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177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Abstract Sex characteristics exhibit significant disparities in various human diseases, including prevalent cardiovascular diseases, cancers, metabolic disorders, autoimmune diseases, and neurodegenerative diseases. Risk profiles and pathological manifestations of these diseases exhibit notable variations between sexes. The underlying reasons for these sex disparities encompass multifactorial elements, such as physiology, genetics, and environment. Recent studies have shown that human body systems demonstrate sex-specific gene expression during critical developmental stages and gene editing processes. These genes, differentially expressed based on different sex, may be regulated by androgen or estrogen-responsive elements, thereby influencing the incidence and presentation of cardiovascular, oncological, metabolic, immune, and neurological diseases across sexes. However, despite the existence of sex differences in patients with human diseases, treatment guidelines predominantly rely on male data due to the underrepresentation of women in clinical trials. At present, there exists a substantial knowledge gap concerning sex-specific mechanisms and clinical treatments for diverse diseases. Therefore, this review aims to elucidate the advances of sex differences on human diseases by examining epidemiological factors, pathogenesis, and innovative progress of clinical treatments in accordance with the distinctive risk characteristics of each disease and provide a new theoretical and practical basis for further optimizing individualized treatment and improving patient prognosis.

Abstract While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.

Mid-ocean ridges are unique, tectonically active geographical units on Earth that profoundly control the ocean environment and dynamics at the global scale. However, high-resolution topographic data from mid-ocean ridges are rarely available due to the difficulty in detecting ocean floors, which further limits ocean research at the global scale. Here, we divide the global mid-ocean ridge system into 2805 tiles and reconstruct their high-resolution topography by using a transfer learning approach with freely available low-resolution digital elevation models (DEMs) and limited high-resolution DEMs. A high-frequency terrain feature-based deep residual network is proposed to generate high-resolution global mid-ocean ridge DEMs. In this network, topographic knowledge related to mid-ocean ridges is integrated and quantified to improve the learning efficiency and reconstruction quality of the network. A series of verifications and evaluations demonstrate the reliability of reconstructed topographies for submarine topography research. We observe that reconstructed topography can achieve good environmental understanding and information acquisition in the global mid-ocean ridge range. We find that the complexity of the previous terrain environment is underestimated by 26.63% in terms of the slope gradient and by 14.95% in terms of terrain relief, while a 101.10% information improvement can be obtained for the reconstructed topography. The reconstructed topography indicates that diverse and intricate topographical environments of mid-ocean ridges exist among different ocean regions. The proposed transfer learning method for reconstructing high-resolution mid-ocean ridge topographies is valuable and can be utilized for reconstructing information in regions that are difficult to observe directly and lack sufficient data.

Cardiac remodeling after myocardial infarction is one of the key factors affecting patient prognosis. Myocardial fibrosis is an important pathological link of adverse ventricular remodeling after myocardial infarction, and early fibrosis is reversible. Timely detection and intervention can effectively prevent its progression to irreversible ventricular remodeling. Although imaging modalities such as CMR and echocardiography can identify fibrosis, their sensitivity and specificity are limited, and they cannot detect early fibrosis or its activity level. Positron emission tomography (PET) allows non-invasive visualization of cellular and subcellular processes and can monitor and quantify molecules and proteins in the fibrotic pathway. It is valuable in assessing the extent of early myocardial fibrosis progression, selecting appropriate treatments, evaluating response to therapy, and determining the prognosis. In this article, we present a brief overview of mechanisms underlying myocardial fibrosis following myocardial infarction and several routine imaging techniques currently available for assessing fibrosis. Then, we focus on the application of PET molecular imaging in detecting fibrosis after myocardial infarction.

Background Adverse left ventricular remodeling is a significant cardiovascular predictor for patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF). However, the remodeling indexes reflecting left ventricular spherization by myocardial perfusion imaging are underexplored. Methods and Results 727 patients (mean age 59.8±13.5 years, 329 women) diagnosed or suspected coronary artery disease with preserved LVEF who underwent resting myocardial perfusion imaging were retrospectively enrolled. The myocardial perfusion imaging findings including the total perfusion deficit and sphericity indexes (shape index (SI) and eccentricity index (EI) obtained from gated (QGS) and non‐gated (QPS) images) were collected. Major adverse cardiovascular events (MACE) were followed up for 45.1±22.0 months. All patients were divided into 4 subgroups based on total perfusion deficit at 10% and LVEF at 65%. Univariable comparative analyses were performed in 5 cohorts (all patients and 4 subgroups). Patients who experienced MACE displayed higher SI and/or lower EI (all P

Abstract Reconstructing ancient transportation networks is critical to studying past human mobility patterns. China’s Haidai region was a thriving political and economic hub during the Bronze and Early Iron Ages. We used GIS spatial analysis techniques to build a “Settlement Interaction Model” based on archaeological data from the Haidai region during the Bronze and Early Iron Age (Shang Dynasty, Western Zhou Dynasty, Spring & Autumn Period, and Warring States period). The eight-level road network maps with traffic attributes were distinguished based on topography and settlement size. The total lengths of the road networks were estimated to be 19,112 km in the Shang Dynasty, 35,269 km in the Western Zhou Dynasty, 51,555 km in the Spring & Autumn Period, and 77,456 km in the Warring States Period, with the average road flows of 6.6, 31.7, 42.8, and 75.5, respectively. The Z score and one-sample t-test (p

Abstract Background Recent researches have found a strong correlation between the triglyceride-glucose (TyG) index or the atherogenic index of plasma (AIP) and cardiovascular disease (CVD) risk. However, there is a lack of research on non-invasive and rapid prediction of cardiovascular risk. We aimed to develop and validate a machine-learning model for predicting cardiovascular risk based on variables encompassing clinical questionnaires and oculomics. Methods We collected data from the Korean National Health and Nutrition Examination Survey (KNHANES). The training dataset (80% from the year 2008 to 2011 KNHANES) was used for machine learning model development, with internal validation using the remaining 20%. An external validation dataset from the year 2012 assessed the model’s predictive capacity for TyG-index or AIP in new cases. We included 32122 participants in the final dataset. Machine learning models used 25 algorithms were trained on oculomics measurements and clinical questionnaires to predict the range of TyG-index and AIP. The area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1 score were used to evaluate the performance of our machine learning models. Results Based on large-scale cohort studies, we determined TyG-index cut-off points at 8.0, 8.75 (upper one-third values), 8.93 (upper one-fourth values), and AIP cut-offs at 0.318, 0.34. Values surpassing these thresholds indicated elevated cardiovascular risk. The best-performing algorithm revealed TyG-index cut-offs at 8.0, 8.75, and 8.93 with internal validation AUCs of 0.812, 0.873, and 0.911, respectively. External validation AUCs were 0.809, 0.863, and 0.901. For AIP at 0.34, internal and external validation achieved similar AUCs of 0.849 and 0.842. Slightly lower performance was seen for the 0.318 cut-off, with AUCs of 0.844 and 0.836. Significant gender-based variations were noted for TyG-index at 8 (male AUC=0.832, female AUC=0.790) and 8.75 (male AUC=0.874, female AUC=0.862) and AIP at 0.318 (male AUC=0.853, female AUC=0.825) and 0.34 (male AUC=0.858, female AUC=0.831). Gender similarity in AUC (male AUC=0.907 versus female AUC=0.906) was observed only when the TyG-index cut-off point equals 8.93. Conclusion We have established a simple and effective non-invasive machine learning model that has good clinical value for predicting cardiovascular risk in the general population.

