The Marssonina rosae effector MrSEP43 suppresses rose immunity by targeting the orphan protein RcBROG.

Rose black spot disease, caused by Marssonina rosae (syn. Diplocarpon rosae), is one of the most widespread diseases of field-grown roses worldwide. Pathogens have been found to interfere with or stimulate plant immune response through the secreted effectors. However, the molecular mechanism involved in inhibition of rose immune response by M. rosae effectors remains poorly understood. In this study, we identified the effector MrSEP43, which played a pivotal role in promoting the virulence of M. rosae and enhancing rose susceptibility by reducing callose deposition, H2O2 accumulation, and the expression of defense genes in jasmonic acid signaling pathway. Through Y2H, BiFC, and LUC assays, MrSEP43 was proved to interact with the rose orphan protein RcBROG. RcBROG, which was a positive regulator of defense against M. rosae, enhanced rose resistance by increasing callose deposition, H2O2 accumulation, and expression of RcERF1 in the ethylene signaling pathway. Overall, our findings suggested that the virulence effector MrSEP43 from M. rosae specifically targeted the orphan protein RcBROG to suppress rose immune response to M. rosae. These results provided new insight into how M. rosae manipulated and successfully colonized rose leaves, and were essential for preventing the breakdown of resistance to rose black spot disease.

Relationship between serum apolipoprotein B and risk of all-cause and cardiovascular disease mortality in individuals with hypertension: a prospective cohort study.

BACKGROUND: Dyslipidemia frequently coexists with hypertension in the population. Apolipoprotein B (ApoB) is increasingly considered a more potent predictor of cardiovascular disease (CVD). Abnormal levels of serum ApoB can potentially impact the mortality risk. METHODS: The prospective cohort study employed data from the National Health and Nutrition Examination Survey (NHANES), which was performed between 2005 and 2016, with follow-ups extended until December 2019. Serum ApoB concentrations were quantified using nephelometry. In line with the NHANES descriptions and recommendations, the reference ranges for ApoB concentrations are 55-140 and 55-125 mg/dL for men and women, respectively. Participants were categorized into low, normal, and high ApoB levels. The low and high groups were combined into the abnormal group. In this study, all-cause mortality (ACM) and CVD mortality (CVM) were the endpoints. Survey-weighted cox hazards models were used for evaluating the correlation between serum ApoB levels and ACM and CVM. A generalized additive model (GAM) was employed to examine the dose-dependent relationship between ApoB levels and mortality risk. RESULTS: After a median of 95 (interquartile range: 62-135) months of follow-up, 986 all-cause and 286 CVD deaths were recorded. The abnormal ApoB group exhibited a trend toward an elevated risk of ACM in relative to the normal group (HR 1.22, 95% CI: 0.96-1.53). The risk of CVM was elevated by 76% in the ApoB abnormal group (HR 1.76, 95% CI: 1.28-2.42). According to the GAM, there existed a nonlinear association between serum ApoB levels and ACM (P = 0.005) and CVM (P = 0.009). CONCLUSIONS: In the US hypertensive population, serum Apo B levels were U-shaped and correlated with ACM and CVM risk, with the lowest risk at 100 mg/dL. Importantly, abnormal Apo B levels were related to an elevated risk of ACM and CVM. These risks were especially high at lower Apo B levels. The obtained findings emphasize the importance of maintaining appropriate Apo B levels to prevent adverse outcomes in hypertensive individuals.

Marein, a novel natural product for restoring chemo-sensitivity to cancer cells through competitive inhibition of ABCG2 function.

The pivotal roles of ATP-binding cassette (ABC) transporters in drug resistance have been widely appreciated. Here we report that marein, a natural product from Coreopsis tinctoria Nutt, is a potent chemo-sensitizer in drug resistant cancer cells overexpressing ABCG2 transporter. We demonstrate that marein can competitively inhibit efflux activity of ABCG2 protein and increase the intracellular accumulation of the chemotherapeutic drugs that belong to substrate of this transporter. We further show that marein can bind to the conserved amino acid residue F439 of ABCG2, a critical site for drug-substrate interaction. Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

Indole-3 acetic acid negatively regulates rose black spot disease resistance through antagonizing the salicylic acid signaling pathway via jasmonic acid.

