally, 1 represents the fourth example of Lycopodium alkaloids characterized by a 5/5/5/5/6 pentacyclic ring system with a 1-aza-7-oxabicyclo[2.2.1]heptane moiety. These known compounds 2, 3, 5, and 6 were isolated from H. goebelii for the first time. Compounds 1-6 were evaluated for acetylcholinesterase, butyrylcholinesterase and monoamine oxidase B inhibitory activities in vitro.

Social frailty and the incidence of motoric cognitive risk syndrome in older adults.

INTRODUCTION: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. However, whether social frailty (integrated from multiple social factors) is associated with MCR is still unclear. METHODS: We included 4657 individuals without MCR at Round 1 of the NHATS as the discovery sample, and 3075 newly recruited individuals from Round 5 of the NHATS as the independent validation sample. Social frailty was assessed by five social items. MCR was defined as the presence of both subjective cognitive complaints and slow gait speed in individuals without dementia or mobility disability. RESULTS: Compared with normal individuals, those with social frailty had higher risk of incident MCR (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.34-1.84). Each additional unfavorable social item was associated with an increased risk of MCR (HR: 1.32, 95% CI: 1.22-1.43). DISCUSSION: Social frailty was associated with an increased risk of incident MCR in older adults. HIGHLIGHTS: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. Social frailty that integrated from multiple social factors was associated with an increased risk of incident MCR. Social frailty should be included in the early screening of individuals to identify those at higher risk of MCR.

Lycocasine A, a Lycopodium Alkaloid from Lycopodiastrum casuarinoides and Its Acid-Sensing Ion Channel 1a Inhibitory Activity.

A novel Lycopodium alkaloid, lycocasine A (1), and seven known Lycopodium alkaloids (2-8), were isolated from Lycopodiastrum casuarinoides. Their structures were determined through NMR, HRESIMS, and X-ray diffraction analysis. Compound 1 features an unprecedented 5/6/6 tricyclic skeleton, highlighted by a 5-aza-tricyclic[6,3,1,02,6]dodecane motif. In bioactivity assays, compound 1 demonstrated weak inhibitory activity against acid-sensing ion channel 1a.

Three-dimensional analysis of puncture needle path through safety triangle approach PLD and design of puncture positioning guide plate.

OBJECTIVE: In this study, the three-dimensional relationship between the optimal puncture needle path and the lumbar spinous process was discussed using digital technology. Additionally, the positioning guide plate was designed and 3D printed in order to simulate the surgical puncture of specimens. This plate served as an important reference for the preoperative simulation and clinical application of percutaneous laser decompression (PLD). METHOD: The CT data were imported into the Mimics program, the 3D model was rebuilt, the ideal puncture line N and the associated central axis M were developed, and the required data were measured. All of these steps were completed. A total of five adult specimens were chosen for CT scanning; the data were imported into the Mimics program; positioning guide plates were generated and 3D printed; a simulated surgical puncture of the specimens was carried out; an X-ray inspection was carried out; and an analysis of the puncture accuracy was carried out. RESULTS: (1) The angle between line N and line M was 42°~55°, and the angles between the line M and 3D plane were 1°~2°, 5°~12°, and 78°~84°, respectively; (2) As the level of the lumbar intervertebral disc decreases, the distance from point to line and point to surface changes regularly; (3) The positioning guide was designed with the end of the lumbar spinous process and the posterior superior iliac spine on both sides as supporting points. (4) Five specimens were punctured 40 times by using the guide to simulate surgical puncture, and the success rate was 97.5%. CONCLUSION: By analyzing the three-dimensional relationship between the optimal puncture needle path and the lumbar spinous process, the guide plate was designed to simulate surgical puncture, and the individualized safety positioning of percutaneous puncture was obtained.