Platelet Membrane-Encapsulated Nanocomplexes Based on Profundity Scavenging ROS Strategy for Myocardial Infarction Therapy.

Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.

ROS-Suppression Nanoplatform Combined Activation of STAT3/Bcl-2 Pathway for Preventing Myocardial Infarction in Mice.

Myocardial infarction (MI) is the leading cause of death worldwide. The most effective way to treat myocardial infarction is to rescue ischemic cardiomyocytes. After an ischemic event, the overproduction of reactive oxygen species (ROS) is a key driver of myocardial injury. The produced ROS affects mitochondrial function and induces apoptosis in cardiomyocytes. This was accomplished by constructing platelet-membrane-encapsulated ROS-responsive drug-releasing nanoparticles (PMN@NIC-MalNPs) to deliver malonate and niclosamide (NIC). The results revealed that PMN@NIC-MalNPs degraded and released malonate and niclosamide in a high-level ROS microenvironment, effectively reducing the oxidative stress and apoptosis rate. By enhancing basal mitochondrial oxygen consumption rate (OCR), adenosine triphosphate (ATP) production, and spare respiratory capacity (SRC) in vitro, reduced the oxidative stress levels and restored mitochondrial function. In vivo studies revealed that the PMN@NIC-MalNPs improved cardiac dysfunction, inhibited succinate dehydrogenase (SDH) activity, increased ATP production, and reduced the myocardial infarct size in myocardial infarction model mice. Further, transcriptome analysis and Western blot revealed that PMN@NIC-MalNPs prevented apoptosis by activating the expressions of the signal transducer and activator of transcription 3 (STAT3) and Bcl-2, and inhibiting the expression of Bax. Thus, this study provides a novel therapeutic solution for treating myocardial infarction and predicting the viability of an antioxidant and antiapoptotic therapeutic solution in the treatment of myocardial injury.

Survival analysis of comprehensive treatment in Chinese patients with metastatic melanoma: A retrospective analysis.

BACKGROUND: Most of the current progression of immune checkpoint inhibitors for malignant melanoma is based on data from Caucasians in Western countries, but the benefit of Chinese patients is limited, mainly due to different pathological subtypes. The patients in western countries are mainly skin melanoma (about 90%), while the acral and mucosal types are dominant in China, accounting for 41.8% and 22.6% respectively. Acral and mucosal melanoma have lower response rates to immunotherapy and chemotherapy. OBJECTIVE: Whether immune checkpoint inhibitors can improve the survival of Chinese patients with malignant melanoma, therefore, we conducted a retrospective analysis. METHODS: We analyzed 53 patients with metastatic melanoma treated in our hospital to evaluate the efficacy and safety of PD-1 mAb in Chinese patients with metastatic melanoma, and performed univariate and multivariate analyses of prognostic factors that may affect overall survival (OS). RESULTS: In a study of 125 patients with advanced malignant melanoma, 53 patients participated, with a median follow-up of 16 months. Among these, 69.8% died, and 30.2% remained on treatment. Median progression-free survival (PFS) was 6 months, and median OS was 19 months. Patients treated with immune checkpoint inhibitors had improved outcomes, with a median PFS of 7 months and a median OS of 24 months. Patients with bone metastasis and aberrant Lactate dehydrogenase (LDH) post-treatment had worse prognoses, while immunotherapy was a protective factor. Subgroup analysis showed the benefits of immunotherapy across various patient characteristics. No unexpected toxicities were observed. CONCLUSION: The study highlights the efficacy of immune checkpoint inhibitors, particularly PD-1 mAb, in improving survival outcomes for Chinese patients with metastatic melanoma.

Glycolate oxidase gene family identification and functional analyses in cotton resistance to Verticillium wilt.

