Bifunctional hydroformylation on heterogeneous Rh-WOx pair site catalysts.

Metal-catalysed reactions are often hypothesized to proceed on bifunctional active sites, whereby colocalized reactive species facilitate distinct elementary steps in a catalytic cycle1-8. Bifunctional active sites have been established on homogeneous binuclear organometallic catalysts9-11. Empirical evidence exists for bifunctional active sites on supported metal catalysts, for example, at metal-oxide support interfaces2,6,7,12. However, elucidating bifunctional reaction mechanisms on supported metal catalysts is challenging due to the distribution of potential active-site structures, their dynamic reconstruction and required non-mean-field kinetic descriptions7,12,13. We overcome these limitations by synthesizing supported, atomically dispersed rhodium-tungsten oxide (Rh-WOx) pair site catalysts. The relative simplicity of the pair site structure and sufficient description by mean-field modelling enable correlation of the experimental kinetics with first principles-based microkinetic simulations. The Rh-WOx pair sites catalyse ethylene hydroformylation through a bifunctional mechanism involving Rh-assisted WOx reduction, transfer of ethylene from WOx to Rh and H2 dissociation at the Rh-WOx interface. The pair sites exhibited >95% selectivity at a product formation rate of 0.1 gpropanal cm-3 h-1 in gas-phase ethylene hydroformylation. Our results demonstrate that oxide-supported pair sites can enable bifunctional reaction mechanisms with high activity and selectivity for reactions that are performed in industry using homogeneous catalysts.

STEEL enables high-resolution delineation of spatiotemporal transcriptomic data.

Advances in spatial transcriptomics enlarge the use of single cell technologies to unveil the expression landscape of the tissues with valuable spatial context. Here, we propose an unsupervised and manifold learning-based algorithm, Spatial Transcriptome based cEll typE cLustering (STEEL), which identifies domains from spatial transcriptome by clustering beads exhibiting both highly similar gene expression profiles and close spatial distance in the manner of graphs. Comprehensive evaluation of STEEL on spatial transcriptomic datasets from 10X Visium platform demonstrates that it not only achieves a high resolution to characterize fine structures of mouse brain but also enables the integration of multiple tissue slides individually analyzed into a larger one. STEEL outperforms previous methods to effectively distinguish different cell types/domains of various tissues on Slide-seq datasets, featuring in higher bead density but lower transcript detection efficiency. Application of STEEL on spatial transcriptomes of early-stage mouse embryos (E9.5-E12.5) successfully delineates a progressive development landscape of tissues from ectoderm, mesoderm and endoderm layers, and further profiles dynamic changes on cell differentiation in heart and other organs. With the advancement of spatial transcriptome technologies, our method will have great applicability on domain identification and gene expression atlas reconstruction.

Histone demethylase IBM1-mediated meiocyte gene expression ensures meiotic chromosome synapsis and recombination.

Histone methylation and demethylation play important roles in plant growth and development, but the involvement of histone demethylation during meiosis is poorly understood. Here we show that disruption of Arabidopsis thaliana INCREASE IN BONSAI METHYLATION 1 (IBM1) causes incomplete synapsis, chromosome entanglement and reduction of recombination during meiosis, leading to sterility. Interestingly, these ibm1 meiotic defects are rescued by mutations in either SUVH4/KYP or CMT3. Using transcriptomic analyses we show that mutation of IBM1 down-regulates thousands of genes expressed in meiocytes, and that expression of about 38% of these genes are restored to wild type levels in ibm1 cmt3 double mutants. Changes in the expression of 437 of these, including the ARABIDOPSIS MEI2-LIKE AML3-5 genes, are correlated with a significant reduction of gene body CHG methylation. Consistently, the aml3 aml4 aml5 triple have defects in synapsis and chromosome entanglement similar to ibm1. Genetic analysis shows that aml3 aml4 aml5 ibm1 quadruple mutants resembles the ibm1 single mutant. Strikingly, over expression of AML5 in ibm1 can partially rescue the ibm1 meiotic defects. Taken together, our results demonstrate that histone demethylase IBM1 is required for meiosis likely via coordinated regulation of meiocyte gene expression during meiosis.

Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Can MRI Help Inform Which Men With a History of Multifocal High-Grade Prostatic Intraepithelial Neoplasia or Atypical Small Acinar Proliferation Remain at an Elevated Risk for Clinically Significant Prostate Cancer?

