WRKY53 negatively regulates rice cold tolerance at the booting stage by fine-tuning anther gibberellin levels.

Cold tolerance at the booting (CTB) stage is a major factor limiting rice (Oryza sativa L.) productivity and geographical distribution. A few cold-tolerance genes have been identified, but they either need to be overexpressed to result in CTB or cause yield penalties, limiting their utility for breeding. Here, we characterize the function of the cold-induced transcription factor WRKY53 in rice. The wrky53 mutant displays increased CTB, as determined by higher seed setting. Low temperature is associated with lower gibberellin (GA) contents in anthers in the wild type but not in the wrky53 mutant, which accumulates slightly more GA in its anthers. WRKY53 directly binds to the promoters of GA biosynthesis genes and transcriptionally represses them in anthers. In addition, we uncover a possible mechanism by which GA regulates male fertility: SLENDER RICE1 (SLR1) interacts with and sequesters two critical transcription factors for tapetum development, UNDEVELOPED TAPETUM1 (UDT1), and TAPETUM DEGENERATION RETARDATION (TDR), and GA alleviates the sequestration by SLR1, thus allowing UDT1 and TDR to activate transcription. Finally, knocking out WRKY53 in diverse varieties increases cold tolerance without a yield penalty, leading to a higher yield in rice subjected to cold stress. Together, these findings provide a target for improving CTB in rice.

Switching CO2 Electroreduction toward Ethanol by Delocalization State-Tuned Bond Cleavage.

The electrochemical CO2 reduction reaction by copper-based catalysts features a promising approach to generate value-added multicarbon (C2+) products. However, due to the unfavored formation of oxygenate intermediates on the catalyst surface, the selectivity of C2+ alcohols like ethanol remains unsatisfactory compared to that of ethylene. The bifurcation point (i.e., the CH2═CHO* intermediate adsorbed on Cu via a Cu-O-C linkage) is critical to the C2+ product selectivity, whereas the subsequent cleavage of the Cu-O or the O-C bond determines the ethanol or ethylene pathway. Inspired by the hard-soft acid-base theory, in this work, we demonstrate an electron delocalization tuning strategy of the Cu catalyst by a nitrene surface functionalization approach, which allows weakening and cleaving of the Cu-O bond of the adsorbed CH2═CHO*, as well as accelerating hydrogenation of the C═C bond along the ethanol pathway. As a result, the nitrene-functionalized Cu catalyst exhibited a much-enhanced ethanol Faradaic efficiency of 45% with a peak partial current density of 406 mA·cm-2, substantially exceeding that of unmodified Cu or amide-functionalized Cu. When assembled in a membrane electrode assembly electrolyzer, the catalyst presented a stable CO2-to-ethanol conversion for >300 h at an industrial current density of 400 mA·cm-2.

Metabolic profiling of peri-implant crevicular fluid in peri-implantitis.

OBJECTS: This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI). MATERIALS AND METHODS: Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities. RESULTS: Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus. CONCLUSIONS: This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.

Association of dietary selenium intake and all-cause mortality of Parkinson's disease and its interaction with blood cadmium level: a retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is a slowly progressive neurodegenerating disease that may eventually lead to disabling condition and pose a threat to the health of aging populations. This study aimed to explore the association of two potential risk factors, selenium and cadmium, with the prognosis of Parkinson's disease as well as their interaction effect. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 to 2015-2016 and National Death Index (NDI). Participants were classified as Parkinson's patients by self-reported anti-Parkinson medications usage. Cox regression models and restricted cubic spline models were applied to evaluate the association between PD mortality and selenium intake level as well as blood cadmium level. Subgroup analysis was also conducted to explore the interaction between them. RESULTS: A total of 184 individuals were included. In full adjusted cox regression model (adjusted for age, gender, race, hypertension, pesticide exposure, smoking status and caffeine intake), compared with participants with low selenium intake, those with normal selenium intake level were significantly associated with less risk of death (95%CI: 0.18-0.76, P = 0.005) while no significant association was found between low selenium intake group and high selenium group (95%CI: 0.16-1.20, P = 0.112). Restricted cubic spline model indicated a nonlinear relationship between selenium intake and PD mortality (P for nonlinearity = 0.050). The association between PD mortality and blood cadmium level was not significant (95%CI: 0.19-5.57, P = 0.112). However, the interaction term of selenium intake and blood cadmium showed significance in the cox model (P for interaction = 0.048). Subgroup analysis showed that the significant protective effect of selenium intake existed in populations with high blood cadmium but not in populations with low blood cadmium. CONCLUSION: Moderate increase of selenium intake had a protective effect on PD mortality especially in high blood cadmium populations.