Glycolate oxidase (GOX) plays an important role in the regulation of photorespiration and photosynthesis in plants. However, as one of the main enzymes to produce the second messenger hydrogen peroxide (H2O2), its functions in response to pathogens are still poorly understood. In this study, we carried out genome-wide identification, and 14 GOX genes were identified in Gossypium hirsutum. These GOX genes are located on 10 chromosomes and divided into hydroxyacid-oxidases (HAOX) and GOX groups. After infection with Verticillium dahliae Kleb., six GOX gene expression levels were changed. Moreover, H2O2, salicylic acid (SA), and the content and activity of GOX increased in cotton. GhHAOX2-D-silenced plants showed more wilting than control plants after infection with V. dahliae. Additionally, H2O2 accumulation and SA content were reduced in GhHAOX2-D-silenced plants. The expression levels of GhPAL, GhPAD4, and GhPR1 and the lignin content of the silenced plants were significantly lower than those of the control plants. These results indicate that GhHAOX2-D is a positive regulator of Verticillium wilt tolerance in cotton and may promote H2O2 accumulation via the synergistic effects of GOX genes and SA. Collectively, GOX genes play an important role in cotton resistance to Verticillium wilt.

Postoperative circulating tumor DNA detection and CBLB mutations are prognostic biomarkers for gastric cancer.

BACKGROUND: Several studies have demonstrated that circulating tumor DNA (ctDNA) can be used to predict the postoperative recurrence of several cancers. However, there are few studies on the use of ctDNA as a prognosis tool for gastric cancer (GC) patients. OBJECTIVE: This study aims to determine whether ctDNA could be used as a prognostic biomarker in GC patients through multigene-panel sequencing. METHODS: Using next-generation sequencing (NGS) Multigene Panels, the mutational signatures associated with the prognosis of GC patients were identified. We calculated the survival probability with Kaplan-Meier and used the Log-rank test to compare survival curves between ctDNA-positive and ctDNA-negative groups. Potential application of radiology combined with tumor plasma biomarker analysis of ctDNA in GC patients was carried out. RESULTS: Disease progression is more likely in ctDNA-positive patients as characterized clinically by a generally higher T stage and a poorer therapeutic response (P < 0.05). ctDNA-positive patients also had worse overall-survival (OS: P = 0.203) and progression-free survival (PFS: P = 0.037). The combined analysis of ctDNA, radiological, and serum biomarkers in four patients indicated that ctDNA monitoring can be a good complement to radiological and plasma tumor markers for GC patients. Kaplan-Meier analysis using a cohort of GC patients in the TCGA database showed that patients with CBLB mutations had shorter OS and PFS than wild-type patients (OS: P = 0.0036; PFS: P = 0.0027). CONCLUSIONS: This study confirmed the utility and feasibility of ctDNA in the prognosis monitoring of gastric cancer.

HrTPS12 gene dramatically enhanced insect resistance of sea buckthorn to infection by fruit fly (Rhagoletis batava obseuriosa Kol.).

BACKGROUND: Terpenoids emitted from plants are important for regulating plant-insect interaction. However, it is still unclear how terpenoids affect the host defense system. There are few reports of terpenoids' involvement in the mechanisms that regulate woody plants' insect resistance. RESULTS: The (E)-ß-ocimene of terpenes was only found in RBO-resist leaves, and its content was higher than that of other type terpenes. Further, we also found (E)-ß-ocimene had a significant avoidance effect on RBO and reached 87.5% of the highest avoidance rate. Meanwhile, overexpression of HrTPS12 in Arabidopsis increased the HrTPS12 expression level, (E)-ß-ocimene content, and enhanced the defense against RBO. However, silencing HrTPS12 in sea buckthorn revealed that the expression levels of HrTPS12 and (E)-ß-ocimene significantly decreased, causing the attraction effect on RBO. CONCLUSION: HrTPS12 was an up-regulator, which improves sea buckthorn resistance to RBO by regulating the synthesis of volatile (E)-ß-ocimene. These results provide in-depth information about the interaction between RBO and sea buckthorn and provide a theoretical basis for developing plant-based insect repellents that can be used to manage RBO. © 2023 Society of Chemical Industry.