MAIN CONCLUSION: IAA cooperates with JA to inhibit SA and negatively regulates rose black spot disease resistance. Black spot disease caused by the fungus Marssonina rosae is the most prevalent and severe ailment in rose cultivation, leading to the appearance of black spots on leaves and eventual leaf fall, significantly impacting the utilization of roses in gardens. Salicylic acid (SA) and jasmonic acid (JA) are pivotal hormones that collaborate with indole-3 acetic acid (IAA) in regulating plant defense responses; however, the detailed mechanisms underlying the induction of black spot disease resistance by IAA, JA, and SA remain unclear. In this study, transcript analysis was conducted on resistant (R13-54) and susceptible (R12-26) lines following M. rosae infection. In addition, the impact of exogenous interference with IAA on SA- and JA-mediated disease resistance was examined. The continuous accumulation of JA, in synergy with IAA, inhibited activation of the SA signaling pathway in the early infection stage, thereby negatively regulating the induction of effective resistance to black spot disease. IAA administration alleviated the inhibition of SA on JA to negatively regulate the resistance of susceptible strains by further enhancing the synthesis and accumulation of JA. However, IAA did not contribute to the negative regulation of black spot resistance when high levels of JA were inhibited. Virus-induced gene silencing of RcTIFY10A, an inhibitor of the JA signaling pathway, further suggested that IAA upregulation led to a decrease in disease resistance, a phenomenon not observed when the JA signal was inhibited. Collectively, these findings indicate that the IAA-mediated negative regulation of black spot disease resistance relies on activation of the JA signaling pathway.

Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

Fabrication of large-area photonic crystal-modified X-ray scintillator imager for optical coding imaging.

The limited pattern area of periodic nanostructures limits the development of practical devices. This study introduces an X-ray interference lithography (XIL) stitching technique to fabricate a large-area (1.5 cm × 1.5 cm) two-dimensional photonic crystal (PhC) on the YAG: Ce scintillator, which functions as an encoder in a high numerical aperture optical encoding imaging system to effectively capture high-frequency information. An X-ray imaging experiment revealed a substantial 7.64 dB improvement in the signal-to-noise ratio (SNR) across a large field of view (2.6 mm × 2.6 mm) and achieved comparable or superior image quality with half the exposure dose. These findings have significant implications for advancing practical applications of X-ray imaging.

Cooperative correction method for distortion and dispersion of deflected field of view in Risley-prism bionic-human-eye imaging systems.

The Risley-prism imaging system (RPIS) is a powerful way to achieve bionic human eye imaging with great advantages on large field of view (FOV) and variable resolution imaging owing to the autonomous controlled deflection of light. But the imaging dispersion originating from nonlinear and uneven light deflection results in limited imaging wavelength that seriously hinders its application. The existing solutions for imaging dispersion mainly rely on the hardware, which generally has bulky structure and limited improvement on image. Besides, the existing image evaluation methods for dispersion are not suitable for RPIS due to inhomogeneous dispersion. Herein, this paper systematically analyzes the mechanism and characteristics of dispersion in the RPIS, and proposes a cooperative correction method for image distortion and dispersion of multiple-color imaging, achieving the elimination of distortion and dispersion simultaneously without changing the optical structure. A dispersion evaluation index based on Pearson's correlation coefficient (PCC) is also established, and the objectivity and validity of the index are proved by experiments. Furthermore, a kind of compact RPIS based on an RGB camera is built, and both indoor and outdoor experiments are conducted. The experimental results demonstrate that proposed algorithm has strong universality and robustness for various scenes and targets.

Superior predictive value of estimated pulse wave velocity for all-cause and cardiovascular disease mortality risk in U.S. general adults.

