Integrin αvß3 and LHRH Receptor Double Directed Nano-Analogue Effective Against Ovarian Cancer in Mice Model.

Introduction: The high mortality rate of malignant ovarian cancer is attributed to the absence of effective early diagnosis methods. The LHRH receptor is specifically overexpressed in most ovarian cancers, and the integrin αvß3 receptor is also overexpressed on the surface of ovarian cancer cells. In this study, we designed LHRH analogues (LHRHa)/RGD co-modified paclitaxel liposomes (LHRHa-RGD-LP-PTX) to target LHRH receptor-positive ovarian cancers more effectively and enhance the anti-ovarian cancer effects. Methods: LHRHa-RGD-LP-PTX liposomes were prepared using the thin film hydration method. The morphology, physicochemical properties, cellular uptake, and cell viability were assessed. Additionally, the cellular uptake mechanism of the modified liposomes was investigated using various endocytic inhibitors. The inhibitory effect of the formulations on tumor spheroids was observed under a microscope. The co-localization with lysosomes was visualized using confocal laser scanning microscopy (CLSM), and the in vivo tumor-targeting ability of the formulations was assessed using the IVIS fluorescent imaging system. Finally, the in vivo anti-tumor efficacy of the formulations was evaluated in the armpits of BALB/c nude mice. Results: The results indicated that LHRHa-RGD-LP-PTX significantly enhanced cellular uptake in A2780 cells, increased cytotoxicity, and hand a more potent inhibitory effect on tumor spheroids of A2780 cells. It also showed enhanced co-localization with endosomes or lysosome in A2780 cells, improved tumor-targeting capability, and demonstrated an enhanced anti-tumor effect in LHRHR-positive ovarian cancers. Conclusion: The designed LHRHa-RGD-LP-PTX liposomes significantly enhanced the tumor-targeting ability and therapeutic efficacy for LHRH receptor-positive ovarian cancers.

Fast SPECT/CT planar bone imaging enabled by deep learning enhancement.

BACKGROUND: The application of deep learning methods in rapid bone scintigraphy is increasingly promising for minimizing the duration of SPECT examinations. Recent works showed several deep learning models based on simulated data for the synthesis of high-count bone scintigraphy images from low-count counterparts. Few studies have been conducted and validated on real clinical pairs due to the misalignment inherent in multiple scan procedures. PURPOSE: To generate high quality whole-body bone images from 2× and 3× fast scans using deep learning based enhancement method. MATERIALS AND METHODS: Seventy-six cases who underwent whole-body bone scans were enrolled in this prospective study. All patients went through a standard scan at a speed of 20 cm/min, which followed by fast scans consisting of 2× and 3× accelerations at speeds of 40 and 60 cm/min. A content-attention image restoration approach based on Residual-in-Residual Dense Block (RRDB) is introduced to effectively recover high-quality images from fast scans with fine-details and less noise. Our approach is robust with misalignment introduced from patient's metabolism, and shows valid count-level consistency. Learned Perceptual Image Patch Similarity (LPIPS) and Fréchet Inception Distance (FID) are employed in evaluating the similarity to the standard bone images. To further prove our method practical in clinical settings, image quality of the anonymous images was evaluated by two experienced nuclear physicians on a 5-point Likert scale (5 =  excellent) . RESULTS: The proposed method reaches the state-of-the-art performance on FID and LPIPS with 0.583 and 0.176 for 2× fast scans and 0.583 and 0.185 for 3× fast scans. Clinic evaluation further demonstrated the restored images had a significant improvement compared to fast scan in image quality, technetium 99m-methyl diphosphonate (Tc-99 m MDP) distribution, artifacts, and diagnostic confidence. CONCLUSIONS: Our method was validated for accelerating whole-body bone scans by introducing real clinical data. Confirmed by nuclear medicine physicians, the proposed method can effectively enhance image diagnostic value, demonstrating potential for efficient high-quality fast bone imaging in practical settings.

Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer.

