Lipid-lowering Therapies and Long-term Stroke Prevention in East Asians: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Stroke prevention is a pressing global health priority, with reducing elevated lipids recognized as a key strategy. East Asians, constituting over 1.6 billion individuals and the largest racial group worldwide, are a key demographic in this effort. Yet, the effectiveness of lipid-lowering therapies for stroke prevention in this population remains uncertain. AIMS AND METHODS: We conducted a systematic review and meta-analysis of large-scale randomized controlled trials (RCTs) with at least 3 years of follow-up to evaluate the long-term impact of lipid-lowering therapies on stroke incidence in East Asians. We systematically searched four electronic databases up to January 11, 2024. The association was quantified using relative risk (RR) with a 95% confidence interval (CI), and between-study heterogeneity was evaluated using the I2 statistic. Additionally, we utilized the Cochrane Risk of Bias Tool to assess the risk of bias in each included RCT and applied the GRADE approach to evaluate the certainty of the evidence. RESULTS: This study incorporated data from 9 large-scale RCTs involving 54,354 participants. Our findings of overall analyses revealed that lipid-lowering therapies did not significantly affect the long-term incidence of all strokes (9 RCTs; 54,354 participants; RR, 0.98 [95% CI, 0.87-1.10]; P = 0.75), ischemic stroke (7 RCTs; 52,059 participants; RR, 0.91 [95% CI, 0.79-1.04]; P = 0.16), or hemorrhage stroke (7 RCTs; 52,059 participants; RR, 1.24 [95% CI, 0.97-1.59]; P = 0.09) in East Asians. Notably, there was no evidence of heterogeneity or publication bias, and the quality of evidence assessed using GRADE methodologies was rated as high. Sensitivity analyses confirmed the robustness of our results, with no single study significantly affecting the overall findings. Furthermore, subgroup analyses consistently supported the conclusions, further bolstering the reliability of our study. CONCLUSIONS: Lipid-lowering therapies did not demonstrate any beneficial effects on long-term stroke prevention among East Asians.

Introduction of the difluoromethyl group at the meta- or para-position of pyridines through regioselectivity switch.

Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C-H-difluoromethylation of pyridines represents a highly efficient economic way to access these azines. However, the direct meta-difluoromethylation of pyridines has remained elusive and methods for site-switchable regioselective meta- and para-difluoromethylation are unknown. Here, we demonstrate the meta-C-H-difluoromethylation of pyridines through a radical process by using oxazino pyridine intermediates, which are easily accessed from pyridines. The selectivity can be readily switched to para by in situ transformation of the oxazino pyridines to pyridinium salts upon acid treatment. The preparation of various meta- and para-difluoromethylated pyridines through this approach is presented. The mild conditions used also allow for the late-stage meta- or para-difluoromethylation of pyridine containing drugs. Sequential double functionalization of pyridines is presented, which further underlines the value of this work.

Meta-Selective Copper-Catalyzed C-H Arylation of Pyridines and Isoquinolines through Dearomatized Intermediates.

C(sp2)-H functionalization offers an efficient strategy for the synthesis of various elaborated N-containing heteroarenes. Along these lines, oxazino pyridines that can be readily prepared from pyridines, have been introduced as powerful substrates in radical- and ionic-mediated meta-C-H functionalization. However, the regioselective meta-C-H arylation of pyridines remains a great challenge. Herein, a copper-catalyzed meta-selective C-H arylation of pyridines and isoquinolines through bench-stable dearomatized intermediates is reported. Electrophilic aryl-Cu(III) species, generated from readily accessible aryl I(III) reagents, enable the efficient meta-arylation of a broad range of pyridines and isoquinolines. The method also allows the meta-selective alkenylation of these heteroarenes using the corresponding alkenyl I(III)-reagents. Late-stage arylation of drug-derived pyridines and larger-scale experiments demonstrate the potential of this synthetic methodology.

Multi-spectroscopies and molecular docking insights into the interaction mechanism and antioxidant activity of isoquercetin and zein nanoparticles.

