Assessing vaginal microbiome through Vaginal Microecology Evaluation System as a predictor for in vitro fertilization outcomes: a retrospective study.

Objective: This study aims to evaluate the effectiveness of the Vaginal Microecology Evaluation System (VMES) in assessing the dynamics of the vaginal microbiome (VM) throughout the process of in vitro fertilization and embryo transfer (IVF-ET). Furthermore, it seeks to explore the potential correlation between distinct types of VM ecology and the success rate of IVF-ET. Methods: This study employed VMES to ascertain the composition of the VM. Data were collected from infertile women who underwent their initial IVF-ET treatment for tubal factor between January 2018 and December 2021. A retrospective analysis of pregnancy outcomes resulting from their fresh embryo transfer was conducted to determine the predictive significance of the vaginal microenvironment. Results: We demonstrate that VMES is able to predict IVF-ET outcomes in patients diagnosed with Bacterial Vaginosis (BV). Notably, a discernible shift in the VM was observed in a decent subset of patients following Controlled Ovarian Stimulation (COS), though this phenomenon was not universal across all participants. Specifically, there was a noteworthy increase in the proportion of patients exhibiting BV and uncharacterized dysbiosis subsequent to COS. Furthermore, our investigation revealed a significant correlation between VM and both the live birth rate and early miscarriage rate. Employing a multivariable logistic regression model, we identified that VM status pre-COS, VM status post-COS, patient age, and the number of embryos transferred emerged as independent predictors of the live birth rate. Conclusion: Our study suggests that, during IVF-ET treatment, the VMES can effectively detect changes in the VM, which are strongly correlated with the pregnancy outcome of IVF-ET procedures.

Physical Adversarial Attack Meets Computer Vision: A Decade Survey.

Despite the impressive achievements of Deep Neural Networks (DNNs) in computer vision, their vulnerability to adversarial attacks remains a critical concern. Extensive research has demonstrated that incorporating sophisticated perturbations into input images can lead to a catastrophic degradation in DNNs' performance. This perplexing phenomenon not only exists in the digital space but also in the physical world. Consequently, it becomes imperative to evaluate the security of DNNs-based systems to ensure their safe deployment in real-world scenarios, particularly in security-sensitive applications. To facilitate a profound understanding of this topic, this paper presents a comprehensive overview of physical adversarial attacks. Firstly, we distill four general steps for launching physical adversarial attacks. Building upon this foundation, we uncover the pervasive role of artifacts carrying adversarial perturbations in the physical world. These artifacts influence each step. To denote them, we introduce a new term: adversarial medium. Then, we take the first step to systematically evaluate the performance of physical adversarial attacks, taking the adversarial medium as a first attempt. Our proposed evaluation metric, hiPAA, comprises six perspectives: Effectiveness, Stealthiness, Robustness, Practicability, Aesthetics, and Economics. We also provide comparative results across task categories, together with insightful observations and suggestions for future research directions.

Revealing the Freezing-Induced Alteration in Microplastic Behavior and Its Implication for the Microplastics Released from Seasonal Ice.

Ice can serve as a significant temporary repository and conveyance mechanism for microplastics (MPs). MPs present in the water column can become entrapped within developing ice formations, subsequently being sequestered and transported by ice floes. With changing temperatures, MPs stored in ice can be released back into the environment, while freezing conditions can alter the properties of MPs, ultimately affecting the fate of MPs in the environment. Freezing of MPs in freshwater ice results in the aggregation of MP particles due to physical compression, leading to an increase in particle size once the MPs are released from the ice. The freezing-induced aggregation enhances buoyancy effects, accelerating the settling/rising velocity of MPs in water. Additionally, freezing can lead to enhanced surface wetting alterations, thus improving the dispersion of hydrophobic MPs. The presence of salt in the water can mitigate the effect of freezing on MPs due to the formation of a brine network within the ice structure, which reduces the pressure on MPs entrapped by ice. In cold regions, numerous MPs undergo freezing and thawing, re-entering the water column.