OBJECTIVES: To evaluate the diagnostic value of plasma exosomal miR-223 and its combination with CA125 for the diagnosis of early-stage epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Exosomes derived from the plasma of 78 EOC patients, 40 patients with epithelial benign ovarian tumors, and 52 healthy participants were isolated using the ultracentrifugation method and identified by transmission electron microscopy (TEM) and western blot. RESULTS: The expression of exosomal miR-223 was significantly upregulated in the plasma of EOC patients compared to that in healthy subjects and patients with benign diseases. The combination of exosomal miR-223 and CA125 from plasma had an equivalent area under the ROC curve (AUC) to CA125 alone for discriminating between EOC and non-EOC cases, including healthy subjects and benign ovarian tumors. However, the AUC value of the combination was 0.944 (95% CI: 0.899-0.990) for differentially diagnosing early-stage EOC from healthy subjects, slightly higher than that of CA125 alone (0.928, 95% CI: 0.875-0.981), with a sensitivity and specificity of 0.9784 and 0.885, respectively. CONCLUSION: Our data suggest that plasma exosomal miR-223 can be used as a complement to CA125 to increase the diagnostic power for differentiating early-stage EOC from healthy subjects.

Positive 18 F-FDG and Negative 68 Ga-FAPI-04 Findings in a Patient With Gallbladder Adenocarcinoma.

ABSTRACT: Radiolabeled fibroblast activation protein inhibitor (FAPI) is considered as a potential alternative agent to 18 F-FDG for tumor-specific imaging. We report 18 F-FDG and 68 Ga-FAPI-04 PET/MR findings in a 67-year-old woman with gallbladder adenocarcinoma. The lesions showed intense 18 F-FDG uptake but limited 68 Ga-FAPI-04 uptake in PET/MR. This case emphasizes the necessity for nuclear clinicians to exercise caution when assessing gallbladder lesions with limited 68 Ga-FAPI-04 uptake, underscoring the continued relevance of 18 F-FDG in this diagnostic domain.

Coupling Between Human Brain Cortical Thickness and Glucose Metabolism from Regional to Connective Level: A Positron Emission Tomography/Magnetic Resonance Imaging Study.

Background: Balance between brain structure and function is implicated in aging and many brain disorders. This study aimed to investigate the coupling between brain structure and function using 18F-fludeoxyglucose positron emission tomography (PET)/magnetic resonance imaging (MRI). Methods: One hundred thirty-eight subjects who underwent brain 18F-FDG PET/MRI were recruited. The structural and functional coupling at the regional level was explored by calculating within-subject Spearman's correlation between glucose metabolism (GluM) and cortical thickness (CTh) across the cortex for each subject, which was then correlated with age to explore its physiological effects. Then, subjects were divided into groups of middle-aged and young adults and older adults (OAs); structural connectivity (SC) based on CTh and functional connectivity (FC) based on GluM were constructed for the two groups, respectively, followed by exploring the connective-level structural and functional coupling on SC and FC matrices. The global and local efficiency values of the brain SC and FC were also evaluated. Results: Of the subjects, 97.83% exhibited a significant negative correlation between regional CTh and GluM (r = -0.24 to -0.71, p < 0.05, FDR correction), and this CTh-GluM correlation was negatively correlated with age (R = -0.35, p < 0.001). For connectivity matrices, many regions showed positive correlation between SC and FC, especially in the OA group. Besides, FC exhibited denser connections than SC, resulting in both higher global and local efficiency, but lower global efficiency when the network size was corrected. Conclusions: This study found couplings between CTh and GluM at both regional and connective levels, which reflected the aging progress, and might provide new insight into brain disorders. Impact statement The intricate interplay between brain structures and functions plays a pivotal role in unraveling the complexities inherent in the aging process and the pathogenesis of neurological disorders. This study revealed that 97.83% subjects showed negative correlation between the brain's regional cortical thickness and glucose metabolism, while at the connective level, many regions showed positive correlations between structural and functional connectivity. The observed coupling at the regional and connective levels reflected physiological progress, such as aging, and provides insights into the brain mechanisms and potential implications for the diagnosis and treatment of brain disorders.

