Inhibition of the RLR signaling pathway by SARS-CoV-2 ORF7b is mediated by MAVS and abrogated by ORF7b-homologous interfering peptide.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and characterized by dysregulated immune response. Studies have shown that the SARS-CoV-2 accessory protein ORF7b induces host cell apoptosis through the tumor necrosis factor alpha (TNF-α) pathway and blocks the production of interferon beta (IFN-ß). The underlying mechanism remains to be investigated. In this study, we found that ORF7b facilitated viral infection and production, and inhibited the RIG-I-like receptor (RLR) signaling pathway through selectively interacting with mitochondrial antiviral-signaling protein (MAVS). MAVS439-466 region and MAVS Lys461 were essential for the physical association between MAVS and ORF7b, and the inhibition of the RLR signaling pathway by ORF7b. MAVSK461/K63 ubiquitination was essential for the RLR signaling regulated by the MAVS-ORF7b complex. ORF7b interfered with the recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) and the activation of the RLR signaling pathway by MAVS. Furthermore, interfering peptides targeting the ORF7b complex reversed the ORF7b-suppressed MAVS-RLR signaling pathway. The most potent interfering peptide V disrupts the formation of ORF7b tetramers, reverses the levels of the ORF7b-inhibited physical association between MAVS and TRAF6, leading to the suppression of viral growth and infection. Overall, this study provides a mechanism for the suppression of innate immunity by SARS-CoV-2 infection and the mechanism-based approach via interfering peptides to potentially prevent SARS-CoV-2 infection.IMPORTANCEThe pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and continues to be a threat to public health. It is imperative to understand the biology of SARS-CoV-2 infection and find approaches to prevent SARS-CoV-2 infection and ameliorate COVID-19. Multiple SARS-CoV-2 proteins are known to function on the innate immune response, but the underlying mechanism remains unknown. This study shows that ORF7b inhibits the RIG-I-like receptor (RLR) signaling pathway through the physical association between ORF7b and mitochondrial antiviral-signaling protein (MAVS), impairing the K63-linked MAVS polyubiquitination and its recruitment of tumor necrosis factor receptor-related factor 6 (TRAF6) to MAVS. The most potent interfering peptide V targeting the ORF7b-MAVS complex may reverse the suppression of the MAVS-mediated RLR signaling pathway by ORF7b and prevent viral infection and production. This study may provide new insights into the pathogenic mechanism of SARS-CoV-2 and a strategy to develop new drugs to prevent SARS-CoV-2 infection.

Developing and validating the nurse-patient relationship scale (NPRS) in China.

BACKGROUND: Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. PURPOSE: This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. METHODS: A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach's α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. RESULTS: The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach's α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. CONCLUSION: The NPRS is a valid tool measuring nurse-patient relationship in China.

Identification of bZIP Transcription Factors That Regulate the Development of Leaf Epidermal Cells in Arabidopsis thaliana by Single-Cell RNA Sequencing.

Epidermal cells are the main avenue for signal and material exchange between plants and the environment. Leaf epidermal cells primarily include pavement cells, guard cells, and trichome cells. The development and distribution of different epidermal cells are tightly regulated by a complex transcriptional regulatory network mediated by phytohormones, including jasmonic acid, and transcription factors. How the fate of leaf epidermal cells is determined, however, is still largely unknown due to the diversity of cell types and the complexity of their regulation. Here, we characterized the transcriptional profiles of epidermal cells in 3-day-old true leaves of Arabidopsis thaliana using single-cell RNA sequencing. We identified two genes encoding BASIC LEUCINE-ZIPPER (bZIP) transcription factors, namely bZIP25 and bZIP53, which are highly expressed in pavement cells and early-stage meristemoid cells. Densities of pavement cells and trichome cells were found to increase and decrease, respectively, in bzip25 and bzip53 mutants, compared with wild-type plants. This trend was more pronounced in the presence of jasmonic acid, suggesting that these transcription factors regulate the development of trichome cells and pavement cells in response to jasmonic acid.

Inhibition of SARS-CoV-2 replication by a ssDNA aptamer targeting the nucleocapsid protein.

The nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer's stability, a circular bivalent form, cb-N-Apt17, was designed and evaluated. Our findings demonstrated that cb-N-Apt17 exhibited improved stability, enhanced binding affinity, and superior inhibition of N protein LLPS; thus, it has the potential inhibition ability on viral replication. These results provide valuable evidence supporting the potential of cb-N-Apt17 as a promising candidate for the development of antiviral therapies against COVID-19.IMPORTANCEVariants of SARS-CoV-2 pose a significant challenge to currently available COVID-19 vaccines and therapies due to the rapid epitope changes observed in the viral spike protein. However, the nucleocapsid (N) protein of SARS-CoV-2, a highly conserved structural protein, offers promising potential as a target for inhibiting viral replication. The N protein forms complexes with genomic RNA, interacts with other viral structural proteins during virion assembly, and plays a critical role in evading host innate immunity by impairing interferon production during viral infection. In this investigation, we discovered a single-stranded DNA aptamer, designated as N-Apt17, exhibiting remarkable affinity and specificity for the N protein. Notably, N-Apt17 disrupts the liquid-liquid phase separation (LLPS) of the N protein. To enhance the stability and molecular recognition capabilities of N-Apt17, we designed a circular bivalent DNA aptamer termed cb-N-Apt17. In both in vivo and in vitro experiments, cb-N-Apt17 exhibited increased stability, enhanced binding affinity, and superior LLPS disrupting ability. Thus, our study provides essential proof-of-principle evidence supporting the further development of cb-N-Apt17 as a therapeutic candidate for COVID-19.

Laser frequency noise characterization using high-finesse plano-concave optical microresonators.

Characterizing laser frequency noise is essential for applications including optical sensing and coherent optical communications. Accurate measurement of ultra-narrow linewidth lasers over a wide frequency range using existing methods is still challenging. Here we present a method for characterizing the frequency noise of lasers using a high-finesse plano-concave optical microresonator (PCMR) acting as a frequency discriminator. To enable noise measurements at a wide range of laser frequencies, an array of PCMRs was produced with slight variations of thickness resulting in a series of discriminators operating at a series of periodical frequencies. This method enables measuring the frequency noise over a wide linewidth range (15 Hz to <100 MHz) over the 1440-1630 nm wavelength range. To assess the performance of the method, four different lasers were characterized, and the results were compared to the estimations of a commercial frequency noise analyzer.

Aqueous synthesis of perovskite precursors for highly efficient perovskite solar cells.

High-purity precursor materials are vital for high-efficiency perovskite solar cells (PSCs) to reduce defect density caused by impurities in perovskite. In this study, we present aqueous synthesized perovskite microcrystals as precursor materials for PSCs. Our approach enables kilogram-scale mass production and synthesizes formamidinium lead iodide (FAPbI3) microcrystals with up to 99.996% purity, with an average value of 99.994 ± 0.0015%, from inexpensive, low-purity raw materials. The reduction in calcium ions, which made up the largest impurity in the aqueous solution, led to the greatest reduction in carrier trap states, and its deliberate introduction was shown to decrease device performance. With these purified precursors, we achieved a power conversion efficiency (PCE) of 25.6% (25.3% certified) in inverted PSCs and retained 94% of the initial PCE after 1000 hours of continuous simulated solar illumination at 50°C.

Regulation of the migration of colorectal cancer stem cells via the TLR4/MyD88 signaling pathway by the novel surface marker CD14 following LPS stimulation.

Cell surface markers are most widely used in the study of cancer stem cells (CSCs). However, cell surface markers that are safely and stably expressed in CSCs have yet to be identified. Colonic CSCs express leukocyte CD14. CD14 binding to the ligand lipopolysaccharide (LPS) is involved in the inflammatory response via the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway. TLR4 and MyD88 have been reported to promote the proliferation, metastasis and tumorigenicity of colon cancer cells, which is consistent with the characteristics of CSCs. In the present study, the proposed experimental method to detect cell proliferation, metastasis and tumorigenesis was used to confirm that, under LPS stimulation, CD14 promoted the proliferation, migration and tumorigenesis of colonic CSCs via the TLR4/MyD88 signaling pathway. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess the proliferation and migration of the cells. Colony formation and nude mouse xenograft assays were used to assess the capacity of cells to form tumors. Using western blotting and reverse transcription-quantitative PCR, the mRNA and protein levels of CD14, TLR4 and MyD88 were examined. It was confirmed that CD14 promoted the proliferation, metastasis and tumorigenesis of colon CSCs in response to LPS stimulation via the TLR4/MyD88 signaling pathway, and CD14+ colon cancer cells were successfully isolated and sorted. According to the results of proliferation assay, it was determined that CD14 regulated the LPS-induced proliferation of colon CSCs. CD14, TLR4 and MyD88 protein and mRNA expression was upregulated in colon CSCs in response to LPS stimulation. This indicates a potential novel target for colon CSC-related studies.

