The epidemiology and clinical features of post-exposure prophylaxis for rabies: A retrospective study of 9772 cases.

Background: In December 2015, the World Health Organization, the World Animal Health Organization, and the Food and Agriculture Organization of the United Nations convened the International Congress on the elimination of rabies in Geneva. How to use epidemiological factors of post-exposure prophylaxis to prevent rabies has become the focus of attention. Objective: To analyze the epidemiological characteristics of 9772 patients with rabies in a four-year period in one hospital, to clarify the outbreak law of rabies and to explore the corresponding prevention and control strategies. Methods: The epidemiological data of rabies patients were collected from the infectious disease reporting information management system of the hospital from July 2018 to June 2022. The distributional characteristics of 13 influencing factors were analyzed using the chi-square test and linear regression. Results: There was a significant correlation between the number of wounds and age, and the numbers of female and male patients were close. People over the age of 44 were more likely to get bites or scratches on their lower extremity (P<0.0001). There was a greater possibility for elderly people to be bitten by dogs (P<0.0001). Dogs preferred to bite or scratch lower limbs (P<0.0001), while cats upper limbs (P<0.0001). Upper limbs were more possibly attacked by animals at home (P<0.0001). There were significant correlations among exposure grade, wound treatment and number of wounds. Conclusions: Lower extremity protection is needed for the elderly and when encountering dogs, and more attention needs to be paid to the upper extremities when encountering cats and household pets, as well as pets that are cute but need to be protected from bites or scratches.

The Type Strain of Bifidobacterium indicum Scardovi and Trovatelli 1969 (Approved Lists 1980) is ATCC 25912, not DSM 20214, and Rejection to Reclassify Bifidobacterium coryneforme as Bifidobacterium indicum.

In 2018, Nouioui et al. proposed that Bifidobacterium coryneforme was a later synonym of Bifidobacterium indicum on the basis of the digital DNA-DNA hybridization (dDDH) value (85.0%) between B. coryneforme LMG 18911T and B. indicum LMG 11587T. However, in the study of Scardovi et al. (1970), the type strains of B. indicum and B. coryneforme only exhibited 60% DNA-DNA hybridization value. In the present study, the genomes of B. coryneforme CGMCC 1.2279T, B. coryneforme JCM 5819T, B. indicum JCM 1302T, B. indicum CGMCC 1.2275T, B. indicum DSM 20214T, B. indicum LMG 27437T, B. indicum ATCC 25912T, B. indicum KCTC 3230T, B. indicum CCUG 34985T, were sequenced, and the taxonomic relationship between B. coryneforme and B. indicum was re-evaluated. On the basis of the results presented here, (i) ATCC 25912 and DSM 20214 deposited by Vittorio Scardovi are two different strains; (ii) the type strain of B. indicum is ATCC 25912T (= JCM 1302T = LMG 27437T = CGMCC 1.2275T = KCTC 3230T), and not DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587); (iii) B. coryneforme and B. indicum represent two different species of the genus Bifidobacterium; (iv) strain DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587) belongs to B. coryneforme.

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

MixFormer: End-to-End Tracking With Iterative Mixed Attention.

Visual object tracking often employs a multi-stage pipeline of feature extraction, target information integration, and bounding box estimation. To simplify this pipeline and unify the process of feature extraction and target information integration, in this paper, we present a compact tracking framework, termed as MixFormer, built upon transformers. Our core design is to utilize the flexibility of attention operations, and we propose a Mixed Attention Module (MAM) for simultaneous feature extraction and target information integration. This synchronous modeling scheme allows us to extract target-specific discriminative features and perform extensive communication between target and search area. Based on MAM, we build our MixFormer trackers simply by stacking multiple MAMs and placing a localization head on top. Specifically, we instantiate two types of MixFormer trackers, a hierarchical tracker MixCvT, and a non-hierarchical simple tracker MixViT. For these two trackers, we investigate a series of pre-training methods and uncover the different behaviors between supervised pre-training and self-supervised pre-training in our MixFormer trackers. We also extend the masked autoencoder pre-training to our MixFormer trackers and design the new competitive TrackMAE pre-training technique. Finally, to handle multiple target templates during online tracking, we devise an asymmetric attention scheme in MAM to reduce computational cost, and propose an effective score prediction module to select high-quality templates. Our MixFormer trackers set a new state-of-the-art performance on seven tracking benchmarks, including LaSOT, TrackingNet, VOT2020, GOT-10 k, OTB100, TOTB and UAV123. In particular, our MixViT-L achieves AUC scores of 73.3% on LaSOT, 86.1% on TrackingNet and 82.8% on TOTB.

Cadmium phytoremediation potential of Houttuynia cordata: Insights from growth, uptake, and rhizosphere mechanisms.

