The effectiveness of psychological treatments for obsessive-compulsive disorders: a meta-analysis of randomized controlled trials published over last 30 years.

BACKGROUND: Although numerous studies have examined the effects of psychological treatments for obsessive-compulsive disorder (OCD), their overall effectiveness remains unclear. We aimed to estimate their overall effect by combining all available randomized controlled trials (RCTs) comparing psychological treatments to control groups for OCD. METHODS: We conducted a meta-analysis of 48 RCTs with 55 comparisons published between 1992 and 1 January 2023. The primary outcome was OCD symptom severity, with Hedges' g calculated at post-treatment and follow-up. Random-effects models were employed for all analyses, and the risk of bias was assessed. RESULTS: In general, psychological treatments demonstrated a significantly large effect (g = -1.14; 95% CI [-1.31 to -0.97]; I2 = 72.23%) on reducing OCD symptom severity post-treatment, this finding remained consistent across measures and after excluding outliers, but lost significance in the sensitivity analysis for only studies with low risk of bias. Type of treatment, control group and treatment format were associated with treatment effects. Moreover, more severe baseline OCD symptom severity predicted higher degree of treatment efficacy. No significant differences were observed in dropout rates between the treatment and control groups. Treatment effects lost significance at 3-6 and 6-12 month follow-ups. 87% of RCTs were rated at high risk of bias. CONCLUSIONS: Psychological treatments are effective in reducing OCD symptom severity. However, caution should be exercised when interpreting these results due to the high heterogeneity and risk of bias across RCTs. Future studies with more rigorous methodology are required, as well as studies examining their long-term effectiveness.

The effectiveness of unguided self-help psychological interventions for obsessive-compulsive disorder: A meta-analysis of randomized controlled trials.

BACKGROUND: Evidence-based psychological interventions exist for individuals with obsessive-compulsive disorder (OCD), but many individuals with OCD are unable to access them because of barriers, such as geographical isolation, treatment cost, and stigma etc. Unguided self-help psychological intervention has emerged as a potential solution to this problem. However, there is limited research on its overall effectiveness. This study aimed to address this gap. METHODS: Comprehensive searches from inception to 1st Jan 2023 were conducted in both international (PubMed, Embase, PsycINFO, International clinical trials registry platform of WHO) and Chinese (China National Knowledge Infrastructure, WeiPu, WanFang, Chinese Clinical Trial Registry) databases. The registered protocol is accessible at https://doi.org/10.17605/OSF.IO/FKB5W. We included randomized controlled trials (RCTs) comparing unguided self-help psychological interventions to control groups for individuals with OCD. The primary outcome was OCD symptom severity, with Hedges' g calculated post-intervention. Heterogeneity was deemed to be low, moderate, and high if the I2 value was quantified 25%, 50%, and 75% respectively. Relative Risks (RRs) was calculated for dropout rates post-intervention. Random-effects models were used for all analyses. RESULTS: 12 RCTs comparing unguided self-help psychological interventions to control groups were identified, with a total of 20 comparisons and 769 OCD patients. Overall, unguided self-help psychological interventions demonstrated a significant moderate effect on reducing OCD symptom severity (g = -0.42; 95% CI [-0.69; -0.14]) compared to control groups, with a moderate heterogeneity (I2 = 59%; 95% CI [22.73; 78.38]). This finding remained significant in sensitivity analyses for the self-rated Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; k = 7, g = -0.46; 95% CI [-0.71; -0.2]) and after removing an outlier (g = -0.37; 95% CI [-0.55; -0.19]), but not for the clinician-rated Y-BOCS (k = 4, g = -0.78; 95% CI [-2.75; 1.19]) and Obsessive Compulsive Inventory-Revised (k = 6, g = -0.26; 95% CI [-0.53; 0]). Subgroup analyses revealed a significant difference in effect size between studies conducting intention-to-treat and completers-only analyses (p = .01). The completers-only analyses demonstrated a moderate significant effect (g = -0.65; 95% CI [-1.08; -0.21]), whereas the effect of the intention-to-treat analyses was not significant (g = -0.18; 95% CI [-0.36; 0]). Participants in the unguided self-help groups exhibited a significantly higher dropout rate (RR = 2.08; 95% CI [1.53; 2.81]) compared to control groups. Furthermore, participants recruited from the community had a higher likelihood of dropping out compared to those recruited from clinical settings (p < .001). Additionally, participants who received cognitive-behavioural therapy intervention were more likely to drop out than those who received other types of intervention (p < .001). Most trials (92%) were rated at a high risk of bias. CONCLUSION: Unguided self-help psychological interventions demonstrate potential effectiveness in alleviating OCD symptom severity post-intervention. However, caution should be exercised when interpreting the results due to high risk of bias across trials and the relatively small sample size. And the considerable dropout rate might hinder treatment effects. Future studies with strict methodology should investigate the long-term effectiveness of unguided self-help psychological interventions for OCD, explore the reasons for high dropout rates, and improve intervention adherence.