DSCAM Deficiency Leads to Premature Spine Maturation and Autism-like Behaviors.

Mutations in some cell adhesion molecules (CAMs) cause abnormal synapse formation and maturation, and serve as one of the potential mechanisms of autism spectrum disorders (ASDs). Recently, DSCAM (Down syndrome cell adhesion molecule) was found to be a high-risk gene for autism. However, it is still unclear how DSCAM contributes to ASD. Here, we show that DSCAM expression was downregulated following synapse maturation, and that DSCAM deficiency caused accelerated dendritic spine maturation during early postnatal development. Mechanistically, the extracellular domain of DSCAM interacts with neuroligin1 (NLGN1) to block the NLGN1-neurexin1ß (NRXN1ß) interaction. DSCAM extracellular domain was able to rescue spine overmaturation in DSCAM knockdown neurons. Precocious spines in DSCAM-deficient mice showed increased glutamatergic transmission in the developing cortex and induced autism-like behaviors, such as social novelty deficits and repetitive behaviors. Thus, DSCAM might be a repressor that prevents premature spine maturation and excessive glutamatergic transmission, and its deficiency could lead to autism-like behaviors. Our study provides new insight into the potential pathophysiological mechanisms of ASDs.SIGNIFICANCE STATEMENTDSCAM is not only associated with Down syndrome but is also a strong autism risk gene based on large-scale sequencing analysis. However, it remains unknown exactly how DSCAM contributes to autism. In mice, either neuron- and astrocyte-specific or pyramidal neuron-specific DSCAM deficiencies resulted in autism-like behaviors and enhanced spatial memory. In addition, DSCAM knockout or knockdown in pyramidal neurons led to increased dendritic spine maturation. Mechanistically, the extracellular domain of DSCAM binds to NLGN1 and inhibits NLGN1-NRXN1ß interaction, which can rescue abnormal spine maturation induced by DSCAM deficiency. Our research demonstrates that DSCAM negatively modulates spine maturation, and that DSCAM deficiency leads to excessive spine maturation and autism-like behaviors, thus providing new insight into a potential pathophysiological mechanism of autism.

Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia.

BACKGROUND: Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive combination therapies that often include dopamine agonists. OBJECTIVE: Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses. METHODS: Different regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug categories were investigated in parallel groups of rats receiving either L-dopa monotreatment or L-dopa combined with ropinirole. RESULTS: We defined chronic regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment inducing overall similar abnormal involuntary movement scores. Compared with the monotreatment group, animals receiving the L-dopa-ropinirole combination exhibited an overall lower striatal expression of ∆FosB with a distinctive compartmental distribution. The expression of angiogenesis markers and blood-brain barrier hyperpermeability was markedly reduced after L-dopa-ropinirole cotreatment compared with L-dopa monotreatment. Moreover, significant group differences were detected upon examining the response to candidate antidyskinetic drugs. In particular, compounds modulating D1 receptor signaling had a stronger effect in the L-dopa-only group, whereas both amantadine and the selective NMDA antagonist MK801 produced a markedly larger antidyskinetic effect in L-dopa-ropinirole cotreated animals. CONCLUSIONS: Cotreatment with ropinirole altered LID-related neuroplasticity and pharmacological response profiles. The impact of adjuvant dopamine agonist treatment should be taken into consideration when investigating LID mechanisms and candidate interventions in both clinical and experimental settings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

MICAL2PV suppresses the formation of tunneling nanotubes and modulates mitochondrial trafficking.