[Application of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency].

OBJECTIVE: To explore the value of whole exome sequencing for the inferential analysis of recessive genetic disease carrier status for couples with a child died of Primary immunodeficiency (PID). METHODS: Clinical data was collected from four couples with a childbearing history of PID who had sought genetic counseling and undergone genetic testing at Henan Provincial People's Hospital from February 2017 to December 2021. Whole exome sequencing (WES) was performed on both partners of each couple, and candidate variants were validated by Sanger sequencing and fluorescent quantitative PCR. Prenatal diagnosis was conducted on fetuses of these couples after confirming the variants. RESULTS: A total of six variants were detected in four genes including IL2RG, BTK, CYBB, and DUOX2. Among these, the c.1265G>A and c.3329G>A variants of the DUOX2 gene and the c.676C>T variant of the IL2RG gene were previously known as pathogenic variants. On the other hand, the Exon5_8del variant of the IL2RG gene, the c.184_185delAC variant of the BTK gene, and the c.472A>T variant of the CYBB gene were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the IL2RG: Exon5_8del, BTK: c.184_185delAC and CYBB: c.472A>T variants were classified as likely pathogenic (PVS1+PM2_Supporting+PP4).Prenatal diagnosis was conducted for three couples during their subsequent pregnancies, and the results revealed that the fetuses had the wild-type genotypes at the c.184_185 position of the BTK gene, the c.472 position of the CYBB gene, and the c.676 position of the IL2RG gene. Follow-up examinations one year after birth has found no abnormality in the infants. CONCLUSION: WES is an important tool to infer and analyze the carrier status for couples who had given births to children died of PID and improve the positive detection rate.

The associations between synaptic density and "A/T/N" biomarkers in Alzheimer's disease: An 18F-SynVesT-1 PET/MR study.

A newly developed SV2A radiotracer, 18F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer's disease (AD) "A/T/N" biomarkers. The study included a cohort of 97 subjects, consisting of 64 patients with cognitive impairment (CI) and 33 individuals with normal cognition (CU). All subjects underwent 18F-SynVesT-1 PET/MR and 18F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent 18F-MK-6240, 18F-FDG PET/CT, plasma Aß42/Aß40 and p-tau181 tests. The differences in synaptic density between the groups and the correlations between synaptic density and AD "A/T/N" biomarkers were analyzed. The results showed that compared to the CU group, the CI with Aß+ (CI+) group exhibited the most pronounced synapse loss in the hippocampus, with some loss also observed in the neocortex. Furthermore, synaptic density in the hippocampus and parahippocampal gyrus showed associations with AD biomarkers detected by both imaging and plasma tests in the CI group. The associations between synaptic density and FDG uptake and hippocampal volume were also observed in the CI+ group. In conclusion, the study demonstrated significant synaptic density loss, as measured by the promising tracer 18F-SynVesT-1, and its close correlation with "A/T/N" biomarkers in patients with both Alzheimer's clinical syndrome and pathological changes.

Microswimmer-Assisted Dual-Signal Sensor for Multiple Targets in Whole Blood.

Accurate detection of biomarkers in whole blood is an important aspect of diagnostic testing but remains a challenge due to various interferences. However, using a self-calibrating two-signal strategy offers a solution that can overcome interference caused by experimental and environmental factors. Here, we proposed a novel microswimmer {methylene blue (MB)@ZIF-90@aptamer-HER2/3,3',5,5'-tetramethylbenzidine (TMB)@ZIF-90@aptamer-ER}-dual-signal (electrochemical and fluorescence) homogeneous sensor based on functionalized ZIF nanomaterials for one-step simultaneous detection of human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) in whole blood. The proposed one-step ZIF-90 synthesis encapsulates TMB and MB with dual-signal properties. HER2 and ER aptamers adsorbed on MB@ZIF-90/TMB@ZIF-90 function as the gate switches. The microswimmer targets the HER2 and ER with adenosine triphosphate (ATP)-driven motion. When targets are present, aptamers dissociate and reduce the microswimmer's surface negative charge. The microswimmer undergoes attack and decomposition by swimming ATP due to the strong coordination force between ATP and Zn2+, leading to the release of MB and TMB. The negative charges on the surface of indium tin oxide enrich MB and TMB with positive charges, thereby increasing the intensities of electrochemical and fluorescence signals. The detection process was completed within 40 min, and the detection limits for ER and HER2 were 8.1 and 5.7 fg/mL respectively, with a linear range of 0.25-20 pg/mL.