Cadmium (Cd) pollutes 7.0 % of China's land area. This study examined the potential of Houttuynia cordata for Cd phytoremediation because of its ability to accumulate Cd in its growth matrix. H. cordata were planted in plastic pots filled with paddy field soils having low (LCd), medium (MCd), and high (HCd) Cd levels of 0.19, 0.69, and 2.91 mg/kg, respectively. After six months of growth, harvested plant parts were evaluated for Cd uptake and tolerance mechanisms. Metabolomics and metagenomics approaches were employed to investigate the soil rhizosphere mechanism. Results showed that the average plant biomass increased as soil Cd increased. The biomass Cd contents surpassed the allowable Cd limits for food (≤ 0.2 mg/kg) and medicinal uses (≤ 0.3 mg/kg). Cd contents were higher in H. cordata roots (30.59-86.27 mg/kg) than in other plant parts (0.63-2.90 mg/kg), with significantly increasing values as Cd soil level increased. Phenolic acids, lipids, amino acids and derivatives, organic acids, and alkaloids comprised the majority (69 in MCd vs HCd and 73 % in LCd vs HCd) of the shared upregulated metabolites. In addition, 13 metabolites specific to H. cordata root exudates were significantly increased. The top two principal metabolic pathways were arginine and proline metabolism, and beta-alanine metabolism. H. cordata increased the abundance of Firmicutes and Glomeromycota across all three Cd levels, and also stimulated the growth of Patescibacteria, Rozellomycota, and Claroideoglomus in HCd. Accordingly, H. cordata demonstrated potential for remediation of Cd-contaminated soils, and safety measures for its production and food use must be highly considered.

The calculated electronic and optical properties of ß-Ga2O3 based on the first principles.

INTRODUCTION: The electronic and optical properties of ß-Ga2O3 have been investigated by CASTEP using first principles. It is found that ß-Ga2O3 has an indirect band gap and the conduction band base is located at the Γ point. The stability of ß-Ga2O3 is demonstrated by the calculation of elastic constants, and the ductility of ß-Ga2O3 is demonstrated by the ratio of Poisson's ratio to shear modulus. The optical property analysis shows that ß-Ga2O3 has a high absorption capacity in the ultraviolet region, but a low absorption capacity in visible and infrared light. CONTEXT: The structure, optical, and electronic properties of ß-Ga2O3 are calculated and analyzed based on first-principles calculation. The optimized structures of ß-Ga2O3 are in good agreement with previously studied. In this paper, the elastic, electronic, and optical properties of ß-Ga2O3 are calculated. METHODS: The CASTEP code was employed to execute these calculations in the present work, where the exchange-correlation interactions were treated in the generalized gradient approximation (GGA) using the Perdew-Burke-Ernzerhof (PBE) functional in the geometry optimizations and electronic and elastic properties.

Bifidobacterium apis sp. nov., isolated from the gut of honeybee (Apis mellifera).

A novel bifidobacterium (designated F753-1T) was isolated from the gut of honeybee (Apis mellifera). Strain F753-1T was characterized using a polyphasic taxonomic approach. Strain F753-1T was phylogenetically related to the type strains of Bifidobacterium mizhiensis, Bifidobacterium asteroides, Bifidobacterium choladohabitans, Bifidobacterium mellis, Bifidobacterium apousia and Bifidobacterium polysaccharolyticum, having 98.4-99.8 % 16S rRNA gene sequence similarities. The phylogenomic tree indicated that strain F753-1T was most closely related to the type strains of B. mellis and B. choladohabitans. Strain F753-1T had the highest average nucleotide identity (94.1-94.5 %) and digital DNA-DNA hybridization (56.3 %) values with B. mellis Bin7NT. Acid production from amygdalin, d-fructose, gentiobiose, d-mannose, maltose, sucrose and d-xylose, activity of α-galactosidase, pyruvate utilization and hydrolysis of hippurate could differentiate strain F753-1T from B. mellis CCUG 66113T and B. choladohabitans JCM 34586T. Based upon the data obtained in the present study, a novel species, Bifidobacterium apis sp. nov., is proposed, and the type strain is F753-1T (=CCTCC AB 2023227T=JCM 36562T=LMG 33388T).

Design, synthesis, and evaluation of novel ferrostatin derivatives for the prevention of HG-induced VEC ferroptosis.

Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated cell death. It has been shown that high glucose (HG) could induce ferroptosis in vascular endothelial cells (VECs), consequently contributing to the development of various diseases. This study synthesized and evaluated a series of novel ferrostatin-1 (Fer-1) derivatives fused with a benzohydrazide moiety to prevent HG-induced VEC ferroptosis. Several promising compounds showed similar or improved inhibitory effects compared to positive control Fer-1. The most effective candidate 12 exhibited better protection against erastin-induced ferroptosis and high glucose-induced ferroptosis in VECs. Mechanistic studies revealed that compound 12 prevented mitochondrial damage, reduced intracellular ROS accumulation, upregulated the expression of GPX4, and decreased the amounts of ferrous ion, LPO and MDA in VECs. However, compound 12 still exhibited undesirable microsomal stability like Fer-1, suggesting the need for further optimization. Overall, the present findings highlight ferroptosis inhibitor 12 as a potential lead compound for treating ferroptosis-associated vascular diseases.