Tunneling nanotubes (TNTs) are actin-rich structures that connect two or more cells and mediate cargo exchange between spatially separated cells. TNTs transport signaling molecules, vesicles, organelles, and even pathogens. However, the molecular mechanisms regulating TNT formation remain unclear and little is known about the endogenous mechanisms suppressing TNT formation in lung cancer cells. Here, we report that MICAL2PV, a splicing isoform of the neuronal guidance gene MICAL2, is a novel TNT regulator that suppresses TNT formation and modulates mitochondrial distribution. MICAL2PV interacts with mitochondrial Rho GTPase Miro2 and regulates subcellular mitochondrial trafficking. Moreover, down-regulation of MICAL2PV enhances survival of cells treated with chemotherapeutical drugs. The monooxygenase (MO) domain of MICAL2PV is required for its activity to inhibit TNT formation by depolymerizing F-actin. Our data demonstrate a previously unrecognized function of MICAL2 in TNT formation and mitochondrial trafficking. Furthermore, our study uncovers a role of the MICAL2PV-Miro2 axis in mitochondrial trafficking, providing a mechanistic explanation for MICAL2PV activity in suppressing TNT formation and in modulating mitochondrial subcellular distribution.

Electrochemical Fe-catalysed radical cyclization for the synthesis of oxindoles.

We report an efficient and sustainable electrocatalytic approach for the synthesis of 3,3-disubstituted 2-oxindoles bearing ester groups from readily accessible N-arylacrylamides and carbazates. The reaction proceeds through an electrochemical iron-catalyzed radical addition/cyclization sequence with a commercially available iron catalyst and carbazates as alkoxycarbonyl radical precursors. This mild and operationally simple method transforms a wide range of structurally diverse N-arylacrylamides into oxindole derivatives in good yields and can be smoothly scaled up for the preparation of synthetically valuable oxindoles that are key intermediates for the synthesis of natural products.

Nucleic Acid Tests for Clinical Translation.

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, in vitro NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.

Fatigue reliability analysis of aeroengine blade-disc systems using physics-informed ensemble learning.

For the fatigue reliability analysis of aeroengine blade-disc systems, the traditional direct integral modelling methods or separate independent modelling methods will lead to low computational efficiency or accuracy. In this work, a physics-informed ensemble learning (PIEL) method is proposed, i.e. firstly, based on the physical characteristics of blade-disc systems, the complex multi-component reliability analysis is split into a series of single-component reliability analyses; moreover, the PIEL model is established by introducing the mapping of multiple constitutive responses and the multi-material physical characteristics into the ensemble learning; finally, the PIEL-based system reliability framework is established by quantifying the failure correlation with the Copula function. The reliability analysis of a typical aeroengine high-pressure turbine blade-disc system is regarded as an example to verify the effectiveness of the proposed method. Compared with the direct Monte Carlo, support vector regression, neural network, ensemble learning and physics-informed neural network, the proposed method exhibits the highest computing accuracy and efficiency, and is validated to be an efficient method for the reliability analysis of blade-disc systems. The current work can provide a novel insight for physics-informed modelling and fatigue reliability analyses. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Improved cryptic plasmids in probiotic Escherichia coli Nissle 1917 for antibiotic-free pathway engineering.

The engineered probiotic Escherichia coli Nissle 1917 (EcN) is expected to be employed in the diagnosis and treatment of various diseases. However, the introduced plasmids typically require antibiotics to maintain genetic stability, and the cryptic plasmids in EcN are usually eliminated to avoid plasmid incompatibility which may change the inherent probiotic characteristics. Here, we provided a simple design to minimize the genetic change of probiotics by eliminating native plasmids and reintroducing the recombinants carrying functional genes. Specific insertion sites in the vectors showed significant differences in the expression of fluorescence proteins. Selected integration sites were applied in the de novo synthesis of salicylic acid, leading to a titer of 142.0 ± 6.0 mg/L in a shake flask with good production stability. Additionally, the design successfully realized the biosynthesis of ergothioneine (45 mg/L) by one-step construction. This work expands the application scope of native cryptic plasmids to the easy construction of functional pathways. KEY POINTS: • Cryptic plasmids of EcN were designed to express exogenous genes • Insertion sites with different expression intensities in cryptic plasmids were provided • Target products were stably produced by engineering cryptic plasmids.

