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1.
Chem Sci ; 15(16): 5814-5831, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38665512

RESUMO

The development of reductive electrosynthetic reactions is often enabled by the oxidation of a sacrificial metal anode, which charge-balances the reductive reaction of interest occurring at the cathode. The metal oxidation is frequently assumed to be straightforward and innocent relative to the chemistry of interest, but several processes can interfere with ideal sacrificial anode behavior, thereby limiting the success of reductive electrosynthetic reactions. These issues are compounded by a lack of reported observations and characterization of the anodes themselves, even when a failure at the anode is observed. Here, we weave lessons from electrochemistry, interfacial characterization, and organic synthesis to share strategies for overcoming issues related to sacrificial anodes in electrosynthesis. We highlight common but underexplored challenges with sacrificial anodes that cause reactions to fail, including detrimental side reactions between the anode or its cations and the components of the organic reaction, passivation of the anode surface by an insulating native surface film, accumulation of insulating byproducts at the anode surface during the reaction, and competitive reduction of sacrificial metal cations at the cathode. For each case, we propose experiments to diagnose and characterize the anode and explore troubleshooting strategies to overcome the challenge. We conclude by highlighting open questions in the field of sacrificial-anode-driven electrosynthesis and by indicating alternatives to traditional sacrificial anodes that could streamline reaction optimization.

2.
Metab Eng ; 83: 193-205, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38631458

RESUMO

Consolidated bioprocessing (CBP) of lignocellulosic biomass holds promise to realize economic production of second-generation biofuels/chemicals, and Clostridium thermocellum is a leading candidate for CBP due to it being one of the fastest degraders of crystalline cellulose and lignocellulosic biomass. However, CBP by C. thermocellum is approached with co-cultures, because C. thermocellum does not utilize hemicellulose. When compared with a single-species fermentation, the co-culture system introduces unnecessary process complexity that may compromise process robustness. In this study, we engineered C. thermocellum to co-utilize hemicellulose without the need for co-culture. By evolving our previously engineered xylose-utilizing strain in xylose, an evolved clonal isolate (KJC19-9) was obtained and showed improved specific growth rate on xylose by ∼3-fold and displayed comparable growth to a minimally engineered strain grown on the bacteria's naturally preferred substrate, cellobiose. To enable full xylan deconstruction to xylose, we recombinantly expressed three different ß-xylosidase enzymes originating from Thermoanaerobacterium saccharolyticum into KJC19-9 and demonstrated growth on xylan with one of the enzymes. This recombinant strain was capable of co-utilizing cellulose and xylan simultaneously, and we integrated the ß-xylosidase gene into the KJC19-9 genome, creating the KJCBXint strain. The strain, KJC19-9, consumed monomeric xylose but accumulated xylobiose when grown on pretreated corn stover, whereas the final KJCBXint strain showed significantly greater deconstruction of xylan and xylobiose. This is the first reported C. thermocellum strain capable of degrading and assimilating hemicellulose polysaccharide while retaining its cellulolytic capabilities, unlocking significant potential for CBP in advancing the bioeconomy.


Assuntos
Clostridium thermocellum , Engenharia Metabólica , Polissacarídeos , Clostridium thermocellum/metabolismo , Clostridium thermocellum/genética , Polissacarídeos/metabolismo , Polissacarídeos/genética , Xilose/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Celulose/metabolismo , Xilosidases/metabolismo , Xilosidases/genética
3.
JACS Au ; 3(8): 2280-2290, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37654576

RESUMO

Mg0 is commonly used as a sacrificial anode in reductive electrosynthesis. While numerous methodologies using a Mg sacrificial anode have been successfully developed, the optimization of the electrochemistry at the anode, i.e., Mg stripping, remains empirical. In practice, electrolytes and organic substrates often passivate the Mg electrode surface, which leads to high overall cell potential causing poor energy efficiency and limiting reaction scale-up. In this study, we seek to understand and manipulate the Mg metal interfaces for a more effective counter electrode in tetrahydrofuran. Our results suggest that the ionic interactions between the cation and the anion of a supporting electrolyte can influence the electrical double layer, which impacts the Mg stripping efficiency. We find halide salt additives can prevent passivation on the Mg electrode by influencing the composition of the solid electrolyte interphase. This study demonstrates that, by tailoring the electrolyte composition, we can modify the Mg stripping process and enable a streamlined optimization process for the development of new electrosynthetic methodologies.