PURPOSE: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy. MATERIALS AND METHODS: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy. Men with an MRI prior to the index biopsy were excluded. We compared the proportion of men with ≥ GG2 CaP (Grade Group 2 prostate cancer) on repeat biopsy among the following groups with the χ2 test: no MRI, PIRADS (Prostate Imaging-Reporting and Data System) ≥ 4, and PIRADS ≤ 3. Multivariable models were used to estimate the adjusted association between MRI findings and ≥ GG2 CaP on repeat biopsy. RESULTS: Among the 207 men with a previous diagnosis of ASAP/multifocal HGPIN that underwent a repeat biopsy, men with a PIRADS ≥ 4 lesion had a higher proportion of ≥ GG2 CaP (56%) compared with men without an MRI (12%, P < .001). A lower proportion of men with PIRADS ≤ 3 lesions had ≥ GG2 CaP (3.0%) compared with men without an MRI (12%, P = .13). In the adjusted model, men with a PIRADS 4 to 5 lesion had higher odds (OR: 11.4, P < .001) of ≥ GG2 CaP on repeat biopsy. CONCLUSIONS: MRI is a valuable diagnostic tool to triage which men with a history of ASAP or multifocal HGPIN on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP.

Conversion to Radical Nephrectomy From Robotic Partial Nephrectomy Is Most Commonly Due to Anatomic and Oncologic Complexity.

PURPOSE: Partial nephrectomy is standard-of-care treatment for small renal masses. As utilization of partial nephrectomy increases and includes larger and complex tumors, the risk of conversion to radical nephrectomy likely increases. We evaluated incidence and reason for conversion to radical nephrectomy in patients scheduled for partial nephrectomy by surgeons participating in MUSIC (the Michigan Urologic Surgery Improvement Collaborative). MATERIALS AND METHODS: All patients in whom robotic partial nephrectomy was planned were stratified by completed procedure (robotic partial nephrectomy vs radical nephrectomy). Preoperative and intraoperative records were reviewed for preoperative assessment of difficulty and reason for conversion. Patient, tumor, pathologic, and practice variables were compared between cohorts. RESULTS: Of 650 patients scheduled for robotic partial nephrectomy, conversion to radical nephrectomy occurred in 27 (4.2%) patients. No conversions to open were reported. Preoperative documentation indicated a plan for possible conversion in 18 (67%) patients including partial with possible radical (n = 8), partial vs radical (n = 6), or likely radical nephrectomy (n = 4). Intraoperative documentation indicated that only 5 (19%) conversions were secondary to bleeding, with the remaining conversions due to tumor complexity and/or oncologic concerns. Patients undergoing conversion had larger (4.7 vs 2.8 cm, P < .001) and higher-complexity tumors (64% vs 6%, P < .001) with R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score ≥ 10. The converted cases had a higher rate of ≥ pT3 (27% vs 8.4%, P = .008). CONCLUSIONS: There was a low rate of conversion from robotic partial to radical nephrectomy in the MUSIC-KIDNEY (Kidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative, and an even lower risk of conversion due to uncontrolled bleeding. Targeted review of each conversion identified appropriate decision-making based on oncologic risk in most cases.

Spatiotemporal transcriptome atlas reveals gene regulatory patterns during the organogenesis of the rapid growing bamboo shoots.

Bamboo with its remarkable growth rate and economic significance, offers an ideal system to investigate the molecular basis of organogenesis in rapidly growing plants, particular in monocots, where gene regulatory networks governing the maintenance and differentiation of shoot apical and intercalary meristems remain a subject of controversy. We employed both spatial and single-nucleus transcriptome sequencing on 10× platform to precisely dissect the gene functions in various tissues and early developmental stages of bamboo shoots. Our comprehensive analysis reveals distinct cell trajectories during shoot development, uncovering critical genes and pathways involved in procambium differentiation, intercalary meristem formation, and vascular tissue development. Spatial and temporal expression patterns of key regulatory genes, particularly those related to hormone signaling and lipid metabolism, strongly support the hypothesis that intercalary meristem origin from surrounded parenchyma cells. Specific gene expressions in intercalary meristem exhibit regular and dispersed distribution pattern, offering clues for understanding the intricate molecular mechanisms that drive the rapid growth of bamboo shoots. The single-nucleus and spatial transcriptome analysis reveal a comprehensive landscape of gene activity, enhancing the understanding of the molecular architecture of organogenesis and providing valuable resources for future genomic and genetic studies relying on identities of specific cell types.

