Signed Distance Correlation (SiDCo): an online implementation of distance correlation and partial distance correlation for data-driven network analysis.

MOTIVATION: There is a need for easily accessible implementations that measure the strength of both linear and non-linear relationships between metabolites in biological systems as an approach for data-driven network development. While multiple tools implement linear Pearson and Spearman methods, there are no such tools that assess distance correlation. RESULTS: We present here SIgned Distance COrrelation (SiDCo). SiDCo is a GUI platform for calculation of distance correlation in omics data, measuring linear and non-linear dependencies between variables, as well as correlation between vectors of different lengths, e.g. different sample sizes. By combining the sign of the overall trend from Pearson's correlation with distance correlation values, we further provide a novel "signed distance correlation" of particular use in metabolomic and lipidomic analyses. Distance correlations can be selected as one-to-one or one-to-all correlations, showing relationships between each feature and all other features one at a time or in combination. Additionally, we implement "partial distance correlation," calculated using the Gaussian Graphical model approach adapted to distance covariance. Our platform provides an easy-to-use software implementation that can be applied to the investigation of any dataset. AVAILABILITY AND IMPLEMENTATION: The SiDCo software application is freely available at https://complimet.ca/sidco. Supplementary help pages are provided at https://complimet.ca/sidco. Supplementary Material shows an example of an application of SiDCo in metabolomics.

Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages.

A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.

Disparate temperature-dependent virus-host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium.

Since its emergence in December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally and become a major public health burden. Despite its close phylogenetic relationship to SARS-CoV, SARS-CoV-2 exhibits increased human-to-human transmission dynamics, likely due to efficient early replication in the upper respiratory epithelium of infected individuals. Since different temperatures encountered in the human upper and lower respiratory tract (33°C and 37°C, respectively) have been shown to affect the replication kinetics of several respiratory viruses, as well as host innate immune response dynamics, we investigated the impact of temperature on SARS-CoV-2 and SARS-CoV infection using the primary human airway epithelial cell culture model. SARS-CoV-2, in contrast to SARS-CoV, replicated to higher titers when infections were performed at 33°C rather than 37°C. Although both viruses were highly sensitive to type I and type III interferon pretreatment, a detailed time-resolved transcriptome analysis revealed temperature-dependent interferon and pro-inflammatory responses induced by SARS-CoV-2 that were inversely proportional to its replication efficiency at 33°C or 37°C. These data provide crucial insight on pivotal virus-host interaction dynamics and are in line with characteristic clinical features of SARS-CoV-2 and SARS-CoV, as well as their respective transmission efficiencies.

Dimerization and autophosphorylation of the MST family of kinases are controlled by the same set of residues.

The Hippo pathway controls tissue growth and regulates stem cell fate through the activities of core kinase cassette that begins with the Sterile 20-like kinase MST1/2. Activation of MST1/2 relies on trans-autophosphorylation but the details of the mechanisms regulating that reaction are not fully elucidated. Proposals include dimerization as a first step and include multiple models for potential kinase-domain dimers. Efforts to verify and link these dimers to trans-autophosphorylation were unsuccessful. We explored the link between dimerization and trans-autophosphorylation for MST2 and the entire family of MST kinases. We analyzed crystal lattice contacts of structures of MST kinases and identified an ensemble of kinase-domain dimers compatible with trans-autophosphorylation. These dimers share a common dimerization interface comprised of the activation loop and αG-helix while the arrangements of the kinase-domains within the dimer varied depending on their activation state. We then verified the dimerization interface and determined its function using MST2. Variants bearing alanine substitutions of the αG-helix prevented dimerization of the MST2 kinase domain both in solution and in cells. These substitutions also blocked autophosphorylation of full-length MST2 and its Drosophila homolog Hippo in cells. These variants retain the same secondary structure as wild-type and capacity to phosphorylate a protein substrate, indicating the loss of MST2 activation can be directly attributed to a loss of dimerization rather than loss of either fold or catalytic function. Together this data functionally links dimerization and autophosphorylation for MST2 and suggests this activation mechanism is conserved across both species and the entire MST family.

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein.

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1-3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.

Fe Site Order and Magnetic Properties of Fe1/4NbS2.