4.
Front Public Health ; 11: 1040851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37655290

RESUMO

Few guidelines exist for the development of socially responsible health policy, and frameworks that balance considerations of data, strategy, and equity are limited. The Intersectionality-Based Policy Analysis (IBPA) framework utilizes a structured questioning process to consider problems and policies, while applying guiding principles of equity, social justice, power, intersectionality, and diversity of knowledge and input. We apply the IBPA framework's guiding principles and questions to the pre-vaccine U.S. COVID-19 policy response. Results suggest the IBPA approach is a promising tool for integrating equity considerations in the development of policy solutions to urgent US public health challenges, including the COVID-19 pandemic. We found the IBPA framework particularly useful in differentiating between problems or policies and representations of problems or policies, and in considering the impacts of representations on different groups. The explicit inclusion of short-, medium- and long-term solutions is a reminder of the importance of holding a long-term vision of the equitable public health system we want while working towards immediate change.


Assuntos
COVID-19 , Vacinas , Humanos , Enquadramento Interseccional , Pandemias , COVID-19/prevenção & controle , Política de Saúde , Formulação de Políticas
5.
Contemp Clin Trials Commun ; 35: 101197, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37671246

RESUMO

Background: Sexual minority women (SMW) and transgender and/or nonbinary (TNB) individuals report an elevated prevalence of posttraumatic stress disorder (PTSD) symptoms and negative alcohol-related outcomes compared to heterosexual women and cisgender people. SMW and TNB individuals also face barriers to utilizing treatment, which can result in delayed or missed appointments. Accessible, feasible, and effective treatment approaches, such as web-based expressive writing (EW) treatments, are needed to address PTSD and negative alcohol-related outcomes in these populations. Method: We describe the design of a mixed-method pilot randomized controlled trial which will compare an EW treatment adapted for SMW and TNB people (stigma-adapted EW) and trauma (i.e., non-adapted) EW with an active (neutral-event) control to determine acceptability and feasibility of a future fully powered randomized controlled trial. The sample will include 150 trauma-exposed SMW and TNB individuals from across the United States who will be randomly assigned to stigma-adapted EW (n = 50), trauma EW (n = 50), or control (n = 50). Participants will be assessed before treatment, one-week after the first writing session, and three-months after the first writing session. This paper identifies steps for evaluating the acceptability and feasibility of the proposed study and determining changes in outcomes resulting from adapted and non-adapted EW treatments to inform refinements. This paper also highlights our strategy for testing theory-driven mediators and moderators of treatment outcomes. Conclusions: This mixed-method pilot trial will inform the first fully powered, self-administered, brief web-based treatment to reduce PTSD symptom severity and negative alcohol-related outcomes among trauma-exposed SMW and TNB individuals.

6.
J Interpers Violence ; 38(19-20): 10723-10748, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37272011

RESUMO

With increased use of social networking sites in recent years, there has also been an increased opportunity for users to fall prey to bullying victimization. However, little is known about the differences between online and in-person victimization in association with depression or how different coping strategies may mediate this relationship among college students. The goal of the current study was to examine whether there were similarities or differences in the extent to which self-reported online and in-person victimization were associated with depressive symptoms in a sample of 210 undergraduate students (72.9% Women; 85.4% Cauasian), as well as whether different problem- and emotion-focused coping may differentially mediate the links between young adult victimization and depressive symptoms. Participants reported depressive symptoms, problem- and emotion-focused coping, and in-person and online victimization. In-person and online victimization independently predicted emotion-focused coping and depressive symptoms in young adults, and both problem- and emotion-focused coping predicted depressive symptoms. Further, emotion-focused coping partially mediated the effect of in-person victimization and depressive symptoms, suggesting that training more effective coping strategies may be an important intervention target to reduce depressive symptoms for those experiencing bullying victimization. Future research should continue to explore how different coping strategies act as a mechanism between victimization and depressive symptoms.