Abstract Background The timely identification and management of ovarian cancer are critical determinants of patient prognosis. In this study, we developed and validated a deep learning radiomics nomogram (DLR_Nomogram) based on ultrasound (US) imaging to accurately predict the malignant risk of ovarian tumours and compared the diagnostic performance of the DLR_Nomogram to that of the ovarian-adnexal reporting and data system (O-RADS). Methods This study encompasses two research tasks. Patients were randomly divided into training and testing sets in an 8:2 ratio for both tasks. In task 1, we assessed the malignancy risk of 849 patients with ovarian tumours. In task 2, we evaluated the malignancy risk of 391 patients with O-RADS 4 and O-RADS 5 ovarian neoplasms. Three models were developed and validated to predict the risk of malignancy in ovarian tumours. The predicted outcomes of the models for each sample were merged to form a new feature set that was utilised as an input for the logistic regression (LR) model for constructing a combined model, visualised as the DLR_Nomogram. Then, the diagnostic performance of these models was evaluated by the receiver operating characteristic curve (ROC). Results The DLR_Nomogram demonstrated superior predictive performance in predicting the malignant risk of ovarian tumours, as evidenced by area under the ROC curve (AUC) values of 0.985 and 0.928 for the training and testing sets of task 1, respectively. The AUC value of its testing set was lower than that of the O-RADS; however, the difference was not statistically significant. The DLR_Nomogram exhibited the highest AUC values of 0.955 and 0.869 in the training and testing sets of task 2, respectively. The DLR_Nomogram showed satisfactory fitting performance for both tasks in Hosmer–Lemeshow testing. Decision curve analysis demonstrated that the DLR_Nomogram yielded greater net clinical benefits for predicting malignant ovarian tumours within a specific range of threshold values. Conclusions The US-based DLR_Nomogram has shown the capability to accurately predict the malignant risk of ovarian tumours, exhibiting a predictive efficacy comparable to that of O-RADS.

Background: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions.Methods: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment.Results: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN.Conclusion: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

ABSTRACTDeep learning-based super-resolution is an essential technique for acquiring high-resolution digital elevation models (DEMs) by enhancing the spatial resolution of low-resolution DEMs. However, current deep learning-based approaches for DEM super-resolution lack comprehensiveness in terrain information reconstruction, resulting in the need to strengthen the rationality of terrain representation. Furthermore, the limited adaptability and extension potential of these approaches restrict their practical applicability and scope, hindering further advancement. As a solution, we introduce a broadly scalable detrending-based deep learning (DTDL) spatially explicit framework for DEM super-resolution. The framework aims to improve DEM reconstruction through data processing and augmentation. It employs detrending to distinguish between large-scale terrain trends and small-scale residuals in DEMs, thereby enhancing the neural network's capacity to learn terrain information. We integrate DTDL with classical super-resolution methods (SRCNN, EDSR, and SRGAN) and conduct experiments in the Alps, Himalayas, and Rockies. The experimental results indicate that the fusion of DTDL with deep learning-based methods enhances the accuracy of terrain reconstruction and the rationality of terrain feature representation, demonstrating strong compatibility and robustness.

Abstract Positron emission tomography/magnetic resonance imaging (PET/MRI) is a hybrid imaging technique that quantitatively combines the metabolic and functional data from positron emission tomography (PET) with anatomical and physiological information from MRI. As PET/MRI technology has advanced, its applications in cancer care have expanded. Recent studies have demonstrated that PET/MRI provides unique advantages in the field of radiotherapy and has become invaluable in guiding precision radiotherapy techniques. This review discusses the rationale and clinical evidence supporting the use of PET/MRI for radiation positioning, target delineation, efficacy evaluation, and patient surveillance. Critical relevance statement This article critically assesses the transformative role of PET/MRI in advancing precision radiotherapy, providing essential insights into improved radiation positioning, target delineation, efficacy evaluation, and patient surveillance in clinical radiology practice. Key points • The emergence of PET/MRI will be a key bridge for precise radiotherapy. • PET/MRI has unique advantages in the whole process of radiotherapy. • New tracers and nanoparticle probes will broaden the use of PET/MRI in radiation. • PET/MRI will be utilized more frequently for radiotherapy. Graphical Abstract

Abstract Background The prevalence of ischemia with non-obstructive coronary artery disease (INOCA) is substantial, but its risk stratification has been suboptimal. Resting SPECT myocardial perfusion imaging (MPI) could provide useful heart information including spherical indices. We aimed to evaluate the prognostic value of spherical indices in individuals with INOCA. Results During a median follow-up of 47.2 ± 20.8 months, 49 (17.2%) patients experienced major adverse cardiac events (MACE). Compared to those without MACE, those with MACE had a higher shape index (SI) (0.60 ± 0.07 vs. 0.58 ± 0.06; P = 0.028) and a lower E2 (eccentricity index calculated by the QPS) (0.81 ± 0.05 vs. 0.83 ± 0.04; P = 0.019). MACE event-free survival analysis revealed significant differences in the SI and E2 among all patients (all log-rank P 0.05). Conclusion For patients with INOCA, spherical indices (especially the SI) were associated with long-term MACE, which could be a preferable indicator for risk stratification and prognostic prediction.

Background: Peripheral arterial calcification is a prevalent condition in patients with type 2 diabetes mellitus (T2DM), resulting in lower-limb amputation and reduced life quality. Non-alcoholic fatty liver disease (NAFLD), which can be simply evaluated using the fatty liver index (FLI), is closely associated with T2DM development. In this study, we aimed to explore the relationship between FLI and lower limb arterial calcification (LLAC) in T2DM patients and to reveal the value of T2DM patients with NAFLD in predicting the occurrence of LLAC. Methods: A total of 77 T2DM patients with LLAC who underwent comprehensive physical and health examinations, serological examinations, as well as lower limb computed tomography imaging at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2018 and January 2019 were enrolled in this study. The FLI was calculated using body mass index, waist circumference, triglycerides, and γ-glutamyl transferase. Additionally, LLAC was evaluated using computed tomography with the Agatston scoring algorithm. The patients were divided into three groups based on their FLI values: Non-liver disease group (FLI