BACKGROUND: Estimated pulse wave velocity (ePWV) has been proposed as a potential approach to estimate carotid-femoral pulse wave velocity. However, the potential of ePWV in predicting all-cause mortality (ACM) and cardiovascular disease mortality (CVM) in the general population is unclear. METHODS: We conducted a prospective cohort study using the data of 33,930 adults (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 until the end of December 2019. The study outcomes included ACM and CVM. Survey-weighted Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between ePWV and ACM and CVM. To further investigate whether ePWV was superior to traditional risk factors in predicting ACM and CVM, comparisons between ePWV and the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) models were performed. Integrated Discriminant Improvement (IDI) and Net Reclassification Improvement (NRI) were employed to analyze differences in predictive ability between models. RESULTS: The weighted mean age of the 33,930 adults included was 45.2 years, and 50.28% of all participants were men. In the fully adjusted Cox regression model, each 1 m/s increase in ePWV was associated with 50% and 49% increases in the risk of ACM (HR 1.50; 95% CI, 1.45-1.54) and CVM (HR 1.49; 95% CI, 1.41-1.57), respectively. After adjusting for FRS, each 1 m/s increase in ePWV was still associated with 29% (HR 1.29; 95% CI, 1.24-1.34) and 34% (HR 1.34; 95% CI, 1.23-1.45) increases in the risk of ACM and CVM, respectively. The area under the curve (AUC) predicted by ePWV for 10-year ACM and CVM were 0.822 and 0.835, respectively. Compared with the FRS model, the ePWV model improved the predictive value of ACM and CVM by 5.1% and 3.8%, respectively, with no further improvement in event classification. In comparison with the PCE model, the ePWV model's ability to predict 10-year ACM and CVM was improved by 5.1% and 3.5%, and event classification improvement was improved by 34.5% and 37.4%. CONCLUSIONS: In the U.S. adults, ePWV is an independent risk factor for ACM and CVM and is independent of traditional risk factors. In the general population aged 20 to 85 years, ePWV has a robust predictive value for the risk of ACM and CVM, superior to the FRS and PCE models. The predictive power of ePWV likely originates from the traditional risk factors incorporated into its calculation, rather than from an indirect association with measured pulse wave velocity.

Using machine learning to trace the pollution sources of disinfection by-products precursors compared to receptor models.

To increase the efficiency of managing backup water resources, it is critical to identify and allocate pollution sources. Source apportionment of dissolved organic matter (DOM) was investigated in our work. Parallel factor analysis (PARAFAC) and the Spearman correlation analysis were used for source identification. After that, a newly hybrid model applying the fuzzy c-means and support vector regression (FCM-SVR) was employed for source apportionment compared to receptor models. The results demonstrated that the FCM-SVR model exhibited excellent generalization, and only required standardization and normalization as pre-processing steps for dataset. According to the results, microbial sources played a key role (28.1 %) in the formation potential of disinfection byproducts (DBPFPs). Additionally, shipping marine sources exhibited a substantial contribution (21.2 %) to DBPFPs. The prediction accuracy of DBPFPs was matched or exceeded receptor models, and the R2 of DOC (0.884) was significantly high. Therefore, we recommend the FCM-SVR model combined with PARAFAC to trace the source of DBPFPs as its significant effectiveness in source identification, source apportionment, and prediction accuracy, possessing the potential for further applicability in tracking more organic compounds. ENVIRONMENTAL IMPLICATION: The disinfection byproducts precursors in water sources, which were thought to be hazardous materials in this study, are proved to be chlorinated into carcinogenic disinfection byproducts (DBPs) during drinking water treatment, However, the source apportionment methods of DBPs are not well developed compared to other inorganic matter, e.g., heavy metals and ammonia nitrogen. We proposed a new FCM-SVR model to trace the source of DBPs, which required easier pre-treatment and resulted a better source apportionment and prediction accuracy. As a result, it could provide a different prospect and useful management advices to trace the source of DBPs.

Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

OBJECTIVES: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl-1/mIU∙l-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). METHODS: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl-1/mIU∙l-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. RESULTS: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. CONCLUSIONS: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl-1/mIU∙l-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03224312).