Multi-modular metabolic engineering and efflux engineering for enhanced lycopene production in recombinant Saccharomyces cerevisiae.

Lycopene has been widely used in the food industry and medical field due to its antioxidant, anti-cancer, and anti-inflammatory properties. However, achieving efficient manufacture of lycopene using chassis cells on an industrial scale remains a major challenge. Herein, we attempted to integrate multiple metabolic engineering strategies to establish an efficient and balanced lycopene biosynthetic system in Saccharomyces cerevisiae. First, the lycopene synthesis pathway was modularized to sequentially enhance the metabolic flux of the mevalonate pathway, the acetyl-CoA supply module, and lycopene exogenous enzymatic module. The modular operation enabled the efficient conversion of acetyl-CoA to downstream pathway of lycopene synthesis, resulting in a 3.1-fold increase of lycopene yield. Second, we introduced acetate as an exogenous carbon source and utilized an acetate-repressible promoter to replace the natural ERG9 promoter. This approach not only enhanced the supply of acetyl-CoA but also concurrently diminished the flux toward the competitive ergosterol pathway. As a result, a further 42.3% increase in lycopene production was observed. Third, we optimized NADPH supply and mitigated cytotoxicity by overexpressing ABC transporters to promote lycopene efflux. The obtained strain YLY-PDR11 showed a 12.7-fold increase in extracellular lycopene level compared to the control strain. Finally, the total lycopene yield reached 343.7 mg/L, which was 4.3 times higher than that of the initial strain YLY-04. Our results demonstrate that combining multi-modular metabolic engineering with efflux engineering is an effective approach to improve the production of lycopene. This strategy can also be applied to the overproduction of other desirable isoprenoid compounds with similar synthesis and storage patterns in S. cerevisiae. ONE-SENTENCE SUMMARY: In this research, lycopene production in yeast was markedly enhanced by integrating a multi-modular approach, acetate signaling-based down-regulation of competitive pathways, and an efflux optimization strategy.

Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved ß-carotene production in Saccharomyces cerevisiae.

BACKGROUND: The limitation of storage space, product cytotoxicity and the competition for precursor are the major challenges for efficiently overproducing carotenoid in engineered non-carotenogenic microorganisms. In this work, to improve ß-carotene accumulation in Saccharomyces cerevisiae, a strategy that simultaneous increases cell storage capability and strengthens metabolic flux to carotenoid pathway was developed using exogenous oleic acid (OA) combined with metabolic engineering approaches. RESULTS: The direct separation of lipid droplets (LDs), quantitative analysis and genes disruption trial indicated that LDs are major storage locations of ß-carotene in S. cerevisiae. However, due to the competition for precursor between ß-carotene and LDs-triacylglycerol biosynthesis, enlarging storage space by engineering LDs related genes has minor promotion on ß-carotene accumulation. Adding 2 mM OA significantly improved LDs-triacylglycerol metabolism and resulted in 36.4% increase in ß-carotene content. The transcriptome analysis was adopted to mine OA-repressible promoters and IZH1 promoter was used to replace native ERG9 promoter to dynamically down-regulate ERG9 expression, which diverted the metabolic flux to ß-carotene pathway and achieved additional 31.7% increase in ß-carotene content without adversely affecting cell growth. By inducing an extra constitutive ß-carotene synthesis pathway for further conversion precursor farnesol to ß-carotene, the final strain produced 11.4 mg/g DCW and 142 mg/L of ß-carotene, which is 107.3% and 49.5% increase respectively over the parent strain. CONCLUSIONS: This strategy can be applied in the overproduction of other heterogeneous FPP-derived hydrophobic compounds with similar synthesis and storage mechanisms in S. cerevisiae.