Sn-10Bi low-bismuth-content solder alloy provides a potential alternative to the currently used Sn-Ag-Cu series due to its lower cost, excellent ductility, and strengthening resulting from the Bi solid solution and precipitation. This study primarily investigates the interfacial evolution and shear strength characteristics of Sn-10Bi joints on a Ni/Au surface finish during the as-soldered and subsequent isothermal aging processes. To improve the joint performance, a 0.2 or 0.5 wt.% dopant of Zn was incorporated into Sn-10Bi solder. The findings demonstrated that a 0.2 or 0.5 wt.% Zn dopant altered the composition of the intermetallic compound (IMC) formed at the interface between the solder and Ni/Au surface finish from Ni3Sn4 to Ni3(Sn, Zn)4. The occurrence of this transformation is attributed to the diffusion of Zn atoms into the Ni3Sn4 lattice, resulting in the substitution of a portion of the Sn atoms by Zn atoms, thereby forming the Ni3(Sn, Zn)4 IMC during the soldering process, which was also verified by calculations based on first principles. Furthermore, a 0.2 or 0.5 wt.% Zn dopant in Sn-10Bi significantly inhibited the Ni3(Sn, Zn)4 growth after both the soldering and thermal aging processes. Zn addition can enhance the shear strength of solder joints irrespective of the as-soldered or aging condition. The fracture mode was determined by the aging durations—with the brittle mode occurring for as-soldered joints, the ductile mode occurring for aged joints after 10 days, and again the brittle mode for joints after 40 days of aging.

Staphylococcus aureus has become one of the most common pathogens in clinical tissue infection, and it is easy to form biofilm. Incomplete removal of biofilms often leads to recurrent infections, and more serious is the possibility of bacteria developing drug resistance. Therefore, the effective eradication of refractory biofilms is essential. Herein, a temperature-sensitive hydrogel was prepared by doping the photothermal carbon dots (PTCDs) chelated by Ag+, and the AIPH which could produce alkyl radicals in response to heat into the thermodissolved gelatin. Under the irradiation of 660 nm laser, the PTCDs generated heat to dissolve the hydrogel, and promoted chelation of silver ions in PTCDs for chemical sterilization. Meanwhile, the heat generated by the PTCDs induced the 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) to produce alkyl free radical sterilization, achieving the purpose of photothermal/thermodynamic/chemical synergistic to kill Staphylococci aureus and destroy its biofilm. Therefore, the biocompatible PTCDs@Ag-AIPH hydrogel proposed in this study was a promising composite that could eliminate biofilms and promoted wound healing, showing good potential in future biomedical applications.

CRISPR-based screens have discovered novel functional genes involving in diverse tumor biology and elucidated the mechanisms of the cancer pathological states. Recently, with its randomness and unbiasedness, CRISPR screens have been used to discover effector genes with previously unknown roles for AML. Those novel targets are related to AML survival resembled cellular pathways mediating epigenetics, synthetic lethality, transcriptional regulation, mitochondrial and energy metabolism. Other genes that are crucial for pharmaceutical targeting and drug resistance have also been identified. With the rapid development of novel strategies, such as barcodes and multiplexed mosaic CRISPR perturbation, more potential therapeutic targets and mechanism in AML will be discovered. In this review, we present an overview of recent progresses in the development of CRISPR-based screens for the mechanism and target identification in AML and discuss the challenges and possible solutions in this rapidly growing field.

Social pain, a multifaceted emotional response triggered by interpersonal rejection or criticism, profoundly impacts mental well-being and social interactions. While prior research has implicated the right ventrolateral prefrontal cortex (rVLPFC) in mitigating social pain, the precise neural mechanisms and downstream effects on subsequent social attitudes remain elusive. This study employed transcranial magnetic stimulation (TMS) integrated with fMRI recordings during a social pain task to elucidate these aspects. Eighty participants underwent either active TMS targeting the rVLPFC (n = 41) or control stimulation at the vertex (n = 39). Our results revealed that TMS-induced rVLPFC facilitation significantly reduced self-reported social pain, confirming the causal role of the rVLPFC in social pain relief. Functional connectivity analyses demonstrated enhanced interactions between the rVLPFC and the dorsolateral prefrontal cortex, emphasizing the collaborative engagement of prefrontal regions in emotion regulation. Significantly, we observed that negative social feedback led to negative social attitudes, whereas rVLPFC activation countered this detrimental effect, showcasing the potential of the rVLPFC as a protective buffer against adverse social interactions. Moreover, our study uncovered the impact role of the hippocampus in subsequent social attitudes, a relationship particularly pronounced during excitatory TMS over the rVLPFC. These findings offer promising avenues for improving mental health within the intricate dynamics of social interactions. By advancing our comprehension of the neural mechanisms underlying social pain relief, this research introduces novel intervention strategies for individuals grappling with social distress. Empowering individuals to modulate rVLPFC activation may facilitate reshaping social attitudes and successful reintegration into communal life.

Abstract In clinical trials involving patients with HER2 (ERBB2 receptor tyrosine kinase 2) positive gastric cancer, the efficacy of the HER2-targeted drug lapatinib has proven to be disappointingly poor. Under the persistent pressure exerted by targeted drug therapy, a subset of tumor cells exhibit acquired drug resistance through the activation of novel survival signaling cascades, alongside the proliferation of tumor cells that previously harbored mutations conferring resistance to the drug. This study was undertaken with the aim of elucidating in comprehensive detail the intricate mechanisms behind adaptive resistance and identifying novel therapeutic targets that hold promise in the development of effective lapatinib-based therapies for the specific subset of patients afflicted with gastric cancer. We have successfully established a gastric cancer cell line with acquired lapatinib resistance, designated as HGC-27-LR cells. Utilizing comprehensive coding and noncoding transcriptome sequencing analysis, we have identified key factors that regulate lapatinib resistance in HGC-27 cells. We have compellingly validated that among all the lncRNAs identified in HGC-27-LR cells, a novel lncRNA (long noncoding RNA) named NONHSAT160169.1 was found to be most notably upregulated following exposure to lapatinib treatment. The upregulation of NONHSAT160169.1 significantly augmented the migratory, invasive, and stemness capabilities of HGC-27-LR cells. Furthermore, we have delved into the mechanism by which NONHSAT160169.1 regulates lapatinib resistance. The findings have revealed that NONHSAT160169.1, which is induced by the p-STAT3 (signal transducer and activator of transcription 3) nuclear transport pathway, functions as a decoy that competitively interacts with hsa-let-7c-3p and thereby abrogates the inhibitory effect of hsa-let-7c-3p on SOX2 (SRY-box transcription factor 2) expression. Hence, our study has unveiled the NONHSAT160169.1/hsa-let-7c-3p/SOX2 signaling pathway as a novel and pivotal axis for comprehending and surmounting lapatinib resistance in the treatment of HER2-positive gastric cancer.