Strontium-modified titanium substrate promotes osteogenic differentiation of MSCs and implant osseointegration via upregulating CDH2.

OBJECTIVES: Our previous studies showed that strontium (Sr)-modified sand-blasted, large grit, acid etched titanium surface (Sr-SLA) is beneficial for osseointegration; however, the supporting mechanisms have not been explored in detail. MATERIALS AND METHODS: Whole-transcriptome RNA sequencing of peri-implant bone tissue was performed, and CDH2 was selected as a key mediator of Sr-SLA-mediated osseointegration. To test this hypothesis, a lentivirus-mediated vector targeting the silencing of the CDH2 gene was used in mesenchymal stem cells (MSCs) prior to seeding on Ti substrates. The effects of CDH2 interference on MSCs vitality, differentiation, and ß-catenin signaling activity were evaluated. In vivo, a recombinant adeno-associated virus 9 vector carrying an artificial siRNA that target CDH2 (AAV9-CDH2i) was intravenously injected in mice, followed by tibial surgery with implant placement. Osseointegration were monitored using micro-CT analysis. RESULTS: CDH2 expression in MSCs on Sr-SLA was higher than the control group, which was in parallel with the enhanced cell migration, adhesion, and upregulation of early osteogenic markers. Knocking down CDH2 in MSCs resulted in decreased cell viability and osteogenic differentiation, and the elevated biocompatibility and osteoinductive effect of Sr-SLA were greatly diminished. Surprisingly, Sr-SLA-induced upregulation of CDH2 was not followed by restriction of ß-catenin signaling because Sr-SLA also promoted the expression and nuclear translocation of ß-catenin. Systemic administration of AAV9-CDH2i effectively knocked down CDH2 expression in bone marrow cells, and in turn, inhibited bone formation induced by Sr-SLA. CONCLUSIONS: The results indicated that CDH2 is required for Sr-SLA-mediated bone regeneration, which reveals a new mechanism to explain the osteoinductive effect of Sr-SLA. Thus, biomaterial modifications targeting CDH2 may help improve early osseointegration and bone healing.

Diagnostic Value of Salivary Real-Time Quaking-Induced Conversion in Parkinson's Disease and Multiple System Atrophy.

BACKGROUND: Aggregation of α-synuclein (oligomeric α-syn) has been considered as the pathological hallmark of Parkinson's disease (PD) and multiple system atrophy (MSA). Studies showed oligomeric α-syn/total α-syn ratio was increased in the saliva of patients with PD, suggesting that seeding activity of salivary oligomeric α-syn may be a novel biomarker for the diagnosis of PD and MSA. OBJECTIVE: This study aimed to evaluate the diagnostic value of salivary α-syn seeding activity in patients with PD and MSA. METHODS: A total of 75 patients with PD, 18 patients with MSA, and 36 nonneurodegenerative healthy control subjects underwent salivary α-syn real-time quaking-induced conversion (RT-QuIC) assay. RESULTS: Salivary α-syn RT-QuIC assay distinguished patients with PD with 76.0% sensitivity (95% confidence interval [CI], 66.1-85.9) and 94.4% specificity (95% CI, 86.6-100.0). RT-QuIC assay sensitivity reached 61.1% (95% CI, 36.2-86.1) in patients with MSA. No significant differences were observed in the diameter of salivary α-syn fibrils examined by electron microscopy and in thioflavin T fluorescence intensity of salivary α-syn fibrils detected by RT-QuIC assay between patients with PD and MSA. Notably, the lag phase of RT-QuIC assay from patients with PD was significantly shorter than that of patients with MSA, which might be clinically applicable to the discrimination between PD and MSA. CONCLUSIONS: Salivary α-syn seeding activity may serve as a novel biomarker for the clinical diagnosis of PD and MSA.© 2022 International Parkinson and Movement Disorder Society © 2022 International Parkinson and Movement Disorder Society.

LncRNA CASC2 Alleviates Sepsis-induced Acute Lung Injury by Regulating the miR-152-3p/PDK4 Axis.