Comparative short-term efficacy and acceptability of a combination of pharmacotherapy and psychotherapy for depressive disorder in children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Although the clinical efficacy and safety of combination of pharmacotherapy and psychotherapy in the treatment of depressive disorders in children and adolescents have been studied, the results remain controversial. This meta-analysis aimed to study the short-term efficacy and acceptability of combined therapy for children and adolescents with depressive disorders. METHODS: We conducted a systematic search in multiple databases for randomised controlled trials (RCTs), up to 31 December 2020, that assessed the combination of pharmacotherapy and psychotherapy against other active treatment options (pharmacotherapy, psychotherapy and placebo combined psychotherapy) in children and adolescents ( ≤ 18 years old) with depressive disorder. This study was registered with PROSPERO (CRD42020196701). RESULTS: A total of 14 RCTs involving 1,325 patients were included. For the primary and secondary outcomes, there were no statistically significant differences between the compared interventions in terms of remission (odds ratios [OR] = 1.37; 95% confidence interval [CI]: 0.93 to 2.04), acceptability (OR = 0.99; 95% CI: 0.72 to 1.38), efficacy (standardised mean differences = -0.07; 95% CI: -0.32 to 0.19), and suicidality (OR = 1.17; 95% CI: 0.67 to 2.06). Limited evidence showed that the combination of fluoxetine (OR = 1.90, 95% CI: 1.10 to 3.29) or non-selective serotonin reuptake inhibitors (non-SSRI) (OR = 2.46, 95% CI: 1.06 to 5.72) with cognitive-behavioural therapy (CBT) was superior to other active treatment options. Most included trials were rated as 'some concerns' in terms of risk of bias assessment. CONCLUSION: There is no evidence from the limited available data that all combined therapies are superior to other active treatment options for the acute treatment of depressive disorder in children and adolescents. However, it showed that fluoxetine or non-SSRI pharmacotherapies combined with CBT might be superior to other therapies in short-term. Mixed characteristics (e.g. age) and small sample size of non-SSRI combined therapy may influence the generalisability of the results.

Harm or protection? Two-sided consequences of females' susceptible responses to multiple threats.

The target article presented a plausible argument that females' susceptibility to threats might be self-protection for staying alive, but some evidence requires scrutiny. We need to consider (1) the biases of narrative reviews, (2) subjective life quality, and (3) the shadow side of extreme reactions to threats before concluding that females' threat-based response is a self-protection mechanism that promotes survival.

Conditional automaticity: interference effects on the implicit memory retrieval process.

Many studies have indicated that executing a secondary task during encoding has little influence on implicit memory (priming effect). However, relatively few studies have discussed the effect of interference on implicit memory during retrieval. Our previous studies found asymmetry between implicit encoding and retrieval processes, with the priming effect disrupted by retrieval interference. Therefore, the present study investigated why and how the priming effect is affected by interference at retrieval. We adopted a dual-task paradigm, with a lexical decision task as the memory task and an odd-even decision task as the interference task. The effect of interference during retrieval was assessed by comparing the performance in the interference condition with that in the full-attention condition. In Experiment 1, we observed that the priming effect was absent in the synchronous retrieval interference condition. In Experiment 2, asynchronous interference was also found to block the priming effect. To verify the assumption that the priming effect is sensitive to attentional resource competition during retrieval, we used two different manipulations (an extended stimulus interval in the dual-task paradigm, Experiment 3, and an interference inhibition manipulation, Experiment 4) known to reduce attentional distraction. In these experiments, the priming effect was protected from interference effects. We suggest that implicit memory retrieval could be regarded as a conditional automatic process that depends on a configuration of the cognitive system by attention and task sets. If the limited resources are occupied by another task, the implicit retrieval process can be impacted.