Abstract Background Periodontitis is the most common oral disease and is closely related to immune infiltration in the periodontal microenvironment and its poor prognosis is related to the complex immune response. The progression of periodontitis is closely related to necroptosis, but there is still no systematic study of long non-coding RNA (lncRNA) associated with necroptosis for diagnosis and treatment of periodontitis. Material and methods Transcriptome data and clinical data of periodontitis and healthy populations were obtained from the Gene Expression Omnibus (GEO) database, and necroptosis-related genes were obtained from previously published literature. FactoMineR package in R was used to perform principal component analysis (PCA) for obtaining the necroptosis-related lncRNAs. The core necroptosis-related lncRNAs were screened by the Linear Models for Microarray Data (limma) package in R, PCA principal component analysis and lasso algorithm. These lncRNAs were then used to construct a classifier for periodontitis with logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the model. The CIBERSORT method and ssGSEA algorithm were used to estimate the immune infiltration and immune pathway activation of periodontitis. Spearman’s correlation analysis was used to further verify the correlation between core genes and periodontitis immune microenvironment. The expression level of core genes in human periodontal ligament cells (hPDLCs) was detected by RT-qPCR. Results A total of 10 core necroptosis-related lncRNAs (10-lncRNAs) were identified, including EPB41L4A-AS1, FAM30A, LINC01004, MALAT1, MIAT, OSER1-DT, PCOLCE-AS1, RNF144A-AS1, CARMN, and LINC00582. The classifier for periodontitis was successfully constructed. The Area Under the Curve (AUC) was 0.952, which suggested that the model had good predictive performance. The correlation analysis of 10-lncRNAs and periodontitis immune microenvironment showed that 10-lncRNAs had an impact on the immune infiltration of periodontitis. Notably, the RT-qPCR results showed that the expression level of the 10-lncRNAs obtained was consistent with the chip analysis results. Conclusions The 10-lncRNAs identified from the GEO dataset had a significant impact on the immune infiltration of periodontitis and the classifier based on 10-lncRNAs had good detection efficiency for periodontitis, which provided a new target for diagnosis and treatment of periodontitis.

Abstract Recent years have witnessed significant progress in quantum communication and quantum internet with the emerging quantum photonic chips, whose characteristics of scalability, stability, and low cost, flourish and open up new possibilities in miniaturized footprints. Here, we provide an overview of the advances in quantum photonic chips for quantum communication, beginning with a summary of the prevalent photonic integrated fabrication platforms and key components for integrated quantum communication systems. We then discuss a range of quantum communication applications, such as quantum key distribution and quantum teleportation. Finally, the review culminates with a perspective on challenges towards high-performance chip-based quantum communication, as well as a glimpse into future opportunities for integrated quantum networks.

Coronary artery disease (CAD) is caused by atherosclerotic lesions in the coronary vessels. Endoplasmic reticulum stress (ERS) acts in cardiovascular disease, and its role in CAD is not clear. A total of 13 differentially expressed ERS-related genes (DEERSRGs) in CAD were identified. Functional enrichment analysis demonstrated the DEERSRGs were mainly enriched in endoplasmic reticulum (ER)-related pathways. Then, eight genes (RCN2, HRC, DERL2, RNF183, CRH, TMED2, PPP1R15A, and IL1A) were authenticated as ERS-related biomarkers in CAD by least absolute shrinkage and selection operator (LASSO). The receiver operating characteristic (ROC) analysis showed that the LASSO logistic model constructed based on biomarkers had a better diagnostic effect, which was confirmed by the ANN and GSE23561 datasets. Also, ROC results showed that seven of the eight biomarkers had better diagnostic effects. The nomogram model had good predictive power, and biomarkers were mostly enriched in pathways associated with CAD. The biomarkers were significantly associated with 10 immune cells, and RCN2, DERL2, TMED2, and RNF183 were negatively correlated with most chemokines. Eight biomarkers had significant correlations with both immunoinhibitors and immunostimulators. In addition, eight biomarkers were significantly different in both CAD and control samples, CRH and HRC were upregulated in CAD. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that RCN2, HRC, DERL2, CRH, and IL1A were consistent with the bioinformatics analysis. RCN2, HRC, DERL2, RNF183, CRH, TMED2, PPP1R15A, and IL1A were identified as biomarkers of CAD. Functional enrichment analysis and immunoassays for biomarkers provide new ideas for the treatment of CAD.

With the rising incidence of cancer, radiotherapy has become an increasingly popular treatment modality. However, radiation-induced skin injuries (RSIs) have emerged as a commonly reported side effect of radiotherapy, thereby presenting a significant challenge in the field of radiotherapy. In this study, we report the successful synthesis of a photosensitive hydrogel via amide reaction for grafting the photosensitive group, methacrylate anhydride (MA), onto chitosan (CHI) and gelatin (GEL), with subsequent physical incorporation of epigallocatechin gallate (EGCG). The resulting composite photosensitive hydrogels exhibited favorable swelling properties, rheological properties, and biocompatibility, which promote angiogenesis and demonstrate notable therapeutic efficacy against RSIs. These findings provide valuable insights into the clinical utility of EGCG composite hydrogels for the effective management of RSIs.

Moringa oleifera Lam. leaf is not only a new food resource in China, but also a traditional medicinal plant. It is commonly used in the folk to alleviate constipation, but its laxative mechanism is not fully understood. Hence we investigated it in loperamide-induced functional constipation (FC) mice. The results showed that MOAE significantly regulated not only gastrointestinal hormones and neurotransmitters in serum but also important gastrointestinal motility factors in the enteric nervous system (ENS)-interstitial cells of Cajal (ICCs)-smooth muscle cell (SMC) network. Meanwhile, MOAE attenuated intestinal inflammation, increased cecal short-chain fatty acid levels and colonic antimicrobial peptide expression, and improved the impaired intestinal barrier function in loperamide-induced FC mice. In addition, MOAE also increased fecal water content by inhibiting the mRNA expression of colonic aquaporins (Aqp3 and Aqp4) in FC mice. Interestingly and importantly, MOAE affected the intestinal microbiota by inhibiting some key “constipation-causing” microbiota, such as Bacteroidaceae, Clostridiaceae, Bacteroides, and Ruminococcus, and promoting the growth of other important “constipation-curing” microbiota, such as Butyricoccus, Tyzzerella, and Desulfovibrio. These important taxa are significantly associated with a variety of indicators of constipation. These findings suggest that MOAE can promote defecation through its rich chemical composition to modulate the ENS-ICCs-SMCs network and the gut microecosystem.