The purpose of this study was to compare and characterize the theoretical properties and interaction mechanisms of zein and isoquercetin (ISO) from experimental and theoretical perspectives. Zein nanoparticles with different ISO concentrations (ZINPs) were prepared by the antisolvent precipitation method. The experimental results indicated all particles appeared spherical. When the mass ratio of zein to ISO was 10:1, the encapsulation efficiency of ZINPs reached 88.19 % with an average diameter of 126.67 nm. The multispectral method and molecular docking results confirmed that hydrogen bonding and van der Waals force played a dominant role for the binding of ISO to zein, and the primary fluorescence quenching mechanism for zein by ISO was static quenching. Furthermore, ZINPs had greater solubility and antioxidant activity, as well as inhibited the release of ISO during simulated gastrointestinal digestion processes. This research contributes to the understanding of the non-covalent binding mechanism between zein and ISO, providing a theoretical basis for the construction of ISO active carriers.

Genomics comparisons of three chromosome-level mudskipper genome assemblies reveal molecular clues for water-to-land evolution and adaptation.

INTRODUCTION: Mudskippers are a large group of amphibious fishes that have developed many morphological and physiological capacities to live on land. Genomics comparisons of chromosome-level genome assemblies of three representative mudskippers, Boleophthalmus pectinirostris (BP), Periophthalmus magnuspinnatus (PM) and P. modestus (PMO), may be able to provide novel insights into the water-to-land evolution and adaptation. METHODS: Two chromosome-level genome assemblies for BP and PM were respectively sequenced by an integration of PacBio, Nanopore and Hi-C sequencing. A series of standard assembly and annotation pipelines were subsequently performed for both mudskippers. We also re-annotated the PMO genome, downloaded from NCBI, to obtain a redundancy-reduced annotation. Three-way comparative analyses of the three mudskipper genomes in a large scale were carried out to discover detailed genomic differences, such as different gene sizes, and potential chromosomal fission and fusion events. Comparisons of several representative gene families among the three amphibious mudskippers and some other teleosts were also performed to find some molecular clues for terrestrial adaptation. RESULTS: We obtained two high-quality haplotype genome assemblies with 23 and 25 chromosomes for BP and PM respectively. We also found two specific chromosome fission events in PM. Ancestor chromosome analysis has discovered a common fusion event in mudskipper ancestor. This fusion was then retained in all the three mudskipper species. A loss of some SCPP (secretory calcium-binding phosphoprotein) genes were identified in the three mudskipper genomes, which could lead to reduction of scales for a part-time terrestrial residence. The loss of aanat1a gene, encoding an important enzyme (arylalkylamine N-acetyltransferase 1a, AANAT1a) for dopamine metabolism and melatonin biosynthesis, was confirmed in PM but not in PMO (as previously reported existence in BP), suggesting a better air vision of PM than both PMO and BP. Such a tiny variation within the genus Periophthalmus exemplifies to prove a step-by-step evolution for the mudskippers' water-to-land adaptation. CONCLUSION: These high-quality mudskipper genome assemblies will become valuable genetic resources for in-depth discovery of genomic evolution for the terrestrial adaptation of amphibious fishes.

Non-covalent interaction between hemp seed globulin and two hemp seed phenolic compounds: Mechanism and effects on protein structure, bioactivity, and in vitro simulated digestion.

This study focused on elucidating the non-covalent interactions between hemp seed globulin (GLB) and two hemp seed phenolic compounds, Cannabisin A (CA) and Cannabisin B (CB), and to explore these interactions on the protein's structure, conformation, and functionality. Fluorescence quenching and thermodynamic analysis revealed that static quenching governed non-covalent interaction processes, with hydrogen bonds and van der Waals forces functioning as major forces. This was further substantiated by molecular docking studies. The binding affinity order was CA > CB, indicating that the specific phenolic compound had a notable impact on the binding affinity. Furthermore, when complexed with CA, Tyr and Trp residues were exposed to a more hydrophilic environment than when complexed with CB. It was noted that the complexation with either CA or CB consistently affects GLB's secondary structure, particle size, and ζ-potential. GLB treated with the phenolic compounds exhibited enhanced ABTS and DPPH scavenging activities and improved digestibility compared to untreated GLB. Furthermore, the non-covalent interactions significantly increased CA's water solubility, highlighting GLB as a promising natural carrier for hydrophobic bioactive components. These findings hold potential implications for enhancing hemp seed protein applications within the food industry by positively influencing its functional properties and bioactivity.

