Biomarker identification and risk prediction model development for differentiated thyroid carcinoma lung metastasis based on primary lesion proteomics.

PURPOSE: The rising global high incidence of differentiated thyroid carcinoma (DTC) has led to a significant increase in patients presenting with lung metastasis of DTC (LMDTC). This population poses a significant challenge in clinical practice, necessitating the urgent development of effective risk stratification methods and predictive tools for lung metastasis. EXPERIMENTAL DESIGN: Through proteomic analysis of large samples of primary lesion and dual validation employing parallel reaction monitoring and immunohistochemistry, we identified eight hub proteins as potential biomarkers. By expanding the sample size and conducting statistical analysis on clinical features and hub protein expression, we constructed three risk prediction models. RESULTS: This study identified eight hub proteins-SUCLG1/2, DLAT, IDH3B, ACSF2, ACO2, CYCS and VDAC2- as potential biomarkers for predicting DTC lung metastasis risk. We developed and internally validated three risk prediction models incorporating both clinical characteristics and hub protein expression. Our findings demonstrated that the combined prediction model exhibited optimal predictive performance, with the highest discrimination (AUC: 0.986) and calibration (Brier score: 0.043). Application of the combined prediction model within a specific risk threshold (0-0.97) yielded maximal clinical benefit. Finally, we constructed a nomogram based on the combined prediction model. CONCLUSIONS: As a large sample size study in lung metastatic DTC research, the identification of biomarkers through primary lesion proteomics and the development of risk prediction models integrating clinical features and hub protein biomarkers offer valuable insights for predicting DTC lung metastasis and establishing personalised treatment strategies.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

Clinical manifestations and the prenatal diagnosis of trisomy 7 mosaicism: Two case reports.

BACKGROUND: The clinical manifestations of trisomy 7 mosaicism are diverse and nonspecific, so prenatal diagnosis is very difficult. CASE SUMMARY: Two pregnant women with abnormal prenatal screening results were included. One was a 22-year-old woman (G1P0). At 31st week of gestation, ultrasound revealed that the posterior horn of the left lateral ventricle was 10 mm and the right renal pelvis had a separation of 7 mm. The other pregnant woman was 33 years old (G2P1L1A0), and her fetus was found to have a cardiac malformation at the 24th week of gestation. Copy number variation sequencing, whole-exome sequencing and karyotype analysis were carried out after amniocentesis, and both fetuses were diagnosed with trisomy 7 mosaicism. After parental counseling, one woman continued the pregnancy, and the other woman terminated the pregnancy. CONCLUSION: In trisomy 7 mosaicism, the low proportion of trisomy does not lead to abortion, but can result in abnormal fetal development, which can be detected via ultrasound. Therefore, clinicians need to pay more attention to various aspects of fetal growth and development, combining with imaging, cellular, molecular genetics and other methods to perform comprehensive evaluations of fetuses to provide more reliable genetic counseling for pregnant women.

Melatonin alleviates endoplasmic reticulum stress and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens.