Human activity and climate change accelerate the extinction risk to non-human primates in China.

Human activity and climate change affect biodiversity and cause species range shifts, contractions, and expansions. Globally, human activities and climate change have emerged as persistent threats to biodiversity, leading to approximately 68% of the ~522 primate species being threatened with extinction. Here, we used habitat suitability models and integrated data on human population density, gross domestic product (GDP), road construction, the normalized difference vegetation index (NDVI), the location of protected areas (PAs), and climate change to predict potential changes in the distributional range and richness of 26 China's primate species. Our results indicate that both PAs and NDVI have a positive impact on primate distributions. With increasing anthropogenic pressure, species' ranges were restricted to areas of high vegetation cover and in PAs surrounded by buffer zones of 2.7-4.5 km and a core area of PAs at least 0.1-0.5 km from the closest edge of the PA. Areas with a GDP below the Chinese national average of 100,000 yuan were found to be ecologically vulnerable, and this had a negative impact on primate distributions. Changes in temperature and precipitation were also significant contributors to a reduction in the range of primate species. Under the expected influence of climate change over the next 30-50 years, we found that highly suitable habitat for primates will continue to decrease and species will be restricted to smaller and more peripheral parts of their current range. Areas of high primate diversity are expected to lose from 3 to 7 species. We recommend that immediate action be taken, including expanding China's National Park Program, the Ecological Conservation Redline Program, and the Natural Forest Protection Program, along with a stronger national policy promoting alternative/sustainable livelihoods for people in the local communities adjacent to primate ranges, to offset the detrimental effects of anthropogenic activities and climate change on primate survivorship.

Antiferromagnetism and Phase Stability of CrMnFeCoNi High-Entropy Alloy.

It has long been suspected that magnetism could play a vital role in the phase stability of multicomponent high-entropy alloys. However, the nature of the magnetic order, if any, has remained elusive. Here, by using elastic and inelastic neutron scattering, we demonstrate evidence of antiferromagnetic order below ∼80 K and strong spin fluctuations persisting to room temperature in a single-phase face-centered cubic (fcc) CrMnFeCoNi high-entropy alloy. Despite the chemical complexity, the magnetic structure in CrMnFeCoNi can be described as γ-Mn-like, with the magnetic moments confined in alternating (001) planes and pointing toward the ⟨111⟩ direction. Combined with first-principles calculation results, it is shown that the antiferromagnetic order and spin fluctuations help stabilized the fcc phase in CrMnFeCoNi high-entropy alloy.

A paper-based ratiometric fluorescence sensor based on carbon dots modified with Eu3+ for the selective detection of tetracycline in seafood aquaculture water.

Paper-based ratiometric fluorescence sensors are normally prepared using two or more types of fluorescent materials on a paper chip for simple, low-cost and fast detection. However, the choice of multi-step and one-step modifications on the paper chip affects the analytical performance. Herein, a novel paper-based dual-emission ratiometric fluorescence sensor was designed for the selective detection of tetracycline (TC). Carbon dots (CDs) modified with Eu3+ were combined with a sealed paper-based microfluidic chip by two methods: one-step grafting of CDs-Eu3+ on paper and step-by-step grafting of CDs and Eu3+ on paper. The analytical performance was studied and optimized respectively. The red fluorescence of Eu3+ at 450 nm is enhanced and the blue fluorescence of CDs at 617 nm is quenched by energy transfer in the presence of TC. Under optimal conditions, TC is selectively determined in the linear range from 0.1 µM to 100 µM with a detection limit of 0.03 µM by the step-by-step grafting method. In addition, the sealed paper chip could effectively prevent pollution and volatilization from the reagent. This technique has been used to analyze TC in seafood aquaculture water with satisfactory results.

KF-catalyzed direct thiomethylation of carboxylic acids with DMSO to access methyl thioesters.