SP1 transcriptionally upregulates the expression of APOC3 in KGN cells to promote disease progression by regulating TLR2/NF-κB signalling pathway.

INTRODUCTION: Apolipoprotein C3 (APOC3) is known for its important functions in metabolism-related diseases. However, the function and molecular mechanism of APOC3 in polycystic ovarian syndrome (PCOS) have not been reported. MATERIAL AND METHODS: Quantitative polymerase chain reaction and western blot assays were used to detect the expression of APOC3 in KGN cells. Small interference APOC3 (siAPOC3) was applied to reduce APOC3 expression, and the proliferation ability of human granulosa cell line (KGN cells) was measured by cell counting kit-8 and colony formation assays. The protein levels of key genes related to apoptosis were detected by western blot assay. The transcriptional regulator of APOC3 was predicted by the UCSC and PROMO website, and verified by dual luciferase assay. siAPOC3 and pcDNA3.1-specific protein 1 (SP1) vector were co-transfected into KGN cells to detect the function of SP1 and APOC3 in KGN cells. RESULTS: APOC3 was overexpressed in KGN cells, and siAPOC3 transfection significantly reduced the growth ability of KGN cells and increased the apoptosis ability of KGN cells. SP1 directly bound to the promoter of APOC3 and transcriptional regulated APOC3 expression. Overexpression of SP1 increased the growth ability of KGN cells and decreased the apoptosis ability of KGN cells, which were reversed after siAPOC3 transfection. The increased levels of toll-like receptor 2 (TLR2) and p65 phosphorylation (p-P65) nuclear factor kappa B (NF-κB) caused by SP1 overexpression were inhibited by siAPOC3 transfection. APOC3, transcriptionally regulated by SP1, promoted the growth of KGN cells, and inhibited the apoptosis by regulating TLR2/NF-κB signalling pathway.

A Novel Platform of MOF for Sonodynamic Therapy Advanced Therapies.

Metal-organic frameworks (MOFs) combined with sonodynamic therapy (SDT) have been introduced as a new and efficient treatment method. The critical advantage of SDT is its ability to penetrate deep tissues and concentrate energy on the tumor site to achieve a non-invasive or minimally invasive effect. Using a sonosensitizer to generate reactive oxygen species (ROS) under ultrasound is the primary SDT-related method of killing tumor cells. In the presence of a sonosensitizer, SDT exhibits a more lethal effect on tumors. The fast development of micro/nanotechnology has effectively improved the efficiency of SDT, and MOFs have been broadly evaluated in SDT due to their easy synthesis, easy surface functionalization, high porosity, and high biocompatibility. This article reviews the main mechanism of action of sonodynamic therapy in cancer treatment, and also reviews the applications of MOFs in recent years. The application of MOFs in sonodynamic therapy can effectively improve the targeting ability of SDT and the conversion ability of reactive oxygen species, thus improving their killing ability on cancer cells. This provides new ideas for the application of micro/nano particles in SDT and cancer therapy.

[Expert consensus on the genetic diagnosis for Dystrophinopathies].

Dystrophinopathies, including Duchenne muscular dystrophy, Becker muscular dystrophy and dilated cardiomyopathy, are X-linked recessive genetic disorders due to variants of the dystrophin gene, which can seriously affect quality of life and health. Genetic diagnosis plays a crucial role in their diagnosis, treatment, and prevention. How to rationally select and standardize the use of various genetic techniques is a skill that clinicians must acquire. By compiling expertise of experts from the relevant areas and guidelines published home and abroad, this consensus has provided a guidance from the perspective of genetic diagnosis for the selection of genetic techniques, testing strategies, and detection process for dystrophinopathies.