A SiO2 Hybrid Enzyme-Based Biosensor with Enhanced Electrochemical Stability for Accuracy Detection of Glucose.

A novel enzyme-based biosensor for glucose detection is successfully developed using layer-by-layer assembly technology. The introduction of commercially available SiO2 was found to be a facile way to improve overall electrochemical stability. After 30 CV cycles, the proposed biosensor could retain 95% of its original current. The biosensor presents good detection stability and reproducibility with the detection concentration range of 1.96 × 10-9 to 7.24 × 10-7 M. This study demonstrated that the hybridization of cheap inorganic nanoparticles was a useful method in preparing high-performance biosensors with a much lower cost.

A Novel Frameless Laser Stereotaxis System for Neurosurgical Interventions.

OBJECTIVE: The aim of the article is to introduce a novel laser-based frameless stereotactic device that can locate intracranial lesions quickly and with computed tomograph (CT)/magnetic resonance imaging (MRI) films. Preliminary experiences of application in 416 cases are also summarized. METHODS: From August in 2020 to October in 2022, a total of 416 cases of new minimalist laser stereotactic surgery have been performed on 415 patients. Of the 415 patients, 377 had intracranial hematomas, while the remaining cases were brain tumors or brain abscesses. Postoperative CT was used to evaluate the accuracy of catheterization of 405 patients according to the MISTIE study. The duration time of locating was recorded. Rebleeding refers to the definition: Compared with preoperative CT, the relative volume of postoperative hematoma increases by >33% or absolute volume increase >12.5 mL. RESULTS: According to postoperative CT, the accuracy of 405 stereotactic catheterization cases was good in 346 cases (85.4%) and suboptimal in 59 cases (14.6%), with no poor results. Postoperative rebleeding occurred in 4 spontaneous cerebral hemorrhage cases and 1 brain biopsy case. The average localization time of supratentorial lesions was 13.2 minutes in the supine position, 21.5 minutes in the lateral position, and 27.6 minutes in the prone position. CONCLUSIONS: The new laser-based frameless stereotactic device is simple in principle and convenient in positioning operation of brain hematoma and abscess puncture, brain biopsy and tumor surgery, and appropriate to the precision requirements in most craniocerebral surgery.

The transcription factor GhWRKY70 from gossypium hirsutum enhances resistance to verticillium wilt via the jasmonic acid pathway.

BACKGROUND: The WRKY transcription factors play significant roles in plant growth, development, and defense responses. However, in cotton, the molecular mechanism of most WRKY proteins and their involvement in Verticillium wilt tolerance are not well understood. RESULTS: GhWRKY70 is greatly up-regulated in cotton by Verticillium dahliae. Subcellular localization suggests that GhWRKY70 is only located in the nucleus. Transcriptional activation of GhWRKY70 further demonstrates that GhWRKY70 function as a transcriptional activator. Transgenic Arabidopsis plants overexpressing GhWRKY70 exhibited better growth performance and higher lignin content, antioxidant enzyme activities and jasmonic acid (JA) levels than wild-type plants after infection with V. dahliae. In addition, the transgenic Arabidopsis resulted in an enhanced expression level of AtAOS1, a gene related to JA synthesis, further leading to a higher JA accumulation compared to the wild type. However, the disease index (DI) values of the VIGS-treated cotton plants with TRV:WRKY70 were also significantly higher than those of the VIGS-treated cotton plants with TRV:00. The chlorophyll and lignin contents of TRV:WRKY70 plants were significantly lower than those of TRV:00 plants. GhAOS1 expression and JA abundance in TRV:WRKY70 plants were decreased. The GhWRKY70 protein was confirmed to bind to the W-box element in the promoter region of GhAOS by yeast one-hybrid assay and transient expression. CONCLUSION: These results indicate that the GhWRKY70 transcription factor is a positive regulator in Verticillium wilt tolerance of cotton, and may promote the production of JA via regulation of GhAOS1 expression.