With dimethyl sulfoxide (DMSO) as the methylthio source, a KF-catalyzed strategy was employed for the direct thiomethylation of carboxylic acids with DMSO for the preparation of methyl thioesters. In this process, a wide range of methyl thioesters were obtained in moderate to excellent yields. This novel strategy features the first use of DMSO as a methylthiolating agent for the construction of methyl thioesters, transition metal-free conditions, inexpensive reagents, easy workup, broad substrate scope and sustainability. Additionally, this procedure can be readily scaled up to a gram scale.

Activating Biocake Communities Retards Jumps of Transmembrane Pressure in Membrane Bioreactors.

Sudden jump of transmembrane pressure (TMP) in membrane bioreactors (MBRs), associated with abrupt aggravation of membrane fouling, limits practical applications of MBRs and calls for effective mitigation strategies. While the TMP jump is generally related to the bacterial activity of biocakes, the mechanisms underlying the TMP jump remain unclear. Herein, we conducted various backwash protocols with different nutrient (e.g., nitrate and sodium acetate) loadings on fouled membranes in MBRs to reveal the critical role of bacterial activity of biocakes for the TMP jump. The filtration tests showed a lower TMP jump rate for the membrane backwashed with a nutrient solution (a mixture of 180 mg/L NaNO3 and 200 mg/L NaAc, averaged at 1.40 kPa/d) than that backwashed with tap water (averaged at 3.56 kPa/d), implying that TMP jump could be efficiently mitigated by providing sufficient nutrients to biocake bacteria. The characterization of biocakes showed that high-nutrient solution backwash considerably increased bacterial viability and activity, while considerably reducing biomolecule accumulation on membranes. The keystone taxa (e.g., g_Aeromonas and o_Chitinophagaceae) in the network of nutrient-enriched biocake communities were involved in nitrate reduction and biomolecule degradation. Ecological null model analyses revealed that the deterministic manner mainly shaped biocake communities with high-nutrient availability. Overall, this study highlights the significance of the bacterial activity of biocakes for TMP development and provides potential alternatives for controlling membrane fouling.

Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer.

An efficient protocol for direct coupling of maleimides and indolines at the C7-position was achieved under Rh(III) catalysis. Thirty four novel indoline-maleimide conjugates were prepared in good to excellent yields using this method. All compounds were evaluated for their anti-proliferative effect against colorectal cell lines. Among them, compound 3ab showed the most potent anti-proliferative activity against the CRC cells, and displayed low toxicity in the normal cell. Further investigation indicated that 3ab could effectively suppress the proliferation and migration of CRC cells, along with inducing cell cycle arrest and apoptosis. Mechanistic studies revealed that compound 3ab inhibited the proliferation of CRC cells via suppressing the AKT/GSK-3ß pathway. In vivo evaluation demonstrated remarkable antitumor effect of 3ab (10 mg/kg) in the HCT116 xenograft model with no obvious toxicity, which is superior to that of 5-Fluorouracil (20 mg/kg). Therefore, conjugate 3ab could be considered as a potential CRC therapy agent for further development.

Stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and verteporfin for glioblastoma therapy.

BACKGROUND: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. RESULTS: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. CONCLUSION: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.

A spatiotemporal atlas of organogenesis in the development of orchid flowers.

Development of floral organs exhibits complex molecular mechanisms involving the co-regulation of many genes specialized and precisely functioning in various tissues and developing stages. Advance in spatial transcriptome technologies allows for quantitative measurement of spatially localized gene abundance making it possible to bridge complex scenario of flower organogenesis with genome-wide molecular phenotypes. Here, we apply the 10× Visium technology in the study of the formation of floral organs through development in an orchid plant, Phalaenopsis Big Chili. Cell-types of early floral development including inflorescence meristems, primordia of floral organs and identity determined tissues, are recognized based on spatial expression distribution of thousands of genes in high resolution. In addition, meristematic cells on the basal position of floral organs are found to continuously function in multiple developmental stages after organ initiation. Particularly, the development of anther, which primordium starts from a single spot to multiple differentiated cell-types in later stages including pollinium and other vegetative tissues, is revealed by well-known MADS-box genes and many other downstream regulators. The spatial transcriptome analyses provide comprehensive information of gene activity for understanding the molecular architecture of flower organogenesis and for future genomic and genetic studies of specific cell-types.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

Hypoxia-responsive AIEgens for precise disease theranostics.