Heat stroke: Pathogenesis, diagnosis, and current treatment.

Recently, the incidence of heat-related illnesses has exhibited a steadily upward trend, which is closely associated with several environmental factors such as climate change and air pollution. The progression of heat-related illnesses is a continuous process and can progress to the terminal period when it transforms into heat stroke, the most severe form. Heat stroke is markedly by a core body temperature above 40°C and central nervous system dysfunction. Current knowledge suggests that the pathogenesis of heat stroke is complex and varied, including inflammatory response, oxidative stress, cell death, and coagulation dysfunction. This review consolidated recent research progress on the pathophysiology and pathogenesis of heat stroke, with a focus on the related molecular mechanisms. In addition, we reviewed common strategies and sorted out the drugs in various preclinical stages for heat stroke, aiming to offer a comprehensive research roadmap for more in-depth researches into the mechanisms of heat stroke and the reduction in the mortality of heat stroke in the future.

Distraction force promotes the osteogenic differentiation of Gli1+ cells in facial sutures via primary cilia-mediated Hedgehog signaling pathway.

BACKGROUND: Trans-sutural distraction osteogenesis (TSDO) involves the application of distraction force to facial sutures to stimulate osteogenesis. Gli1+ cells in the cranial sutures play an important role in bone growth. However, whether Gli1+ cells in facial sutures differentiate into bone under distraction force is unknown. METHODS: 4-week-old Gli1ER/Td and C57BL/6 mice were used to establish a TSDO model to explore osteogenesis of zygomaticomaxillary sutures. A Gli1+ cell lineage tracing model was used to observe the distribution of Gli1+ cells and explore the role of Gli1+ cells in facial bone remodeling. RESULTS: Distraction force promoted bone remodeling during TSDO. Fluorescence and two-photon scanning images revealed the distribution of Gli1+ cells. Under distraction force, Gli1-lineage cells proliferated significantly and co-localized with Runx2+ cells. Hedgehog signaling was upregulated in Gli1+ cells. Inhibition of Hedgehog signaling suppresses the proliferation and osteogenesis of Gli1+ cells induced by distraction force. Subsequently, the stem cell characteristics of Gli1+ cells were identified. Cell-stretching experiments verified that mechanical force promoted the osteogenic differentiation of Gli1+ cells through Hh signaling. Furthermore, immunofluorescence staining and RT-qPCR experiments demonstrated that the primary cilia in Gli1+ cells exhibit Hedgehog-independent mechanosensitivity, which was required for the osteogenic differentiation induced by mechanical force. CONCLUSIONS: Our study indicates that the primary cilia of Gli1+ cells sense mechanical stimuli, mediate Hedgehog signaling activation, and promote the osteogenic differentiation of Gli1+ cells in zygomaticomaxillary sutures.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.

Isotoosendanin inhibits triple-negative breast cancer metastasis by reducing mitochondrial fission and lamellipodia formation regulated by the Smad2/3-GOT2-MYH9 signaling axis.

Triple-negative breast cancer (TNBC) is incurable and prone to widespread metastasis. Therefore, identification of key targets for TNBC progression is urgently needed. Our previous study revealed that isotoosendanin (ITSN) reduced TNBC metastasis by targeting TGFßR1. ITSN is currently used as an effective chemical probe to further discover the key molecules involved in TNBC metastasis downstream of TGFßR1. The results showed that GOT2 was the gene downstream of Smad2/3 and that ITSN decreased GOT2 expression by abrogating the activation of the TGF-ß-Smad2/3 signaling pathway through directly binding to TGFßR1. GOT2 was highly expressed in TNBC, and its knockdown decreased TNBC metastasis. However, GOT2 overexpression reversed the inhibitory effect of ITSN on TNBC metastasis both in vitro and in vivo. GOT2 interacted with MYH9 and hindered its binding to the E3 ubiquitin ligase STUB1, thereby reducing MYH9 ubiquitination and degradation. Moreover, GOT2 also enhanced the translocation of MYH9 to mitochondria and thus induced DRP1 phosphorylation, thereby promoting mitochondrial fission and lamellipodia formation in TNBC cells. ITSN-mediated inhibition of mitochondrial fission and lamellipodia formation was associated with reduced GOT2 expression. In conclusion, ITSN prevented MYH9-regulated mitochondrial fission and lamellipodia formation in TNBC cells by enhancing MYH9 protein degradation through a reduction in GOT2 expression, thus contributing to its inhibition of TNBC metastasis.