Transition-metal dichalcogenides (TMDs) have long been attractive to researchers for their diverse properties and high degree of tunability. Most recently, interest in magnetically intercalated TMDs has resurged due to their potential applications in spintronic devices. While certain compositions featuring the absence of inversion symmetry such as Fe1/3NbS2 and Cr1/3NbS2 have garnered the most attention, the diverse compositional space afforded through the host matrix composition as well as intercalant identity and concentration is large and remains relatively underexplored. Here, we report the magnetic ground state of Fe1/4NbS2 that was determined from low-temperature neutron powder diffraction as an A-type antiferromagnet. Despite the presence of overall inversion symmetry, the pristine compound manifests spin polarization induced by the antiferromagnetic order at generic k points, based on density functional theory band-structure calculations. Furthermore, by combining synchrotron diffraction, pair distribution function, and magnetic susceptibility measurements, we find that the magnetic properties of Fe1/4NbS2 are sensitive to the Fe site order, which can be tuned via electrochemical lithiation and thermal history.

Chemistry of Quantum Spin Liquids.

Quantum spin liquids are an exciting playground for exotic physical phenomena and emergent many-body quantum states. The realization and discovery of quantum spin liquid candidate materials and associated phenomena lie at the intersection of solid-state chemistry, condensed matter physics, and materials science and engineering. In this review, we provide the current status of the crystal chemistry, synthetic techniques, physical properties, and research methods in the field of quantum spin liquids. We highlight a number of specific quantum spin liquid candidate materials and their structure-property relationships, elucidating their fascinating behavior and connecting it to the intricacies of their structures. Furthermore, we share our thoughts on defects and their inevitable presence in materials, of which quantum spin liquids are no exception, which can complicate the interpretation of characterization of these materials, and urge the community to extend their attention to materials preparation and data analysis, cognizant of the impact of defects. This review was written with the intention of providing guidance on improving the materials design and growth of quantum spin liquids, and to paint a picture of the beauty of the underlying chemistry of this exciting class of materials.

Improving Hepatitis B Screening at Family Health Centers Using Quality Improvement and Electronic Medical Record Tools.

Chronic hepatitis B viral (HBV) infection is associated with significant morbidity and mortality with endemic areas carrying most of the global burden of HBV disease. Current HBV screening rates in the United States are suboptimal. We aimed to improve HBV screening rates at regional family health centers serving high-risk refugee populations by 20% over 2 years. We used quality improvement (QI) methodology and implemented interventions providing electronic medical record (EMR)-enabled HBV screening tools within known clinical workflows. EMR tools captured country-of-origin data to identify persons from HBV-endemic regions with provision of a laboratory order set to ensure performance of appropriate HBV screening tests. The project was initiated prior to the COVID pandemic but continued during the pandemic with imposed social isolation measures. We nevertheless demonstrated 4 statistical process control chart shifts and achieved our QI smart aim. Further, we demonstrated a high HBV detection rate (8.2%-12.8%) among persons identified for screening.

Use of Pantoea agglomerans ASB05 as a biocontrol agent to inhibit the growth of Salmonella enterica on intact cantaloupe melons.

AIMS: To identify biocontrol agents to prevent the growth of Salmonella serotype Enterica on cantaloupe melons during the pre- and postharvest periods. METHODS AND RESULTS: We created a produce-associated bacterial library containing 8736 isolates and screened it using an in-vitro fluorescence inhibition assay to identify bacteria that inhibit the growth of S. Enterica. One isolate, Pantoea agglomerans ASB05, was able to grow, persist, and inhibit the growth of S. Enterica on intact cantaloupe melons under simulated pre- and postharvest conditions. We also demonstrated that the growth inhibition of S. Enterica by P. agglomerans ASB05 was due to the production of a phenazine type antibiotic. CONCLUSIONS: Pantoea agglomerans ASB05 is an effective biocontrol agent for the prevention of S. Enterica growth on intact cantaloupe melons in both the pre- and postharvest environments.

Unpacking Vietnamese L2 Students' Motivation for and Engagement in Intercultural Language Learning.

Intercultural language learning (ICLL) has become an important concept that drives English learners' attention to the understanding and application of cultural elements in their English learning process; however, the learning motivation for and engagement in the proliferation of culture in English language teaching vary from one context to another. This study aimed to unpack L2 students' motivation for and engagement in ICLL, and the correlation between the two research variables. A group of 198 L2 students, who were learning at a high school in Vietnam, were recruited based on a convenience sampling technique. A closed-ended questionnaire was employed for data collection. The sociolinguistic perspective was adopted for data analysis using the SPSS software. The findings unraveled that Vietnamese L2 students had a high level of motivation for ICLL, and they tended to get engaged in ICLL actively; however, their level of emotional engagement in ICLL seemed higher than their behavioral and cognitive engagement in ICLL. Additionally, a positive correlation between Vietnamese L2 students' motivation for and engagement in ICLL was significantly found. This study recommends pedagogical implications in an attempt to enhance the quality of intercultural language teaching and learning in the research context and other similar ones.