Emotional labour and turnover intention among nurses in China: Mediating effects of nurse-patient relationship and self-rated health.

AIM: This study tested the mediating role of the nurse-patient relationship and self-rated health in the effect of emotional labour on turnover intention among nurses in China. BACKGROUND: The underlying mechanism behind the effect of emotional labour on turnover intention remains inadequately understood. INTRODUCTION: Nurses with a high level of emotional labour are predisposed to experiencing poor health and tension in their relationships with patients, which may increase turnover intention. METHODS: A cross-sectional survey of 527 nurses in a public tertiary hospital in Qiqihar, located in China's Heilongjiang province, was conducted. Emotional labour and turnover intention were assessed using existing validated scales containing multiple items, while the nurse-patient relationship and self-rated health were assessed using single items, respectively. Baron and Kenny's causal steps and the Karlson/Holm/Breen method were adopted to test the mediating effects of the nurse-patient relationship and self-rated health in the association between emotional labour and turnover intention after adjusting for variations in sociodemographic and job characteristics. RESULTS: Emotional labour was positively associated with turnover intention. Self-rated poor health and a disharmonious nurse-patient relationship partially mediated the positive effect of emotional labour on turnover intention. CONCLUSIONS: Emotional labour significantly affects the turnover intention of nurses working in public tertiary hospitals in China, and this effect is partially mediated by self-rated health and the nurse-patient relationship. IMPLICATIONS FOR NURSING PRACTICE AND NURSING POLICY: Giving more attention to nurses' negative emotions and work attitudes is crucial. Developing comprehensive strategies for enhancing nurses' emotional management ability, promoting their physical and psychological well-being, and improving nurse-patient relationship to reduce nurses' turnover.

A sensitive coumarin fluorescence sensor designed for isoprene detection and imaging research in plants.

The release of isoprene by plants is considered to be an adaptation to the environment. Herein, a highly selective coumarin fluorescent probe (DMIC) was designed for detecting isoprene. When isoprene came into contact with the maleimide of DMIC, an electrophilic addition process took place. The powerful push-pull effect of DMIC was disrupted. Simultaneously, intramolecular charge transfer was initiated. This enabled DMIC to achieve rapid detection of isoprene within 5 min. Furthermore, excellent linearity was observed in the concentration range of 1-560 ppm (R2 = 0.996). A limit of detection is 1.6 ppm. DMIC was applied to in vitro studies of plant release of liberated isoprene. By monitoring the release of isoprene from different tree species throughout the day, the dynamics of isoprene release from plants throughout the day have been successfully revealed. In addition, the release of isoprene varied considerably among different tree species. In particular, the biocompatibility of DMIC allowed for the in vivo detection of isoprene using fluorescence imaging. The results successfully revealed the dynamics of isoprene release in plants under stress. The amount of isoprene that a plant produced increased with the severity of the stress it experienced. This suggested that the level of isoprene content in plants could be used as a preliminary indicator of the physiological health status of plants. This research demonstrates great potential for clarifying signal transduction in biological systems. It provided ideas for further understanding the biology of isoprene.

Caffeine supplementation improves the cognitive abilities and shooting performance of elite e-sports players: a crossover trial.

We explored the effect of 3 mg/kg of caffeine supplementation on the cognitive ability and shooting performance of elite e-sports players. Nine e-sports players who had received professional training in e-sports and had won at least eighth place in national-level e-sports shooting competitions. After performing three to five familiarization tests, we employed a single blind, randomized crossover design to divide participants into caffeine trial (CAF) and placebo trial (PL). The CAF trial took capsules with 3 mg/kg of caffeine, whereas the PL trial took a placebo capsule. After a one-hour rest, the Stroop task, the visual search ability test, and the shooting ability test were conducted. The CAF trial's performance in the Stroop task in terms of congruent condition (P = 0.023) and visual search reaction time with 20 items (P = 0.004) was significantly superior to those of the PL trial. In the shooting test, the CAF trial's kill ratio (P = 0.020) and hit accuracy (P = 0.008) were significantly higher, and the average time to target (P = 0.001) was significantly shorter than those of the PL trial. Caffeine supplementation significantly improves e-sports players' reaction times and shooting performance.