Assuntos
Bullying , Vítimas de Crime , Adulto Jovem , Humanos , Feminino , Masculino , Depressão , Emoções , Adaptação Psicológica
7.
8.
Chemistry ; 29(46): e202301045, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37309269

RESUMO

Samarium diiodide (SmI2 ) is widely used as a strong one-electron reducing agent and is often employed to form C-C bonds in complex systems. Despite their utility, SmI2 and related salts suffer from several drawbacks that render the use of Sm reducing agents in large-scale synthesis impractical. Here, we report factors influencing the electrochemical reduction of Sm(III) to Sm(II), towards the goal of electrocatalytic Sm(III) reduction. We probe the effect of supporting electrolyte, electrode material, and Sm precursor on Sm(II)/(III) redox and on the reducing power of the Sm species. We find that the coordination strength of the counteranion of the Sm salt affects the reversibility and redox potential of the Sm(II)/(III) couple and establish that the counteranion primarily determines the reducibility of Sm(III). Electrochemically generated SmI2 performs similarly to commercial SmI2 solutions in a proof-of-concept reaction. The results will provide fundamental insight to facilitate the development of Sm-electrocatalytic reactions.

9.
J Psychopathol Clin Sci ; 132(5): 577-589, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37347909

RESUMO

Limited research has examined how multiple forms of oppression (e.g., racism, heterosexism, transphobia)-manifesting across multiple levels (e.g., interpersonal, structural)-can place Black and Latinx lesbian, gay, bisexual, transgender, queer, and other sexual/gender minority (LGBTQ+) adolescents at increased risk for internalizing psychopathology, including depression. Utilizing a national sample of 2,561 Black and Latinx LGBTQ+ adolescents (aged 13-17), we examined associations among depressive symptoms and several adolescent-focused manifestations of stigma, including: (a) interpersonal racial/ethnic bullying, (b) interpersonal sexual orientation bullying, (c) nine state-level forms of structural stigma or protection for LGBTQ+ adolescents, and (d) a new adolescent-focused composite index of state-level anti-LGBTQ+ structural stigma. Racial/ethnic bullying and sexual orientation bullying were found to be prevalent among the sample and were associated-both independently and jointly-with increased depressive symptoms. One harmful state-level anti-LGBTQ+ structural stigma indicator (i.e., anti-LGBTQ+ community attitudes) and seven protective state-level anti-LGBTQ+ structural stigma indicators (e.g., conversion therapy bans) were associated with odds of depressive symptoms, in the expected directions. Black and Latinx LGBTQ+ adolescents residing in states with greater overall anti-LGBTQ+ structural stigma reported increased depressive symptoms, even when adjusting for racial/ethnic and sexual orientation bullying. Additionally, Black and Latinx LGBTQ+ adolescents living in the most stigmatizing states demonstrated 32% increased odds of depressive symptoms, as compared to those living in the most LGBTQ+ affirming states. Multilevel, intersectional interventions could have optimal effects on the mental health and resilience of Black and Latinx LGBTQ+ adolescents. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Negro ou Afro-Americano , Depressão , Hispânico ou Latino , Minorias Sexuais e de Gênero , Estigma Social , Adolescente , Feminino , Humanos , Masculino , Depressão/epidemiologia , Depressão/etnologia , Depressão/etiologia , Depressão/psicologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Minorias Sexuais e de Gênero/estatística & dados numéricos , Comportamento Sexual/etnologia , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Estados Unidos/epidemiologia , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Bullying/psicologia , Bullying/estatística & dados numéricos
10.
J Consult Clin Psychol ; 91(3): 150-164, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36780265