Kinetic Regulation of the Mammalian Sterile 20-like Kinase 2 (MST2).

Canonically, MST1/2 functions as a core kinase of the Hippo pathway and noncanonically during both apoptotic signaling and with RASSFs in T-cells. Faithful signal transduction by MST1/2 relies on both appropriate activation and regulated substrate phosphorylation by the activated kinase. Considerable progress has been made in understanding the molecular mechanisms regulating the activation of MST1/2 and identifying downstream signaling events. Here, we investigated the ability of MST2 to phosphorylate a peptide substrate and how that activity is regulated. Using a steady-state kinetic system, we parse the contribution of different factors to substrate phosphorylation, including the domains of MST2, phosphorylation, caspase cleavage, and complex formation. We found that in the unphosphorylated state, the SARAH domain stabilizes interactions with a peptide substrate and promotes turnover. Phosphorylation drives the activity of MST2, and once activated, MST2 is not further regulated by complex formation with other Hippo pathway components (SAV1, MOB1A, and RASSF5). We also show that the phosphorylated, caspase-cleaved MST2 is as active as the full-length one, suggesting that caspase-stimulated activity arises through noncatalytic mechanisms. The kinetic analysis presented here establishes a framework for interpreting how signaling events and post-translational modifications contribute to the signaling of MST2 in vivo.

Validity testing of the conspiratorial thinking and anti-expert sentiment scales during the COVID-19 pandemic across 24 languages from a large-scale global dataset.

In this study, we tested the validity across two scales addressing conspiratorial thinking that may influence behaviours related to public health and the COVID-19 pandemic. Using the COVIDiSTRESSII Global Survey data from 12 261 participants, we validated the 4-item Conspiratorial Thinking Scale and 3-item Anti-Expert Sentiment Scale across 24 languages and dialects that were used by at least 100 participants per language. We employed confirmatory factor analysis, measurement invariance test and measurement alignment for internal consistency testing. To test convergent validity of the two scales, we assessed correlations with trust in seven agents related to government, science and public health. Although scalar invariance was not achieved when measurement invariance test was conducted initially, we found that both scales can be employed in further international studies with measurement alignment. Moreover, both conspiratorial thinking and anti-expert sentiments were significantly and negatively correlated with trust in all agents. Findings from this study provide supporting evidence for the validity of both scales across 24 languages for future large-scale international research.

Intimate partner violence during pregnancy and maternal and child health outcomes: a scoping review of the literature from low-and-middle income countries from 2016 - 2021.

BACKGROUND: Intimate partner violence (IPV) during pregnancy is significantly associated with negative outcomes for both mother and child. Current evidence indicates an association between low levels of social support and IPV, however there is less evidence from low-and-middle income countries (LMIC) than high-income countries. Globally, the COVID-19 pandemic has radically altered how women can access social support. Hence since 2020, studies investigating IPV and pregnancy have occurred within the changing social context of the pandemic. OBJECTIVE: This scoping review summarizes the evidence from LMICs about the effects of IPV during pregnancy on maternal and child health. The review includes the impact of the COVID-19 pandemic on social support as mentioned in studies conducted since 2020. DESIGN: Library databases were used to identify papers from 2016 to 2021. These studies reported the maternal and child health outcomes of IPV during pregnancy, and described how social support during pregnancy, and the COVID-19 pandemic, were associated with rates of IPV during pregnancy. Observational study designs, qualitative and mixed methods studies were included. RESULTS: Twenty - six studies from 13 LMICs were included. Half (n = 13) were cross sectional studies which only collected data at one time-point. IPV during pregnancy was significantly associated with higher odds of postpartum depression, low birth weight, preterm birth and less breastfeeding in the year after birth. Lower levels of social support increased the odds of experiencing IPV during pregnancy, whilst higher levels of social support reduced antenatal anxiety and depression in women experiencing IPV during pregnancy. Of the four studies that investigated IPV during pregnancy throughout the COVID-19 pandemic, only one compared prevalence before and after the pandemic and unexpectedly reported a lower prevalence. CONCLUSIONS: Further research on the impact of IPV during pregnancy on maternal and child outcomes in LMICs is required, especially evidence from longitudinal studies investigating a wider range of outcomes. To date, there is limited evidence on the impact of the COVID-19 pandemic on IPV during pregnancy in LMICs, and this should be prioritized as the pandemic continues to affect women's access to social support globally.

Ln2 (SeO3 )2 (SO4 )(H2 O)2 (Ln=Sm, Dy, Yb): A Mixed-Ligand Pathway to New Lanthanide(III) Multifunctional Materials Featuring Nonlinear Optical and Magnetic Anisotropy Properties.