MiR-216a-3p inhibits the proliferation and invasion of fibroblast-like synoviocytes by targeting dual-specificity phosphatase 5.

Dual-specificity phosphatase 5 (DUSP5) is a novel anti-inflammatory modulator in many inflammatory diseases. However, the role of DUSP5 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) remains unknown. In this study, we aimed to explore the biological function and regulation of DUSP5 in FLS. We found that lower DUSP5 expression level was detected in collagen-induced arthritis (CIA) and synoviocyte MH7A. Overexpression of DUSP5 markedly decreased the proliferation, migration, and invasion of MH7A, which correlated with suppressing the phosphorylation of extracellular signal-regulated kinase (ERK). Moreover, DUSP5 was identified as a novel target gene of miR-216a-3p, which was upregulated in FLS. Therefore, DUSP5 expression was negatively regulated by miR-216a-3p, and the effect of DUSP5 overexpression on FLS was reversed by miR-216a-3p mimics. Overall, our study demonstrates that DUSP5 is a miR-216a-3p target gene and its anti-inflammatory function in FLS via inactivation of ERK. These results revealed that the miR-216a-3p/DUSP5 pathway may play a crucial role in the malignant behavior of FLS, which may serve as a new target for the treatment of RA.

Retraction notice to "Globularifolin exerts anticancer effects on glioma U87 cells through inhibition of Akt/mTOR and MEK/ERK signaling pathways in vitro and inhibits tumor growth in vivo" [Biochmie 142C (2017) 144-151].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Reason for retraction: Figures 5 and 7B show shared images with Figures 4 and 7 of a publication in Mol Med Reports, Zeng et al. (2018) 10.3892/mmr.2018.8599. The two manuscripts were submitted from different laboratories at almost exactly the same time. The authors were contacted but did not respond to the allegation.

A Cross-Sectional Study of Depression, Anxiety, and Insomnia Symptoms in People in Quarantine During the COVID-19 Epidemic.

Objective: To investigate the status and influential factors of depression, anxiety, and insomnia among people in quarantine during COVID-19. Methods: Data was collected from August 2020 to November 2021 through an online survey of 1,360 people in a quarantined hotel. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI) were used to assess different mental symptoms. Results: 19.9% (n = 270), 17.6% (n = 239) and 7.1% (n = 97) of participants had depression, anxiety and insomnia. Married (OR = 0.641, 95% CI = 0.450-0.915) was a protective factor for depression. Chronic disease (OR = 2.579, 95% CI = 1.416-4.698) was a risk factor for insomnia. No psychiatric medication history was a protective factor for depression (OR = 0.227, 95% CI = 0.068-0.757) and insomnia (OR = 0.240, 95%CI = 0.078-0.736). Female, history of mental illness, low moods at check-in, and partial/cannot understand the quarantine policies were risk factors for anxiety, depression, and insomnia. Conclusion: People in quarantine had problems with depression, anxiety, and insomnia. Female, low moods at check-in, and partial/cannot understand the quarantine policies had significant impacts. It is necessary to help quarantined people understand quarantine policies, reduce negative emotions and improve sleep quality.

One-pot self-assembly fabrication of chitosan coated hollow sphere for pH/ glutathione dual responsive drug delivery.

Chitosan-coated poly (methacrylic acid) (PMAA) hollow spheres with 64 ± 3% drug loading capacity and low drug leakage (7 ± 2%, 54 h) were prepared through a novel one-pot two-step self-assembly process. Site-specific doxorubicin (DOX) loading and chitosan coating were achieved by electrostatic interaction to fulfill efficient drug loading and well-controlled drug release behavior. In vitro drug release profile revealed the pH and glutathione (GSH) dual responsive fast triggered drug release behavior, reaching 62 ± 3% during the first 10 h. And completely drug release could be achieved in 54 h. The high drug content and sensitive tumor microenvironment responsibility lead to similar anti-cancer efficiency with free doxorubicin in in vitro MTT assay. This self-assembly guided one-pot two-step fabrication process was proved to be an effective and convenient way to prepare the well-defined multi-layer structure and might be further employed in fabricating high-performance drug delivery systems.

