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Organic anion-transporting polypeptides (OATP) 1B1 and OATP1B3, encoded by the SLCOgene family of the solute carrier superfamily, are involved in the disposition of many exogenous and endogenous compounds. Preclinical rodent models help assess risks of pharmacokinetic interactions, but interspecies differences in transporter orthologs and expression limit direct clinical translation. An OATP1B transgenic mouse model comprising a rodent Slco1a/1bgene cluster knockout and human SLCO1B1and SLCO1B3gene insertions provides a potential physiologically relevant preclinical tool to predict pharmacokinetic interactions. Pharmacokinetics of exogenous probe substrates, pitavastatin and pravastatin, and endogenous OATP1B biomarkers, coproporphyrin-I and coproporphyrin-III, were determined in the presence and absence of known OATP/Oatp inhibitors, rifampin or silymarin (an extract of milk thistle [Silybum marianum]), in wild-type FVB mice and humanized OATP1B mice. Rifampin increased exposure of pitavastatin (4.6- and 2.8-fold), pravastatin (3.6- and 2.2-fold), and coproporphyrin-III (1.6- and 2.1-fold) in FVB and OATP1B mice, respectively, but increased coproporphyrin-I AUC0–24honly (1.8-fold) in the OATP1B mice. Silymarin did not significantly affect substrate AUC, likely because the silymarin flavonolignan concentrations were at or below their reported IC50values for the relevant OATPs/Oatps. Silymarin increased the Cmaxof pitavastatin 2.7-fold and pravastatin 1.9-fold in the OATP1B mice. The data of the OATP1B mice were similar to those of the pitavastatin and pravastatin clinical data; however, the FVB mice data more closely recapitulated pitavastatin clinical data than the data of the OATP1B mice, suggesting that the OATP1B mice are a reasonable, though costly, preclinical strain for predicting pharmacokinetic interactions when doses are optimized to achieve clinically relevant plasma concentrations.

Background: The overdose crisis is increasingly characterized by opioid and stimulant co-use. Despite effective pharmacologic treatment for both opioid use disorder (OUD) and contingency management for stimulant use disorders, most individuals with these co-occurring conditions are not engaged in treatment. Hospitalization is an important opportunity to engage patients and initiate treatment, however existing hospital addiction care is not tailored for patients with co-use and may not meet the needs of this population.Methods: Semi-structured interviews were conducted with hospital providers about their experiences and perspectives treating patients with opioid and stimulant co-use. We used directed content analysis to identify common experiences and opportunities to improve hospital-based treatment for patients with co-use.Results: From qualitative interviews with 20 providers, we identified 4 themes describing how co-use complicated hospital-based substance use treatment: (1) patients’ unstable circumstances impacting the treatment plan, (2) co-occurring withdrawals are difficult to identify and treat, (3) providers holding more stigmatizing views of patients with co-use, and (4) stimulant use is often “ignored” in the treatment plans. Participants also described a range of potential opportunities to improve hospital-based treatment of co-use that fall into 3 categories: (1) provider practice changes, (2) healthcare system changes, and (3) development and validation of clinical tools and treatment approaches.Conclusions: We identified unique challenges providing hospital addiction medicine care to patients who use both opioids and stimulants. These findings inform the development, implementation, and testing of hospital-based interventions for patients with co-use.

Child sex abuse (CSA) is a specific category of crime for which the presumption of guilt may be particularly high, especially for defendant categories stereotypically associated with the crime. The current study utilized survey methodology to examine the magnitude of the presumption of guilt for CSA, as well as stereotypes associating perpetrator race and relationship to the victim with likelihood of CSA. Participants (N= 220) indicated the percentage of CSA allegations they believed to be true, and rank-ordered racial and relationship categories they believed most likely to commit CSA. Female (77%) and male (71%) participants believed most CSA allegations were true. White men and stepfathers were ranked as the most likely perpetrators compared to Hispanic men, Black men, other male relatives, neighbors, and others. These data suggest that alleged perpetrators of CSA are particularly likely to be perceived negatively, especially if they possess stereotypical racial and relational characteristics.