Hemp seed globulin-alginate nanoparticles for encapsulation of Cannabisin A with enhanced colloidal stability and antioxidant activity.

This study develops hemp seed globulin (GLB)-alginate (ALG) nanoparticles (GANPs) for Cannabisin A (CA) stabilization under environmental stress and during pepsin digestion. The optimal GLB: ALG mass ratio of 1: 1.5 was determined for GANPs formation at pH 3.5, resulting in a high yield of 95.13 ± 0.91 %, a ζ-potential of -35.73 ± 1.04 mV, a hydrodynamic diameter of 470.67 ± 11.36 nm, and a PDI of 0.298 ± 0.016. GANPs were employed to encapsulate CA, achieving a high loading capacity of 13.48 ± 0.04 µg mg-1. FTIR analysis demonstrated that the formation of CA-GLB-ALG nanoparticles (CGANPs) involves electrostatic interactions, hydrogen bonding, and hydrophobic interactions. XRD and DSC analyses revealed that CA is amorphous within the CGANPs. CGANPs demonstrated remarkable dispersion stability as well as resistance to high ionic strength and high-temperature treatments, indicating their potential as efficient hydrophobic drug-delivery vehicles. When compared to free CA, CA coated within CGANPs displayed greater DPPH/ABTS scavenging activity. Furthermore, the ALG-shelled nanoparticles protected GLB from pepsin digestion and slowed the release of CA throughout the release process, extending their stay on the intestinal wall mucosa. These findings imply that CGANPs is an ideal delivery vehicle for CA as they may expand the application of CA in food items.

Effect of hydrochloric acid and citric acid with ultrasound processing on characteristics of superfine-ground pectic polysaccharides from okra (Abelmoschus esculentus L.) peel.

The structural properties and biological activities of okra pectic polysaccharides (OPs) were impacted by various extraction methods. Based on commonly grinding (40, 100 meshes) and superfine grinding okra powders, two extraction solvents (hydrochloric acid, HA; citric acid, CA) were used firstly. Next, the extraction yield, physical and chemical properties, molecular structure and functional properties of OPs were analyzed by non-ultrasonic treatment and ultrasound-assisted superfine grinding method. The outcomes demonstrated that the extraction yield of OPs rose as the particle size of the powder decreased. HA-OPs had higher molecular weight (Mw), apparent viscosity and emulsification ability than CA-OPs. CA-OPs had higher esterification degree (DE), solubility and total sugar content, and higher amounts of rhamnogalacturonan-I (RG-I) segments. Compared with OPs without ultrasound-assisted extraction, ultrasound-assisted superfine grinding extraction exhibited higher sugar content, antioxidant capacity, emulsification ability, lower Mw, DE and apparent viscosity. Finally, the correlation between structure and function of OPs was further quantified. The antioxidant capacity was positively correlated with RG-I content, and negatively correlated with DE and Mw. The emulsification ability was mainly positively correlated with the GlcA of OPs. This study provides a theoretical basis for the development of OPs foods with clear structure-function relationship, which would be instructive for the application of OPs in food and cosmetics.

Activation of assembly factor for spindle microtubules triggers progression of renal cell carcinoma via Wnt3a pathway.

Renal cell carcinoma, shorted as RCC is a well-known urological cancer with high level of morbidity and mortality. Although the regulatory role of the spindle microtubule assembly factor (ASPM) in tumor progression has been established, its relationship to the development of RCC remains unclear. To determine the significance of this gene in RCC, we examined its expression in RCC patients in the TCGA database and compared ASPM level between clinical samples of normal tissues and RCC tissues collected at our center. The prognostic relevance of ASPM was assessed by generating Kaplan-Meier survival curves and log-rank functions. Following alteration of ASPM expression using sh-ASPM or oe-ASPM transfection, RCC cell characteristics were evaluated through CCK-8, Transwell, and colony formation assays. Western blot analysis was conducted to measure levels of genes affected by ASPM, and rescue experiments were performed to explore the involvement of Wnt3a signaling in ASPM-mediated malignancy in RCC. Our findings indicate that ASPM is upregulated in RCC samples, and its levels are associated with the long-term survival of RCC patients. ASPM promotes the migration, proliferation, and invasiveness of RCC cells, and the Wnt3a pathway may be implicated in this process. In conclusion, these results indicate that ASPM contributes to the cancer progression of RCC by targeting the Wnt3a signaling pathway.