Screening for primary aldosteronism on and off interfering medications.

OBJECTIVE: To determine whether antihypertensives will affect diagnostic accuracy of the aldosterone-to-renin ratio (ARR) to an extent that is clinically relevant. METHODS: Confirmatory tests were used to confirm or exclude PA diagnosis. Area under the receiver operating characteristic curve (AUC), specificity and sensitivity of ARR performance in different conditions were calculated. RESULTS: 208 PA and 78 essential hypertension (EH), and 125 PA and 206 EH patients, were included in the retrospective and prospective cohort, respectively. AUC of ARR on interfering medications was comparable to ARR off interfering medications (retrospective: 0.82 vs. 0.87, p = 0.20; prospective: 0.78 vs. 0.84, p = 0.07). At a threshold of 20 pg/µIU, the sensitivity of ARR on interfering medications was lower (11.1-23.2%) while the specificity was higher (10.2-15.2%) than ARR off interfering medications. However, when the ARR threshold on interfering medications was lowered to 10 pg/µIU, both the sensitivity (retrospective: 0.91 vs. 0.90, p = 0.61; prospective: 0.86 vs. 0.82, p = 0.39) and specificity (retrospective: 0.49 vs. 0.59, p = 0.20; prospective: 0.58 vs. 0.66, p = 0.10) were comparable to the ARR threshold off interfering medications. CONCLUSION: Using ARR to screen for PA whilst taking interfering antihypertensive drugs is feasible in most cases, but the ARR threshold needs to be reduced. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04991961.

Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism.

OBJECTIVE: Adrenal venous sampling (AVS) is recommended for identifying the subtype of primary aldosteronism before making a surgical treatment decision, but failed cannulation of one adrenal vein is common. To evaluate whether using results of one adrenal vein during AVS could accurately predict unilateral primary aldosteronism. METHODS: A retrospective study was conducted in primary aldosteronism patients receiving bilaterally or unilaterally successful AVS. The aldosterone-cortisol ratio from the adrenal vein divided by the aldosterone-cortisol ratio from the inferior vena cava (IVC) was calculated as the AV/IVC index. RESULTS: The study examined 455 patients with primary aldosteronism, including 347 patients with unilateral primary aldosteronism. Among them, 250 and 125 patients received non- adrenocorticotropic hormone (ACTH) and ACTH-stimulated AVS, respectively, and 80 patients received both forms of AVS. Under non-ACTH-stimulated AVS, AUC of the AV/IVC index to diagnose ipsilateral and contralateral primary aldosteronism were 0.778 and 0.924, respectively. The specificity was 100% for both, with sensitivities of 5 and 26%, respectively, when using cutoffs of 17.05 to diagnose ipsilateral primary aldosteronism and 0.15 to diagnose contralateral primary aldosteronism. When using cutoffs of 3.60 and 0.70, the specificity decreased, but if combined with CT results (ipsilateral or contralateral adrenal nodules larger than 10 mm), the specificity could be maintained at 99%, with sensitivities of 33 and 45%, respectively. Under ACTH-stimulated AVS, the AV/IVC index showed similar accuracy to diagnose ipsilateral and contralateral primary aldosteronism. CONCLUSION: The unilateral AV/IVC index can be used to diagnose unilateral primary aldosteronism during AVS. Combining CT results can increase the accuracy further.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Three-dimensional visualization of the vascular bundle in a branched bamboo node.