Superficial circumflex iliac artery perforator propeller flap for penoscrotal extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare intra-epidermal adenocarcinoma, and reconstruction of the penoscrotal region remains a clinical challenge. The superficial circumflex iliac artery perforator (SCIP) flap has been successfully used as a free flap, while its application as a propeller flap in the reconstruction of penoscrotal EMPD defect is rarely reported. The objective was to evaluate the safety and efficacy of the SCIP propeller flap in the reconstruction of penoscrotal defects in EMPD. METHODS: Between September 2010 and August 2022, consecutive patients diagnosed with penoscrotal EMPD were enrolled. All patients underwent penoscrotal EMPD excision and reconstruction with SCIP propeller flap combined with other flaps or skin grafts on individual defects. Demographic information, surgical parameters, postoperative complications, patient satisfaction, and recurrence rates were analyzed. RESULTS: Twenty-four patients (mean age, 73 ± 8.8 years; mean BMI, 23.98 ± 3.62 kg/m2) with 33 SCIP propeller flaps (mean size 120.1 cm2; range, 24-208 cm2) were included, and the mean defect size was 67.4 cm2 (range, 12-255 cm2). The mean operative duration was 385.4 ± 146.8 min. Fifteen patients received autologous full-thickness skin grafts, and four received other flaps simultaneously. All flaps survived without total or partial loss, and all donor sites achieved primary closure, though local hematoma (one case) and limited skin graft necrosis (two cases) were observed. All patients experienced complete wound healing and maintained penoscrotal morphology and function without recurrent lesions over a mean follow-up of 59 months. CONCLUSIONS: The SCIP propeller flap seems a safe and effective reconstructive method for penoscrotal EMPD. LEVEL OF EVIDENCE: IV.

Recent trends in Tuina for chronic pain management: A bibliometric analysis and literature review.

BACKGROUND: The utilization of Tuina as a therapeutic intervention for the management of chronic pain has experienced a gradually increase in its popularity, and the purpose of this bibliometric analysis is to offer a comprehensive understanding of the current state and frontier trends, as well as to provide recommendations for future research directions. METHODS: Publications on Tuina for chronic pain published between 2004 and 2023 were retrieved from the Web of Science Core Collection (WoSCC). Microsoft Excel, CiteSpace, VOSViewer, and the R package "bibliometrix" were used to quantitatively analyse the annual publication volume, countries/regions, journals, institutions, cited references, authors, and keywords. RESULTS: A total of 287 publications were retrieved. The number of annual publications on the use of Tuina for treating chronic pain has gradually increased. Most publications were published in China and the United States. Notably, the most productive institution and author were identified as Shanghai University of Traditional Chinese Medicine and Min Fang, respectively. Medicine ranked first as the most influential affiliate and most productive journal. These publications came from 1,650 authors, among whom Edzard Ernst had the most co-citations. Keyword analysis revealed that the new research frontier was low back pain. CONCLUSION: The utilization of Tuina for the treatment of chronic pain has been gaining increasing recognition. Acupuncture, randomised controlled trials, systematic reviews, etc. were the main research subjects. Furthermore, low back pain is the new research frontier. This study provides an in-depth perspective on Tuina for chronic pain, which provides valuable reference material for clinicians with insights of therapeutic strategy, educators with valuable topics, and researchers with new research directions.

Separation and purification of benzylester glucosides and derivatives from tubers of Gymnadenia conopsea (L.) R. Br. by linear gradient counter-current chromatography combined with elution-extrusion mode.