Introducing single cell stereo-sequencing technology to transform the plant transcriptome landscape.

Single cell RNA-sequencing (scRNA-seq) advancements have helped detect transcriptional heterogeneities in biological samples. However, scRNA-seq cannot currently provide high-resolution spatial transcriptome information or identify subcellular organs in biological samples. These limitations have led to the development of spatially enhanced-resolution omics-sequencing (Stereo-seq), which combines spatial information with single cell transcriptomics to address the challenges of scRNA-seq alone. In this review, we discuss the advantages of Stereo-seq technology. We anticipate that the application of such an integrated approach in plant research will advance our understanding of biological process in the plant transcriptomics era. We conclude with an outlook of how such integration will enhance crop improvement.

Patterns of sleep quality and its influence factors: A latent class model among students of medical university in Hubei Province, China.

BACKGROUND: Sleep problem among undergraduate students has become one of the most pressing public health problems. This study aimed to explore the latent class of sleep patterns and the factors affecting sleep in Chinese students of medical university. METHODS: 3423 students participated in the cross-sectional study. The survey consisted of the reduced Morningness-Evening Questionnaire, the Pittsburgh Sleep Quality Index, and Health-Promoting Lifestyle Profile-II. Latent profile analysis and multinominal logistic regression analysis were performed. RESULTS: Three potential sleep categories were identified: "sleep disorder group" (1.87 %), "daytime dysfunction group" (24.42 %), and "good sleep group" (73.71 %). Compared with the "good sleep group," the "sleep disorder group" showed monthly living expenses (RMB) ≥ 3000 yuan (OR) = 13.04), interpersonal relationships as poor (OR = 3.71), health status as poor (OR = 45.09), circadian rhythm as eveningness (OR = 6.17), and poor health-promoting lifestyles (OR = 2.090) as its risk factors (all p < 0.05). Meanwhile, sophomore (OR = 1.75), junior (OR = 1.52), interpersonal relationships as poor (OR = 1.88), health status as poor (OR = 4.62), intermediate-chronotype (OR = 2.19), eveningness chronotype (OR = 5.66), and health-promoting lifestyles as poor (OR = 1.55) were identified as risk factors for the "daytime dysfunction group" (all p < 0.05). LIMITATIONS: Causal conclusions can not be drawn and recall bias in data collection. CONCLUSIONS: Significant population heterogeneity was found in the sleep quality. Implementing targeted interventions focusing on circadian rhythm and lifestyle is crucial to improve the sleep quality of students with different conditions.

Calculation of carbon emissions in wastewater treatment and its neutralization measures: A review.

As the pursuit of "carbon neutrality" gains momentum, the emphasis on low-carbon solutions, emphasizing energy conservation and resource reuse, has introduced fresh challenges to conventional wastewater treatment approaches. Precisely evaluating carbon emissions in urban water supply and drainage systems, wastewater treatment plants, and establishing carbon-neutral operating models has become a pivotal concern in the future of wastewater treatment. Regrettably, limited research has been devoted to carbon accounting and the development of carbon-neutral strategies for wastewater treatment. In this review, to facilitate comprehensive carbon accounting, we initially recognizes direct and indirect carbon emission sources in the wastewater treatment process. We then provide an overview of several major carbon accounting methods and propose a carbon accounting framework. Furthermore, we advocate for a systemic perspective, highlighting that achieving carbon neutrality in wastewater treatment extends beyond the boundaries of wastewater treatment plants. We assess current technical measures both within and outside the plants that contribute to achieving carbon-neutral operations. Encouraging the application of intelligent algorithms for the multifaceted monitoring and control of wastewater treatment processes is paramount. Supporting resource and energy recycling is also essential, as is recognizing the benefits of synergistic wastewater treatment technologies. We advocate a systematic, multi-level planning approach that takes into account a wide range of factors. Our goal is to offer valuable insights and support for the practical implementation of water environment management within the framework of carbon neutrality, and to advance sustainable socio-economic development and contribute to a more environmentally responsible future.

DNA demethylation of promoter region orchestrates SPI-1-induced ADAMTS-5 expression in articular cartilage of osteoarthritis mice.