Follicular atresia in chickens reduces the number of follicles that can further develop, leading to decrease egg laying. Endoplasmic reticulum stress (ERS) can initiate a unique pathway inducing the apoptosis of follicular granulosa cells, thus reducing egg laying. Melatonin (MEL) is involved in the regulation of follicle development, ovulation, and oocyte maturation, and is closely related to follicle fate. Mammalian target of Rapamycin (mTOR) signaling pathway plays an important role in cell growth regulation, and that there is a possible crosstalk between melatonin and mTOR activity in granular cells maturation and ovulation. This study aimed to investigate whether MEL inhibits ERS and follicular granulosa cell apoptosis by regulating ATF4 to activate mTOR signaling pathway in chickens. Frist, we established an in vitro ERS cell model using tunicamycin (TM). The results showed that different concentrations of TM exhibited dose-dependent inhibition of cell activity and induction of granulosa cells (P<0.01). Therefore, we chose 5 µg/mL of TM and a treatment time for 6 h as the optimal concentration for the following experiments. Then we investigate whether melatonin can inhibit ERS. TM treatment decreased the cell viability and Bcl-2 expression, increasing ROS levels and the mRNA expression of Grp78, ATF4, CHOP, PERK, eIF-2α, and BAX (P<0.01), whereas TM+MEL treatment significantly inhibited these changes (P<0.01). Then we explored whether melatonin protects follicular granulosa cells from ERS-induced apoptosis through the mammalian target of rapamycin (mTOR) signaling pathway by regulating ATF4, we found that ATF4 knockdown inhibited ERS by decreasing the expression of ERS-related genes and proteins and activating mTOR signaling pathway by increasing the protein expression of p4E-BP1 and pT389-S6K (P<0.001), while these changes were promoted by TM+si-ATF4+MEL treatment (P<0.01). These results indicate that MEL could alleviate TM-induced ERS by regulating ATF4 to activate mTOR signaling pathway in follicular granulosa cells, thus providing a new perspective for prolonging the laying cycle in chickens.

Hypoxia, hypoxia-inducible factors and inflammatory bowel diseases.

Adequate oxygen supply is essential for maintaining the body's normal physiological function. In chronic inflammatory conditions such as inflammatory bowel disease (IBD), insufficient oxygen reaching the intestine triggers the regulatory system in response to environmental changes. However, the pathogenesis of IBD is still under investigation. Recent research has highlighted the significant role of hypoxia in IBD, particularly the involvement of hypoxia-inducible factors (HIF) and their regulatory mechanisms, making them promising therapeutic targets for IBD. This review will delve into the role of hypoxia, HIF, and the associated hypoxia-inflammatory microenvironment in the context of IBD. Potential interventions for addressing these challenging gastrointestinal inflammatory diseases will also be discussed within this framework.

Morphologic and Functional Assessment of Photoreceptors in Laser Induced Retinopathy Using Adaptive Optics-SLO and Microperimetry.

PURPOSE: To assess the cone photoreceptors morphology and associated retinal sensitivity in laser-induced retinopathy (LIR) using adaptive optics Scanning Laser Ophthalmoscopy (AO-SLO) and microperimetry (MP). DESIGN: Cohort study. METHODS: This study included 13 patients (15 eyes) with LIR and 38 age-matched healthy volunteers (38 eyes). Participants underwent comprehensive evaluations including AO-SLO, MP, and spectral-domain OCT. Lesion morphology, cone density, dispersion and regularity in AO-SLO were assessed and correlated with visual function. RESULTS: In AO-SLO images, LIR lesions were predominantly characterized by hyporeflective regions, suggesting potential cone loss at the fovea, accompanied by the presence of sizable clumps of hyperreflective material within these lesions. The average size of lesions in affected eyes was 97,128±107,478µm², ranging from 6,705 to 673,348µm². Compared to the healthy contralateral eye and control group, LIR demonstrated significantly reduced cone density, increased cone dispersion, and notably decreased cone regularity in all four quadrants at 3° eccentricity (all P values <0.05). Lesion morphology in AO-SLO correlated with EZ defects observed in OCT, showing a positive correlation in size (r = 0.84, P<0.001) but not with retinal sensitivities (P = 0.09). Similarly, cone density at 3° eccentricity did not correlate with retinal sensitivities (P = 0.13). CONCLUSIONS AND RELEVANCE: The study provides crucial insights into the morphological and functional impacts of LIR on cone photoreceptors, revealing significant morphological changes in cones that do not consistently align with functional outcomes. This research highlights the need for continued exploration into the relationship between retinal structure and function in LIR, and the importance of heightened public awareness and preventive strategies to mitigate the risk of LIR.

Favorable Outcomes of Liver Transplantation for Hepatopulmonary Syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. METHODS: Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. RESULTS: Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P = .003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P = .001). CONCLUSION: Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS.

Serum Iron Overload Activates the SMAD Pathway and Hepcidin Expression of Hepatocytes via SMURF1.