Quinacrine is active in preclinical models of glioblastoma through suppressing angiogenesis, inducing oxidative stress and activating AMPK.

The poor prognosis of glioblastoma requires new innovative treatment strategies. We and others have shown that targeting tumor as well as angiogenesis in glioblastoma are effective therapeutic strategies. In line with these efforts, this work reveals that Quinacrine, an antimalarial drug, is a dual inhibitor of angiogenesis and glioblastoma. Using multiple glioblastoma cell lines, we found that Quinacrine inhibited proliferation and induced apoptosis in these cells, and acted in synergy with Temozolomide. Quinacrine potently inhibited tubular structure formations of glioblastoma microvascular endothelial cell (GMVEC) isolated from glioblastoma patients, especially for early stage tubular structure formation. Although Quinacrine induces apoptosis in GMVEC, the anti-angiogenic activity of Quinacrine is independent of its pro-apoptotic activity in GMVECs. Quinacrine inhibits glioblastoma angiogenesis and growth in vivo, and acts synergistically with Temozolomide in inhibiting glioblastoma growth in mice. Mechanistically, we found that Quinacrine acts on glioblastoma through inducing oxidative stress, impairing mitochondrial function and activating AMP-activated protein kinase (AMPK). Our work is the first to demonstrate the anti-angiogenic activity of Quinacrine. Our findings highlight Quinacrine as an attractive candidate to support treatment of glioblastoma.

M2-Macrophage-Derived Exosomes Promote Meningioma Progression through TGF-ß Signaling Pathway.

Tumor-associated macrophages (TAMs) have been shown to be an essential component of the tumor microenvironment and facilitate the proliferation and invasion of a variety of malignancies. However, the contribution of TAMs to meningioma progression has not been characterized in detail. In this study, we aimed to discover a novel regulatory pathway by which exosome-mediated M2-polarized macrophages participate in meningioma tumorigenesis and progression. Methods. First, the distribution and functional phenotype of macrophages in meningioma tissues were assessed by immunohistochemistry. Macrophage-derived exosomes (MDEs) were characterized, and further cell coculture experiments were performed to explore the effects of M2-MDEs on the proliferation, migration, and invasion of meningioma cells. RNA sequencing was used to analyze the transcriptomic signatures in meningioma cells treated with M2-MDEs. Three-dimensional tumorspheres and xenograft tumor models were used to evaluate the effects of M2-MDEs on meningioma tumorigenesis and development. Results. We found that M2 macrophages were enriched in meningioma tissue. Coculture with meningioma cells induced the M2 polarization of macrophages. We also found that M2-MDEs were able to significantly promote cell proliferation, cell migration, cell invasion, and tumorigenesis in meningiomas. Bioinformatic analysis suggested that the TGF-ß pathway was activated in meningioma cells treated with M2-MDEs. Functional experiments demonstrated that blocking the TGF-ß signaling pathway could effectively reverse the tumor-promotive effects mediated by M2-MDEs. Conclusions. Overall, our study showed that M2-MDEs promoted meningioma development and invasion by activating the TGF-ß signaling pathway. Targeting exosome-mediated intercellular communication in the tumor microenvironment may be a novel therapeutic strategy for meningioma patients.

Graphene Oxide, a Novel Nanomaterial as Soil Water Retention Agent, Dramatically Enhances Drought Stress Tolerance in Soybean Plants.