Tubers of Gymnadenia conopsea (L.) R. Br. (Orchidaceae), a traditional medicine and food homologous plant, has a broad application and development prospect in the food and drug industries. Benzylester glucosides, the main effective active components in this plant, are difficult to separate due to their similar structures and high polarity. In this study, linear gradient counter-current chromatography was used to separate benzylester glucosides and derivatives, combined with elution-extrusion mode. The main separation parameters were optimized, including the ratio of mobile phase and sample loading. Finally, seven compounds were successfully separated, including 4-hydroxybenzyl alcohol (1), 4-hydroxybenzaldehyde (2), dactylorhin B (3), loroglossin (4), dactylorhin A (5), 4-(ethoxymethyl) phenol (6), and militarine (7). The structures were analyzed by mass spectrometry and nuclear magnetic resonance spectrometry. According to our findings, the established method was an efficient approach to separate benzylester glucosides and derivatives from tubers of G. conopsea. The established strategy could be applied to purify other similar high-polarity compounds from complex natural products.

T-distributed Stochastic Neighbor Network for unsupervised representation learning.

Unsupervised representation learning (URL) is still lack of a reasonable operator (e.g. convolution kernel) for exploring meaningful structural information from generic data including vector, image and tabular data. In this paper, we propose a simple end-to-end T-distributed Stochastic Neighbor Network (TsNet) for URL with clustering downstream task. Concretely, our TsNet model has three major components: (1) an adaptive connectivity distribution learning module is presented to construct a pairwise graph for preserving the local structure of generic data; (2) a T-distributed stochastic neighbor embedding based loss function is designed to learn a transformation between embeddings and original data, which improves the discrimination of representations; (3) a nonlinear parametric mapping is learned via our TsNet on an unsupervised generalized manner, which can address the "out-of-sample" issue. By combining these components, our method is able to considerably outperform previous related unsupervised learning approaches on visualization and clustering of generic data. A simple deep neural network equipped on our model respectively achieves 74.90%, 76.56% ACC and NMI, which is 8% relative improvement over previous state-of-the-art on real single-cell RNA-sequencing (scRNA-seq) datasets clustering.

Placenta-derived mesenchymal stem cells promote diabetic wound healing via exosomal protein interaction networks.

There is a lack of effective treatment options for diabetic refractory wounds, which presents a critical clinical issue that needs to be addressed urgently. Our research has demonstrated that human placenta-derived mesenchymal stem cells (plaMSCs) facilitate the migration and proliferation of HaCat cells, thereby enhancing diabetic wound healing primarily via the exosomes derived from plaMSCs (plaMSCs-Ex). Using label-free proteomics, plaMSCs and their exosomes were analysed for proteome taxonomic content in order to explore the underlying effective components mechanism of plaMSCs-Ex in diabetic wound healing. Differentially expressed proteins enriched in plaMSCs-Ex were identified and underwent bioinformatics analysis including GO annotation, KEGG pathway enrichment, gene set enrichment analysis (GSEA) and protein-protein interaction analysis (PPI). Results showed that the proteins enriched in plaMSCs-Ex are significantly involved in extracellular matrix organisation, epithelium morphogenesis, cell growth, adhesion, proliferation and angiogenesis. PPI analysis filtered 2 wound healing-related clusters characterised by hub proteins such as POSTN, FN1, SPARC, TIMP1, SERPINE1, LRP1 and multiple collagens. In brief, the exosomal proteins derived from plaMSCs reveal diverse functions of regeneration and tissue remodelling based on proteomics analysis and potentially play a role in diabetic wound healing.

Association of tumor immune infiltration and prognosis with homologous recombination repair genes mutations in early triple-negative breast cancer.