RESUMO

OBJECTIVE: Lesbian, gay, bisexual, and queer (LGBQ)-affirmative cognitive behavioral therapy (CBT) focused on minority stress processes can address gay and bisexual men's transdiagnostic mental and behavioral health concerns. Identifying moderators of treatment outcomes may inform the mechanisms of LGBQ-affirmative CBT and subpopulations who may derive particular benefit. METHOD: Data were from a clinical trial in which gay and bisexual men with mental and behavioral health concerns were randomized to receive Effective Skills to Empower Effective Men (ESTEEM; an LGBQ-affirmative transdiagnostic CBT; n = 100) or one of two control conditions (n = 154): LGBQ-affirmative community mental health treatment (CMHT) or HIV counseling and testing (HCT). The preregistered outcome was a comorbidity index of depression, anxiety, alcohol/drug problems, and human immunodeficiency virus (HIV) transmission risk behavior at 8-month follow-up (i.e., 4 months postintervention). A two-step exploratory machine learning process was employed for 20 theoretically informed baseline variables identified by study therapists as potential moderators of ESTEEM efficacy. Potential moderators included demographic factors, pretreatment comorbidities, clinical facilitators, and minority stress factors. RESULTS: Racial/ethnic minority identification, namely as Black or Latino, was the only statistically significant moderator of treatment efficacy (B = -3.23, 95% CI [-5.03, -1.64]), t(197) = -3.88, p < .001. Racially/ethnically minoritized recipients (d = -0.71, p < .001), but not White/non-Latino recipients (d = 0.22, p = .391), had greater reductions in comorbidity index scores in ESTEEM compared to the control conditions. This moderation was driven by improvements in anxiety and alcohol/drug use problems. DISCUSSION: Black and Latino gay and bisexual men experiencing comorbid mental and behavioral health risks might particularly benefit from a minority stress-focused LGBQ-affirmative CBT. Future research should identify mechanisms for this moderation to inform targeted treatment delivery and dissemination. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Terapia Cognitivo-Comportamental , Minorias Sexuais e de Gênero , Masculino , Feminino , Humanos , Etnicidade , Grupos Minoritários/psicologia , Bissexualidade/psicologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-36754849

RESUMO

Mg-S batteries are a promising next-generation system for beyond conventional Li-ion chemistry. The Mg-S architecture pairs a Mg metal anode with an inexpensive, high-capacity S8 cathode. However, S8-based cathodes exhibit the "polysulfide shuttle" effect, wherein soluble partially reduced Sx2- species generated at the cathode diffuse to and react with the anode. While dissolved polysulfides may undergo reactions to form Li+-permeable layers in Li-S systems, the interfaces on Mg anodes are passivating. In this work, we probe the reactivity of various Mg polysulfide solutions at the Mg anode interface. Mg polysulfide solutions are prepared without any chelating agents to closely mimic conditions in a Mg-S cell. The polysulfides are synthesized by reacting Mg metal and S8 in electrolyte, and the speciation is controlled by varying the Mg:S precursor ratio. S-poor precursor ratios produce magnesium polysulfide solutions with a higher proportion of short-chain polysulfides that react at the Mg anode faster than the longer-chain analogues. Anode passivation can be slowed by shifting the polysulfide equilibria toward longer-chain polysulfides through addition of S8.

12.
J Interpers Violence ; 38(13-14): 8692-8720, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36789733

RESUMO

Intensive longitudinal designs (e.g., experience sampling methods [ESMs]) hold promise for examining the dynamic interplay between daily adversity, coping strategies, and behavioral and mental health issues among marginalized populations. However, few studies have used intensive longitudinal designs with sexual minority women (SMW), an understudied and at-risk population. We assessed feasibility and acceptability of using once-daily, interval-contingent ESM with 161 trauma-exposed SMW (Mage = 29.1, SD = 7.57); 20.5% nonbinary; 32.3% queer; 52.2% people of color; 14.3% with annual incomes ≤$9,999; and 30.4% in Southern United States (U.S.). SMW completed one comprehensive online baseline assessment and once-daily brief online assessments for 14 days. Daily surveys assessed past-24-hour stressors, stress responses, and behavioral and mental health symptoms. At the end of the 14-day ESM period, SMW answered three open-ended questions about participating in this study and about research with SMW. Regarding feasibility, 151 participants (94.0%) initiated the post-baseline ESM study portion and 72 (45.0%) completed all 14 daily surveys. An average of 11.70 (median = 13, SD = 3.31) daily surveys (83.5%) were completed by those who initiated the ESM. ESM completion level varied by race/ethnicity and U.S. region. Qualitative acceptability data revealed several themes, namely that SMW (1) enjoyed participating and felt positively about the ESM experience, (2) felt supported to reflect on impacts of early and ongoing stressors, (3) appreciated the chance to self-reflect and challenge existing thought patterns and coping behaviors, (4) recognized their capacity to tolerate trauma-related distress, (5) recommended that researchers focus on SMW's diverse stressors and daily experiences, (6) wanted a rationale for providing sensitive information and more space to narrate their experiences, and (7) recognized the need for affirmative treatment and policies. Findings could inform modifications to ESM protocols to improve their feasibility and acceptability among trauma-exposed SMW and promote ongoing utility of this valuable method.