Different effects of feedback-induced emotion and material-induced emotion on memory.

The function of emotion in enhancing memory has been proven by a large number of studies. However, previous studies mainly used emotional materials to induce emotions, and far fewer studies have examined how neutral stimuli and emotional event connections affect memory. In Experiment 1, the feedback from the results was used as an emotional event to explore the impact of connected emotions on memory. In Experiment 2, emotional materials were used to induce emotions, and the effects on memory in the two studies were compared. The emotions induced by the feedback resulted in positive emotions having the strongest effects on memory, while negative emotions had the weakest memory effect. However, when the emotional materials were used, there were different outcomes: negative emotional memories were the best, and neutral memories were the worst. Based on these results, we may conclude that different emotion-inducing methods have different effects on memory and that emotionally enhanced memory is not applicable to all emotion-inducing modes.

Cognitive mechanisms and neurological foundations of companion animals' role in enhancing human psychological well-being.

The impact of companion animals on human psychological health has garnered widespread attention. Research demonstrates that companion animals contribute positively in various ways, including reducing depression, anxiety, stress, and fostering positive emotions in humans. Recent studies have revealed significant changes in the activity levels of human emotion-related cortical areas (such as the frontal cortex and amygdala) and neurotransmitter (e.g., oxytocin, cortisol) secretion due to interaction with companion animals. However, research in this domain is still in a nascent stage, with many unknowns in the cognitive neural mechanisms involved. This paper proposes that to understand the cognitive mechanisms through which companion animals affect human psychological health, we need to examine changes in emotional cognitive processing. It aims to uncover the neurological underpinnings of how companion animals enhance human psychological well-being from the perspective of brain connectivity. This approach is expected to provide theoretical support and direction for future research and practical applications in this field.

Looking back on life: An updated meta-analysis of the effect of life review therapy and reminiscence on late-life depression.

BACKGROUND: Twenty years ago, we confirmed the effectiveness of life review therapy and reminiscence (LRT-REM) to treat late-life depression in a meta-analysis. In the current study, we aimed to examine the most updated evidence on the effects of LRT-REM in older adults with depression. METHODS: We systematically searched records in English and Chinese databases up to December 2022 and included randomized controlled studies comparing LRT-REM with control conditions in older adults with depression. Outcomes included depression, anxiety, quality of life, and life satisfaction. Effect sizes (Hedges' g) at post-treatment were pooled with random effects meta-analyses. RESULTS: 42 studies with 3361 depressed older adults (≥60 years) met the selection criteria. We found a significant and large effect of LRT-REM (g = 1.41, p < 0.001) on late-life depression, corresponding to a number-needed-to-treat (NNT) of 1.98. Heterogeneity shrunk from high (I2 = 86.78) to moderate (I2 = 46.87) after excluding eight detected outliers. There were no significant differences between the examined subgroups except for the type of control condition. The effects of LRT-REM were not statistically significant at follow-up when corrected for publication bias. The quality of many included studies was not optimal. LIMITATIONS: The quality of many included studies was not optimal, with a high risk of bias. CONCLUSIONS: LRT-REM may be effective for treating late-life depression, but long-term effects are unclear. More research is needed on the effects of LRT-REM, especially when guided by (para)professional or lay therapists in low- and middle-income countries.

Identification, Expression and Evolutional Analysis of Two cyp19-like Genes in Amphioxus.