Bottom-up assembly of optically nonlinear and magnetically anisotropic lanthanide materials involving precisely placed spin carriers and optimized metal-ligand coordination offers a potential route to developing electronic architectures for coherent radiation generation and spin-based technologies, but the chemical design historically has been extremely hard to achieve. To address this, we developed a worthwhile avenue for creating new noncentrosymmetric chiral Ln3+ materials Ln2 (SeO3 )2 (SO4 )(H2 O)2 (Ln=Sm, Dy, Yb) by mixed-ligand design. The materials exhibit phase-matching nonlinear optical responses, elucidating the feasibility of the heteroanionic strategy. Ln2 (SeO3 )2 (SO4 )(H2 O)2 displays paramagnetic property with strong magnetic anisotropy facilitated by large spin-orbit coupling. This study demonstrates a new chemical pathway for creating previously unknown polar chiral magnets with multiple functionalities.

A lineage CLOUD for neoblasts.

In planarians, pluripotency can be studied in vivo in the adult animal, making these animals a unique model system where pluripotency-based regeneration (PBR)-and its therapeutic potential-can be investigated. This review focuses on recent findings to build a cloud model of fate restriction likelihood for planarian stem and progenitor cells. Recently, a computational approach based on functional and molecular profiling at the single cell level was proposed for human hematopoietic stem cells. Based on data generated both in vivo and ex vivo, we hypothesized that planarian stem cells could acquire multiple direction lineage biases, following a "badlands" landscape. Instead of a discrete tree-like hierarchy, where the potency of stem/progenitor cells reduces stepwise, we propose a Continuum of LOw-primed UnDifferentiated Planarian Stem/Progenitor Cells (CLOUD-PSPCs). Every subclass of neoblast/progenitor cells is a cloud of likelihood, as the single cell transcriptomics data indicate. The CLOUD-HSPCs concept was substantiated by in vitro data from cell culture; therefore, to confirm the CLOUD-PSPCs model, the planarian community needs to develop new tools, like live cell tracking. Future studies will allow a deeper understanding of PBR in planarian, and the possible implications for regenerative therapies in human.

Increasing kinase domain proximity promotes MST2 autophosphorylation during Hippo signaling.

The Hippo pathway plays an important role in developmental biology, mediating organ size by controlling cell proliferation through the activity of a core kinase cassette. Multiple upstream events activate the pathway, but how each controls this core kinase cassette is not fully understood. Activation of the core kinase cassette begins with phosphorylation of the kinase MST1/2 (also known as STK3/4). Here, using a combination of in vitro biochemistry and cell-based assays, including chemically induced dimerization and single-molecule pulldown, we revealed that increasing the proximity of adjacent kinase domains, rather than formation of a specific protein assembly, is sufficient to trigger autophosphorylation. We validate this mechanism in cells and demonstrate that multiple events associated with the active pathway, including SARAH domain-mediated homodimerization, membrane recruitment, and complex formation with the effector protein SAV1, each increase the kinase domain proximity and autophosphorylation of MST2. Together, our results reveal that multiple and distinct upstream signals each utilize the same common molecular mechanism to stimulate MST2 autophosphorylation. This mechanism is likely conserved among MST2 homologs. Our work also highlights potential differences in Hippo signal propagation between each activating event owing to differences in the dynamics and regulation of each protein ensemble that triggers MST2 autophosphorylation and possible redundancy in activation.

Measuring association among censored antibody titer data.

Censoring due to a limit of detection or limit of quantification happens quite often in many medical studies. Conventional approaches to deal with censoring when analyzing these data include, for example, the substitution method and the complete case (CC) analysis. More recently, maximum likelihood estimation (MLE) has been increasingly used. While the CC analysis and the substitution method usually lead to biased estimates, the MLE approach appears to perform well in many situations. This article proposes an MLE approach to estimate the association between two measurements in the presence of censoring in one or both quantities. The central idea is to use a copula function to join the marginal distributions of the two measurements. In various simulation studies, we show that our approach outperforms existing conventional methods (CC and substitution analyses). In addition, rank-based measures of global association such as Kendall's tau or Spearman's rho can be studied, hence, attention is not only confined to Pearson's product-moment correlation coefficient capturing solely linear association. We have shown in our simulations that our approach is robust to misspecification of the copula function or marginal distributions given a small association. Furthermore, we propose a straightforward MLE method to fit a (multiple) linear regression model in the presence of censoring in a covariate or both the covariate and the response. Given the marginal distribution of the censored covariate, our method outperforms conventional approaches. We also compare and discuss the performance of our method with multiple imputation and missing indicator model approaches.