Assuntos
Homossexualidade Feminina , Minorias Sexuais e de Gênero , Feminino , Humanos , Estados Unidos , Adulto , Avaliação Momentânea Ecológica , Estudos de Viabilidade , Identidade de Gênero
13.
Behav Med ; 49(2): 183-194, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34870567

RESUMO

Trauma-exposed sexual minority women (SMW) are at elevated risk of posttraumatic stress disorder (PTSD) and hazardous drinking compared to trauma-exposed heterosexual women. To understand whether these problems might be exacerbated during times of elevated societal stress, we collected data from a New York-based sample of trauma-exposed SMW between April 2020 and August 2020, a period of notable, compounding societal stressors, including: (a) living in or near one of the first epicenters of the coronavirus disease 2019 (COVID-19) epidemic in the United States and (b) living through multiple high-profile occurrences of racism-related police violence and subsequent racial unrest. SMW (n = 68) completed online self-report questionnaires related to trauma, PTSD symptoms, and alcohol use, and a subset (n = 29) completed semi-structured qualitative interviews. PsycINFO was searched with terms related to SMW, PTSD, and alcohol use to identify studies with samples of SMW from articles published within the last 10 years to which we could compare our sample; this produced nine studies. Welch's t-tests and Chi-square analyses revealed that SMW within our sample reported significantly higher PTSD symptom severity, probable PTSD, and hazardous drinking indicators (i.e., alcohol use disorder and heavy episodic drinking) between April 2020 and August 2020 compared to similar samples (i.e., trauma-exposed SMW and general samples of SMW) assessed previously. Qualitative reports also indicated that the societal stressors of 2020 contributed to mental and behavioral health concerns. These results underscore the need for integrated PTSD and alcohol use prevention and intervention efforts for trauma-exposed SMW during times of heightened societal stress.Supplemental data for this article is available online at https://doi.org/10.1080/08964289.2021.2006132 .


Assuntos
Alcoolismo , COVID-19 , Minorias Sexuais e de Gênero , Transtornos de Estresse Pós-Traumáticos , Feminino , Estados Unidos/epidemiologia , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Consumo de Bebidas Alcoólicas/epidemiologia
14.
Arch Sex Behav ; 52(5): 1869-1895, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35978203

RESUMO

Across the lifespan, most sexual minority individuals experience the closet-a typically prolonged period in which no significant others know their sexual identity. This paper positions the closet as distinct from stigma concealment given its typical duration in years and absolute removal from sources of support for an often-central identity typically during a developmentally sensitive period. The Developmental Model of the Closet proposed here delineates the vicarious learning that takes place before sexual orientation awareness to shape one's eventual experience of the closet; the stressors that take place after one has become aware of their sexual orientation but has not yet disclosed it, which often takes place during adolescence; and potential lifespan-persistent mental health effects of the closet, as moderated by the structural, interpersonal, cultural, and temporal context of disclosure. The paper outlines the ways in which the model both draws upon and is distinct from earlier models of sexual minority identity formation and proposes several testable hypotheses and future research directions, including tests of multilevel interventions.


Assuntos
Minorias Sexuais e de Gênero , Adolescente , Humanos , Masculino , Feminino , Estigma Social , Comportamento Sexual , Revelação , Adaptação Psicológica
15.
Front Microbiol ; 13: 948369, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003933