Bamboo is a natural vascular bundle (VB) reinforced composite material used in more than 10 fields such as construction and furniture. The nodes in bamboo are crucial to its mechanical properties, but understanding of its performance is limited by lack of knowledge about the three-dimensional (3D) structure of the node. This work aimed to non-destructively identify the multi-dimensional characteristics of the VB in a bamboo branched node (BN) using X-ray microtomography (µCT). The VB was segmented from the BN using deep learning combined with the Watershed algorithm. The 3D model reconstruction and characterization of the VB were also conducted. It was found that the structure of VBs showed significant changes along the height of the BN. The VBs formed a complex 3D structure, VBs of the culm are connected with those of the branch, and the connectivity of the conducting tissue and fibers was 88.91% and 99.95%, respectively. The conducting tissue and the fibers had similar shapes but varying thicknesses, which enabled VBs to perform both water transport and mechanical support functions. The volumes fraction of parenchyma, fibers, and conducting tissue in the BN were 61.3%, 35.3%, and 3.4%, respectively, but the tissue proportion of the different heights of the BN varied from each other. The nodal ridge was a mechanical weak point of the BN, with a maximum fibers proportion of 43.8%. This study contributes to understanding the relationship of VBs between the branch and the culm. It provides a structural perspective for understanding the mechanical properties of BN and a theoretical basis for optimizing bamboo utilization efficiency.

Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism: The ADOPA Randomized Clinical Trial.

Importance: Adrenal venous sampling (AVS) is usually recommended to distinguish between unilateral and bilateral primary aldosteronism (PA) before definitive surgical or medical treatment is offered. Whether a treatment decision based on AVS with or without corticotropin (ACTH) stimulation leads to different biochemical and clinical remission rates in patients with PA remains unclear. Objective: To evaluate whether treatment decisions based on AVS with or without ACTH stimulation lead to different biochemical and clinical remission rates in patients with PA. Design, Setting, and Participants: This randomized clinical trial (RCT) was conducted at a tertiary hospital in China from July 8, 2020, to February 20, 2023, among patients with PA aged 18 to 70 years. Patients were followed up for 12 months after the initiation of treatment. An intention-to-diagnose analysis was conducted. Interventions: Patients were randomly assigned to undergo either ACTH-stimulated or non-ACTH-stimulated AVS. Main Outcomes and Measures: The primary end point was the proportion of patients with complete biochemical remission after 12 months of follow-up. Secondary outcomes included the proportion of patients who achieved complete clinical remission after 12 months of follow-up, dosages of antihypertensive agents, rate of successful bilateral AVS, and adverse events. Results: Of 228 patients with PA, 115 were randomized to the non-ACTH-stimulated group (median age, 50.0 years [IQR, 41.0-57.0 years]; 70 males [60.9%]) and 113 to the ACTH-stimulated group (median age, 50.0 years [IQR, 43.5-56.5 years]; 63 males [55.8%]). A total of 68 patients (59.1%) underwent adrenalectomy in the non-ACTH group and 65 (57.5%) in the ACTH group. There was no significant difference in the proportion of patients with complete biochemical remission who were managed on the basis of AVS with vs without ACTH stimulation (with: 56 of 113 [49.6%]; without: 59 of 115 [51.3%]; P = .79). There also was no significant difference in the proportion of patients who achieved complete clinical remission between the non-ACTH and ACTH groups (26 of 115 [22.6%] and 31 of 113 [27.4%], respectively; P = .40). The intensity of therapy with antihypertensives, successful catheterization of bilateral adrenal veins, and incidence of adverse events did not significantly differ between the non-ACTH and ACTH groups. Conclusions and Relevance: In this RCT, treatment of PA on the basis of non-ACTH-stimulated or ACTH-stimulated AVS did not lead to significant differences in clinical outcomes for the patients. These results suggest that ACTH stimulation during AVS may not have clinical benefit, at least in the Chinese population. Trial Registration: ClinicalTrials.gov Identifier: NCT04461535.

Exogenous Jasmonic Acid Alleviates Blast Resistance Reduction Caused by LOX3 Knockout in Rice.