Background and Aims: Liver iron overload can induce hepatic expression of bone morphogenic protein (BMP) 6 and activate the BMP/SMAD pathway. However, serum iron overload can also activate SMAD but does not induce BMP6 expression. Therefore, the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain unclear. This study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD pathway. Methods: A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin (Holo-Tf). A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 days. Western blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of hepcidin. Results: Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to BMP6. The E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression; specifically, SMURF1 expression dramatically decreased when the serum iron concentration was increased. Additionally, the expression of SMURF1 substrates, which are important molecules involved in the transduction of BMP/SMAD signaling, was significantly upregulated. Furthermore, in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron overload. Conclusions: SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.

Particle-Based Artificial Antigen-Presenting Cell Systems for T Cell Activation in Adoptive T Cell Therapy.

T cell-based adoptive cell therapy (ACT) has emerged as a promising treatment for various diseases, particularly cancers. Unlike other immunotherapy modalities, ACT involves directly transferring engineered T cells into patients to eradicate diseased cells; hence, it necessitates methods for effectively activating and expanding T cells in vitro. Artificial antigen-presenting cells (aAPCs) have been widely developed based on biomaterials, particularly micro- and nanoparticles, and functionalized with T cell stimulatory antibodies to closely mimic the natural T cell-APC interactions. Due to their vast clinical utility, aAPCs have been employed as an off-the-shelf technology for T cell activation in FDA-approved ACTs, and the development of aAPCs is constantly advancing with the emergence of aAPCs with more sophisticated designs and additional functionalities. Here, we review the recent advancements in particle-based aAPCs for T cell activation in ACTs. Following a brief introduction, we first describe the manufacturing processes of ACT products. Next, the design and synthetic strategies for micro- and nanoparticle-based aAPCs are discussed separately to emphasize their features, advantages, and limitations. Then, the impact of design parameters of aAPCs, such as size, shape, ligand density/mobility, and stiffness, on their functionality and biomedical performance is explored to provide deeper insights into the design concepts and principles for more efficient and safer aAPCs. The review concludes by discussing current challenges and proposing future perspectives for the development of more advanced aAPCs.

Three-dimensional reconstruction of industrial parts from a single image.

This study proposes an image-based three-dimensional (3D) vector reconstruction of industrial parts that can generate non-uniform rational B-splines (NURBS) surfaces with high fidelity and flexibility. The contributions of this study include three parts: first, a dataset of two-dimensional images is constructed for typical industrial parts, including hexagonal head bolts, cylindrical gears, shoulder rings, hexagonal nuts, and cylindrical roller bearings; second, a deep learning algorithm is developed for parameter extraction of 3D industrial parts, which can determine the final 3D parameters and pose information of the reconstructed model using two new nets, CAD-ClassNet and CAD-ReconNet; and finally, a 3D vector shape reconstruction of mechanical parts is presented to generate NURBS from the obtained shape parameters. The final reconstructed models show that the proposed approach is highly accurate, efficient, and practical.

Fluid Inverse Volumetric Modeling and Applications from Surface Motion.

In this study, we devise a framework for volumetrically reconstructing fluid from observable, measurable free surface motion. Our innovative method amalgamates the benefits of deep learning and conventional simulation to preserve the guiding motion and temporal coherence of the reproduced fluid. We infer surface velocities by encoding and decoding spatiotemporal features of surface sequences, and a 3D CNN is used to generate the volumetric velocity field, which is then combined with 3D labels of obstacles and boundaries. Concurrently, we employ a network to estimate the fluid's physical properties. To progressively evolve the flow field over time, we input the reconstructed velocity field and estimated parameters into the physical simulator as the initial state. Our approach yields promising results for both synthetic fluid generated by different fluid solvers and captured real fluid. The developed framework naturally lends itself to a variety of graphics applications, such as 1) effective reproductions of fluid behaviors visually congruent with the observed surface motion, and 2) physics-guided re-editing of fluid scenes. Extensive experiments affirm that our novel method surpasses state-of-the-art approaches for 3D fluid inverse modeling and animation in graphics.