The aim of this study was to evaluate the mutation spectrum of homologous recombination repair (HRR) genes and its association with tumor immune infiltration and prognosis in triple-negative breast cancer (TNBC). TNBC patients (434 patients from Ruijin cohort) were evaluated with targeted next-generating sequencing for mutations in HRR genes. The frequencies of mutations were compared with public reference cohorts (320 TNBC patients from METABRIC, 105 from TCGA, and 225 from MSKCC 2018). Associations between mutation status and tumor immune infiltration and prognosis were analyzed. HRR genes mutations were seen in 21.89% patients, with BRCA1/2 mutations significantly enriched in tumors with breast/ovarian cancer family history (P = 0.025) and high Ki-67 levels (P = 0.018). HRR genes mutations were not related with recurrence-free survival (RFS) (adjusted P = 0.070) and overall survival (OS) (adjusted P = 0.318) for TNBC patients, regardless of carboplatin treatment (P > 0.05). Moreover, tumor immune infiltration and PD-L1 expression was positively associated with HRR or BRCA1/2 mutation (all P < 0.001). Patients with both HRR mutation and high CD8+ T cell counts had the best RFS and OS, whereas patients with no HRR mutation and low CD8+ T cell counts had the worst outcomes (RFS P < 0.001, OS P = 0.019). High frequency of HRR gene mutations was found in early TNBC, with no prognostic significance. Immune infiltration and PD-L1 expression was positively associated with HRR mutation, and both HRR mutation and high CD8+ T cell infiltration levels were associated with superior disease outcome.

Surface-Engineered Polygonatum Sibiricum Polysaccharide CaCO3 Microparticles as Novel Vaccine Adjuvants to Enhance Immune Response.

Micro- and nanoparticles delivery systems have been widely studied as vaccine adjuvants to enhance immunogenicity and sustain long-term immune responses. Polygonatum sibiricum polysaccharide (PSP) has been widely studied as an immunoregulator in improving immune responses. In this study, we synthesized and characterized cationic modified calcium carbonate (CaCO3) microparticles loaded with PSP (PEI-PSP-CaCO3, CTAB-PSP-CaCO3), studied the immune responses elicited by PEI-PSP-CaCO3 and CTAB-PSP-CaCO3 carrying ovalbumin (OVA). Our results demonstrated that PEI-PSP-CaCO3 significantly enhanced the secretion of IgG and cytokines (IL-4, IL-6, IFN-γ, and TNF-α) in vaccinated mice. Additionally, PEI-PSP-CaCO3 induced the activation of dendritic cells (DCs), T cells, and germinal center (GC) B cells in draining lymph nodes (dLNs). It also enhanced lymphocyte proliferation, increased the ratio of CD4+/CD8+ T cells, and elevated the frequency of CD3+ CD69+ T cells in spleen lymphocytes. Therefore, PEI-PSP-CaCO3 microparticles induced a stronger cellular and humoral immune response and could be potentially useful as a vaccine delivery and adjuvant system.

Proanthocyanidin surface preconditioning of dental pulp stem cell spheroids enhances dimensional stability and biomineralization in vitro.

AIM: Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold-free microtissue-based dental pulp regeneration. Surface collagen cross-linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross-linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)-derived 3D cell spheroids. METHODOLOGY: Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross-linking. Microtissue viability was examined by live/dead staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA-preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA-preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F-actin expressions. PA-preconditioned macrotissues were subjected to histological analysis, including haematoxylin-eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP-1) expressions. RESULTS: PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse-section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP-1 expressions in macrotissues. Additionally, PA preconditioning induced higher F-actin and DSPP expression in microtissues, while inhibition of F-actin activity by cytochalasin B attenuated PA-induced dimensional change and DSPP upregulation. CONCLUSION: PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC-derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold-free tissue engineering applications in regenerative dentistry.

Comparison of clinical outcomes of a corneal wavefront- and topography-guided platforms for laser in situ keratomileusis on virgin eyes: an expanded cohort study.