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 (collectively, OATP1B) transporters encoded by the solute carrier organic anion transporter (SLCO)genes mediate uptake of multiple pharmaceutical compounds. Nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease (NAFLD), decreases OATP1B abundance. This research characterized the pathologic and pharmacokinetics effects of three diet- and one chemical-induced NAFLD model in male and female humanized OATP1B mice, which comprises knock-out of rodent Oatp orthologs and insertion of human SLCO1B1and SLCO1B3.Histopathology scoring demonstrated elevated steatosis and inflammation scores for all NAFLD-treatment groups. Female mice had minor changes in SLCO1B1expression in two of the four NAFLD treatment groups, and pitavastatin (PIT) area under the concentration-time curve (AUC) increased in female mice in only one of the diet-induced models. OATP1B3 expression decreased in male and female mice in the chemical-induced NAFLD model, with a coinciding increase in PIT AUC, indicating the chemical-induced model may better replicate changes in OATP1B3 expression and OATP substrate disposition observed in NASH patients. This research also tested a reported multifactorial pharmacokinetic interaction between NAFLD and silymarin, an extract from milk thistle seeds with notable OATP-inhibitory effects. Males showed no change in PIT AUC, whereas female PIT AUC increased 1.55-fold from the diet alone and the 1.88-fold from the combination of diet with silymarin, suggesting that female mice are more sensitive to pharmacokinetic changes than male mice. Overall, the humanized OATP1B model should be used with caution for modeling NAFLD and multifactorial pharmacokinetic interactions.SIGNIFICANCE STATEMENTAdvanced stages of NAFLD cause decreased hepatic OATP1B abundance and increase systemic exposure to OATP substrates in human patients. The humanized OATP1B mouse strain may provide a clinically relevant model to recapitulate these observations and predict pharmacokinetic interactions in NAFLD. This research characterized three diet-induced and one drug-induced NAFLD model in a humanized OATP1B mouse model. Additionally, a multifactorial pharmacokinetic interaction was observed between silymarin and NAFLD.

Active processes drive biological dynamics across various scales and include subcellular cytoskeletal remodelling, tissue development in embryogenesis and the population-level expansion of bacterial colonies. In each of these, biological functionality requires collective flows to occur while self-organised structures are protected. However, the mechanisms by which active flows can spontaneously constrain their dynamics to preserve structure are not known. Here, by studying collective flows and defect dynamics in active nematic films, we demonstrate the existence of a self-constraint, namely a two-way, spontaneously arising relationship between activity-driven isosurfaces of flow boundaries and mesoscale nematic structures. We show that self-motile defects are tightly constrained to viscometric surfaces, which are contours along which the vorticity and the strain rate are balanced. This in turn reveals that self-motile defects break mirror symmetry when they move along a single viscometric surface. This is explained by an interdependence between viscometric surfaces and bend walls, which are elongated narrow kinks in the orientation field. These findings indicate that defects cannot be treated as solitary points. Instead, their associated mesoscale deformations are key to the steady-state coupling to hydrodynamic flows. This mesoscale cross-field self-constraint offers a framework for tackling complex three-dimensional active turbulence, designing dynamic control into biomimetic materials and understanding how biological systems can employ active stress for dynamic self-organisation.

The drug overdose epidemic in the US necessitates detailed and timely data to inform public health responses. In this article we describe how an electronic health record (EHR) data-sharing collaboration across health systems in Minnesota that was developed in response to the COVID-19 pandemic was adapted to monitor trends in substance use–related hospital and emergency department (ED) visits. We found large increases in methamphetamine- and opioid-involved hospital and ED visits. Throughout the study period, Native American, Black, and multiple-race people experienced the highest rates of drug-involved hospital and ED visits. Monitoring drug-involved health care use through EHR data has the potential to help public health officials detect trends in near real time before mortality spikes and may also inform early intervention. The use of EHR data also allows for detailed monitoring of the impact of the drug overdose epidemic across racial and ethnic groups.