The mechanism of sex determination and differentiation in animals remains a central focus of reproductive and developmental biology research, and the regulation of sex differentiation in amphioxus remains poorly understood. Cytochrome P450 Family 19 Subfamily A member 1 (CYP19A1) is a crucial sex differentiation gene that catalyzes the conversion of androgens into estrogens. In this study, we identified two aromatase-like genes in amphioxus: cyp19-like1 and cyp19-like2. The cyp19-like1 is more primitive and may represent the ancestral form of cyp19 in zebrafish and other vertebrates, while the cyp19-like2 is likely the result of gene duplication within amphioxus. To gain further insights into the expression level of these two aromatase-like, we examined their expression in different tissues and during different stages of gonad development. While the expression level of the two genes differs in tissues, both are highly expressed in the gonad primordium and are primarily localized to microsomal membrane systems. However, as development proceeds, their expression level decreases significantly. This study enhances our understanding of sex differentiation mechanisms in amphioxus and provides valuable insights into the formation and evolution of sex determination mechanisms in vertebrates.

Electrophysiological evidence for the effectiveness of images versus text in warnings.

Warning sign plays an important role in risk avoidance. Many studies have found that images are better warnings than text, while others have revealed flaws of image-only warning signs. To better understand the factors underlying the effectiveness of different types of warning signs (image only, text only, or image and text), this study adopted event-related potential technology to explore the differences at the neurocognitive level using the oddball paradigm and the Go/No-go paradigm. Together, the behavioral and electroencephalogram results showed that text-only warnings had the lowest effectiveness, but there was little difference between the image-only and image-and-text warnings. The differences in the effects of the three warning signs were mainly in the areas of attention and cognitive control, implying differences in the underlying cognitive processes. Therefore, in the design of warning signs, the effects of different design attributes on cognitive processing should be taken into account based on actual needs in order to improve the effectiveness of the signs.

The relationship between Chinese college students' mate preferences and their parents' education level.

Parents have an influence on the formation of their children's mate preferences. This research conducted two studies to test the relationship between parents' education level and the gender role characteristics (masculinity and femininity) of ideal mate for college students, and the moderating role of urban-rural residence on this relationship. In study 1, 1,033 participants (627 females) reported their explicit attitude toward gender role characteristics for an ideal mate via the Chinese Sex Role Inventory-50. In study 2, we recruited 130 participants (66 females) and used an implicit association test to measure their implicit attitude. Regression-based analyses showed that the higher education level of parents was significantly associated with female students' mate preferences with high-femininity but low-masculinity traits. For male students, the higher education level of parents was associated with their explicit (not implicit) preferences of mates with high-masculinity but low-femininity traits. The significant moderating effect of urban-rural residence was observed in explicit preference, with the different patterns in gender groups. In conclusion, parents with higher educational attainment might bring up children who are more likely to embrace a partner with non-traditional gender roles (e.g., androgynous individuals, feminine men or masculine women).

The difference in the warning effect of different warning signs.

Introduction. Warning signs play a very important role in safeguarding life and property in dangerous situations. Previous studies have mainly focused on the physical properties of warning signs, and few studies have been conducted on the different types. Methods. In Experiment 1, the oddball paradigm and the go/no-go paradigm were used to study the warning effect of different types of warning signs. In Experiment 2, the dual-task paradigm was adopted. Results. In Experiment 1, the results showed that a warning sign with text as content had the worst warning effect, followed by the combination of image and text, and a warning sign with an image as content had the best warning effect. In Experiment 2, it was found that different types of warning signs would have different effects on the performance of the secondary task. Conclusions. The reason for this may be the different processing methods used for text and image. Therefore, in dangerous situations that require a quick response, simple and understandable graphics should be used as the content of warning signs. In complex circumstances, it may be necessary to use a combination of image and text for warning sign content.

Does gender role explain a high risk of depression? A meta-analytic review of 40 years of evidence.