Drought is one of the most severe environmental stressors that place major constraints on the growth of soybeans (Glycine max L.). Graphene oxide (GO) is a nanomaterial that can promote plant growth without toxic effects. In this study, the physiological and molecular responses to drought stress with GO treatment were examined. We discovered that the relative water content (RWC) of stems and leaves treated with GO was 127 and 128% higher than that of the WT plants, respectively. The root parameters in GO-treated soybeans were increased by 33, 38, 34, and 35% than WT plants in total root length, root surface area, root diameter, and root volume, respectively. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) were also increased by 29, 57, 28, and 66%, respectively. However, the relative conductivity (REC), malondialdehyde (MDA), and hydrogen peroxide (H2O2) accumulation were remarkably decreased. Furthermore, the content of drought-related hormones JA, SA, and ABA in GO-treated soybeans increased by 32, 34, and 67% than WT plants, respectively. At the molecular level, the effects of GO treatment were manifested by relatively higher expression of four drought-related genes: GmP5CS, GmGOLS, GmDREB1, and GmNCED1. Taken together, our findings revealed that GO could directly increase plant defense enzymes, hormone content, and the expression of drought-related genes, thereby improving the soybean's ability to resist drought. These findings could provide new opportunities for improving drought tolerance in soybeans through effective soil water retention agents.

Endoscopic follow-up of mucosal defect after hot versus cold snare polypectomy in animal model.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) has received increasing attention in recent years, but few studies have assessed defect repair after polypectomy. Therefore, we compared the repair of mucosal defect after CSP and hot snare polypectomy (HSP) in a rabbit model. METHODS: Resection of normal colonic mucosa using both HSP and CSP were performed in 40 male New Zealand white rabbits by an experienced endoscopist. Follow-up colonoscopy was performed after 7 and 15 days by another endoscopist. We assessed mucosal defect repair, status of healing, scar formation, and intraoperative or delayed complications (including perforation and bleeding). RESULTS: Eight animals died of intraoperative or delayed perforation; follow-up colonoscopy was performed in 32 animals. On follow-up colonoscopy at 7 days after operation, 78.1% cases in the CSP group showed healing of mucosal defect compared with none in the HSP group (P < 0.001); mucosal repair score in the CSP group was significantly higher than HSP group (P < 0.001). On follow-up colonoscopy at 15 days, mucosal defect after CSP had completely healed in all cases (100%) versus 96.9% after HSP (P = 0.313). Among these healed defects, scar formation was observed in 2 of 32 cases in the CSP group compared with 19 of 31 in the HSP group (P < 0.001). Intraoperative perforation rate was significantly higher in the HSP group (15% vs 2.5%; P = 0.048). CONCLUSIONS: Mucosal defect repair after CSP is quicker compared with HSP and is more likely to result in scarless healing. HSP is more likely to cause perforation in the thin colon walls.

HrTCP20 dramatically enhance drought tolerance of sea buckthorn (Hippophae rhamnoides L). by mediating the JA signaling pathway.

Sea buckthorn, an important ecological and economical tree species, have remarkable drought and salt resistance. The plant-specific transcription factor TCPs play important roles in plant growth, development, and stress responses. However, in sea buckthorn, the molecular mechanism of TCP proteins and their involvement in drought stress are unknown. Here, we found that the expression of HrTCP20 was significantly up-regulated in sea buckthorn under drought stress. Overexpression of HrTCP20 in Arabidopsis thaliana showed that the superoxide dismutase (SOD), polyphenol oxidase (POD), and chlorophyll (SPAD) content was significantly increased by 1.37 and 1.35 times. However, the malondialdehyde (MDA) content decreased by 0.51 times. Our studies further confirmed that silencing HrTCP20 by virus-induced gene silencing (VIGS) led to a decrease in the content of defense enzymes, relative water content (RWC), and an increase of relative electrical conductivity (REC). Silencing HrTCP20 also caused the jasmonic acid (JA) content to decrease in the VIGS-treated tree. Interestingly, we found that JA accumulation content and the expression of HrLOX2, an essential enzyme for JA synthesis, was significantly inhibited in HrTCP20-silenced sea buckthorn under drought stress. Yeast two-hybrid analysis also showed that HrTCP20 is directly bound to HrLOX2. Taken together, the HrTCP20 transcription factor was a positive regulator in drought resistance of sea buckthorn. Further, our findings will provide comprehensive insights into the forest tree defence system of drought stress.