RESUMO

3-Hydroxybutyrate (3HB) is a product of interest as it is a precursor to the commercially produced bioplastic polyhydroxybutyrate. It can also serve as a platform for fine chemicals, medicines, and biofuels, making it a value-added product and feedstock. Acetogens non-photosynthetically fix CO2 into acetyl-CoA and have been previously engineered to convert acetyl-CoA into 3HB. However, as acetogen metabolism is poorly understood, those engineering efforts have had varying levels of success. 3HB, using acetyl-CoA as a precursor, can be synthesized by a variety of different pathways. Here we systematically compare various pathways to produce 3HB in acetogens and discover a native (S)-3-hydroxybutyryl-CoA dehydrogenase, hbd2, responsible for endogenous 3HB production. In conjunction with the heterologous thiolase atoB and CoA transferase ctfAB, hbd2 overexpression improves yields of 3HB on both sugar and syngas (CO/H2/CO2), outperforming the other tested pathways. These results uncovered a previously unknown 3HB production pathway, inform data from prior metabolic engineering efforts, and have implications for future physiological and biotechnological anaerobic research.

16.
J Consult Clin Psychol ; 90(7): 582-599, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35901370

RESUMO

OBJECTIVES: This randomized controlled trial examined whether an 11-week synchronous (i.e., real-time) online training in lesbian, gay, bisexual, transgender, queer, and other sexual or gender diverse (LGBTQ)-affirmative cognitive behavioral therapy (CBT) could lead to increased uptake of this practice at LGBTQ community centers across 20 U.S. states and internationally. METHOD: A total of 121 mental health providers (Mage = 37.74; 78.5% LGBTQ; 60.3% non-Hispanic/Latinx White) were randomized to receive the 11-week training either immediately (n = 61) or after a 4-month wait (n = 60). At baseline and 4 and 8 months after baseline, participants self-reported their LGBTQ-affirmative competency, cultural humility, and knowledge of the minority stress theory and practice skills underlying LGBTQ-affirmative CBT. To objectively assess uptake of LGBTQ-affirmative CBT, participants demonstrated, through simulated practice, how they would respond to two video-based clinical vignettes. RESULTS: Compared to wait-list, participants in the immediate training condition reported greater improvements in self-reported cultural competence (d = 1.24), minority stress knowledge (d = 0.78), LGBTQ-affirmative CBT knowledge (d = 0.78), and LGBTQ-affirmative CBT skills familiarity (d = 0.91) and use (d = 0.96); effects persisted 8 months postbaseline. Cultural humility showed no significant difference by condition (d = 0.07). In objectively coded assessments of simulated practice, participants in the training condition demonstrated greater uptake of LGBTQ-affirmative practice skills (d = 0.82). CONCLUSIONS: Findings preliminarily suggest that mental health providers can be trained to deliver LGBTQ-affirmative CBT using the low-cost, efficient reach of online training. This training can help disseminate evidence-based mental health care to LGBTQ individuals and support its implementation across practice settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Terapia Cognitivo-Comportamental , Minorias Sexuais e de Gênero , Adulto , Bissexualidade/psicologia , Competência Cultural , Feminino , Humanos , Comportamento Sexual
18.
Org Lett ; 24(21): 3802-3806, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35594569

RESUMO

An enantioselective Diels-Alder (DA) reaction of α-acyloxy enones has been developed to synthesize chiral oxidized cyclohexenes. Yttrium(III) triflate, in conjunction with a chiral pyridinebisimidazoline (PyBim) ligand, was found to catalyze the asymmetric [4 + 2] cycloaddition with a variety of dienes and α-acyloxy enone dienophiles. Using this method, terpinene-4-ol, a key intermediate in the synthesis of commercial herbicide cinmethylin, can be prepared in four steps from isoprene. A combination of kinetic data and NMR studies support a mechanism involving reversible binding of a dienophile to a yttrium catalyst followed by cycloaddition with a diene as the rate-determining step.


Assuntos
Monoterpenos , Polienos , Reação de Cicloadição , Polienos/química , Estereoisomerismo , Ítrio
19.
J Thorac Cardiovasc Surg ; 164(5): 1318-1326.e3, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35469597