Bioactive polyphenols separated from hemp seed shells ameliorate H2 O2 -induced oxidative stress injury in human umbilical vein endothelial cells.

In the present study, we investigated the protection of hemp seed polyphenols on human umbilical vein endothelial cells (HUVEC) from H2 O2 -mediated oxidative stress injury. Fractions with different polarities were obtained by separating the hemp seed extract using HPD300 macroporous resin-packed column. The fraction, desorbed by 50% ethanol, is rich in polyphenol (789.51 ± 21.92 mg GAE/g) and has the highest antioxidant activity in vitro. HPLC-QTOF-MS/MS identified the main polyphenol components in hemp seed shells: 4 hydroxycinnamic acid amides and 15 lignanamides. The protective effects of hemp seed polyphenol against oxidative-stress injury in HUVEC cells were evaluated by cell viability, intracellular antioxidant parameters, and cell apoptosis assay. After HUVEC cells were precultured with 50 µg/ml hemp seed polyphenols, the cell viability increased significantly from 53.07 ± 2.46% (model group) to 80.65 ± 1.32% (p < 0.01). In addition, the pretreatment of HUVEC cells with polyphenol could substantially increase their intracellular superoxide dismutase activity and reduce their intracellular reactive oxygen species level, malondialdehyde content, and lactate dehydrogenase leakage index. These findings demonstrate the defensive potential of hemp seed polyphenol in reducing the incidence of cardiovascular disease. PRACTICAL APPLICATION: Hemp seed shell waste is produced while producing hemp seed kernel and has abundant phenolic compounds. This research showed that hemp seed polyphenol has potent antioxidant activity in vitro and protects HUVEC cells against H2 O2 -induced oxidative stress injury, suggesting that hemp seed polyphenol has the defensive potential to reduce the incidence of cardiovascular disease. These results indicated that polyphenol separated from hemp seed shells is valuable for further research and development, which will improve the utilization rate of hemp seed.

CMTM Family and Gastrointestinal Tract Cancers: A Comprehensive Review.

Gastrointestinal tract cancers are a highly heterogeneous group of malignant diseases, contributing significantly to the burden of death worldwide. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTMs) plays important roles in cancer development and progression. Since the first member was cloned, there have been abundant studies on the relationships between the CMTM family and human cancers. It has been reported that the CMTM family has a large potential prognostic value for multiple cancers. Meanwhile, upregulated or downregulated expression of the family members was related to advanced tumor stage, metastasis, and overall survival. Studies have also reported that these proteins play critical roles in antitumor immunity. We performed a systematic review to sum up the latest advances of CMTM family' roles in gastrointestinal tract cancers, with a primary focus on hepatocellular carcinoma and gastric carcinoma.

Desymmetric Partial Reduction of Malonic Esters.

Desymmetrization of easily available disubstituted malonic esters is a rewarding strategy to access structurally diverse quaternary stereocenters. Particularly, asymmetric reduction of malonic esters would generate a functional group with a lower oxidation state than the remaining ester, thus allowing for more chemoselective derivatization. Here, we report a new set of conditions for the zinc-catalyzed desymmetric hydrosilylation of malonic esters that afford aldehydes as the major product. Compared with alcohol-selective desymmetrization, the partial reduction uses a higher concentration of silanes and new pipecolinol-derived tetradentate ligands, proposedly to switch the pathway of zinc hemiacetal intermediates from elimination to silylation. As a result, high aldehyde-to-alcohol ratios and enantioselectivity of aldehydes are obtained from malonic esters with a large collection of substituents. Together with the abundant reactivity of aldehydes, the partial reduction has enabled an expeditious synthesis of bioactive compounds and natural metabolites containing a quaternary stereocenter.

Genomic analysis of a recombinant coxsackievirus A19 identified in Xinxiang, China, in 2019.