Abstract Background The IQ-SPECT system is equipped with multifocal collimators and uses ordered-subset conjugate gradient minimization (OSCGM) as its reconstruction algorithm, achieving a shorter acquisition time than conventional SPECT. Left ventricular ejection fraction (LVEF) is overestimated by conventional SPECT in patients with small heart size. In this study, we compared IQ-SPECT with conventional SPECT and cardiovascular magnetic resonance (CMR) for the estimation of LVEF in patients with small hearts (males: EDV ≤ 60 ml, ESV ≤ 25 ml; females: EDV ≤ 45 ml, ESV ≤ 20 ml). Methods The study consisted of 49 consecutive patients (20 normal and 29 with small heart size) undergoing gated myocardial perfusion imaging (GMPI) with a 99mTc-labelled agent during stress or rest to assess the risk of coronary artery disease (CAD). The data were reconstructed using filtered back-projection (FBP) for conventional SPECT and OSCGM for IQ-SPECT. ESV, EDV, and LVEF were calculated using quantitative gated SPECT (QGS). To determine the optimal ordered-subset reconstruction parameters, we compared the LVEF from SPECT to the corresponding measurement from CMR. Results EDV, ESV, and LVEF values obtained from IQ-SPECT and conventional SPECT showed that the results of these two forms of SPECT were significantly correlated, although the EDV and ESV obtained by IQ-SPECT were higher than those obtained by conventional SPECT. IQ-SPECT yielded lower LVEF measurements than conventional SPECT (normal heart size: 50.6 ± 4.3% vs. 73.4 ± 8.4%, P = 0.002; small heart size: 62.1 ± 7.8% vs. 75.0 ± 11.4%, P 0.05; small heart size: 62.1 ± 7.8% vs. 64.6 ± 8.8%, P > 0.05). Five subsets (S) and 12 iterations (I) did not differ significantly in LVEF between CMR and IQ-SPECT for patients with small hearts (64.6 ± 8.8% vs. 62.1 ± 7.8%, P = 0.120), while 3 S and 10 I were the best parameters for patients with normal heart size (50.6 ± 4.3% vs. 53.1 ± 5.8%, P = 0.117). Conclusion With CMR as the standard, IQ-SPECT yields more reliable LVEF values than conventional SPECT for populations with small heart size. The best reconstruction parameters from IQ-SPECT were 5 S and 12 I for patients with small hearts.

BackgroundClaustrophobia is a psychological disease. It is estimated to occur in 2.1–14.3% of all magnetic resonance imaging (MRI) examinations. Mindfulness decompression is an effective means to treat and reduce fear and anxiety. There is a rare report on the application of mindfulness-based stress reduction therapy in the magnetic resonance examinations of patients with claustrophobia to date.PurposeThe purpose of this study is to explore the intervention effect of mindfulness respiratory decompression therapy on the MRI inspection of patients with claustrophobia.MethodsA total of 86 patients with claustrophobia requiring MRI in our hospital from January 2018 to December 2020 were divided into two groups. The control group was given routine psychological nursing, and the observation group was given a mindfulness breathing technique on the basis of the control group. Before and after the intervention, we compared the intervention effect, satisfaction with nurses’ psychological intervention technique, severe autonomic nervous symptoms during the examination, self-rating anxiety scale (SAS) scores, and profile of mood states revised (POMS-R) scores.ResultsThe total effective rate of intervention in the observation group was 90.90%, which was significantly higher (χ2 = 6.857, p = 0.00004) than that in the control group (26.19%). Severe autonomic nervous symptoms in the observation group were significantly lower than those in the control group (p

Background: Tanshinone IIA (TIIA) is the major lipid-soluble active ingredient of the traditional Chinese medicine Salvia miltiorrhiza, which slows down atherosclerosis (AS). However, it remains unclear whether TIIA has the potential to enhance macrophage efferocytosis and thereby improve atherosclerosis.Objective: The focus of this examination was to determine if TIIA could reduce lipid accumulation and treat AS by enhancing efferocytosis.Methods: Firstly, we conducted in vivo experiments using LDLR knockout (LDLR−/−) mice for a period of 24 weeks, using histopathological staining, immunofluorescence and Western blot experiments to validate from the efficacy and mechanism parts, respectively; in addition, we utilized cells to validate our study again in vitro. The specific experimental design scheme is as follows: In vivo, Western diet-fed LDLR−/− mice for 12 weeks were constructed as an AS model, and normal diet-fed LDLR−/− mice were taken as a blank control group. The TIIA group and positive control group (atorvastatin, ATO) were intervened for 12 weeks by intraperitoneal injection (15 mg/kg/d) and gavage (1.3 mg/kg/d), respectively. In vitro, RAW264.7 cells were cultured with ox-LDL (50 ug/mL) or ox-LDL (50 ug/mL) + TIIA (20 uM/L or 40 uM/L). Pathological changes in aortic plaques and foam cell formation in RAW264.7 cells were evaluated using Masson and Oil Red O staining, respectively. Biochemical methods were used to detect lipid levels in mice. The immunofluorescence assay was performed to detect apoptotic cells and efferocytosis-related signal expression at the plaques. RT-qPCR and Western blot were carried out to observe the trend change of efferocytosis-related molecules in both mouse aorta and RAW264.7 cells. We also used the neutral red assay to assess RAW264.7 cells’ phagocytic capacity.Results: Compared with the model group, TIIA decreased serum TC, TG, and LDL-C levels (p < 0.01), reduced the relative lumen area of murine aortic lipid-rich plaques (p < 0.01), enhanced the stability of murine aortic plaques (p < 0.01), reduced ox-LDL-induced lipid build-up in RAW264.7 cells (p < 0.01), and upregulated efferocytosis-related molecules expression and enhance the efferocytosis rate of ox-LDL-induced RAW264.7 cells.Conclusion: TIIA might reduce lipid accumulation by enhancing the efferocytosis of macrophages and thus treat AS.

IntroductionTumor immunotherapy targeting PD-L1 has emerged as one of the powerful tools for tumor therapy. Numerous studies indicate that tumor-targeted drugs critically have an influence on the interaction between the immune system and tumors by changing the expression of PD-L1, which is beneficial for immunotherapy. Our study provided novel evidence for improving the drug regimen in tumor targeted therapy and immunotherapy.MethodsThe expression of PD-L1 on SKBR3, MDA-MB-231, MCF7, 4T1, MC38 and B16 cells was evaluated by flow cytometry after treatment with six preclinical targeted drugs (ARN-509, AZD3514, Galeterone, Neratinib, MLN8237 and LGK974). AURKA was knockdowned by using the specific siRNA or CRISPR-Cas9 technology. In the 4T1-breast tumor and colorectal cancer xenograft tumor models, we determined the number of infiltrated CD3+ and CD8+ T cells in tumor tissues by IHC.ResultsWe found that AURKA inhibitor MLN8237 promoted the expression of PD-L1 in a time- and concentration-dependent manner while exerted its antitumor effect. Knockdown of AURKA could induce the upregulation of PD-L1 on SKBR3 cells. MLN8237-induced PD-L1 upregulation was mainly associated with the phosphorylation of STAT3. In the 4T1-breast tumor xenograft model, the infiltrated CD3+ and CD8+ T cells decreased after treatment with MLN8237. When treated with MLN8237 in combination with anti-PD-L1 antibody, the volumes of tumor were significantly reduced and accompanied by increasing the infiltration of CD3+ and CD8+ T cells in colorectal cancer xenograft tumor model.DiscussionOur data demonstrated that MLN8237 improved the effect of immunology-related therapy on tumor cells by interacting with anti-PD-L1 antibody, which contributed to producing creative sparks for exploring the possible solutions to overcoming drug resistance to tumor targeted therapy.

Berberine is a plant-derived benzylisoquinoline alkaloid with diverse pharmaceutical activities, however, the production of berberine from medicinal plants and organic synthesis remains unsustainable. Here, the authors report the complete biosynthesis of berberine in yeast by engineering genes from plants and bacteria.