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) continues to be a major cause of cancer deaths. Previous investigation has suggested that metformin use can contribute to improved outcomes in NSCLC patients. However, this association is not uniform in all analyzed cohorts, implying that patient characteristics might lead to disparate results. Identification of patient characteristics that affect the association of metformin use with clinical benefit might clarify the drug's effect on lung cancer outcomes and lead to more rational design of clinical trials of metformin's utility as an intervention. In this study, we examined the association of metformin use with long-term mortality benefit in patients with NSCLC and the possible modulation of this benefit by body mass index (BMI) and smoking status, controlling for other clinical covariates. METHODS: This was a retrospective cohort study in which we analyzed data from the Veterans Affairs (VA) Tumor Registry in the United States. Data from all patients with stage I NSCLC from 2000 to 2016 were extracted from a national database, the Corporate Data Warehouse that captures data from all patients, primarily male, who underwent treatment through the VA health system in the United States. Metformin use was measured according to metformin prescriptions dispensed to patients in the VA health system. The association of metformin use with overall survival (OS) after diagnosis of stage I NSCLC was examined. Patients were further stratified according to BMI and smoking status (previous vs current) to examine the association of metformin use with OS across these strata. RESULTS: Metformin use was associated with improved survival in patients with stage I NSCLC (average hazard ratio, 0.82; P < .001). An interaction between the effect of metformin use and BMI on OS was observed (χ2 = 3268.42; P < .001) with a greater benefit of metformin use observed in patients as BMI increased. Similarly, an interaction between smoking status and metformin use on OS was also observed (χ2 = 2997.05; P < .001) with a greater benefit of metformin use observed in previous smokers compared with current smokers. CONCLUSIONS: In this large retrospective study, we showed that a survival benefit is enjoyed by users of metformin in a robust stage I NSCLC patient population treated in the VA health system. Metformin use was associated with an 18% improved OS. This association was stronger in patients with a higher BMI and in previous smokers. These observations deserve further mechanistic study and can help rational design of clinical trials with metformin in patients with lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Metformina , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metformina/uso terapêutico , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Estados Unidos
20.
Appl Environ Microbiol ; 88(6): e0239321, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35138930

RESUMO

Using the Wood-Ljungdahl pathway, acetogens can nonphotosynthetically fix gaseous C1 molecules, preventing them from entering the atmosphere. Many acetogens can also grow on liquid C1 compounds such as formate and methanol, which avoid the storage and mass transfer issues associated with gaseous C1 compounds. Substrate redox state also plays an important role in acetogen metabolism and can modulate products formed by these organisms. Butyribacterium methylotrophicum is an acetogen known for its ability to synthesize longer-chained molecules such as butyrate and butanol, which have significantly higher values than acetate or ethanol, from one-carbon (C1) compounds. We explored B. methylotrophicum's C1 metabolism by varying substrates, substrate concentrations, and substrate feeding strategies to improve four-carbon product titers. Our results showed that formate utilization by B. methylotrophicum favored acetate production and methanol utilization favored butyrate production. Cofeeding of both substrates produced a high butyrate titer of 4 g/liter when methanol was supplied in excess to formate. Testing of formate feeding strategies, in the presence of methanol, led to further increases in the butyrate to acetate ratio. Mixotrophic growth of liquid and gaseous C1 substrates expanded the B. methylotrophicum product profile, as ethanol, butanol, and lactate were produced under these conditions. We also showed that B. methylotrophicum is capable of producing caproate, a six-carbon product, presumably through chain elongation cycles of the reverse ß-oxidation pathway. Furthermore, we demonstrated butanol production via heterologous gene expression. Our results indicate that both selection of appropriate substrates and genetic engineering play important roles in determining titers of desired products. IMPORTANCE Acetogenic bacteria can fix single-carbon (C1) molecules. However, improvements are needed to overcome poor product titers. Butyribacterium methylotrophicum can naturally ferment C1 compounds into longer-chained molecules such as butyrate alongside traditional acetate. Here, we show that B. methylotrophicum can effectively grow on formate and methanol to produce high titers of butyrate. We improved ratios of butyrate to acetate through adjusted formate feeding strategies and produced higher-value six-carbon molecules. We also expanded the B. methylotrophicum product profile with the addition of C1 gases, as the organism produced ethanol, butanol, and lactate. Furthermore, we developed a transformation protocol for B. methylotrophicum to facilitate genetic engineering of this organism for the circular bioeconomy.


Assuntos
Monóxido de Carbono , Clostridium , Acetatos/metabolismo , Monóxido de Carbono/metabolismo , Clostridium/metabolismo , Metanol/metabolismo
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