Experimental study on flow characteristics of jet ventilation in crossflow in confined mine spaces.

The increasing depth of mine excavation presents greater challenges in mine ventilation and in managing cooling energy consumption. Therefore, there is an urgent need for comprehensive research on jet ventilation influenced by low-speed crossflows. This study investigated the impact of flow velocity ratios (R) and jet exit diameters (d) on flow-field distribution and flow characteristics through velocity measurements and smoke flow visualization experiments. The results of the study revealed two distinct types of air lakes formed by jet ventilation in crossflow (JVIC), with one being wall-attached and the other suspended. Notably, a significant secondary flow phenomenon was observed in the near-field near the upper wall. Additionally, the deflection angle (θj) of JVIC decreases as R and d/D increase, leading to the formation and movement of a semi-confined point (SP) and a confined point (CP) in the -x direction. Moreover, the wall confinement effect diminishes the jet's diffusion and deflection ability in the -z direction, leading to increased penetration in the x direction. Before the formation of the SP, the deflection section of the jet lengthens, followed by a rapid shortening upon its formation. Finally, the study further developed empirical equations for the jet axial trajectory and diffusion width.

Type I [4σ + 4π] vs [4σ + 4π - 1] Cycloadditions Accessing Medium-Sized Carbocycles and Discovery of a Liver X Receptor ß-Selective Ligand.

The transition-metal-catalyzed [4 + 4] cycloaddition leading to cyclooctanoids has been centralizing on dimerization between 1,3-diene type substrates. Here, we extend a [4σ + 4π - 1] and [4σ + 4π] cycloaddition strategy to access the 7/8-membered fused carbocycles through Rh-catalyzed coupling between the 4σ-donor (benzocyclobutenones) and pendant diene (4π) motifs. The two pathways can be controlled by adjusting the solvated CO concentration. A broad scope (>40 examples) of 5-6-7 and 5-6-8 polyfused carbocycles was obtained with good yields (up to 90%). The density functional theory (DFT) calculations, kinetic monitoring and 13C-labeling experiments were carried out, suggesting a plausible mechanism. Notably, the 5-6-7 tricycle 2v was found to be a very rare, potent, and selective ligand for the liver X receptor ß (KD=0.64 µM), which is a potential therapeutic target for cholesterol-metabolism-related fatal diseases.

CwJAZ4/9 negatively regulates jasmonate-mediated biosynthesis of terpenoids through interacting with CwMYC2 and confers salt tolerance in Curcuma wenyujin.

Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.

Multi-omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma.

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.

PagPXYs improve drought tolerance by regulating reactive oxygen species homeostasis in the cambium of Populus alba × P. glandulosa.

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, '84K'). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control '84K'. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.

Design, synthesis, and evaluation of formylpiperazine analogs of Ferrostatin-1 as novel improved ferroptosis inhibitors.

In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.

Evaluation of novel promoters for vascular tissue-specific gene expression in Populus.

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.

Microstructure and Properties of Aluminum-Graphene-SiC Matrix Composites after Friction Stir Processing.

Enhancing the mechanical properties of conventional ceramic particles-reinforced aluminum (Al 1060) metal matrix composites (AMCs) with lower detrimental phases is difficult. In this research work, AMCs are reinforced with graphene nanosheet (GNS) and hybrid reinforcement (GNS combined with 20% SiC, synthesized by shift-speed ball milling (SSBM), and further fabricated by two-pass friction stir processing (FSP). The effect of GNS content and the addition of SiC on the microstructure and mechanical properties of AMCs are studied. The microstructure, elemental, and phase composition of the developed composite are examined using SEM, EDS, and XRD techniques, respectively. Mechanical properties such as hardness, wear, and tensile strength are analyzed. The experimental results show that the GNS and the SiC are fairly distributed in the Al matrix via SSBM, which is beneficial for the mechanical properties of the composites. The maximum tensile strength of the composites is approximately 171.3 MPa in AMCs reinforced by hybrid reinforcements. The tensile strength of the GNS/Al composites increases when the GNS content increases from 0 to 1%, but then reduces with the further increase in GNS content. The hardness increases by 2.3%, 24.9%, 28.9%, and 41.8% when the Al 1060 is reinforced with 0.5, 1, 2% GNS, and a hybrid of SiC and GNS, respectively. The SiC provides further enhancement of the hardness of AMCs reinforced by GNS. The coefficient of friction decreases by about 7%, 13%, and 17% with the reinforcement of 0.5, 1, and 2% GNS, respectively. Hybrid reinforcement has the lowest friction coefficient (0.41). The decreasing friction coefficient contributes to the self-lubrication of GNSs, the reduction in the contact area with the substrate, and the load-bearing ability of ceramic particles. According to this study, the strengthening mechanisms of the composites may be due to thermal mismatch, grain refinement, and Orowan looping. In summary, such hybrid reinforcements effectively improve the mechanical and tribological properties of the composites.