PURPOSE: To compare the clinical outcomes of myopiacorrected with corneal-wavefront-guided (CWG) laser in situ keratomileusis (LASIK) with AMARIS 1050S (SCHWIND eye-tech-solutions GmbH & Co. KG) and corneal-topography-guided (CTG) LASIK with WaveLight EX500 (Alcon Laboratories, Fort Worth, TX). METHODS: In this prospective, pseudo-randomized expanded cohort study, a total of 266 patients were subjected to binocular LASIK surgery, either with WaveLight EX500 (WaveLight group) or Amaris 1050S (AMARIS group) platforms. Data related to right eyes were selected for analysis. Corneal higher-order aberration (HOA) was selected as the primary endpoint; while visual acuity and refraction were the secondary endpoints. All the endpoints were assessed at 3 months postoperatively. RESULTS: There were 134 eyes in the AMARIS group and 132 eyes in the WaveLight group. After 3 months of postoperative follow-up, spherical and coma aberrations were significantly lower (P < 0.05) in the WaveLight group (spherical aberration: - 0.104 ± 0.199 µm; coma aberration: - 0.117 ± 0.202 µm) in comparison with the AMARIS group (spherical aberrations: 0.254 ± 0.146 µm; coma aberrations: 0.316 ± 0.297 µm). In the AMARIS group, 96.3% of the eyes achieved an uncorrected distance visual acuity (UDVA) of 20/20 while in the WaveLight group, 96.2% of the eyes achieved an UDVA of 20/20. Furthermore, the mean postoperative manifest refraction spherical equivalent (MRSE) was - 0.02 ± 0.28 in the AMARIS group and - 0.05 ± 0.21 in the WaveLight group (P = 0.34). CONCLUSIONS: Both WaveLight EX500 and Amaris 1050S LASIK showed excellent refractive and visual outcomes. In addition, the WaveLight group showed minimal spherical and coma aberrations when compared to the AMARIS group.

A comparative study of shockwave intravascular lithotripsy and conventional percutaneous coronary intervention in the treatment of severe coronary artery calcification lesions.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of intravascular lithotripsy (IVL) in the treatment of severe coronary artery calcification (CAC) lesions. METHODS: In this study, we selected patients diagnosed with severe CAC lesions confirmed by coronary angiography (CAG) who were hospitalized in Yulin First People's Hospital between December 2021 and December 2022 and required percutaneous coronary intervention (PCI). Using a random number table, we divided all patients into the IVL group and the PCI group in the order of interventional therapy. We compared both groups in terms of the surgical success rate, intraoperative manipulation characteristics, procedural complication, and cumulative incidence of major adverse cardiovascular events (MACE). RESULTS: (1) There were no differences in the surgical success rate, incidence of MACE, and occurrence of procedural complication between the two groups; (2) Compared with the conventional PCI group, patients in the IVL group used fewer predilatation balloons, and the difference was statistically significant (all P < 0.05); (3) Compared with the conventional PCI group, patients in the IVL group had lesser surgery time and lesser radiation time, with lesser proportion of patients who were assisted with stent implantation using coronary artery rotational atherectomy, and this difference was statistically significant (P < 0.05); (4) The mean stent diameter and length in the IVL group was greater than those in the conventional PCI group but the difference was not statistically significant (P > 0.05). CONCLUSION: In this study, we found that IVL was a highly safe and effective procedure in the treatment of severe CAC lesions that did not increase the surgery and radiation time, and it could also reduce the use of predilatation balloons, thus improving the management of CAC lesions. Thus, IVL can be a novel choice in treating severe CAC lesions.

A near complete genome assembly of the East Friesian sheep genome.

Advancements in sequencing have enabled the assembly of numerous sheep genomes, significantly advancing our understanding of the link between genetic variation and phenotypic traits. However, the genome of East Friesian sheep (Ostfriesisches Milchschaf), a key high-yield milk breed, remains to be fully assembled. Here, we constructed a near-complete and gap-free East Friesian genome assembly using PacBio HiFi, ultra-long ONT and Hi-C sequencing. The resulting genome assembly spans approximately 2.96 Gb, with a contig N50 length of 104.1 Mb and only 164 unplaced sequences. Remarkably, our assembly has captured 41 telomeres and 24 centromeres. The assembled sequence is of high quality on completeness (BUSCO score: 97.1%) and correctness (QV: 69.1). In addition, a total of 24,580 protein-coding genes were predicted, of which 97.2% (23,891) carried at least one conserved functional domain. Collectively, this assembly provides not only a near T2T gap-free genome, but also provides a valuable genetic resource for comparative genome studies of sheep and will serve as an important tool for the sheep research community.