Land surface curvature (LSC) is a basic attribute of topography and influences local effects of gravitational energy and surface material transport. However, the calculation of LSCs based on triangulated irregular networks (TINs) has not been fully studied, which restricts further geoscience studies based on TIN digital elevation models (DEMs). The triangular facets and vertices of a TIN are both expressions of the land surface; therefore, based on their adjacency relationship, the LSCs can be calculated. In this study, we propose a mathematical vector framework for LSC calculation based on TINs. We define LSCs from the perspectives of the curvature tensor, slope and normal contour direction vectors, and then provide the calculation operators for LSCs based on both TIN triangular facets and vertices. Next, based on a mathematically simulated surface, we find that the TIN-based method exhibits similar effects on the scale as the grid-based methods and very low error sensitivity. In addition, based on different real landform cases with various data sources, we perform experiments involving land surface concavity–convexity and hillslope unit classification by using the TIN-based method. The results show that the TIN-based method can enhance the performance of TINs in landform classification over grid-based DEM methods. The proposed mathematical vector framework for LSC calculation can improve other geoscience studies based on TINs.

Abstract Purpose We aimed to investigate the effect and significance of the rotation method with variable-angle anterior probe corrected for the depth of two kidneys on the determination of glomerular filtration rate (GFR) in total and single kidneys by the renal dynamic imaging Gates method. Methods Seventy-two patients who underwent dynamic renal imaging by the rotation method and abdominal CT in our hospital were collected in the present study. CT scanning, rotation method, Tonnesen's formula, and Li-Qian's formula were compared in terms of the depth of two kidneys, the depth difference between the two kidneys, and the total renal and single GFR obtained by substituting the renal depth values into Gates' formula. Results ①The depth of kidneys and GFR: Compared to CT, Tonnesen's formula significantly underestimated the depth of both kidneys and the total and single renal GFR (P 0.05), with a strong agreement and with the least bias in the values measured by the rotation method. ②Renal depth difference: Compared to CT, Tonnesen's formula and Li-Qian's formula underestimated the difference in depth between the two kidneys (P 0.05). The depth difference was positively correlated with the resulting changes in single renal function (|R(CT)-R(Li-Qian)|) and (|R(Rotation)-R(Li-Qian)|) (r = 0.881, 0.641, P

Abstract Background CZT-SPECT has good agreement in the evaluation of mechanical synchronization compared with conventional SPECT. The aim of this study was to evaluate the correlation between left ventricular mechanical contraction synchrony and left ventricular systolic function by gated myocardial perfusion imaging (GMPI) using cadmium–zine–telluride (CZT) single photon emission computed tomography (SPECT). Methods This retrospective study involved 371 patients (239 males and 132 females, mean age 61.06 ± 11.78 years old) who underwent GMPI at the Nuclear Medicine Department of Shanxi Cardiovascular Hospital from January 2020 to August 2020. Systolic synchrony parameters and left ventricular systolic function parameters were calculated via Emory Cardiac Toolbox, including PP, PSD, PHB, HS, HK, EDV, ESV, and LVEF. Based on LVEF value, patients were divided into the severe reduction group (group 1, 127 cases, EF 0.001). PP was significantly higher in group 1, relative to group 3 (t = 2.43, P 0.001). HS and HK were negatively correlated with EDV and ESV (r = − 0.700 to − 0.594, P

Abstract Background Peripheral biomarkers are increasingly vital non-invasive methods for monitoring coronary artery disease (CAD) progression. Their superiority in early detection, prognosis evaluation and classified diagnosis is becoming irreplaceable. Nevertheless, they are still less explored. This study aimed to determine and validate the diagnostic and therapeutic values of differentially expressed immune-related genes (DE-IRGs) in CAD. Methods We downloaded clinical information and RNA sequence data from the GEO database. We used R software, GO, KEGG and Cytoscape to analyze and visualize the data. A LASSO method was conducted to identify key genes for diagnostic model construction. The ssGSEA analysis was used to investigate the differential immune cell infiltration. Besides, we constructed CAD mouse model (low-density lipoprotein receptor deficient mice with high fat diet) to discover the correlation between the screened genes and severe CAD progress. We further uncovered the role of IL13RA1 might play in atherosclerosis. Results A total of 762 differential genes were identified between the peripheral blood of 218 controls and 199 CAD patients, which were significantly associated with infection, immune response and neural activity. 58 DE-IRGs were obtained by overlapping the differentially expressed genes(DEGs) and immune-related genes downloaded from ImmpDb database. Through LASSO regression, CCR9, CER1, CSF2, IL13RA1, INSL5, MBL2, MMP9, MSR1, NTS, TNFRSF19, CXCL2, HTR3C, IL1A, and NR4A2 were distinguished as peripheral biomarkers of CAD with eligible diagnostic capabilities in the training set (AUC = 0.968) and test set (AUC = 0.859). The ssGSEA analysis showed that the peripheral immune cells had characteristic distribution in CAD and also close relationship with specific DE-IRGs. RT-qPCR test showed that CCR9, CSF2, IL13RA1, and NTS had a significant correlation with LDLR−/− mice. IL13RA1 knocked down in RAW264.7 cell lines decreased SCARB1 and ox-LDL-stimulated CD36 mRNA expression, TGF-β, VEGF-C and α-SMA protein levels and increased the production of IL-6, with downregulation of JAK1/STAT3 signal pathway. Conclusions We constructed a diagnostic model of advanced-stage CAD based on the screened 14 DE-IRGs. We verified 4 genes of them to have a strong correlation with CAD, and IL13RA1 might participate in the inflammation, fibrosis, and cholesterol efflux process of atherosclerosis by regulating JAK1/STAT3 pathway.

Allostimulated CD8+ T cells (aCD8+ T cells), as the main mediators of acute liver rejection (ARJ), are hyposensitive to apoptosis due to the inactivation of death receptor FAS-mediated pathways and fail to allow tolerance induction, eventually leading to acute graft rejection. Although tacrolimus (FK506), the most commonly used immunosuppressant (IS) in the clinic, allows tolerance induction, its use is limited because its target immune cells are unknown and it is associated with increased incidences of malignancy, infection, and nephrotoxicity, which substantially impact long-term liver transplantation (LTx) outcomes. The dark agouti (DA)-to-Lewis rat LTx model is a well-known ARJ model and was hence chosen for the present study. We show that both hepatocyte growth factor (HGF) (cHGF, containing the main form of promoting HGF production) and recombinant HGF (h-rHGF) exert immunoregulatory effects mainly on allogeneic aCD8+ T cell suppression through FAS-mediated apoptotic pathways by inhibiting cMet to FAS antagonism and Fas trimerization, leading to acute tolerance induction. We also showed that such inhibition can be abrogated by treatment with neutralizing antibodies against cMet (HGF-only receptor). In contrast, we did not observe these effects in rats treated with FK506. However, we observed that the effect of anti-rejection by FK506 was mainly on allostimulated CD4+ T cell (aCD4+ T cell) suppression and regulatory T cell (Treg) promotion, in contrast to the mechanism of HGF. In addition, the protective mechanism of HGF in FK506-mediated nephrotoxicity was addressed. Therefore, HGF as a tolerance inducer, whether used in combination with FK506 or as monotherapy, may have good clinical value. Additional roles of these T-cell subpopulations in other biological systems and studies in these fields will also be meaningful.