BACKGROUND: Acute lung injury (ALI) is an early complication of sepsis and it is also considered as an important cause of high mortality in sepsis patients. This research aimed to explore the potential role and mechanism of long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in sepsis-induced ALI. METHODS: The levels of CASC2, microRNA-152-3p (miR-152-3p) and pyruvate dehydrogenase kinase 4 (PDK4) in sepsis patients and LPS-treated HPAEpiC were detected by quantitative real-time PCR and western blot. Cell viability and apoptosis were assessed by Counting Kit-8 (CCK-8) assay and flow cytometry. The concentrations of inflammatory factors were tested by Enzyme-linked immunosorbent assay. Oxidative stress was evaluated by the levels of reactive oxygen species and superoxide dismutase using corresponding commercial kits. The targeting relationship between miR-152-3p and CASC2 or PDK4 was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: CASC2 and PDK4 were down-regulated, while miR-152-3p was up-regulated in sepsis patients and LPS-stimulated HPAEpiC. Overexpression of CASC2 relieved the LPS-resulted cell viability inhibition, apoptosis promotion, inflammatory and oxidative damages in HPAEpiC. In addition, miR-152-3p was a miRNA target of CASC2 and CASC2 alleviated cell injury in LPS-disposed HPAEpiC by sponging miR-152-3p. Moreover, miR-152-3p directly targeted PDK4 and CASC2 increased the PDK4 expression by depending on the sponge effect on miR-152-3p. Meanwhile, inhibition of miR-152-3p attenuated LPS-triggered HPAEpiC injury by upregulating the level of PDK4. CONCLUSION: These results suggested that CASC2 ameliorated the LPS-induced injury in HPAEpiC via regulating miR-152-3p/PDK4 pathway.

Calculation of the estimated glomerular filtration rate using the 2021 CKD-EPI creatinine equation and whole blood creatinine values measured with Radiometer ABL 827 FLEX.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) can be calculated using serum/plasma creatinine measured with automated chemistry analyzers. It is unclear whether eGFR can be calculated using creatinine values measured in whole blood (WB creatinine). The aim of this study is to determine the comparability between the eGFR calculated using WB creatinine and plasma creatinine. METHODS: Blood samples from 1,073 patients presented to the emergency department (ED), perioperative areas, intensive care unit (ICU) or nuclear medicine were used to determine the accuracy of WB creatinine. For each sample, WB creatinine was first measured with Radiometer ABL827 FLEX blood gas analyzer, then plasma creatinine was measured with Roche Cobas702 chemistry analyzer after samples were centrifuged. In a subset of 247 samples with the information of age and sex, whole blood eGFR (WB eGFR) and plasma eGFR were calculated using WB creatinine and plasma creatinine and the 2021 chronic kidney disease epidemiology collaboration (CKD-EPI) creatinine equation, respectively. RESULTS: WB creatinine correlated with plasma creatinine linearly with a slope of 1.06 and an intercept of -0.01. The coefficient of determination (R2) was 0.99. WB eGFR correlated with plasma eGFR linearly with a slope of 0.95, intercept of -1.63, and R2 of 0.97. Comparing to plasma eGFR, the sensitivity and specificity for WB eGFR to identify those with high risk (eGFR<30 mL/min/1.73 m2) and low risk (eGFR>45 mL/min/1.73 m2) for kidney injuries was 100 and 92.2%, respectively. The overall concordance in classifying the four stages of kidney damage between WB eGFR and plasma eGFR was 87.9%. CONCLUSIONS: WB creatinine measured with Radiometer ABL827 Flex can be used to calculate eGFR using the 2021 CKD-EPI creatinine equation. The sensitivity and specificity for WB eGFR to identify those with high and low risks for potential kidney injuries are acceptable in patients needing rapid assessment of their kidney functions.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

[Application of patient-reported outcome measures in the diagnosis and treatment of male urethral stricture: An update].