[Genetic analysis of a Chinese pedigree with Cohen syndrome due to compound heterozygous variants of VPS13B gene].

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome. METHODS: A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation. RESULTS: The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant. CONCLUSION: The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.

Gender specific sexual dysfunction in patients with depression.

Background: This study aims to investigate the factors associated with sexual dysfunction (SD), with a particular focus on the influence of sex on the occurrence and severity of this condition in patients with major depressive disorder (MDD). Method: Sociodemographic and clinical assessments were conducted on 273 patients with MDD (female = 174, male = 99), including the ASEX, QIDS-SR16, GAD-7, and PHQ-15. Univariate analyses, independent samples t-test, Chi-square test, and Fisher's exact test were used as appropriate, and logistic regression analysis was used to identify correlation factors for SD. Statistical analyses were performed using the Statistical Analysis System (SAS 9.4). Result: SD was reported in 61.9% of the participants (ASEX score = 19.6 ± 5.5), and the prevalence of it in females (75.3%, ASEX score = 21.1 ± 5.4) was significantly higher than that in males (38.4%, ASEX score = 17.1 ± 4.6). Factors associated with SD included being female, being aged 45 years or above, having a low monthly income (≤750 USD), feeling more sluggish than usual (a QIDS-SR16 Item 15 score of 1 or above), and having somatic symptoms (evaluated with the total score of PHQ15). Limitation: The use of antidepressants and antipsychotics might be a confounding factor affecting sexual function. Also, the lack of information in the clinical data regarding the number, duration, and time of onset of the episodes limits the richness of the results. Conclusion: Our findings reveal the sex differences in the prevalence and severity of SD in patients with MDD. Evaluated with the ASEX score, female patients showed significantly worse sexual function than male patients. Being female, having a low monthly income, being aged 45 years or above, feeling sluggish, and having somatic symptoms may increase the risk of SD in patients with MDD.

Fluorescence detection platform of metal-organic frameworks for biomarkers.

Sensitive and selective detection of biomarkers is crucial in the study and early diagnosis of diseases. With the continuous development of biosensing technologies, fluorescent biosensors based on metal-organic frameworks have attracted increasing attention in the field of biomarker detection due to the combination of the advantages of MOFs, such as high specific surface area, large porosity, and structure with tunable functionality and the technical simplicity, sensitivity and efficiency and good applicability of fluorescent detection techniques. Therefore, researchers must understand the fluorescence response mechanism of such fluorescent biosensors and their specific applications in this field. Of all biomarkers applicable to such sensors, the chemical essence of nucleic acids, proteins, amino acids, dopamine, and other small molecules account for about a quarter of the total number of studies. This review systematically elaborates on four fluorescence response mechanisms: metal-centered emission (MC), ligand-centered emission (LC), charge transfer (CT), and guest-induced luminescence change (GI), presenting their applications in the detection of nucleic acids, proteins, amino acids, dopamine, and other small molecule biomarkers. In addition, the current challenges of MOFs-based fluorescent biosensors are also discussed, and their further development prospects are concerned.

Intelligent cyclic fire warning sensor based on hybrid PBO nanofiber and montmorillonite nanocomposite papers decorated with phenyltriethoxysilane.