Coxsackievirus A19 (CV-A19) is an enterovirus belonging to the species Enterovirus C, and the prototype strain 8663 was isolated from a patient with Guillain-Barré syndrome in Japan. In this study, we determined the complete genome sequence of a CV-A19 isolate identified in a stool sample from a child with hand, foot, and mouth disease in Xinxiang, Henan, China, in 2019 and named it CV-A19 strain 2019103106/XX/CHN/2019 - 2019103106 for short. The genome of this virus consists of 7409 nucleotides, including a 6624-nucleotide open reading frame encoding a potential polyprotein precursor of 2207 amino acids. Compared with strain 8663, strain 2019103106 showed 85.1% nucleotide sequence identity in the complete genome and 85.6% identity in the VP1 coding region, reflecting their genetic divergence. Phylogenetic analysis of strain 2019103106 and other representative EV-C strains with sequences available in the GenBank database showed that CV-A19 strains could be grouped into two clusters based on the complete or 214-nucleotide partial VP1 coding regions, and 2019103106 belonged to cluster 1, with the closest relationship to CV-A19 strain SWG82 from Shandong, China. Phylogenetic trees based on the P2 and P3 coding regions highlighted the divergence between strains 2019103106 and 8663, implying that strain 2019103106 had undergone recombination. Further recombination analysis suggested that strains V18A-like CV-A1 and BBD26-like CV-A19 probably recombined to yield strain 2019103106. The present study points out the genetic diversity of CV-A19. It expands our understanding of the evolution of the CV-A19 genome, but more genome sequences of epidemic strains are needed to explain the phylogeny and evolutionary history of CV-A19 comprehensively.

Enantioselective Synthesis of Cα-Tetrasubstituted N-Hydroxyl-α-amino Nitriles via Cyanation of Ketonitrones Using Me2(CH2Cl)SiCN.

Here, we report an unprecedented catalytic enantioselective cyanation of ketonitrones enabled by the bifunctional cyanating reagent Me2(CH2Cl)SiCN. This approach allows facile access to optically active N-hydroxyl-α-amino nitriles that are of high synthetic value but difficult to acquire by other methods. The use of bifunctional cyanating reagent Me2(CH2Cl)SiCN not only achieves an enantioselectivity higher than that with TMSCN but also enables various diversification reactions of the resulting silylated adducts. This represents the first enantioselective catalytic nucleophilic addition reaction of unactivated ketone-derived nitrones, exhibiting the potential of such tetrasubstituted C═N bonds for asymmetric synthesis of N-hydroxy α-amino acids and other N-hydroxy tertiary amines.

Catalytic reductive desymmetrization of malonic esters.

Desymmetrization of fully substituted carbons with a pair of enantiotopic functional groups is a practical strategy for the synthesis of quaternary stereocentres, as it divides the tasks of enantioselection and C-C bond formation. The use of disubstituted malonic esters as the substrate of desymmetrization is particularly attractive, given their easy and modular preparation, as well as the high synthetic values of the chiral monoester products. Here, we report that a dinuclear zinc complex with a tetradentate ligand can selectively hydrosilylate one of the carbonyls of malonic esters to give α-quaternary ß-hydroxyesters, providing a promising alternative to the desymmetric hydrolysis using carboxylesterases. The asymmetric reduction features excellent enantiocontrol that can differentiate sterically similar substituents and high chemoselectivity towards the diester motif of substrates. Together with the versatile preparation of malonic ester substrates and post-reduction derivatization, the desymmetric reduction has enabled the synthesis of a diverse array of quaternary stereocentres with distinct structural features.

Coconut genome assembly enables evolutionary analysis of palms and highlights signaling pathways involved in salt tolerance.

Coconut (Cocos nucifera) is the emblematic palm of tropical coastal areas all around the globe. It provides vital resources to millions of farmers. In an effort to better understand its evolutionary history and to develop genomic tools for its improvement, a sequence draft was recently released. Here, we present a dense linkage map (8402 SNPs) aiming to assemble the large genome of coconut (2.42 Gbp, 2n = 32) into 16 pseudomolecules. As a result, 47% of the sequences (representing 77% of the genes) were assigned to 16 linkage groups and ordered. We observed segregation distortion in chromosome Cn15, which is a signature of strong selection among pollen grains, favouring the maternal allele. Comparing our results with the genome of the oil palm Elaeis guineensis allowed us to identify major events in the evolutionary history of palms. We find that coconut underwent a massive transposable element invasion in the last million years, which could be related to the fluctuations of sea level during the glaciations at Pleistocene that would have triggered a population bottleneck. Finally, to better understand the facultative halophyte trait of coconut, we conducted an RNA-seq experiment on leaves to identify key players of signaling pathways involved in salt stress response. Altogether, our findings represent a valuable resource for the coconut breeding community.