Nomogram predicting prostate cancer in patients with negative prebiopsy multiparametric magnetic resonance.

Aim: To build two nomograms for predicting the possibilities of prostate cancer (PCa) and clinically significant PCa (csPCa) in patients with negative prebiopsy multiparametric MRI (mpMRI). Methods: The independent predictors associated with PCa or csPCa in patients with negative mpMRI were determined and served in the construction of the two nomograms. Results: The nomogram predicting PCa consisted of age, positive digital rectal examination, free/total prostate-specific antigen (PSA) ratio and PSA density, while age, positive digital rectal examination and PSA density comprised the nomogram predicting csPCa. The negative predictive value of mpMRI for PCa and csPCa improved from 77.1 and 87.5% to 90.4 and 96.1%, respectively, in the training cohort (n = 376) and from 81.9 and 89.0% to 91.8 and 96.5%, respectively, in the validation cohort (n = 127) when combined with the two nomograms. Conclusion: The negative predictive value of negative mpMRI for the detection of PCa or csPCa was improved with the results of the nomograms.

When a patient has an elevated PSA level, a prostate biopsy is frequently required to diagnose prostate cancer (PCa). However, many men are not diagnosed with PCa or have indolent PCa, which means they are subjected to unnecessary biopsies that may lead to bleeding, pain and infection. With the development of multiparametric MRI (mpMRI), more biopsy-naive patients will undergo mpMRI to minimize unnecessary biopsies. Nonetheless, some patients with negative mpMRI findings but elevated levels of prostate-specific antigen still undergo prostate biopsies to rule out the possibility of MRI-invisible cancer, driving a potential for unnecessary biopsies. Therefore we developed two prediction models to estimate the likelihood of PCa and clinically significant PCa in patients with negative mpMRI, which may help to select optimal strategies to avoid unnecessary biopsies.

Lignans dramatically enhance the resistance of Fraxinus velutina Torr. by adjusting the dominant bacterium group of Agrilus planipennis Fairmaire.

BACKGROUND: Velvet ash (Fraxinus velutina Torr.) is an important wood and ornamental tree species. Emerald ash borer (EAB), Agrilus planipennis Fairmaire, is a major wood borer of velvet ash. The aim of this study was to identify the secondary metabolites of velvet ash involved in regulating the dominant bacterium group of EAB. RESULTS: The amount of lignans in the phloem of infested trees had increased by 290.96% because of A. planipennis infection. The addition of lignans to the artificial diet significantly reduced the weight of the larvae and decreased the dominant bacterial group in the larval midgut, such as Pseudomonadaceae, Xanthomonadaceae, and Enterobacteriaceae. The FvPLR1, a key gene for lignan synthesis, was obtained based on the phloem transcriptome of velvet ash. The expression of FvPLR1 in the phloem of the infested tree was significantly higher than that in the noninfested tree. Meanwhile, FvPLR1 silenced by virus-induced gene silencing showed that its expression level and the lignan content were decreased by 69.91% and 31.65%, respectively. Interestingly, silencing FvPLR1 induced alterations in the dominant bacteria group in the larvae, with the reverse trend in the lignan-fed treatment. CONCLUSION: The evidence showed that FvPLR1 was a positive regulator. The increasing synthesis of lignans leads to resistance improvement in velvet ash, which will provide comprehensive insights into the tree defense system to wood borer infestation. © 2021 Society of Chemical Industry.