An abundance of early warning graphene-based nano-materials and sensors have been developed to avoid and prevent the critical fire risk of combustible materials. However, there are still some limitations that should be addressed, such as the black color, high-cost and single fire warning response of graphene-based fire warning materials. Herein, we report an unexpected montmorillonite (MMT)-based intelligent fire warning materials that have excellent fire cyclic warning performance and reliable flame retardancy. Combining phenyltriethoxysilane (PTES) molecules, poly(p-phenylene benzobisoxazole) nanofiber (PBONF), and layers of MMT to form a silane crosslinked 3D nanonetwork system, the homologous PTES decorated MMT-PBONF nanocomposites are designed and fabricated via a sol-gel process and low temperature self-assembly method. The optimized nanocomposite paper shows good mechanical flexibility (good recovery after kneading or bending process), high tensile strength of âˆ¼81 MPa and good water resistance. Furthermore, the nanocomposite paper exhibits high-temperature flame resistance (almost unchanged structure and size after 120 s combustion), sensitive flame alarm response (∼0.3 s response once exposure onto a flame), cyclic fire warning performance (>40 cycles), and adaptability to complex fire situations (several fire attack and evacuation scenarios), showing promising applications for monitoring the critical fire risk of combustible materials. Therefore, this work paves a rational way for design and fabrication of MMT-based smart fire warning materials that combine excellent flame shielding and sensitive fire alarm functions.

[Genetic analysis of two children with developmental delay and intellectual disability].

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION: The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

Deep learning enhanced ultra-fast SPECT/CT bone scan in patients with suspected malignancy: quantitative assessment and clinical performance.

Objectives. To evaluate the clinical performance of deep learning-enhanced ultrafast single photon emission computed tomography/computed tomography (SPECT/CT) bone scans in patients with suspected malignancy.Approach. In this prospective study, 102 patients with potential malignancy were enrolled and underwent a 20 min SPECT/CT and a 3 min SPECT scan. A deep learning model was applied to generate algorithm-enhanced images (3 min DL SPECT). The reference modality was the 20 min SPECT/CT scan. Two reviewers independently evaluated general image quality, Tc-99m MDP distribution, artifacts, and diagnostic confidence of 20 min SPECT/CT, 3 min SPECT/CT, and 3 min DL SPECT/CT images. The sensitivity, specificity, accuracy, and interobserver agreement were calculated. The lesion maximum standard uptake value (SUVmax) of the 3 min DL and 20 min SPECT/CT images was analyzed. The peak signal-to-noise ratio (PSNR) and structure similarity index measure (SSIM) were evaluated.Main results. The 3 min DL SPECT/CT images showed significantly superior general image quality, Tc-99m MDP distribution, artifacts, and diagnostic confidence than the 20 min SPECT/CT images (P< 0.0001). The diagnostic performance of the 20 min and 3 min DL SPECT/CT images was similar for reviewer 1 (pairedX2= 0.333,P= 0.564) and reviewer 2 (pairedX2= 0.05,P= 0.823). The diagnosis results for the 20 min (kappa = 0.822) and 3 min DL (kappa = 0.732) SPECT/CT images showed high interobserver agreement. The 3 min DL SPECT/CT images had significantly higher PSNR and SSIM than the 3 min SPECT/CT images (51.44 versus 38.44,P< 0.0001; 0.863 versus 0.752,P< 0.0001). The SUVmaxof the 3 min DL and 20 min SPECT/CT images showed a strong linear relationship (r= 0.991;P< 0.0001).Significance.Ultrafast SPECT/CT with a 1/7 acquisition time can be enhanced by a deep learning method to achieve comparable image quality and diagnostic value to those of standard acquisition.

Visual analysis based on CiteSpace software: a bibliometric study of atrial myxoma.

Objective: To use CiteSpace and VOSviewer visual metrology to analyze the research status, frontier hotspots, and trends in research on atrial myxoma. Methods: The Web of Science core collection database was used to retrieve relevant literature on atrial myxoma from 2001 to 2022. CiteSpace software was used to analyze keywords with a co-occurrence network, co-polymerization class, and burst terms, and a corresponding visual atlas was drawn for analysis. Results: A total of 893 valid articles were included. The country with the highest number of articles was the United States (n = 186). The organization with the highest number of articles was the Mayo Clinic (n = 15). The author with the highest number of articles was Yuan SM (n = 12). The highest cited author was Reynen K (n = 312). The highest cited journal was Annals of Thoracic Surgery (n = 1,067). The most frequently cited literature was published in the New England Journal of Medicine in 1995, which was cited 233 times. The keywords co-occurrence, copolymerization analysis, and Burst analysis revealed that the main research focuses were surgical methods, case reports, and genetic and molecular level studies on the pathogenesis of myxoma. Conclusions: This bibliometric analysis revealed that the main research topics and hotspots in atrial myxoma included surgical methods, case reports, genetic and molecular studies.