Key Clinical Message We reported a 23‐year‐old male patient with panhypopituitarism who underwent two resections for craniopharyngioma and received postoperative hormone replacement therapy. The 99mTc‐MDP bone scan revealed focal high uptake of radioactive nuclide in multiple large joints. The SPECT/CT demonstrated the focal high uptake in their metaphysis. Thus, delayed epiphyseal closure was considered.

Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors’ quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol’s therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol’s anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients.

High Mountain Asia (HMA) is characterized by some of the most complex and rugged terrain conditions in the world. However, high resolution terrain data are not easy to quickly acquire from the area due to difficulties in accessing the region. In this study, we trained a modified super-resolution residual network (MSRResNet) to develop super-resolution (SR) digital elevation models (DEMs) in the HMA areas by using freely available DEM data from the HMA region and limited high resolution (HR) DEMs from other areas to train the model. In this network, a new loss function was constructed that considered the terrain parameters of slope and curvature to constrain the network learning and convergence. The proposed method was applied to and validated by data from the Hengduan Mountains in the southeastern part of HMA, which is a world-famous longitudinal belt of mountains and canyons. A comparative analysis between the current and existing methods (i.e., SRGAN and Bicubic interpolation) was conducted to assess the effectiveness of the proposed approach. The experimental results were also investigated and evaluated by visual inspection and analysis of the terrain parameters. The results demonstrate that the proposed MSRResNet super-resolution process can achieve highly accurate terrain data by downscaling DEMs in HMA. This SR process also outperforms the other comparable methods. Compared to the Bicubic interpolation method, the RMSE and MAE accuracy are improved by 32.17% and 33.97%, and compared to the SRGAN method, the RMSE and MAE accuracy are improved by 39.15% and 32.47%. The HR DEM generated by the new method is more conducive to improving the accuracy of extracted terrain features, such as stream networks. It is promising to apply this model on other areas on Earth or even other planets with terrain similar to that of HMA.

Nanoparticle-based chemophotothermal therapy (CPT) is a promising treatment for multidrug resistant tumors. In this study, a drug nanococktail of DIR825@histone was developed by employing doxorubicin (DOX), NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser. After localized intervention, DIR825@histone penetrated tumor tissues by transcytosis, efficiently entered tumor cells and targeted the cell nuclei. DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release. Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting. Moreover, an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury. Therefore, DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors.

Chimonanthus praecox is an important ornamental plant and cut flower material in China. It blooms in the freezing winter and its flower emits charming fragrance. However, in different region the flowering time is variable. In order to understand the flowering mechanism of Ch. praecox in the winter, we studied the flower bud differentiation in Spring City-Kunming using paraffin sectioning method in the present study. Meanwhile we compared the differentiation process difference from different regions. It was found that the temperature is the key factor for its flower bud differentiation and blossom of Ch. praecox. In the process of bud differentiation, the temperature 20 °C was the optimum for inducing changes from vegetative axillary buds to reproductive buds and subsequent morphological differentiation in Ch. praecox. Furthermore in the first three differentiation periods—tepal primordial stage, staminal primordial stage and pistil primordial stage, Kunming took the shortest time to finish the process due to very rapid temperature rise to 20 °C, whereas, in Zhengzhou the time for these differentiations was the longest, which may be caused by the slow temperature rise. After May, the high temperature stress forced the flower buds into the first long dormant period in all regions except Kunming. In Kunming, the average temperature was only 20–25 °C, so the flower bud continued to differentiate. In all regions, Kunming is the first to complete whole flower bud differentiation even on the early August, and started the second dormancy very early but very long. In the other regions, the plants went through a shorter dormancy and the low temperature broke the dormancy rapidly. Contrarily the plants of Kunming spent a longer period for the low temperature. Thus, the low temperature less than 10 °C is a key factor to breaking the second dormancy. Surely the regular effects of temperature on flower bud differentiation and blossom is very helpful for florescence regulation of Ch. praecox.

BackgroundAtherosclerosis (AS) has long been recognized as a cardiovascular disease and stroke risk factor. A well-known traditional Chinese medicine prescription, Tao Hong decoction (THD), has been proven effective in treating AS, but its mechanism of action is still unclear.ObjectiveTo assess the effects, explore THD’s primary mechanism for treating AS, and provide a basis for rational interpretation of its prescription compatibility.MethodsBased on network pharmacology, we evaluated the mechanism of THD on AS by data analysis, target prediction, the construction of PPI networks, and GO and KEGG analysis. AutoDockTools software to conduct Molecular docking. Then UPLC-Q-TOF-MS was used to identify significant constituents of THD. Furthermore, an AS mice model was constructed and intervened with THD. Immunofluorescence, RT-qPCR, and Western blot were used to verify the critical targets in animal experiments.ResultsThe network pharmacology results indicate that eight core targets and seven core active ingredients play an essential role in this process. The GO and KEGG analysis results suggested that the mechanism is mainly involved in Fluid shear stress and atherosclerosis and Lipid and atherosclerosis. The molecular docking results indicate a generally strong affinity. The animal experiment showed that THD reduced plaque area, increased plaque stability, and decreased the levels of inflammatory cytokines (NF-κB, IL-1α, TNF-α, IL-6, IL-18, IL-1β) in high-fat diet -induced ApoE-/-mice. Decreased levels of PTGS2, HIF-1α, VEGFA, VEGFC, FLT-4, and the phosphorylation of PI3K, AKT, and p38 were detected in the THD-treated group.ConclusionTHD plays a vital role in treating AS with multiple targets and pathways. Angiogenesis regulation, oxidative stress regulation, and immunity regulation consist of the crucial regulation cores in the mechanism. This study identified essential genes and pathways associated with the prognosis and pathogenesis of AS from new insights, demonstrating a feasible method for researching THD’s chemical basis and pharmacology.

Abstract We report a case of accidental local 99mTc‐MDP uptake in left lung on bone scan without pulmonary parenchymal abnormality on SPECT/CT. The abnormal uptake disappeared on repeated bone scan and SPECT/CT after 3 days. It is speculated that the high radioactivity focus is a microthrombus in pulmonary artery.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Plant specialized metabolites occupy unique therapeutic niches in human medicine. A large family of plant specialized metabolites, namely plant polyketides, exhibit diverse and remarkable pharmaceutical properties and thereby great biomanufacturing potential. A growing body of studies has focused on plant polyketide synthesis using plant type III polyketide synthases (PKSs), such as flavonoids, stilbenes, benzalacetones, curcuminoids, chromones, acridones, xanthones, and pyrones. Microbial expression of plant type III PKSs and related biosynthetic pathways in workhorse microorganisms, such as Saccharomyces cerevisiae, Escherichia coli, and Yarrowia lipolytica, have led to the complete biosynthesis of multiple plant polyketides, such as flavonoids and stilbenes, from simple carbohydrates using different metabolic engineering approaches. Additionally, advanced biosynthesis techniques led to the biosynthesis of novel and complex plant polyketides synthesized by diversified type III PKSs. This review will summarize efforts in the past 10 years in type III PKS-catalyzed natural product biosynthesis in microorganisms, especially the complete biosynthesis strategies and achievements.