Plastic debris is thought to be widespread in freshwater ecosystems globally1. However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging2,3. Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 μm) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris4. Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.

The protective efficacy of serum antibodies results from the interplay of antigen-specific B cell clones of different affinities and specificities. These cellular dynamics underlie serum-level phenomena such as original antigenic sin (OAS)—a proposed propensity of the immune system to rely repeatedly on the first cohort of B cells engaged by an antigenic stimulus when encountering related antigens, in detriment to the induction of de novo responses1–5. OAS-type suppression of new, variant-specific antibodies may pose a barrier to vaccination against rapidly evolving viruses such as influenza and SARS-CoV-26,7. Precise measurement of OAS-type suppression is challenging because cellular and temporal origins cannot readily be ascribed to antibodies in circulation; its effect on subsequent antibody responses therefore remains unclear5,8. Here we introduce a molecular fate-mapping approach with which serum antibodies derived from specific cohorts of B cells can be differentially detected. We show that serum responses to sequential homologous boosting derive overwhelmingly from primary cohort B cells, while later induction of new antibody responses from naive B cells is strongly suppressed. Such ‘primary addiction’ decreases sharply as a function of antigenic distance, allowing reimmunization with divergent viral glycoproteins to produce de novo antibody responses targeting epitopes that are absent from the priming variant. Our findings have implications for the understanding of OAS and for the design and testing of vaccines against evolving pathogens.

Goldenseal is a perennial plant native to eastern North America. A recent clinical study reported goldenseal decreased metformin Cmaxand area under the blood concentration versus time curve (AUC) by 27% and 23%, respectively, but half-life and renal clearance were unchanged. These observations suggested goldenseal altered processes involved in metformin absorption. The underlying mechanism(s) remain(s) unknown. One mechanism for the decreased metformin systemic exposure is inhibition by goldenseal of intestinal uptake transporters involved in metformin absorption. Goldenseal extract and three goldenseal alkaloids (berberine, (–)-β-hydrastine, hydrastinine) were tested as inhibitors of organic cation transporter (OCT) 3, plasma membrane monoamine transporter (PMAT), and thiamine transporter (THTR) 2 using human embryonic kidney 293 cells overexpressing each transporter. The goldenseal extract, normalized to berberine content, was the strongest inhibitor of each transporter (IC50: 4.9, 13.1, and 5.8 μM for OCT3, PMAT, and THTR2, respectively). A pharmacokinetic study in mice compared the effects of berberine, (–)-β-hydrastine, goldenseal extract, and imatinib (OCT inhibitor) on orally administered metformin. Goldenseal extract and imatinib significantly decreased metformin Cmaxby 31% and 25%, respectively, and had no effect on half-life. Berberine and (–)-β-hydrastine had no effect on metformin pharmacokinetics, indicating neither alkaloid alone precipitated the interaction in vivo. A follow-up murine study involving intravenous metformin and oral inhibitors examined the contributions of basolateral enteric/hepatic uptake transporters to the goldenseal–metformin interaction. Goldenseal extract and imatinib had no effect on metformin AUC and half-life, suggesting lack of inhibition of basolateral enteric/hepatic uptake transporters. Results may have implications for patients taking goldenseal with drugs that are substrates for OCT3 and THTR2.SIGNIFICANCE STATEMENTGoldenseal is used to self-treat respiratory infections and digestive disorders. We investigated potential mechanisms for the clinical pharmacokinetic interaction observed between goldenseal and metformin, specifically inhibition by goldenseal of intestinal uptake transporters (OCT3, PMAT, THTR2) involved in metformin absorption. Goldenseal extract inhibited all three transporters in vitroand decreased metformin systemic exposure in mice. These data may have broader implications for patients co-consuming goldenseal with other drugs that are substrates for these transporters.