Lipoxygenase 3 (LOX3) is a lipid peroxidase found in rice embryos that is known to affect seed quality. Interestingly, deletion of the LOX3 gene has been shown to improve rice seed quality but decrease resistance to rice blast disease and drought. To investigate these opposing effects, we generated a LOX3 knockout construct (ΔLox3) in rice (Oryza sativa L.) plants. Blast resistance and transcription levels of rice genes in ΔLox3 rice plants and the effects of exogenous jasmonic acid (JA) on resistance and transcriptional levels of rice genes in Magnaporthe oryzae-infected ΔLox3 rice plants were further elucidated. The results showed that the ΔLox3 plants exhibited normal phenotypes, with high levels of methyl-linolenate and reactive oxygen species (ROS), and the genes involved in three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contributed to rice seed quality. M. oryzae-infected ΔLox3 plants exhibited serious blast symptoms with a reduced defense response but increased ROS-mediated cell death, and the genes involved in seven KEGG pathways contributed to rice seed quality. Exogenous JA treatment alleviated blast symptoms in infected ΔLox3 plants by hindering hyphal expansion, inhibiting ROS-mediated cell death, and increasing the defense response, and genes involved in 12 KEGG pathways contributed to rice seed quality. These findings demonstrate that LOX3 plays an important role in rice growth and defense, and its knockout improves rice quality at the expense of disease resistance. Exogenous JA provides a means to compensate for the reduction in defense responses of LOX3 knockout rice lines, suggesting potential applications in agricultural production.

Higher systemic immune-inflammation index and systemic inflammation response index levels are associated with stroke prevalence in the asthmatic population: a cross-sectional analysis of the NHANES 1999-2018.

Background: Significant evidence suggests that asthma might originate from low-grade systemic inflammation. Previous studies have established a positive association between the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI) levels and the risk of stroke. However, it remains unclear whether SII, SIRI and the prevalence of stroke are related in individuals with asthma. Methods: The present cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. SII was calculated using the following formula: (platelet count × neutrophil count)/lymphocyte count. SIRI was calculated using the following formula: (neutrophil count × monocyte count)/lymphocyte count. The Spearman rank correlation coefficient was used to determine any correlation between SII, SIRI, and the baseline characteristics. Survey-weighted logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to determine the association between SII, SIRI, and stroke prevalence. The predictive value of SII and SIRI for stroke prevalence was assessed through receiver operating characteristic (ROC) curve analysis, with the area under the ROC curve (AUC) being indicative of its predictive value. Additionally, clinical models including SIRI, coronary heart disease, hypertension, age, and poverty income ratio were constructed to evaluate their clinical applicability. Results: Between 1999 and 2018, 5,907 NHANES participants with asthma were identified, of which 199 participants experienced a stroke, while the remaining 5,708 participants had not. Spearman rank correlation analysis indicated that neither SII nor SIRI levels exhibited any significant correlation with the baseline characteristics of the participants (r<0.1). ROC curves were used to determine the optimal cut-off values for SII and SIRI levels to classify participants into low- and high-level groups. Higher SII and SIRI levels were associated with a higher prevalence of stroke, with ORs of 1.80 (95% CI, 1.18-2.76) and 2.23 (95% CI, 1.39-3.57), respectively. The predictive value of SIRI (AUC=0.618) for stroke prevalence was superior to that of SII (AUC=0.552). Furthermore, the clinical model demonstrated good predictive value (AUC=0.825), with a sensitivity of 67.1% and specificity of 87.7%. Conclusion: In asthmatics, higher levels of SII and SIRI significantly increased the prevalence of stroke, with its association being more pronounced in individuals with coexisting obesity and hyperlipidaemia. SII and SIRI are relatively stable novel inflammatory markers in the asthmatic population, with SIRI having a better predictive value for stroke prevalence than SII.

A mid-infrared high-performance spectropolarimetry filter based on dual-mode independent modulation.

Spectropolarimetry detection provides multi-dimensional accurate information with broad applications from biomedicine to remote sensing. Existing methods for simultaneously obtaining spectra and polarizations are either large and complex systems or miniaturized devices with too low spectral resolution or poor polarization selectivity, which inherently generate cross-talk of substantial information. Here, we propose a compact and single-chip integrated high-performance mid-infrared spectropolarimetry filter (SPF), whose narrowband spectral and polarization characteristics can be independently modulated by different polarization modes. A SPF is designed with a polarization extinction ratio (ER) over 106, spectral resolution (SR, λ/Δλ) up to 822 and a transmission efficiency of 90% in the mid-infrared band. The experimental ER and SR are over 3 × 104 and up to 387 respectively with a transmission efficiency of 60%. These results agree well with the theoretical results and can accurately obtain spectral and polarization information simultaneously. This device has been used in tumor diagnostics to well distinguish striated muscle and rhabdomyosarcoma tissue for demonstration. It can be easily extended to different wavelength ranges and provides a new and powerful approach for multi-dimensional optical information acquisition, target detection and accurate identification.