Mechanical manipulation for ordered topological defects.

Randomly distributed topological defects created during the spontaneous symmetry breaking are the fingerprints to trace the evolution of symmetry, range of interaction, and order parameters in condensed matter systems. However, the effective mean to manipulate topological defects into ordered form is elusive due to the topological protection. Here, we establish a strategy to effectively align the topological domain networks in hexagonal manganites through a mechanical approach. It is found that the nanoindentation strain gives rise to a threefold Magnus-type force distribution, leading to a sixfold symmetric domain pattern by driving the vortex and antivortex in opposite directions. On the basis of this rationale, sizeable mono-chirality topological stripe is readily achieved by expanding the nanoindentation to scratch, directly transferring the randomly distributed topological defects into an ordered form. This discovery provides a mechanical strategy to manipulate topological protected domains not only on ferroelectrics but also on ferromagnets/antiferromagnets and ferroelastics.

The burden of cardiovascular disease attributable to high body mass index-an observational study.

AIM: This study aims to provide a timely and comprehensive estimate of the current burden and temporal trend of cardiovascular disease (CVD) attributable to high body mass index (HBMI). METHODS: We systematically assessed the current burden and temporal trend of CVD attributable to HBMI by calendar year, age, sex, region, nation, socioeconomic status, and specific CVD based on the most recent Global Burden of Disease Study (GBD) 2019. RESULTS: Globally, the numbers of CVD-related disability-adjusted life years (DALYs) and deaths attributable to HBMI has more than doubled from 1990 to 2019. Conversely, the age-standardized rates (ASRs) of CVD-related DALYs and deaths attributable to HBMI showed a slight downward trend, with estimated annual percentage change (EAPC) of -0.18 and -0.43, respectively. The ASRs of CVD-related DALYs and deaths attributable to HBMI were lower in low and high Socio-demographic Index (SDI) regions in 2019, but higher in middle and high-middle SDI regions. The ASRs of CVD-related DALYs and deaths attributable to HBMI showed a downward trend in the high SDI regions from 1990 to 2019, but showed an upward trend in the low and low-middle SDI regions. The leading causes of CVD burden attributable to HBMI were ischemic heart disease, stroke, hypertensive heart disease, and atrial fibrillation/flutter in 2019. CONCLUSION: The CVD burden attributable to HBMI remains a challenging global health concern. Policymakers in high and increasing burden regions can learn from some valuable experiences of low and decreasing burden regions and develop more targeted and specific strategies to prevent and reduce CVD burden attributable to HBMI.

ncRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29 551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32 969 entries involving 10 480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

Transcriptomic Features of systemic lupus erythematosus Patients in Flare and Changes during Acute In-Hospital Treatment.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. METHODS: RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analyzed and scored to elucidate the transcriptomic changes during treatment. RESULTS: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts, and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. CONCLUSIONS: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Effect of Comprehensive Psychological Intervention on Negative Emotions and Quality of Life in Patients with Acute Myocardial Infarction.

Although acute myocardial infarction (AMI) currently has a high survival rate, the treatment and prognosis are still diffuse negative life events for patients, which will affect their quality of life (QOL) and psychological health. Based on an integrated physiological-psychological-social-medical model, it is necessary to design an intervention program for safeguarding the physical and mental health of AMI patients.This study aimed to explore the influence of psychological intervention on negative emotions and QOL of AMI patients using a randomized controlled trial (RCT) design.Based on convenience sampling and double-blinded group assignment, 101 patients from August 2019 to January 2020 were randomly divided into 2 groups. An intervention group received comprehensive psychological intervention, while a control group received general supportive nursing. Both groups answered questionnaires before and after the intervention, including assessments of anxiety, depression, and QOL.Before the intervention, there were no significant differences between the groups. After intervention, anxiety and depression in the intervention group (n = 48) were significantly lower (P < 0.001) and QOL was markedly improved (P < 0.05) compared to that of the control group (n = 53).Comprehensive psychological intervention contributed to ameliorate negative emotions, enhance confidence in treatment, and improve the QOL of AMI patients.