Participants used a position control system to track the center of a simulated winding roadway with preview that ranged from 0.3 to 1.0 s. Participants’ spatial distributions of attention were measured by perturbing the roadway with different frequency sinusoids at different roadway positions and then measuring the degree to which those frequencies were present in their tracking movements. Consistent with Miller's optimal control theory analysis of tracking with preview, participants exhibited a continuous range of attention, and it lengthened with the amount of displayed preview. When the displayed preview disappeared for 5 s, the time to reach a steady-state level of tracking error based only on feedback control was measured. More displayed preview was strongly correlated with longer times to regress to feedback control. One interpretation of this finding is that when preview is withdrawn, visual sensory memory of the previewed roadway can be used for a fraction of a second to prolong the period of feedforward control. Attention can be shifted to relevant positions of the sensory memory image to anticipate the roadway curvature. However, the quality and usefulness of sensory memory gradually diminishes until the participant can only perform feedback control. When preview was restored, the time to reach steady-state feedforward control was correlated with the range of attention. These findings characterize some of the dynamic aspects of attention when drivers are briefly interrupted from viewing the upcoming roadway. This measurement technique may be useful for characterizing spatially distributed attention in other active control contexts.

Delays in appropriate #VTEProphylaxis increase VTEs! New review: Sex-based differences exist in response to enoxaparin dosing. Male patients have a decreased anti-Xa response to enoxaparin when compared to females, potentially placing them at increased risk of VTE. #TraumaSurg

The current practice of cardiopulmonary bypass (CPB) requires a preoperative priming of the circuit that is frequently performed with crystalloid solutions. Crystalloid priming avoids massive embolism but is unable to eliminate all microbubbles contained in the circuit. In addition, it causes a sudden hemodilution which is correlated with transfusion requirements and an increased risk of cognitive impairment. Several repriming techniques using autologous blood, collectively termed retrograde autologous priming (RAP), have been demonstrated to reduce the hemodilutional impact of CPB. However, the current heterogeneity in the practice of RAP limits its evidence and benefits. Here, we describe hematic antegrade repriming as an easy and reliable method that could be applied with any circuit in the market to decrease transfusion requirements, emboli, and inflammatory responses, reducing costs and the impact of CPB on postoperative recovery.

Two different sarbecoviruses have caused major human outbreaks in the past two decades1,2. Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain2–6. However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses7–11. Here we use high-throughput assays12to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern12but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential.

Objective: Robust disease and syndromic surveillance tools are underdeveloped in the United States, as evidenced by limitations and heterogeneity in sociodemographic data collection throughout the COVID-19 pandemic. To monitor the COVID-19 pandemic in Minnesota, we developed a federated data network in March 2020 using electronic health record (EHR) data from 8 multispecialty health systems.Materials and Methods: In this serial cross-sectional study, we examined patients of all ages who received a COVID-19 polymerase chain reaction test, had symptoms of a viral illness, or received an influenza test from January 3, 2016, through November 7, 2020. We evaluated COVID-19 testing rates among patients with symptoms of viral illness and percentage positivity among all patients tested, in aggregate and by zip code. We stratified results by patient and area-level characteristics.Results: Cumulative COVID-19 positivity rates were similar for people aged 12-64 years (range, 15.1%-17.6%) but lower for adults aged ≥65 years (range, 9.3%-10.7%). We found notable racial and ethnic disparities in positivity rates early in the pandemic, whereas COVID-19 positivity was similarly elevated across most racial and ethnic groups by the end of 2020. Positivity rates remained substantially higher among Hispanic patients compared with other racial and ethnic groups throughout the study period. We found similar trends across area-level income and rurality, with disparities early in the pandemic converging over time.Practice Implications: We rapidly developed a distributed data network across Minnesota to monitor the COVID-19 pandemic. Our findings highlight the utility of using EHR data to monitor the current pandemic as well as future public health priorities. Building partnerships with public health agencies can help ensure data streams are flexible and tailored to meet the changing needs of decision makers.