Physicochemical Properties, Antioxidant and Antidiabetic Activities of Polysaccharides from Quinoa (Chenopodium quinoa Willd.) Seeds.

Quinoa is known for its rich nutrients and bioactive compounds. In order to elucidate the preliminary structural characteristics and biological activity of polysaccharides from quinoa (QPs), five crude polysaccharides (QPE50, QPE60, QPE70, QPE80 and QPE90) were successively fractionated by gradient ethanol, and their physicochemical properties, antioxidant and antidiabetic activities were analyzed. The results implied that their total sugar contents were 52.82%, 63.69%, 67.15%, 44.56%, and 41.01%, and their weight-average molecular weights were 13,785 Da, 6489 Da, 4732 Da, 3318 Da, and 1960 Da, respectively. Glucose was a predominantly monosaccharide in these QPs, which together in QPE50, QPE60, QPE70, QPE80, and QPE90, respectively, made up 94.37%, 87.92%, 92.21%, 100%, and 100% of the total polysaccharide. Congo red test showed that all five QPs contained triple-helix structure. The Fourier transform-infrared spectroscopy (FT-IR) and X-ray diffractometry (XRD) results suggest that the QPs form a semi-crystalline polymer constituted typical functional groups of polysaccharide including CO, CH and OH. The thermogravimetric analysis (TGA) of QPs showed that weight loss was at about 200 °C and 320 °C. The observation from scanning electron microscope (SEM) and atomic force microscope (AFM) image indicated that the morphology of QPs exhibited spherical shape. Antioxidant and antidiabetic assay exhibited that all five QPs samples had certain antioxidant and antidiabetic activities, and QPE90 showed the best antioxidant and antidiabetic activity. Overall, QPs present a promising natural source of food antioxidants and antidiabetic agents.

Calcium Carbonate/Gelatin Methacrylate Microspheres for 3D Cell Culture in Bone Tissue Engineering.

Hydrogel microspheres have been widely used as cell carriers and three-dimensional cell culture matrices. However, these microspheres are associated with several unfavorable properties for bone tissue engineering applications, for example, their surface is too smooth to attach cells and they do not contain inorganic materials. This article presents a new method to overcome these disadvantages by depositing CaCO3 crystals on the hydrogel microsphere surface. Specifically, we used a nonplanar flow-focusing microfluidic device to produce gelatin methacrylate (GelMA)-/Na2CO3-based microspheres. We subsequently obtained CaCO3 crystals by a chemical reaction between Na2CO3 and CaCl2. The efficacy of this method was demonstrated by in vitro experiments with human umbilical vein endothelial cells (HUVEC) and immortalized mouse embryonic fibroblasts (iMEF). Cell culture on GelMA/CaCO3 microspheres showed that cells can easily attach and adhere to GelMA/CaCO3 microspheres and maintain high viability. Alkaline phosphatase (ALP) expression was increased as well. These results suggest that this novel microsphere has a high potential for bone tissue engineering applications. Impact statement Microspheres as cell culture substrates have attracted a great deal of attention. The combination of organic and inorganic materials offers the unique merits in bone tissue engineering. In this study, there are two contributions. First, the organic and inorganic material of gelatin methacrylate (GelMA) and CaCO3 were successfully combined, especially, CaCO3 was formed as crystals to enhance cell attachment. Second, microspheres were successfully fabricated with one-step process: that is, the microfluidic technique was coupled with the CaCO3 precipitation in situ. Cell culture shows that the GelMA/CaCO3 microspheres proposed in this study have a high potential for bone tissue engineering applications.

An array pairing method for localizing distributed sources by acoustic beamforming.

An acoustic beamforming concept is presented that alleviates some misrepresentation caused by deconvolution algorithms that can oversimplify distributed sources as a series of point sources. In the Array Pairing Method (APM) an initial array beamforms the acoustic source, then an iterative randomized array is calculated whereby the square-rooted product of the beamformer output possesses a minimum product of Maximum Sidelobe Level (MSL) and Main Lobe Width (MLW). A single and distributed source simulation and a single and dual speaker experiment using the APM reveal significant improvements in MSL and MLW and resolution in the distributed source region.