Potential of a winterschmidtiid prey mite for the production of the predatory mite Neoseiulus californicus (Acari: Phytoseiidae).

Mass rearing of the predatory mite Neoseiulus californicus (McGregor) (Acari: Phytoseiidae) using natural (prey) methods is costly and laborious, limiting its application in the biological control of pests. A high-production, low-cost method using a prey substitute would help to relieve this problem. Oulenziella bakeri Hughes (Acari: Winterschmidtiidae) could be an alternative prey source, but studies on the reproductive parameters of N. californicus under rearing conditions are lacking. This study evaluated the potential of O. bakeri as an alternative prey in N. californicus rearing by comparing developmental parameters among N. californicus reared on three diets based on an age-stage two-sex life table. We found that the preoviposition period and developmental time of N. californicus did not vary based on diet. The fecundity of N. californicus adults reared on O. bakeri was 29.8 eggs per female, which was lower than that of adults reared on Tetranychus urticae Koch (Acari: Tetranychidae) (42.9 eggs per female); there was no significant difference between O. bakeri and apple pollen (30.2 eggs per female). The oviposition rate of mites fed on O. bakeri was 69% of that fed on T. urticae. Neoseiulus californicus reared on O. bakeri and apple pollen showed the same intrinsic rate of increase (0.25 per day), which was 86% of the rate of those fed on T. urticae. Compared with predatory mites reared on natural prey, N. californicus reared on O. bakeri had a high survival rate and good oviposition and population growth parameters, suggesting that O. bakeri is suitable for the rearing of N. californicus.

Rhodium-Catalyzed Asymmetric Hydroboration/Cyclization of 1,6-Enynes Enabled by Spirosiladiphosphine Ligands: Constructing Chiral Five-Membered Rings with a Boron Handle.

A rhodium-catalyzed enantioselective hydroboration/cyclization reaction of 1,6-enynes is achieved by employing a spirosiladiphosphine ligand. The process allows the synthesis of five-membered hetero- and carbocycles bearing a boron handle with high levels of activity and selectivity. Various enynes and organoboranes (HBdan, HBpin, HBmp, and HBamm) have been accommodated, and enynes containing terminal alkynes have been integrated into the process for the first time. The high yields and selectivities of the transformation highlight the synthetic utility of these novel spirosiladiphosphine ligands.

Sophoridine derivative 6j inhibits liver cancer cell proliferation via ATF3 mediated ferroptosis.

Liver cancer is one of the most lethal malignancies with an annual death of over 830,000 cases. Although targeted therapeutic drugs have achieved certain clinical efficacy, only sorafenib and lenvatinib are currently marketed as first-line targeted drugs to treat patients with advanced liver cancer. Therefore, developing more drugs are urgently needed. Ferroptosis is an iron-dependent programmed cell death (PCD) distinct from known PCDs including apoptosis, necrosis, and autophagy. Targeting ferroptosis is recognized as a promising potential therapeutic modality for liver cancer. Activating transcription factor 3 (ATF3) is an important ferroptosis inducer and targeting ATF3 offers a potential means to cancer therapy. In the present study, we reported for the first time a sophoridine derivative 6j with promising anti-liver cancer effects in vitro and in vivo. Compound 6j could induce liver cancer cells ferroptosis by promoting the accumulation of intracellular Fe2+, reactive oxygen species (ROS), and MDA. Inhibition of ferroptosis by ferrostatin-1 alleviated 6j induced accumulation of Fe2+, ROS, and MDA and restored cell viability. Further study revealed that compound 6j upregulated the expression of ATF3 via ER stress and knockdown of ATF3 by RNA interference attenuated 6j induced ferroptosis and cell proliferation inhibition. This study would provide new insights for the design of ferroptosis inducers and the development of anti-liver cancer drugs.