Xiashengella succiniciproducens gen. nov., sp. nov., a succinate-producing bacterium isolated from an anaerobic digestion tank in the family Marinilabiliaceae of the order Bacteroidales.

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).

The clinical and hemodynamic characteristics of pulmonary hypertension in patients with OSA-COPD overlap syndrome.

BACKGROUND: Our study aimed to assess the clinical and hemodynamic characteristics of pulmonary hypertension (PH) in patients with overlapping obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to OSA-COPD overlap syndrome (OS). METHODS: We enrolled a total of 116 patients with OS, COPD, or OSA who underwent right heart catheterization (RHC) due to suspected PH. We conducted a retrospective analysis of the clinical and hemodynamic characteristics of these patients. RESULTS: Among the three groups (OS group, n = 26; COPD group, n = 36; OSA group, n = 54), the prevalence of PH was higher in the OS group (n = 17, 65.4%)compared to OSA group (n = 26,48.1%) and COPD group (n = 20,55.6 %). Among three groups with PH, the superior vena cava pressure (CVP) and right ventricular pressure (RAP) were higher in the OS group than in the OSA group (P < 0.05). Patients in the OS and COPD groups had higher pulmonary artery wedge pressure (PAWP) than in the OSA group (14.88 ± 4.79 mmHg, 13.45 ± 3.68 mmHg vs. 11.00 ± 3.51 mmHg, respectively, P < 0.05). OS patients with PH exhibited higher respiratory event index (REI), time spent with SpO2 <90%, oxygen desaturation index (ODI), minimal SpO2 (MinSpO2) and mean SpO2 (MSpO2) compared to OS patients without PH. After adjusting for potential covariates, we found that MinSpO2 (OR 0.937, 95 % CI 0.882-0.994, P = 0.032), MSpO2 (OR 0.805, 95% CI 0.682-0.949, P = 0.010), time spent with SpO2 <90% (OR 1.422, 95% CI 1.137-1.780, P = 0.002), and FEV1 % pred (OR 0.977, 95 % CI 0.962-0.993, P = 0.005) were related to the development of PH. CONCLUSIONS: Patients with OS showed higher prevalence of PH, along with higher PAWP, CVP and RAP. Worse nocturnal hypoxemia was found in OS patients with PH.

Synthesis and biological evaluation of 1-phenyl-tetrahydro-ß-carboline-based first dual PRMT5/EGFR inhibitors as potential anticancer agents.

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.

Development and validation of an artificial intelligence model to accurately predict spinopelvic parameters.

OBJECTIVE: Achieving appropriate spinopelvic alignment has been shown to be associated with improved clinical symptoms. However, measurement of spinopelvic radiographic parameters is time-intensive and interobserver reliability is a concern. Automated measurement tools have the promise of rapid and consistent measurements, but existing tools are still limited to some degree by manual user-entry requirements. This study presents a novel artificial intelligence (AI) tool called SpinePose that automatically predicts spinopelvic parameters with high accuracy without the need for manual entry. METHODS: SpinePose was trained and validated on 761 sagittal whole-spine radiographs to predict the sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), T1 pelvic angle (T1PA), and L1 pelvic angle (L1PA). A separate test set of 40 radiographs was labeled by four reviewers, including fellowship-trained spine surgeons and a fellowship-trained radiologist with neuroradiology subspecialty certification. Median errors relative to the most senior reviewer were calculated to determine model accuracy on test images. Intraclass correlation coefficients (ICCs) were used to assess interrater reliability. RESULTS: SpinePose exhibited the following median (interquartile range) parameter errors: SVA 2.2 mm (2.3 mm) (p = 0.93), PT 1.3° (1.2°) (p = 0.48), SS 1.7° (2.2°) (p = 0.64), PI 2.2° (2.1°) (p = 0.24), LL 2.6° (4.0°) (p = 0.89), T1PA 1.1° (0.9°) (p = 0.42), and L1PA 1.4° (1.6°) (p = 0.49). Model predictions also exhibited excellent reliability at all parameters (ICC 0.91-1.0). CONCLUSIONS: SpinePose accurately predicted spinopelvic parameters with excellent reliability comparable to that of fellowship-trained spine surgeons and neuroradiologists. Utilization of predictive AI tools in spinal imaging can substantially aid in patient selection and surgical planning.