Understanding the electronic structure and dynamics of semiconducting nanomaterials at the atomic level is crucial for the realization and optimization of devices in solar energy, catalysis, and optoelectronic applications. We report here on the use of ultrafast X-ray linear dichroism spectroscopy to monitor the carrier dynamics in epitaxial ZnO nanorods after band gap photoexcitation. By rigorously subtracting out thermal contributions and conducting ab initiocalculations, we reveal an overall depletion of absorption cross sections in the transient X-ray spectra caused by photogenerated charge carriers screening the core-hole potential of the X-ray absorbing atom. At low laser excitation densities, we observe phase-space filling by excited electrons and holes separately. These results pave the way for carrier- and element-specific probing of charge transfer dynamics across heterostructured interfaces with ultrafast table-top and fourth-generation X-ray sources.

An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1–3, have activity against diverse sarbecoviruses4–7, and be highly protective through viral neutralization8–11and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics.

The recent emergence of SARS-CoV-2 variants of concern1–10and the recurrent spillovers of coronaviruses11,12into the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here we describe a human monoclonal antibody designated S2X259, which recognizes a highly conserved cryptic epitope of the receptor-binding domain and cross-reacts with spikes from all clades of sarbecovirus. S2X259 broadly neutralizes spike-mediated cell entry of SARS-CoV-2, including variants of concern (B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429), as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of angiotensin-converting enzyme 2 (ACE2) binding to the receptor-binding domain. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile that is limited to a single substitution, G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters (Mesocricetus auratus) against challenge with the prototypic SARS-CoV-2 and the B.1.351 variant of concern, which suggests that this monoclonal antibody is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data reveal a key antigenic site that is targeted by broadly neutralizing antibodies and will guide the design of vaccines that are effective against all sarbecoviruses.

Introduction:The coronavirus disease 2019 (COVID-19) pandemic has caused a global shortage of single-use N95 filtering facepiece respirators (FFRs). A combination of heat and humidity is a promising method for N95 FFR decontamination in crisis-capacity conditions; however, an understanding of its effect on viral inactivation and N95 respirator function is crucial to achieving effective decontamination.Objective:We reviewed the scientific literature on heat-based methods for decontamination of N95 FFRs contaminated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and viral analogues. We identified key parameters for SARS-CoV-2 bioburden reduction while preserving N95 fit and filtration, as well as methods that are likely ineffective.Key Findings:Viral inactivation by humid heat is highly sensitive to temperature, humidity, duration of exposure, and the local microenvironment (e.g., dried saliva). A process that achieves temperatures of 70–85°C and relative humidity >50% for at least 30?min is likely to inactivate SARS-CoV-2 (>3-log reduction) on N95 respirators while maintaining fit and filtration efficiency for three to five cycles. Dry heat is significantly less effective. Microwave-generated steam is another promising approach, although less studied, whereas 121°C autoclave treatments may damage some N95 FFRs. Humid heat will not inactivate all microorganisms, so reprocessed N95 respirators should be reused only by the original user.Conclusions:Effective bioburden reduction on N95 FFRs during the COVID-19 pandemic requires inactivation of SARS-CoV-2 and preservation of N95 fit and filtration. The literature suggests that humid heat protocols can achieve effective bioburden reduction. Proper industrial hygiene, biosafety controls, and clear protocols are required to reduce the risks of N95 reprocessing and reuse.

Measuring the spin structure of protons and neutrons tests our understanding of how they arise from quarks and gluons, the fundamental building blocks of nuclear matter. At long distances, the coupling constant of the strong interaction becomes large, requiring non-perturbative methods to calculate quantum chromodynamics processes, such as lattice gauge theory or effective field theories. Here we report proton spin structure measurements from scattering a polarized electron beam off polarized protons. The spin-dependent cross-sections were measured at large distances, corresponding to the region of low momentum transfer squared between 0.012 and 1.0 GeV2. This kinematic range provides unique tests of chiral effective field theory predictions. Our results show that a complete description of the nucleon spin remains elusive, and call for further theoretical works, for example, in lattice quantum chromodynamics. Finally, our data extrapolated to the photon point agree with the Gerasimov–Drell–Hearn sum rule, a fundamental prediction of quantum field theory that relates the anomalous magnetic moment of the proton to its integrated spin-dependent cross-sections.