Urethral stricture is a common and recurrent male disease, and its treatment has been shifted from endoscopic management to urethroplasty, which has greatly improved the success rate of treatment. However, patients and doctors often have different evaluations of the sexual function and lower urinary tract symptoms after urethroplasty, which has attracted the attention of researchers. In recent years, specific questionnaires or scales have been used to evaluate the effects of preoperative and postoperative treatment, laying more stress on the subjective feelings of the patients. Such questionnaires or scales are called patient-reported outcome measures (PROM). This article reviews the application of PROM in recent studies of urethral stricture, focusing on sexual function and lower urinary tract symptoms, aiming to provide some reference for the development and application of PROM in the diagnosis and treatment of male urethral stricture.

Pelvic Injury Discriminative Model Based on Data Mining Algorithm.

OBJECTIVES: To reduce the dimension of characteristic information extracted from pelvic CT images by using principal component analysis (PCA) and partial least squares (PLS) methods. To establish a support vector machine (SVM) classification and identification model to identify if there is pelvic injury by the reduced dimension data and evaluate the feasibility of its application. METHODS: Eighty percent of 146 normal and injured pelvic CT images were randomly selected as training set for model fitting, and the remaining 20% was used as testing set to verify the accuracy of the test, respectively. Through CT image input, preprocessing, feature extraction, feature information dimension reduction, feature selection, parameter selection, model establishment and model comparison, a discriminative model of pelvic injury was established. RESULTS: The PLS dimension reduction method was better than the PCA method and the SVM model was better than the naive Bayesian classifier (NBC) model. The accuracy of the modeling set, leave-one-out cross validation and testing set of the SVM classification model based on 12 PLS factors was 100%, 100% and 93.33%, respectively. CONCLUSIONS: In the evaluation of pelvic injury, the pelvic injury data mining model based on CT images reaches high accuracy, which lays a foundation for automatic and rapid identification of pelvic injuries.

Circular RNA circVMA21 ameliorates lipopolysaccharide (LPS)-induced acute kidney injury by targeting the miR-199a-5p/NRP1 axis in sepsis.

BACKGROUND: Sepsis is a serious and elusive syndrome caused by infection, with high mortality worldwide. Circular RNAs vacuolar ATPase assembly factor (circVMA21) has been reported to be related to the inflammatory damages in sepsis. This study is designed to explore the role and mechanism of circVMA21 in the lipopolysaccharide (LPS)-induced cell injury in sepsis. METHODS: Cell viability and apoptosis were detected by CCK-8, and flow cytometry assays. CircVMA21, microRNA-199a-5p (miR-199a-5p), and Neuropilin-1 (NRP1) level were determined by RT-qPCR. Protein levels of Bcl-2, Bax, cleaved-caspase 3, and NRP1 were examined by Western blot assay. IL-1ß, IL-6, and TNF-α were detected using ELISA. Superoxide Dismutase (SOD) and glutathione (GSH) were measured by the special kits. The binding relationship between miR-199a-5p and circVMA21 or NRP1 was predicted by Starbase 3.0 and then verified by a dual-luciferase reporter and RIP assays. RESULTS: CircVMA21 and NRP1 were decreased, and miR-199a-5p was increased in LPS-induced THP-1 cells. Moreover, circVMA21 overexpression could repress LPS-mediated cell viability, apoptosis, inflammation, and oxidative stress in THP-1 cells. The mechanical analysis suggested that circVMA21 regulated NRP1 expression through sponging miR-199a-5p. CONCLUSION: CircVMA21 upregulation could attenuate LPS-triggered THP-1 cell injury through modulating the miR-199a-5p/NRP1 axis, hinting an underlying therapeutic strategy for sepsis patients.

Reaching the Full Potential of Electroorganic Synthesis by Paired Electrolysis.

Electroorganic synthesis has recently become a rapidly blossoming research area within the organic synthesis community. It should be noted that electrochemical reaction is always a balanced reaction system with two half-cell reactions-oxidation and reduction. Most electrochemical strategies, however, typically focus on one of the two sides for the desired transformations. Paired electrolysis has two desirable half reactions running simultaneously, thus maximizing the overall margin of atom and energy economy. Meanwhile, the spatial separation between oxidation and reduction is the essential feature of electrochemistry, offering unique opportunities for the development of redox-neutral reactions that would otherwise be challenging to accomplish in a conventional reaction flask setting. This review discusses the most recent illustrative examples of paired electrolysis with special emphasis on sequential and convergent processes.