Specific biomarker-activatable probes have revolutionized theranostics, being beneficial for precision medicine. Hypoxia is a critical pathological characteristic prevalent in numerous major diseases such as cancers, cardiovascular disorders, inflammatory diseases, and acute ischemia. Aggregation-induced emission luminogens (AIEgens) have emerged as a promising tool to tackle the biomedical issues. Of particular significance are the hypoxia-responsive AIEgens, representing a kind of crucial probe capable of delicately sensing and responding to the hypoxic microenvironment, thereby enhancing the precision of disease diagnosis and treatment. In this review, we summarize the recent advances of hypoxia-responsive AIEgens for varied biomedical applications. The hypoxia-responsive structures based on AIEgens, such as azobenzene, nitrobenzene, and N-oxide are presented, which are in response to the reduction property to bring about significant alternations in response spectra and/or fluorescence intensity. The bioapplications including imaging and therapy of tumor and ischemia diseases are discussed. Moreover, the review sheds light on the future challenges and prospects in this field. This review aims to provide comprehensive guidance and understanding into the development of activatable bioprobes, especially the hypoxia-responsive AIEgens for improving the diagnosis and therapy outcome of related diseases.

[Chemical constituents of Viburnum utile and their inhibitory activities against α-glucosidase].

The chemical constituents in the ethanol extract of Viburnum utile were isolated by column chromatography with D101 macroporous resin, silica gel, and Sephadex LH-20. Their structures were identified by spectroscopic techniques such as NMR and MS. All the compounds were evaluated for the inhibitory activities against α-glucosidase. Sixteen compounds were obtained and identified as viburnumide A(1), vitamin E(2), α-amyrin(3), α-tocoquinone(4), narjatamanin B(5), ethyl caffeate(6), naringenin(7), apigenin(8), ethyl ß-D-ribo-hex-3-ulopyranoside(9), trans-p-hydroxycinnamic acid(10), amentoflavone(11), apigenin-7-O-ß-D-glucoside(12), luteolin-7-O-ß-D-glucoside(13), henryoside(14), ursolic acid(15), and 2α-hydroxy-oleanolic acid(16). Among them, compound 1 was a new compound, and compounds 2-16 were isolated from V. utile for the first time. The inhibitory activity(IC_(50) of 4.0 µmol·L~(-1)) of compound 11 against α-glucosidase was comparable to that of the positive control acarbose(IC_(50) of 2.3 µmol·L~(-1)).

Upgrading on Per Protocol versus For Cause surveillance prostate biopsies: An opportunity to decreasing the burden of active surveillance.

BACKGROUND: Most prostate cancer (PC) active surveillance (AS) protocols recommend "Per Protocol" surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for "For Cause" surveillance biopsy (FCSBx) versus PPSBx. METHODS: We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Surveillance prostate biopsies obtained 1 year after diagnosis were classified as either PPSBx or FCSBx. Biopsies were retrospectively deemed FCSBx if any of these criteria were met: PSA velocity > 0.75 ng/mL/year; rise in PSA > 3 ng from baseline; surveillance magnetic resonance imaging (MRI) (sMRI) with a PIRADS ≥ 4; change in DRE. Biopsies were classified PPSBx if none of these criteria were met. The primary outcome was upgrading to ≥GG2 or ≥GG3 on surveillance biopsy. The secondary objective was to assess for the association of reassuring (PIRADS ≤ 3) confirmatory or surveillance MRI findings and upgrading for patients undergoing PPSBx. Proportions were compared with the chi-squared test. RESULTS: We identified 1773 men with GG1 PC in MUSIC who underwent a surveillance biopsy. Men meeting criteria for FCSBx had more upgrading to ≥GG2 (45%) and ≥GG3 (12%) compared with those meeting criteria for PPSBx (26% and 4.9%, respectively, p < 0.001 and p < 0.001). Men with a reassuring confirmatory or surveillance MRI undergoing PPSBx had less upgrading to ≥GG2 (17% and 17%, respectively) and ≥GG3 (2.9% and 1.8%, respectively) disease compared with men without an MRI (31% and 7.4%, respectively). CONCLUSIONS: Patients undergoing PPSBx had significantly less upgrading compared with men undergoing FCSBx. Confirmatory and surveillance MRI seem to be valuable tools to stratify the intensity of surveillance biopsies for men on AS. These data may help inform the development of a risk-stratified, data driven AS protocol.