Two separate commercial products of kratom [Mitragyna speciosa(Korth.) Havil. Rubiaceae] were used to generate reference standards of its indole and oxindole alkaloids. While kratom has been studied for over a century, the characterization data in the literature for many of the alkaloids are either incomplete or inconsistent with modern standards. As such, full 1H and 13C NMR spectra, along with HRESIMS and ECD data, are reported for alkaloids 1–19. Of these, four new alkaloids (7, 11, 17, and 18) were characterized using 2D NMR data, and the absolute configurations of 7, 17, and 18were established by comparison of experimental and calculated ECD spectra. The absolute configuration for the N(4)-oxide (11) was established by comparison of NMR and ECD spectra of its reduced product with those for compound 7. In total, 19 alkaloids were characterized, including the indole alkaloid mitragynine (1) and its diastereoisomers speciociliatine (2), speciogynine (3), and mitraciliatine (4); the indole alkaloid paynantheine (5) and its diastereoisomers isopaynantheine (6) and epiallo-isopaynantheine (7); the N(4)-oxides mitragynine-N(4)-oxide (8), speciociliatine-N(4)-oxide (9), isopaynantheine-N(4)-oxide (10), and epiallo-isopaynantheine-N(4)-oxide (11); the 9-hydroxylated oxindole alkaloids speciofoline (12), isorotundifoleine (13), and isospeciofoleine (14); and the 9-unsubstituted oxindoles corynoxine A (15), corynoxine B (16), 3-epirhynchophylline (17), 3-epicorynoxine B (18), and corynoxeine (19). With the ability to analyze the spectroscopic data of all of these compounds concomitantly, a decision tree was developed to differentiate these kratom alkaloids based on a few key chemical shifts in the 1H and/or 13C NMR spectra.

The prevalence of antibiotic resistance has been increasing globally, and new antimicrobial agents are needed to address this growing problem. We previously reported that a stilbene dimer from Photorhabdusgammaproteobacteria exhibits strong activity relative to its monomer against the multidrug-resistant Gram-positive pathogens methicillin-resistant Staphylococcus aureus(MRSA) and vancomycin-resistant Enterococcus faecalis. Here, we show that related dietary plant stilbene-derived dimers also have activity against these pathogens, and MRSA is unable to develop substantial resistance even after daily nonlethal exposure to the lead compound for a duration of three months. Through a systematic deduction process, we established the mode of action of the lead dimer, which targets the bacterial cell wall. Genome sequencing of modest resistance mutants, mass spectrometry analysis of cell wall precursors, and exogenous lipid II chemical complementation studies support the target as being lipid II itself or lipid II trafficking processes. Given the broad distribution of stilbenes in plants, including dietary plants, we anticipate that our mode of action studies here could be more broadly applicable to multipartite host–bacterium–plant interactions.

This work shows that ZnTe/CdSe core/shell quantum dots synthesized by a standard literature procedure in actuality have an alloyed CdxZn1–xTe core. We employ X-ray absorption spectroscopy (XAS) at all four K-shell ionization edges (Zn, Te, Cd, and Se) and perform global fitting analysis to extract the first-shell bond distances. We combine our XAS results with transmission electron microscopy (TEM) sizing and elemental analyses, which allows us to propose models of the internal particle structure. Our multimodal characterization approach confirms (1) the presence of Cd–Te bonds, (2) cation alloying in the particle core (and the absence of anion alloying), and (3) a patchy pure-phase CdSe shell. We synthesize particles of different shell thicknesses and performed synthetic control studies that allowed us to discard a ZnTe/CdTe/CdSe core/shell/shell structure and confirm the alloyed core/shell structure. Our structural analysis is extended with electronic band structure calculations and UV/vis absorption spectroscopy, demonstrating that the alloyed CdxZn1–xTe/CdSe core/shell quantum dots exhibit a direct band gap, different from the predicted type II band alignment of the intended ZnTe/CdSe core/shell quantum dots. This study highlights the challenges with synthesizing II–VI quantum dot heterostructures and the power of XAS for understanding the internal structure of heterogeneous nanoparticles.