The relationship between NLR, LDL-C/HDL-C, NHR and coronary artery disease.

OBJECTIVE: Chronic inflammation and dyslipidemia are key risk factors for atherosclerotic cardiovascular diseases. We retrospectively explored the association between the neutrophil to lymphocyte ratio (NLR), the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C), and the neutrophil to HDL-C ratio (NHR), and the severity of coronary lesions in patients with acute coronary syndrome (ACS). METHOD: In June 2023, we selected 1210 patients who were diagnosed with ACS based on chest pain from January 2017 to December 2022. Of these, 1100 patients with abnormal coronary angiography were categorized into the experimental group, and 110 patients with normal coronary angiography were classified as the control group. We collected routine blood tests, lipid profiles, and coronary angiography results at admission (before coronary angiography). Patients were then stratified into a control group (Gensini score = 0) and an experimental group (Gensini score = 0) based on the Gensini score. The experimental group was further divided into a low score group (Gensini score < 69) and a high score group (Gensini score ≥ 69). RESULT: 1. Statistically significant differences were observed between the control and experimental groups in terms of gender, age, body mass index (BMI), hypertension, diabetes, smoking history, and counts of neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), red cell distribution width (RDW), total cholesterol (TC), HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR (P<0.05). Furthermore, differences in BMI, hypertension, diabetes, smoking history, NEU, LYM, MON, TC, triglyceride (TG), HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR were significant between the low and high score groups (P<0.05). 2. NEU, LYM, MON, TC, HDL-C, LDL-C, NLR, LDL-C/HDL-C, and NHR showed significant correlations with the Gensini score (r>0.2, P<0.05), with NLR and LDL-C/HDL-C showing the strongest correlations (r = 0.822, P = 0.000). 3. The Receiver Operating Characteristic (ROC) curve indicated that the combination of NLR and LDL-C/HDL-C had superior sensitivity and specificity in predicting the severity of coronary lesions, with a significant difference (P<0.05). The sensitivity was 87.1%, the specificity was 90.9%, and the cut-off point was 2.04. 4. A predictive model was developed based on the ratio of NLR and LDL-C/HDL-C to the Gensini score. The final model score was calculated as 6.803 + 7.029NLR + 13.079LDL-C/HDL-C (R2 = 0.708). CONCLUSION: Compared to NLR, LDL-C/HDL-C, and NHR, the combined NLR and LDL-C/HDL-C ratio is a more accurate marker for assessing the severity of coronary artery disease in ACS patients. Its convenience and effectiveness make it a promising tool for early assessment, timely risk stratification, and appropriate clinical intervention, ultimately improving clinical outcomes for ACS patients.

Regioselective Condensation Polymerization of Propargylic Electrophiles Enabled by Catalytic Element-Cupration.

Here, we report a set of new polymerization reactions enabled by the 1,2-regioselective hydro- and silylcupration of enyne-type propargylic electrophiles. Highly regioregular head-to-tail poly(2-butyne-1,4-diyl)s (HT-PBD), bearing either methyl or silylmethyl side chains, are synthesized for the first time. A rapid entry into carbon-rich copolymers with adjustable silicon content is developed via in situ monomer bifurcation. Furthermore, a one-pot polymerization/semireduction sequence is developed to access a cis-poly(butadiene)-derived backbone by a ligand swap on copper hydride species. Interestingly, borocupration, typically exhibiting identical regioselectivity with its hydro- and silyl analogues, seems to proceed in a 3,4-selective manner. Computational studies suggest the possible role of the propargylic leaving group in this selectivity switch. This work presents a new class of regioregular sp-carbon-rich polymers and meanwhile a novel approach to organosilicon materials.