Osteoarthritis (OA) is one of the most prevalent joint diseases in aged people and characterized by articular cartilage degeneration, synovial inflammation, and abnormal bone remodeling. Recent advances in OA research have clearly shown that OA development is associated with aberrant DNA methylation status of many OA-related genes. As one of most important cartilage degrading proteases in OA, a disintegrin and metalloproteinase with thrombospondin motifs subtype 5 (ADAMTS-5) is activated to mediate cartilage degradation in human OA and experimental murine OA models. The pathological factors and signaling pathways mediating ADAMTS-5 activation during OA development are not well defined and have been a focus of intense research. ADAMTS-5 promoter is featured by CpG islands. So far there have been no reports concerning the DNA methylation status in ADAMTS-5 promoter during OA development. In this study, we sought to investigate DNA methylation status in ADAMTS-5 promoter, the role of DNA methylation in ADAMTS-5 activation in OA, and the underlying mechanisms. The potential for anti-OA intervention therapy which is based on modulating DNA methylation is also explored. Our results showed that DNA methyltransferases 1 (Dnmt1) downregulation-associated ADAMTS-5 promoter demethylation played an important role in ADAMTS-5 activation in OA, which facilitated SPI-1 binding on ADAMTS-5 promoter to activate ADAMTS-5 expression. More importantly, OA pathological phenotype of mice was alleviated in response to Dnmt1-induced DNA methylation of ADAMTS-5 promoter. Our study will benefit not only for deeper insights into the functional role and regulation mechanisms of ADAMTS-5 in OA, but also for the discovery of disease-modifying OA drugs on the basis of ADAMTS-5 via modulating DNA methylation status.

Ratiometric luminescent sensor based on BSA-coated gold/silver nanoclusters for the selective determination and spatiotemporal imaging of gallic acid in plants.

A new fluorescence sensing strategy has been developed. Four bimetallic nanoclusters, gold/silver, gold/copper, gold/molybdenum and gold/cobalt, were prepared using bovine serum albumin (BSA) as a reducing and stabilizing agent. The fluorescence properties of four nanoclusters were explored by solid-state UV and XPS. The gold/silver nanoclusters (BSA-Au/Ag NCs) with the best ratiometric fluorescence properties for gallic acid (GA) in plants were selected to realize the sensitive detection of GA. GA affected the conformation of BSA, thereby disrupting the luminescent environment of the nanoclusters, resulting in a pronounced fluorescence quenching at 566 nm. The ratiometric fluorescence signal (I566/I453) was used for trace detection of GA in plants. It has a wide response range of 1.25-40.0 µM and a low detection limit of 45.27 nM. GA was detected at 19.49 µM in the plant extract, and the spiked recoveries ranged from 96.09 to 104.6%. In addition, due to the non-toxic and biocompatible properties of BSA, BSA-Au/Ag NCs have also been validated for fluorescence imaging of plant tissues. It realized the comparison of GA content in different parts of plants and the difference of GA content in plants after abiotic stress. Therefore, the developed strategy offers potential application for the analytical study of active substances in plants.

The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation.

Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-ß production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-ß signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzyme UBC9 and MAVS. Increased MAVS-UBC9 interaction leads to enhanced SUMOylation of MAVS, inhibiting its ubiquitination, resulting in the inhibition of phosphorylation events involving IKKα, TBK1, and IRF3, thus disrupting IFN-ß signaling. This study highlights the role of the N protein of SARS-CoV-2 in modulating the innate immune response by affecting the MAVS SUMOylation and ubiquitination processes, leading to inhibition of the IFN-ß signaling pathway. These findings shed light on the complex mechanisms utilized by SARS-CoV-2 to manipulate the host's antiviral defenses and provide potential insights for developing targeted therapeutic strategies against severe COVID-19.

68Ga-PSMA-PET/CT in addition to mpMRI in men undergoing biopsy during active surveillance for low- to intermediate-risk prostate cancer: study protocol for a prospective cross-sectional study.

Background: In active surveillance there is significant interest in whether imaging modalities such as multiparametric magnetic resonance imaging (mpMRI) or 68Gallium prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA-PET/CT) can improve the detection of progression to clinically significant prostate cancer (csPCa) and thus reduce the frequency of prostate biopsies and associated morbidity. Recent studies have demonstrated the value of mpMRI in active surveillance; however, mpMRI does miss a proportion of disease progression and thus alone cannot replace biopsy. To date, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown additive value to mpMRI in its ability to detect prostate cancer (PCa) in the primary diagnostic setting. Our objective is to evaluate the diagnostic utility of PSMA-PET to detect progression to csPCa in active surveillance patients. Methods: We will perform a prospective, cross-sectional, partially blinded, multicentre clinical trial evaluating the additive value of PSMA-PET with mpMRI against saturation transperineal template prostate biopsy. Two hundred and twenty-five men will be recruited who have newly diagnosed PCa which is suitable for active surveillance. Following enrolment, patients will undergo a PSMA-PET and mpMRI within 3 months of a repeat 12-month confirmatory biopsy. Patients who remain on active surveillance after confirmatory biopsy will then be planned to have a further mpMRI and PSMA-PET prior to a repeat biopsy in 3-4 years. The primary outcome is to assess the ability of PSMA-PET to detect or exclude significant malignancy on repeat biopsy. Secondary outcomes include (I) assess the comparative diagnostic accuracies of mpMRI and PSMA-PET alone [sensitivity/specificity/negative predictive value (NPV)/positive predictive value (PPV)] to detect progression on biopsy based on predefined histologic criteria for progression; (II) comparison of index lesion identification by template biopsies vs. MRI targeted lesions vs. PSMA targeted lesions; (III) evaluation of concordance of lesions identified on final histopathology and each imaging modality (PSMA-PET and/or mpMRI) in the subset of patients proceeding to RP. Discussion: The results of this trial will define the role of PSMA-PET in active surveillance and potentially reduce the number of biopsies needed to detect progression to csPCa. Trial Registration: The current trial was registered with the ANZCTR on the 3/2/2022 with the trial ID ACTRN12622000188730, it is accessible at https://www.anzctr.org.au/.

Strontium ranelate enriched Ruminococcus albus in the gut microbiome of Sprague-Dawley rats with postmenopausal osteoporosis.

BACKGROUND: Gut microbiome is critical to our human health and is related to postmenopausal osteoporosis (PMO). Strontium ranelate (SrR) is an anti-osteoporosis oral drug that can promote osteoblast formation and inhibit osteoclast formation. However, the effect of SrR on gut microbiome has been rarely studied. Therefore, we investigated the effect of oral SrR on gut microbiome and metabolic profiles. RESULTS: In this study, we used ovariectomized (OVX) Sprague-Dawley rats to construct a PMO model and applied oral SrR for 6 weeks. The relative abundance of intestinal microbiome was investigated by 16S rRNA metagenomic sequencing. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to analyze changes in metabolites of intestinal contents. Results demonstrated that 6-week oral SrR alleviated osteoporosis and significantly changed the composition of the gut microbiome and metabolic profiles of OVX rats. Ruminococcus, Akkermansia and Oscillospira were significantly enriched in the gut of OVX rats after 6-week oral SrR. Especially, the species R. albus showed the greatest importance by a random forest classifier between OVX and OVX_Sr group. The enrichment of R. albus in the gut was positively correlated with bone mineral density and the accumulation of lycopene and glutaric acid, which also significantly elevated after oral SrR. CONCLUSIONS: We discovered that oral SrR can improve bone health while stimulate the accumulation of gut microbe R. albus and metabolites (lycopene and glutaric acid). The results suggested possible connections between oral SrR and the gut-bone axis, which may provide new insight into the treatment/prevention of osteoporosis.

Visible-Blind Narrowband Near-Infrared Photodetector for Precise Real-Time Photoplethysmography Measurement.

The visible-blind narrowband photodetector (NPD) with spectral selective sensitivity to near-infrared (NIR) light is an important technology in the field of cardiovascular health assessment. However, the biological information carried by NIR light constantly changes signals with small amplitude and fast speed, which puts high requirements on the performance of detectors. Herein, visible-blind NIR NPDs were constructed by integrating solution-processable films of perovskite, CuSCN, and organic semiconductors. The NIR response was provided by the organic bulk heterojunction (OBHJ) film with a narrow band gap. A thick perovskite layer was applied to screen the incident visible light and suppress the leakage current in the dark state. CuSCN with a high LUMO level blocked the extraction of the visible-light-induced free electrons. The width of the response window was restricted by adjusting the band gap of the perovskite and the donor/acceptor ratio of the OBHJ film. The optimized NIR NPD exhibits a comprehensive performance including visible-blind response, a tunable response spectrum, a high responsivity/detectivity, and a short response time. In practical photoplethysmography measurements, the detector can record the human heart rate in real time through a noninvasive technique and precisely monitor the whole cardiac cycle, which provides an effective method for early detection of cardiovascular symptoms for timely diagnosis and treatment.