Microswimmer-Based Ultrasensitive Dual-Signal Ratiometric Electrochemical Homogeneous Aptasensor with Functionalized Co-UiO-66 for the Single-Step Detection of HER2 in Whole Blood.

The ability to efficiently detect trace disease biomarkers in whole blood remains an enormous challenge. Researchers have paid more attention to the homogeneous electrochemical ratio biosensor due to its self-calibration capability and improved detection accuracy. However, proportional homogeneous electrochemical sensing is difficult to achieve and typically requires functional modification of the electrode or the preparation of complex materials. Herein, a dual-signal ratiometric aptamer homogeneous electrochemical microswimming detection device with active capture capability and one-step detection of human epidermal growth factor receptor-2 (HER2) is proposed. The homogeneous electrochemical biosensor is fabricated based on a functionalized nanocomposite double-stranded DNA({single-stranded DNA-ferrocene (Fc)-aptamer})@Co-UiO-66 with catalase properties and adsorptive properties to electroactive toluidine blue (TB) molecules. Encapsulation of Co-UiO-66 material with dsDNA (ssDNA-Fc-Apt) containing HER2 aptamer as a gate switch inhibited its ability to adsorb TB molecules. This functionalized Co-UiO-66 material can catalyze hydrogen peroxide. Using hydrogen peroxide as a fuel, it breaks down to release oxygen bubbles, creating a propulsion force that drives dsDNA(ssDNA-Fc-Apt)@Co-UiO-66 target HER2 through whole blood. When the surface dsDNA (ssDNA-Fc-Apt)@Co-UiO-66 recognizes HER2, a strand displacement reaction occurs, and the ssDNA-Fc is released into solution. The HER2 aptamer is coiled because it targets HER2, and the ability to adsorb TB molecules is restored due to the exposed surface of Co-UiO-66. A certain negative voltage is applied to the ITO electrode, and due to the electrostatic attraction, the TB molecules and ssDNA-Fc are adsorbed and enriched on the surface of the electrode by electrostatic attraction, which produces two strong and oppositely changing electrochemical signals, and the electrochemical signals depend on the HER2 concentration. It can sensitively detect HER2 biomarkers in only 40 min with the detection range of 0.0001-10 ng/mL and detection limits as low as 10 fg/mL. The electrochemical microswimmer for the detection of trace disease biomarkers involves a one-step process of capture, signal change, and detection.

Electrochemical detection of the p53 gene using exponential amplification reaction (EXPAR) and CRISPR/Cas12a reactions.

An improved electrochemical sensor has been developed for sensitive detection of the p53 gene based on exponential amplification reaction (EXPAR) and CRISPR/Cas12a. Restriction endonuclease BstNI is introduced to specifically identify and cleave the p53 gene, generating primers to trigger the EXPAR cascade amplification. A large number of amplified products are then obtained to enable the lateral cleavage activity of CRISPR/Cas12a. For electrochemical detection, the amplified product activates Cas12a to digest the designed block probe, which allows the signal probe to be captured by the reduced graphene oxide-modified electrode (GCE/RGO), resulting in an enhanced electrochemical signal. Notably, the signal probe is labeled with large amounts of methylene blue (MB). Compared with traditional endpoint decoration, the special signal probe effectively amplifies the electrochemical signals by a factor of about 15. Experimental results show that the electrochemical sensor exhibits wide ranges from 500 aM to 10 pM and 10 pM to 1 nM, as well as a relatively low limit detection of 0.39 fM, which is about an order of magnitude lower than that of fluorescence detection. Moreover, the proposed sensor shows reliable application capability in real human serum, indicating that this work has great prospects for the construction of a CRISPR-based ultra-sensitive detection platform.