Potential values of formalin-fixed paraffin-embedded tissues for intratumoral microbiome analysis in breast cancer.

Breast cancer (BC) tissues have been proved to harbor microorganisms, which could potentially contribute to oncogenesis. Formalin-fixed paraffin-embedded (FFPE) tissues are the most widespread clinical samples in BC research. To verify the potential of FFPE tissues in microbiological analysis, we analyzed the microbial communities of FFPE and fresh frozen (FF) tumor samples from 30 participants diagnosed with BC deploying 16S rRNA sequencing. The operational taxonomic units (OTUs) analysis showed that 78.55% of OTUs in FFPE samples were consistent with FF samples. The composition of core bacteria did not change much, and there is also no difference in alpha diversity between FFPE and FF (without unclassified bacteria). Taxonomic variation results show that Firmicutes and Bacteroidota phyla, and their major classes, maintained the same proportion under two preservation methods. In addition, the major class Gammaproteobacteria, as well as its dominant orders Burkholderiales and Pseudomonadales all showed no significant difference in paired analysis. Moreover, the Proteobacteria and Actinobacteriota phyla showed no significant difference between FFPE and FF samples after subtracting unclassified bacteria. Therefore, premised with the intrinsic tumor heterogeneity and unclassified bacteria, there are potential values of FFPE tissues for intratumoral microbiome analysis in breast cancer.

Estimated pulse wave velocity is associated with all-cause and cardio-cerebrovascular disease mortality in stroke population: Results from NHANES (2003-2014).

Background: Arterial stiffness is a significant determinant and evaluation of cardio-cerebrovascular disease and all-cause mortality risk in the stroke population. Estimated pulse wave velocity (ePWV) is a well-established indirect measure of arterial stiffness. We examined the association of ePWV with all-cause and cardio-cerebrovascular disease (CCD) mortality in the stroke population in a large sample of US adults. Methods: The study design was a prospective cohort study with data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014, between the ages of 18-85 years, with follow-up through December 31, 2019. 1,316 individuals with stroke among 58,759 participants were identified and ultimately, 879 stroke patients were included in the analysis. ePWV was calculated from a regression equation using age and mean blood pressure according to the following formula: ePWV = 9.587 - (0.402 × age) + [4.560 × 0.001 × (age2)] - [2.621 × 0.00001 × (age2) × MBP] + (3.176 × 0.001 × age × MBP) - (1.832 × 0.01 × MBP). Survey-weighted Cox regression models were used to assess the association between ePWV and all-cause and CCD mortality risk. Results: The high ePWV level group had a higher increased risk of all-cause mortality and CCD mortality compared to the low ePWV level group after fully adjusting for covariates. With an increase in ePWV of 1 m/s, the risk of all-cause and CCD mortality increased by 44%-57% and 47%-72% respectively. ePWV levels were linearly correlated with the risk of all-cause mortality (P for nonlinear = 0.187). With each 1 m/s increase in ePWV, the risk of all-cause mortality increased by 44% (HR 1.44, 95% CI: 1.22-1.69; P < 0.001). When ePWV was <12.1 m/s, an increase in ePWV per 1 m/s was associated with a 119% (HR 2.19, 95% CI: 1.43-3.36; P < 0.001) increase in CCD mortality risk; when ePWV was ≥12.1 m/s, an increase in ePWV per 1 m/s was not associated with in CCD mortality risk. Conclusion: ePWV is an independent risk factor for all-cause and CCD mortality in stroke patients. Higher levels of ePWV are associated with higher all-cause mortality and CCD mortality in stroke patients.