Computational Investigation of the Formation of Substituted Isoindole N-Oxides through the Photo-oxidative Cyclization of 2'-Alkynylacetophenone Oximes.

Our recently published joint experiment-theory study of the photo-oxidative intramolecular cyclization of 2'-alkynylacetophenone oximes, performed in collaboration with the de Lijser group, presented the first reported formation of isoindole N-oxides. That study focused on determining a mechanistic explanation for the unexpected chemistry observed when three 2'-alkynylacetophenone oximes were photo-oxidized with 9,10-dicyanoanthracene (DCA), specifically the derivatives with a phenyl, isopropyl, or n-butyl substituent at the alkynyl group. Here, we use density functional theory to develop a broader understanding of the scope of this chemistry. In particular, we demonstrate that substituents on the alkynyl group and on the central benzene ring can significantly modulate the thermodynamic driving force for oxime radical cation generation when DCA is used as the photosensitizer. In contrast, substituents are shown to have a small impact on the chemical reactivity of the radical cation intermediates. In particular, 5-exo radical cation cyclization, which ultimately results in an isoindole N-oxide product, is always kinetically and sometimes also thermodynamically preferred over 6-endo radical cation cyclization, which would produce an isoquinoline N-oxide product. Overall, this study provides mechanistic insights into the diversity of isoindole N-oxides that can be produced through the photo-oxidative cyclization of 2'-alkynylacetophenone oximes.

Mechanistic Investigation of the Formation of Isoindole N-Oxides in the Electron Transfer-Mediated Oxidative Cyclization of 2'-Alkynylacetophenone Oximes.

This paper describes a joint experiment-theory investigation of the formation and cyclization of 2'-alkynylacetophenone oxime radical cations using photoinduced electron transfer (PET) with DCA as the photosensitizer. Using a combination of experimental 1H and 13C nuclear magnetic resonance (NMR) spectra, high-resolution mass spectrometry, and calculated NMR chemical shifts, we identified the products to be isoindole N-oxides. The reaction was found to be stereoselective; only one of the two possible stereoisomers is formed under these conditions. A detailed computational investigation of the cyclization reaction mechanism suggests facile C-N bond formation in the radical cation leading to a 5-exo intermediate. Back-electron transfer from the DCA radical anion followed by barrierless intramolecular proton transfer leads to the final product. We argue that the final proton transfer step in the mechanism is responsible for the stereoselectivity observed in experiment. As a whole, this work provides new insights into the formation of complex heterocycles through oxime and oxime ether radical cation intermediates produced via PET. Moreover, it represents the first reported formation of isoindole N-oxides.

Spin and Orbital Effects on Asymmetric Exchange Interaction in Polar Magnets: M(IO3)2 (M = Cu and Mn).

Magnetic polar materials feature an astonishing range of physical properties, such as magnetoelectric coupling, chiral spin textures, and related new spin topology physics. This is primarily attributable to their lack of space inversion symmetry in conjunction with unpaired electrons, potentially facilitating an asymmetric Dzyaloshinskii-Moriya (DM) exchange interaction supported by spin-orbital and electron-lattice coupling. However, engineering the appropriate ensemble of coupled degrees of freedom necessary for enhanced DM exchange has remained elusive for polar magnets. Here, we study how spin and orbital components influence the capability of promoting the magnetic interaction by studying two magnetic polar materials, α-Cu(IO3)2 (2D) and Mn(IO3)2 (6S), and connecting their electronic and magnetic properties with their structures. The chemically controlled low-temperature synthesis of these complexes resulted in pure polycrystalline samples, providing a viable pathway to prepare bulk forms of transition-metal iodates. Rietveld refinements of the powder synchrotron X-ray diffraction data reveal that these materials exhibit different crystal structures but crystallize in the same polar and chiral P21 space group, giving rise to an electric polarization along the b-axis direction. The presence and absence of an evident phase transition to a possible topologically distinct state observed in α-Cu(IO3)2 and Mn(IO3)2, respectively, imply the important role of spin-orbit coupling. Neutron diffraction experiments reveal helpful insights into the magnetic ground state of these materials. While the long-wavelength incommensurability of α-Cu(IO3)2 is in harmony with sizable asymmetric DM interaction and low dimensionality of the electronic structure, the commensurate stripe AFM ground state of Mn(IO3)2 is attributed to negligible DM exchange and isotropic orbital overlapping. The work demonstrates connections between combined spin and orbital effects, magnetic coupling dimensionality, and DM exchange, providing a worthwhile approach for tuning asymmetric interaction, which promotes evolution of topologically distinct spin phases.