We investigate the input and propagation characteristics and geometric parametric instability of the partial Gaussian beam limited by the fiber face area in a graded-index multimode fiber. The theoretical simulation shows that the energy of the partial Gaussian beam and the coupling efficiency of the fiber face are restricted by the fiber face area for the different powers and spot sizes of the input Gaussian beam. The spot intensity pattern of the partial Gaussian beam exhibits a standard oscillating distribution in space as the beam undergoes periodic oscillations with propagation. Also, the dynamic evolution process from parametric sidebands to a supercontinuum is affected by the peak power, the spot size of the partial Gaussian beam, and the fiber length. Finally, the experimental output spectra with different powers of the partial Gaussian beam and fiber lengths in a graded-index multimode fiber confirm the prediction of theoretical simulations. This work provides practical guidance for optimizing supercontinuum source expansion and spectral power density.

Abstract Socially engaging robots have been increasingly applied to alleviate depressive symptoms and to improve the quality of social life among different populations. Seeing that depression negatively influences social reward processing in everyday interaction, we investigate this influence during simulated interactions with humans or robots. In this study, 35 participants with mild depression and 35 controls (all from nonclinical populations) finished the social incentive delay task with event-related potential recording, in which they received performance feedback from other persons or from a robot. Compared to the controls, the mild depressive symptom (MDS) group represented abnormalities of social reward processing in the human feedback condition: first, the MDS group showed a lower hit rate and a smaller contingent-negative variation (correlated with each other) during reward anticipation; second, depression level modulated both the early phase (indexed by the feedback-related negativity (FRN)) and the late phase (indexed by the P3) of reward consumption. In contrast, the effect of depression was evident only on FRN amplitude in the robot feedback condition. We suggest that compared to human–human interaction, the rewarding properties of human–robot interaction are less likely to be affected by depression. These findings have implications for the utilization of robot-assisted intervention in clinical practice.

Developing biomarkers for accurately predicting the efficacy of immune checkpoint inhibitor (ICI) therapies is conducive to avoiding unwanted side effects and economic burden. At the moment, the quantification of programmed cell death ligand 1 (PD-L1) in tumor tissues is clinically used as one of the combined diagnostic assays of response to anti-PD-1/PD-L1 therapy. However, the current assays for evaluating PD-L1 remain imperfect. Recent studies are promoting the methodologies of PD-L1 evaluation from rough to precise. Standardization of PD-L1 immunohistochemistry tests is being promoted by using optimized reagents, platforms, and cutoff values. Combining novel in vivo probes with PET or SPECT will probably be of benefit to map the spatio-temporal heterogeneity of PD-L1 expression. The dynamic change of PD-L1 in the circulatory system can also be realized by liquid biopsy. Consider PD-L1 expressed on non-tumor (immune and non-immune) cells, and optimized combination detection indexes are further improving the accuracy of PD-L1 in predicting the efficacy of ICIs. The combinations of artificial intelligence with novel technologies are conducive to the intelligence of PD-L1 as a predictive biomarker. In this review, we will provide an overview of the recent progress in this rapidly growing area and discuss the clinical and technical challenges.

ObjectiveOur goal is to construct an immune-related gene prognostic risk index (IRGPRI) for pancreatic adenocarcinoma (PAAD), and to clarify the immune and molecular features in IRGPRI-defined PAAD subgroups and the benefit of immune checkpoint inhibitors (ICIs) therapy.MethodThrough differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and univariate Cox regression analysis, 16 immune-related hub genes were identified using the Cancer Genome Atlas (TCGA) PAAD dataset (n = 182) and immune gene set. From these genes, we constructed an IRGPRI with the Cox regression method and the IRGPRI was verified based on the Gene Expression Omnibus (GEO) dataset (n = 45). Then, we analyzed the immune and molecular features and the benefit of ICI therapy in IRGPRI-defined subgroups.ResultsFive genes, including S100A16, CD40, VCAM1, TNFRSF4 and TRAF1 were used to construct IRGPRI. As with the results of the GEO cohort, the overall survival (OS) was more favorable in low IRGPRI patients versus high IRGPRI patients. The composite results pointed out that low IRGPRI was associated with immune response-related pathways, high level of CTLA4, low KRAS and TP53 mutation rate, more infiltration of activated memory CD4+ T cells, CD8+ T cells, and more benefits from ICIs therapy. In comparison, high IRGPRI was associated with cancer-related pathways, low expression of CTLA4, high KRAS and TP53 mutation rate, more infiltration of M2 macrophages, and less benefit from ICIs therapies.ConclusionThis IRGPRI is an encouraging biomarker to define the prognosis, immune and molecular features, and benefits from ICIs treatments in PAAD.

Plant styrylpyrones exerting well-established neuroprotective properties have attracted increasing attention in recent years. The ability to synthesize each individual styrylpyrone in engineered microorganisms is important to understanding the biological activity of medicinal plants and the complex mixtures they produce. Microbial biomanufacturing of diverse plant-derived styrylpyrones also provides a sustainable and efficient approach for the production of valuable plant styrylpyrones as daily supplements or potential drugs complementary to the prevalent agriculture-based approach. In this study, we firstly demonstrated the heterogenous biosynthesis of two 7,8-saturated styrylpyrones (7,8-dihydro-5,6-dehydrokavain (DDK) and 7,8-dihydroyangonin (DHY)) and two 7,8-unsaturated styrylpyrones (desmethoxyyangonin (DMY) and yangonin (Y)), in Saccharomyces cerevisiae. Although plant styrylpyrone biosynthetic pathways have not been fully elucidated, we functionally reconstructed the recently discovered kava styrylpyrone biosynthetic pathway that has high substrate promiscuity in yeast, and combined it with upstream hydroxycinnamic acid biosynthetic pathways to produce diverse plant-derived styrylpyrones without the native plant enzymes. We optimized the de novo pathways by engineering yeast endogenous aromatic amino acid metabolism and endogenous double bond reductases and by CRISPR-mediated δ-integration to overexpress the rate-limiting pathway genes. These combinatorial engineering efforts led to the first three yeast strains that can produce diverse plant-derived styrylpyrones de novo, with the titers of DDK, DMY and Y at 4.40 μM, 1.28 μM and 0.10 μM, respectively. This work has laid the foundation for larger-scale styrylpyrone biomanufacturing and the complete biosynthesis of more complicated plant styrylpyrones.

The ventrolateral prefrontal cortex (VLPFC) plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation (spTMS) to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise (down-regulate) or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right VLPFC of the participants’ brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal (measured by self-reported negative feelings) significantly deteriorated when the right (but not the left) VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation.