Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity.

Circular RNAs (circRNAs) produced from back-splicing of exons of pre-mRNAs are widely expressed, but current understanding of their functions is limited. These RNAs are stable in general and are thought to have unique structural conformations distinct from their linear RNA cognates. Here, we show that endogenous circRNAs tend to form 16-26 bp imperfect RNA duplexes and act as inhibitors of double-stranded RNA (dsRNA)-activated protein kinase (PKR) related to innate immunity. Upon poly(I:C) stimulation or viral infection, circRNAs are globally degraded by RNase L, a process required for PKR activation in early cellular innate immune responses. Augmented PKR phosphorylation and circRNA reduction are found in peripheral blood mononuclear cells (PBMCs) derived from patients with autoimmune disease systemic lupus erythematosus (SLE). Importantly, overexpression of the dsRNA-containing circRNA in PBMCs or T cells derived from SLE can alleviate the aberrant PKR activation cascade, thus providing a connection between circRNAs and SLE.

Immunosuppression by Mutated Calreticulin Released from Malignant Cells.

Mutations affecting exon 9 of the CALR gene lead to the generation of a C-terminally modified calreticulin (CALR) protein that lacks the KDEL endoplasmic reticulum (ER) retention signal and consequently mislocalizes outside of the ER where it activates the thrombopoietin receptor in a cell-autonomous fashion, thus driving myeloproliferative diseases. Here, we used the retention using selective hooks (RUSH) assay to monitor the trafficking of CALR. We found that exon-9-mutated CALR was released from cells in response to the biotin-mediated detachment from its ER-localized hook, in vitro and in vivo. Cellular CALR release was confirmed in suitable mouse models bearing exon-9-mutated hematopoietic systems or tumors. Extracellular CALR mediated immunomodulatory effects and inhibited the phagocytosis of dying cancer cells by dendritic cells (DC), thereby suppressing antineoplastic immune responses elicited by chemotherapeutic agents or by PD-1 blockade. Altogether, our results demonstrate paracrine immunosuppressive effects for exon-9-mutated CALR.

Breaking the bottleneck of lead-free perovskite solar cells through dimensionality modulation.

The emerging perovskite solar cell (PSC) technology has attracted significant attention due to its superior power conversion efficiency (PCE) among the thin-film photovoltaic technologies. However, the toxicity of lead and poor stability of lead halide materials hinder their commercialization. In this case, after a decade of effort, various categories of lead-free perovskites and perovskite-like materials have been developed, including tin halide perovskites, double perovskites, defect-structured perovskites, and rudorffites. However, the performance of the corresponding devices still falls short of expectations, especially their PCE. The limitations mainly originate from either the unstable lattice structure of these materials, which causes the distortion of their octahedra, or their low dimensionality (e.g., structural and electronic dimensionality)-correlated poor carrier transport and self-trapping effect, accelerating nonradiative recombination. Therefore, understanding the relationship between the structures and performance in these emerging candidates and leveraging these insights to design or modify new lead-free perovskites is of great significance. Herein, we review the variety of dimensionalities in different categories of lead-free perovskites and perovskite-like materials and conclude that dimensionality is an important aspect among the crucial indexes that determine the performance of lead-free PSCs. In addition, we summarize the modulation of both structural and electronic dimensionality, and the corresponding enhanced optoelectronic properties in different categories. Finally, perspectives on the future development of lead-free perovskites and perovskite-like materials for photovoltaic applications are provided. We hope that this review will provide researchers with a concise overview of these emerging materials and help them leverage dimensionality to break the bottleneck in photovoltaic applications.

Transgenerational plasticity in morphological characteristics and biomass of the invasive plant Xanthium strumarium.

Transgenerational plasticity (TGP) allows a plant to acclimate to external variable environments and is a potential mechanism that explains the range expansion and invasion success of some exotic plants. Most studies explored the traits of TGP associated with the success of exotic plant invasions by comparison studies among exotic, native, invasive, and noninvasive species. However, studies on the TGP of invasive plants in different resource environments are scarce, and the biological mechanisms involved are not well understood. This study aimed to determine the role of TGP in the invasiveness of Xanthium strumarium in northeast China. We measured the plant morphology of aboveground parts and the growth of three generations of the invader under different environmental conditions. The results showed that the intergenerational plasticity of X. strumarium was stronger under stress conditions. We found that the X. strumarium parent generation (F0) grown under water and/or nutrient deficiency conditions transferred the environmental information to their offspring (F1 and F2). The F1 generation grown under high-resource conditions has greater height with larger crown sizes, thicker basal diameters, and higher biomass. Both water and nutrients can affect the intergenerational transmission of plant plasticity, nutrients play a more important role compared with water. The high morphological intergenerational plasticity of X. strumarium under a pressure environment can help it quickly adapt to the new environment and accelerate the rapid expansion of the population in the short term. The root:shoot ratio and reproductive and nutrient distribution of the X. strumarium F0 and F1 generations showed high stability when the growth environment of the F0 generation differed from that of the F1 generation. The stable resource allocation strategy can ensure that the obtained resources are evenly distributed to each organ to maintain the long-term existence of the community. Therefore, the study of intergenerational transmission plasticity is of great significance for understanding the invasion process, mechanism, and prevention of invasive plants.

Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines.

Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps. We identified a facile synthetic protocol via a highly enantioselective one-step process for epinephrine and a two-step process for norepinephrine starting from unprotected α-ketoamines 1b and 1a, respectively. This newly developed enantioselective ruthenium-catalyzed asymmetric transfer hydrogenation was extended to the synthesis of many 1,2-amino alcohol-containing drug molecules such as phenylephrine, denopamine, norbudrine, and levisoprenaline, with enantioselectivities of >99% ee and high isolated yields.

dCas9-guided demethylation of the AKT1 promoter improves milk protein synthesis in a bovine mastitis mammary gland epithelial model induced by using Staphylococcus aureus.

Mastitis is among the main factors affecting milk quality and yield. Although DNA methylation is associated with mastitis, its role in mastitis remains unclear. In this study, a bovine mastitis mammary epithelial cells (BMMECs) model was established via Staphylococcus aureus infection of bovine mammary gland epithelial cells (BMECs). Bisulfite sequencing PCR was used to determine the methylation status of the AKT1 promoter in BMMECs. We found that the degree of the AKT1 promoter methylation in BMMECs was significantly greater than that in BMECs, and the expression levels of genes related to milk protein synthesis were significantly decreased. We used the pdCas9-C-Tet1-SgRNA 2.0 system to regulate the methylation status of the AKT1 promoter. High-efficiency sgRNAs were screened and dCas9-guided AKT1 promoter demethylation vectors were constructed. Following transfection with the vectors, the degree of methylation of the AKT1 promoter was significantly reduced in BMMECs, while AKT1 protein levels increased. When the methylation level of the AKT1 promoter decreased, the synthesis of milk proteins and the expression levels of genes related to milk protein synthesis increased significantly. The viability of the BMMECs was enhanced. Taken together, these results indicate that demethylation guided by the pdCas9-C-Tet1-SgRNA 2.0 system on the AKT1 promoter can reactivate the expression of AKT1 and AKT1/mTOR signaling pathway-related proteins by reducing the AKT1 promoter methylation level and promoting the recovery milk protein expression in BMMECs, thereby alleviating the symptoms of mastitis.

Association of smart elderly care and quality of life among older adults: the mediating role of social support.

BACKGROUND: In the current context of ageing, the field of smart elderly care has gradually developed, contributing to the promotion of health among older adults. While the positive impact on health has been established, there is a scarcity of research examining its impact on the quality of life (QoL). This study aims to investigate the mediating role of social support in the relationship between smart elderly care and QoL among older adults. METHODS: A total of 1313 older adults from Zhejiang Province, China, participated in the study. Questionnaires were used to collect data on participants' basic demographic information, smart elderly care, social support, and QoL. The descriptive analyses of the demographic characteristics and correlation analyses of the three variables were calculated. Indirect effects were tested using bootstrapped confidence intervals (CI). RESULTS: The analysis revealed a positive association between smart elderly care and social support (ß = 0.42, p < 0.01), as well as a positive correlation between social support and QoL (ß = 0.65, p < 0.01). Notably, social support emerged as an important independent mediator (effect size = 0.28, 95% bootstrap CI 0.24 to 0.32) in the relationship between smart elderly care and QoL. CONCLUSIONS: The results of this study underscore the importance of promoting the utilization of smart elderly care and improving multi-faceted social support for older adults, as these factors positively contribute to the overall QoL.

PI3K/AKT/mTORC1 signalling pathway regulates MMP9 gene activation via transcription factor NF-κB in mammary epithelial cells of dairy cows.

Matrix metalloproteinase 9 (MMP9) plays a pivotal role in mammary ductal morphogenesis, angiogenesis and glandular tissue architecture remodeling. However, the molecular mechanism of MMP9 expression in mammary epithelial cells of dairy cows remains unclear. This study aimed to explore the underlying mechanism of MMP9 expression. In this study, to determine whether the PI3K/AKT/mTORC1/NF-κB signalling pathway participates in the regulation of MMP9 expression, we treated mammary epithelial cells with specific pharmacological inhibitors of PI3K (LY294002), mTORC1 (Rapamycin) or NF-κB (Celastrol), respectively. Western blotting results indicated that LY294002, Rapamycin and Celastrol markedly decreased MMP9 expression and P65 nuclear translocation. Furthermore, we found that NF-κB (P65) overexpression resulted in elevated expression of MMP9 protein and activation of MMP9 promoter. In addition, we observed that Celastrol markedly decreases P65-overexpression-induced MMP9 promoter activity. Moreover, the results of the promoter assay indicated that the core regulation sequence for MMP9 promoter activation may be located at -420 ∼ -80 bp downstream from the transcription start site. These observations indicated that the PI3K/AKT/mTORC1 signalling pathway is involved in MMP9 expression by regulating MMP9 promoter activity via NF-κB in the mammary epithelial cells of dairy cows.

Predicting epidemic threshold in complex networks by graph neural network.

To achieve precision in predicting an epidemic threshold in complex networks, we have developed a novel threshold graph neural network (TGNN) that takes into account both the network topology and the spreading dynamical process, which together contribute to the epidemic threshold. The proposed TGNN could effectively and accurately predict the epidemic threshold in homogeneous networks, characterized by a small variance in the degree distribution, such as Erdos-Rényi random networks. Usability has also been validated when the range of the effective spreading rate is altered. Furthermore, extensive experiments in ER networks and scale-free networks validate the adaptability of the TGNN to different network topologies without the necessity for retaining. The adaptability of the TGNN is further validated in real-world networks.

DFT investigation of coupling constant anomalies in substituted ß-lactams.

ß-lactams are a chemically diverse group of molecules with a wide range of biological activities. Having recently observed curious trends in 2JHH coupling values in studies on this structural class, we sought to obtain a more comprehensive understanding of these diagnostic NMR parameters, specifically interrogating 1JCH, 2JCH, and 2JHH, to differentiate 3- and 4-monosubstituted ß-lactams. Further investigation using computational chemistry methods was employed to explore the geometric and electronic origins for the observed and calculated differences between the two substitution patterns.

Clock genes regulate skeletal muscle energy metabolism through NAMPT/NAD+/SIRT1 following heavy-load exercise.

The biological clock is an invisible "clock" in the organism, which can regulate behavior, physiology, and biochemical reactions. However, the relationship between clock genes and energy metabolism in postexercise skeletal muscle is not well known. The purpose of this study was to determine the mechanisms through which peripheral clock genes regulate energy metabolism in skeletal muscle. We analyzed the rhythm of mRNA expression of the clock genes Bmal1 and Clock in skeletal muscle following heavy-load exercise and measured related indicators of mitochondrial structure and function. We obtained the following experimental results. First, heavy-load exercise induced loss of circadian rhythm of Bmal1 between ZT0 and ZT24, and the circadian rhythm of Clock was not restored between ZT0 and ZT72. Second, analysis of mitochondrial morphology in group E showed abnormal swelling and ridge structure damage at ZT0, which recovered somewhat at ZT24 and ZT48, and the damage had essentially disappeared by ZT72. Third, the expression of NAMPT/NAD+/SIRT1 signaling axis proteins in group E was abnormal at ZT0, the content of NAMPT and the activity of SIRT1 significantly increased, and the content of NAD+ significantly decreased. Fourth, the expression of BMAL1 and PGC-1α in group E significantly increased, whereas the ATP and ADP content, as well as the activities of COXII and COXIV, were significantly changed. Finally, the colocalization of BMAL1 and SIRT1 in group E was significantly upregulated at ZT0. These results suggest that the skeletal muscle clock gene Bmal1 may regulate the energy metabolism level of skeletal muscle after exercise through the NAMPT/NAD+/SIRT1 signaling pathway.

Temperature Thresholds of Pyrogenic Dissolved Organic Matter in Heating Experiments Simulating Forest Fires.

Heating temperature (HT) during forest fires is a critical factor in regulating the quantity and quality of pyrogenic dissolved organic matter (DOM). However, the temperature thresholds at which maximum amounts of DOM are produced (TTmax) and at which the DOC gain turns into net DOC loss (TT0) remain unidentified on a component-specific basis. Here, based on solid-state 13C nuclear magnetic resonance, absorbance and fluorescence spectroscopies, and Fourier transform ion cyclotron resonance mass spectrometry, we analyzed variations in DOM composition in detritus and soil with HT (150-500 °C) and identified temperature thresholds for components on structural, fluorophoric, and molecular formula levels. TTmax was similar for detritus and soil and ranged between 225 and 250 °C for bulk dissolved organic carbon (DOC) and most DOM components. TT0 was consistently lower in detritus than in soil. Moreover, temperature thresholds differed across the DOM components. As the HT increased, net loss was observed initially in molecular formulas tentatively associated with carbohydrates and aliphatics, then proteins, peptides, and polyphenolics, and ultimately condensed aromatics. Notably, at temperatures lower than TT0, particularly at TTmax, burning increased the DOC quantity and thus might increase labile substrates to fuel soil microbial community. These composition-specific variations of DOM with temperature imply nonlinear and multiple temperature-dependent wildfire impacts on soil organic matter properties.

Endoscopic Stricturotomy in the Treatment of Refractory Esophageal Anastomotic Strictures.

Refractory esophageal anastomotic strictures are a frequent challenge for endoscopists. The current therapeutic strategies have a significant restenosis rate, and patients usually require repeated sessions and suffer from dysphagia. Therefore, we propose a modified method named endoscopic stricturotomy (ES) to treat refractory esophageal anastomotic strictures. The patients diagnosed with refractory esophageal anastomotic strictures were enrolled in the cohort study. The method of ES is to incise longitudinally only a single strip of mucosa at the most prominent part of fibrotic scar and completely cut fibrotic tissues under the mucosa. The primary endpoint was the times of endoscopic therapies. The secondary endpoints include the effective rate, success rate, recurrence rate, endoscopic treatment intervals, complications, length of hospital stay, and surgical cost. The patients were followed up for at least 6 months after ES. The median anastomotic diameter of 12 patients was 2 mm (range 1 to 4 mm). Dysphagia were dramatically relieved in all patients (dysphagia grade from 3 to 1), the effective rate was 100%. During the follow-up, the 12 patients received a total number of 38 sessions, and the median number of ES sessions was 2.5 (1-9), and the success rate were 83%. Nine of the patients (75%) developed restenosis during follow-up, with a median interval of 38 days (15-315 days). No complications occurred during treatment and following up. The median hospital stay was 2 days (2-2.9 days), and the hospitalization costs was 3887.4 RMB (3632.8 RMB-4116.9 RMB). ES seems to be an effective treatment modality for refractory esophageal anastomotic strictures. Large prospective clinical trials are needed to confirm its utility and its place in the management of refractory esophageal anastomotic strictures (ChiCTR2000032997).

Preoperative Nutritional Status of Infants with Non-Restricted Ventricular Septal Defect and Its Influence on Postoperative Recovery.

PURPOSE: This study described the preoperative nutritional status of infants with nonrestricted ventricular septal defects (VSDs) and evaluated its effect on postoperative recovery. METHODS: We retrospectively collected data from infants with nonrestricted VSD who received surgical treatment in our hospital from January 2020 to December 2021 and analyzed their preoperative nutritional status and postoperative recovery. RESULTS: Fifty (53.8%) patients were underweight (weight for age Z score (WAZ) ≤-1), and 31 (33.3%) patients were malnourished (WAZ ≤-2). The mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery of patients with WAZ ≤-2 were significantly longer than those of patients with WAZ >-2 (p < 0.05). The results of linear correlation analysis showed that age, WAZ and prealbumin were negatively correlated with mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery, respectively. Multiple linear regression analysis showed that mechanical ventilation time = 7.080 - 0.668 WAZ - 0.013 prealbumin - 0.618 age (R2: 0.729, F: 79.773, p: 0.001); duration of intensive care unit admission = 11.775 - 1.385 WAZ - 0.018 prealbumin - 0.102 age (R2: 0.714, F: 74.072, p: 0.001); and hospital stay time = 17.663 - 1.673 WAZ - 0.017 prealbumin - 1.07 age (R2: 0.711, F: 72.842, p: 0.001). CONCLUSION: The incidence of malnutrition in infants with nonrestricted VSD was very high, and malnutrition had a significant adverse effect on postoperative recovery. Malnutrition significantly prolonged mechanical ventilation time, duration of intensive care unit stay and hospital stay after surgery.

First pilot trial of colorectal ESD guided by a new magnetic anchor for ease of placement.

BACKGROUND: In recent years, studies have demonstrated that magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD) is feasible and safe and may facilitate the treatment of all difficult lesions. However, the major problem with MAG-ESD is the inability to deliver the magnetic anchor to the gastrointestinal tract without withdrawal or reinsertion of the endoscope. Therefore, our team developed a magnetic anchor that could be easily inserted through the biopsy channel, facilitating ESD traction and evaluated its effectiveness and safety. METHODS: The study was conducted between October 2020 and June 2021 at The Second Affiliated Hospital of Harbin Medical University, China. One hundred and twelve patients with colorectal tumors treated with ESD were divided into two groups for historical control comparison. A channel-placed magnetic anchor (CPMAG) group and a control group consisting of patients who had conventional ESD without adjuvant traction. The rate of en bloc resection and resection with tumor-free lateral/basal margins (R0 resection), dissection speeds, procedure time, intraoperative bleeding and perforation complications, and postoperative follow-up were compared between the two groups, so as to evaluate the clinical effect and safety of the new magnetic anchor. RESULTS: The en bloc resection and R0 resection rate with CPMAG-ESD were slightly higher than with conventional ESD but this was not statistically significant. The median dissection speeds with CPMAG-ESD were higher than with conventional ESD, but the difference was not statistically significant. Intraoperative bleeding and postoperative complications with the CPMAG-ESD were less than with conventional ESD, but this was not statistically significant. The median operating time was shorter with CPMAG- ESD than with conventional ESD (24.5 min [range 15.8-66.5 min] vs 39 min [range 29-58 min], p = 0.024), and this difference was statistically significant. CONCLUSIONS: The new magnetic anchor-guided ESD technique appears to be a feasible and safe method for treating early colorectal tumors with en bloc resection, with improvement of the submucosal visual field, and less adverse events.

Nitrogen deposition further increases Ambrosia trifida root exudate invasiveness under global warming.

Invasive plants can change the soil ecological environment in the invasion area to adapt to their growth and reproduction through root exudates. Root exudates are the most direct manifestation of plant responses to external environmental changes, but there is a lack of studies on root exudates of invasive plants in the context of inevitable global warming and nitrogen deposition. In this research, we used widely targeted metabolomics to investigate Ambrosia trifida root exudates during seedling and maturity under warming and nitrogen deposition to reveal the possible mechanisms of A. trifida adaptation to climate change. The results showed that the organic acids increased under warming condition but decreased after nitrogen addition in the seedling stage. Phenolic acids increased greatly after nitrogen addition in the mature stage. Most phenolic acids were annotated in the phenylpropane metabolic pathway and tyrosine metabolism. Therefore, nitrogen deposition may increase the adaptability of A. trifida through root exudates, making it more invasive under global warming. The results provide new ideas for preventing and controlling the invasion of A. trifida under climate change.

Structural characterization of Platanthera ussuriensis chloroplast genome and comparative analyses with other species of Orchidaceae.

BACKGROUND: The genus Tulotis has been classified into the genus Platanthera in the present taxonomic studies since the morphological characteristics of this genus is very similar to that of Platanthera. Platanthera ussuriensis, formerly named as Tulotis ussuriensis, is a small terrestrial orchid species and has been listed as wild plant under State protection (category II) in China. An improved understanding of the genomic information will enable future applications of conservation strategy as well as phylogenetic studies for this rare orchid species. The objective of this research was to characterize and compare the chloroplast genome of P. ussuriensis with other closely related species of Orchidaceae. RESULTS: The chloroplast genome sequence of P. ussuriensis is 155,016 bp in length, which included a pair of inverted repeats (IRs) of 26,548 bp that separated a large single copy (LSC) region of 83,984 bp and a small single copy (SSC) region of 17,936 bp. The annotation contained a total of 132 genes, including 86 protein-coding genes, 38 tRNA genes and 8 rRNA genes. The simple sequence repeat (SSR) analysis showed that there were 104 SSRs in the chloroplast genome of P. ussuriensis. RNA editing sites recognition indicated 72 RNA editing events occurred, and all codon changes were C to T conversions. Comparative genomics showed that the chloroplast sequence of Platanthera related species were relatively conserved, while there were still some high variation regions that could be used as molecular markers. Moreover, Platanthera related species showed similar IR/SSC and IR/LSC borders. The phylogenetic analysis suggested that P. ussuriensis had a closer evolutionary relationship with P. japonica followed by the remaining Platanthera species. CONCLUSION: Orchidaceae is a key group of biodiversity protection and also a hot spot group in the plant taxonomy and evolution studies due to their characteristics of high specialization and rapid evolution. This research determined the complete chloroplast genome of P. ussuriensis for the first time, and compared the sequence with other closely related orchid species. These results provide a foundation for future genomic and molecular evolution of the Orchidaceae species, and provide insights into the development of conservation strategy for Platanthera species.

Spontaneous Formation of Lead-Free Cs3 Cu2 I5 Quantum Dots in Metal-Organic-Frameworks with Deep-Blue Emission.

All-inorganic lead-free Cs3 Cu2 I5  perovskite-derivant quantum dots (QDs) have attracted tremendous attention due to their nontoxicity and unique optoelectronic properties. However, the traditional hot-injection method requires high temperatures and multiple ligands to confine the growth of QDs. Herein, a strategy is reported to spontaneously synthesize ultrasmall Cs3 Cu2 I5  QDs within metal-organic-frameworks (MOFs) MOF-74 at room temperature (RT) with an average diameter of 4.33 nm. The obtained Cs3 Cu2 I5  QDs exhibit an evident deep-blue emission with Commission Internationale de L'Eclairage coordinates of (0.17, 0.07), owing to the strong quantum confinement effect. Due to the protection of MOF-74, the Cs3 Cu2 I5  QDs demonstrate superior stability, and the photoluminescence quantum yield retains 89% of the initial value after the storage of 1440 h under the environment with relative humidity exceeding 70%. Besides, triplet-triplet annihilation upconversion emission is observed within the composite of Cs3 Cu2 I5 @MOF-74, which brings out apparent temperature-dependent photoluminescence. This study reveals a facile method for fabricating ultrasmall lead-free perovskite-derivant QDs at RT without multiple ligands. Besides, the temperature-dependent photoluminescence of Cs3 Cu2 I5 @MOF-74 may open up a new way to develop the applications of temperature sensors or other related optoelectronic devices.

Development and Validation of Models to Predict Pathological Outcomes of Radical Prostatectomy in Regional and National Cohorts.

PURPOSE: Prediction models are recommended by national guidelines to support clinical decision making in prostate cancer. Existing models to predict pathological outcomes of radical prostatectomy (RP)-the Memorial Sloan Kettering (MSK) models, Partin tables, and the Briganti nomogram-have been developed using data from tertiary care centers and may not generalize well to other settings. MATERIALS AND METHODS: Data from a regional cohort (Michigan Urological Surgery Improvement Collaborative [MUSIC]) were used to develop models to predict extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node invasion (LNI), and nonorgan-confined disease (NOCD) in patients undergoing RP. The MUSIC models were compared against the MSK models, Partin tables, and Briganti nomogram (for LNI) using data from a national cohort (Surveillance, Epidemiology, and End Results [SEER] registry). RESULTS: We identified 7,491 eligible patients in the SEER registry. The MUSIC model had good discrimination (SEER AUC EPE: 0.77; SVI: 0.80; LNI: 0.83; NOCD: 0.77) and was well calibrated. While the MSK models had similar discrimination to the MUSIC models (SEER AUC EPE: 0.76; SVI: 0.80; LNI: 0.84; NOCD: 0.76), they overestimated the risk of EPE, LNI, and NOCD. The Partin tables had inferior discrimination (SEER AUC EPE: 0.67; SVI: 0.76; LNI: 0.69; NOCD: 0.72) as compared to other models. The Briganti LNI nomogram had an AUC of 0.81 in SEER but overestimated the risk. CONCLUSIONS: New models developed using the MUSIC registry outperformed existing models and should be considered as potential replacements for the prediction of pathological outcomes in prostate cancer.

A Practical Method for the Large-Scale Preparation of the P-Chiral Dihydrobenzoazaphosphole Core by Chemical Resolution.

pivZPhos, as an effective ligand in the Cu-catalyzed asymmetric hydrogenation of ketones and aminoboration of alkenes, is prepared efficiently from the corresponding triflate of P-chiral dihydrobenzoazaphosphole 1. However, the previous approach to 1 by chiral separation is time-consuming and costly, preventing its production and further application on a large scale. In this report, a practical method for the large-scale preparation of 1 was developed via chiral chemical resolution with (1S,2S)-diaminocyclohexane as an effective resolution reagent.