The spatiotemporal distribution of drivers' attention to preview was inferred from their steering movements while tracking a winding roadway in a laboratory setting. For most subjects, the average driving attentional distribution over six daily sessions was relatively stable and generalized across different control devices. However, there was considerable day-to-day variability in the attentional distributions. This variability was modeled as a strong interaction between two dynamic processes, the attentional emphasis of selected regions and inhibition of surrounding regions. The model combines a novel application of a reaction-diffusion model of biological pattern formation with an optimal control model of attention to preview. The combined model treats attentional dynamics as an example of the biological spacing of a limited cognitive resource, which is also shaped by the demands of action.

While aqueous zinc-based batteries have garnered much research on account of their improved safety, lower cost, and easier fabrication over lithium-ion batteries, they remain held back by dendrite growth on the anode. While many different solutions have been proposed, these solutions often greatly complicate the synthesis or materials in the battery. The application of a magnetic field across the battery has been shown to inhibit dendrite formation without the need for any materials or interface engineering. Herein, we provide a study on the effects of low magnetic fields on the electrodeposition and cycling of zinc in various aqueous systems. We demonstrate that although stronger fields have more immediate impacts on the morphology of zinc deposits, low magnetic fields are still suitable for inhibiting dendrite growth over long periods of cycling. Magnetic field strengths as low as 29 mT were shown to decrease charge transfer resistance of zinc ion deposition by up to 54% and to stabilize the cycling of Zn/Zn symmetric cells. Furthermore, the versatility of magnetic field application was demonstrated by affecting the morphology of zinc deposits on both copper and single-walled carbon nanotubes, which are both compatible with anode-free configurations of aqueous zinc-ion batteries.

Organizational citizenship behavior (OCB) refers to voluntary actions members take to benefit organizational function. However, the benefits of OCB for organizations are sometimes countered by detriments for employees who exhibit them, resulting in threats to organizational members’ psychological wellbeing. The present research examined whether social power—the perceived ability to control allocations and outcomes in a social hierarchy—could increase OCB endorsement while buffering against negative personal costs. Indeed, manipulated social power enhanced OCB endorsement. This effect was mediated by increased positive affect and goal seeking among participants assigned to a high-power condition relative to participants assigned to a low-power condition. Further, participants assigned to a high-power (vs. low-power) condition did not report increased occupational burden despite their greater OCB endorsement. Patterns of results were similar among a sample of community members (N= 149; Mage= 37 years) and a sample of university students (N= 129; Mage= 20 years). Organizations might empower members by employing procedural justice principles that facilitate members’ meaningful contributions to workplace operations.

Few experiences direct affect, behavior, and cognition as thoroughly as feelings of power and powerlessness. The present study examined 403 participants’ narrated experiences feeling powerful (n= 196) or powerless (n= 207) using Linguistic Inquiry and Word Count (LIWC) analysis to identify social contexts that might explain the effects of power on emotion expression. Powerful narratives contained more frequent communication about work, whereas powerless narratives contained more frequent communication about sex. Moreover, powerless narratives conveyed greater negative emotionality. A parallel mediation analysis revealed that communication about work and sex helped to explain the association between self-reported feelings of power and expressions of negative emotionality. When participants felt powerful and communicated about work, they expressed lower negative emotionality; when participants felt powerless and communicated about sex, they expressed higher negative emotionality. Modest differences in emotional expression between women and men indicated that power research should report analyses including gender as a control variable. Findings provide direction to the next wave of power research, which should examine organizations and intimate relationships as contexts in which power dynamics are salient.