BACKGROUND: This meta-analytic review aimed to systematically evaluate associations of depression with multiple gender role dimensions (masculinity, femininity, androgyny, and undifferentiated traits) and to determine potential moderators (participant characteristics, study instruments and sociocultural factors) of the relationship. METHODS: Of 4481 initially identified records in three electronic databases, 58 studies published 1978 to 2021 were included for meta-analysis. RESULTS: (1) Association of depression and gender role is moderated by study year and human development indices. (2) Masculinity is a protective factor for depression, while this dominance has declined as life expectancy increases. (3) A negative, weak but significant association between depression and femininity is observed in women, and college students, which starts to emerge with the gradual increase in the national education and income index from 1990 to 2019. (4) Androgynous individuals reported the lowest level of depression as compared with other gender role orientations (masculine, feminine, and undifferentiated trait group). This disparity is becoming more extreme with life expectancy and per capita income index increases. LIMITATIONS: English-language studies were only included in this review. CONCLUSIONS: Androgyny might be the most ideal gender role protecting both women and men from depression.

Effects of two different emotion-inducing methods on the emotional memory of non-clinically depressed individuals.

In the study of emotional memory bias in depressed individuals, most previous studies have used emotional materials, but there were significant differences in the effects of different emotion-inducing methods on face memory. In the present study, two experiments were conducted to explore the effects of different emotion-inducing methods on memory between healthy participants and non-clinically depressed participants. The results from experiment 1 showed that when feedback was used as induction, the memory performance of the non-clinical depression group was significantly higher than that of the healthy group under the condition of negative feedback. Under positive and neutral feedback, there were no significant differences between the two groups. In experiment 2, when emotional materials were used as a mode of induction, no significantly difference in each emotional condition between the healthy and depressed groups was found. The results of the present study show that different methods of emotional induction have different effects on depressed participants. Compared with the emotion induced by the emotional material, the non-clinical depressed participants had a better memory effect induced by negative emotional events.

Structural and functional brain signatures of endurance runners.

Although endurance running (ER) seems to be a simple repetitive exercise, good ER performance also requires and relies on multiple cognitive and motor control processes. Most of previous neuroimaging studies on ER were conducted using a single MRI modality, yet no multimodal study to our knowledge has been performed in this regard. In this study, we used multimodal MRI data to investigate the brain structural and functional differences between endurance runners (n = 22; age = 26.27 ± 6.07 years; endurance training = 6.23 ± 2.41 years) and healthy controls (HCs; n = 20; age = 24.60 ± 4.14 years). Compared with the HCs, the endurance runners showed greater gray matter volume (GMV) and cortical surface area in the left precentral gyrus, which at the same time had higher functional connectivity (FC) with the right postcentral and precentral gyrus. Subcortically, the endurance runners showed greater GMV in the left hippocampus and regional inflation in the right hippocampus. Using the bilateral hippocampi as seeds, further seed-based FC analyses showed higher hippocampal FC with the supplementary motor area, middle cingulate cortex, and left posterior lobe of the cerebellum. Moreover, compared with the HCs, the endurance runners also showed higher fractional anisotropy in several white matter regions, involving the corpus callosum, left internal capsule, left corona radiata, left external capsule, left posterior lobe of cerebellum and bilateral precuneus. Taken together, our findings provide several lines of evidence for the brain structural and functional differences between endurance runners and HCs. The current data suggest that these brain characteristics may have arisen as a result of regular ER training; however, whether they represent the neural correlates underlying the good ER performances of the endurance runners requires further investigations.

The Influence of Social Support on Physical Activity in Chinese Adolescents: The Mediating Role of Exercise Self-Efficacy.

The purpose of this study was to examine the associations of social support and self-efficacy with physical Activity (PA) and the mediating effect of self-efficacy on the relationship between social support and PA in Chinese adolescents. Participants included a total of 2341 Chinese adolescents (aged 12.75 ± 1.46 years). Self-reported instruments, including the physical activity questionnaire for adolescents, the social support revalued scale and the exercise self-efficacy scale, were used to measure physical activity, social support and exercise self-efficacy. Results showed that social support (r = 0.29, p < 0.05) and exercise self-efficacy (r = 0.43, p < 0.05) were significant and positive predictors of PA among Chinese adolescents, and exercise self-efficacy was a significant mediator in the relationship between social support and PA (standardized effect size = 0.15, p < 0.001). Such findings were evident with similar patterns in both male and female adolescents. The findings of this study have indicated the importance of social support and exercise self-efficacy on PA promotion in adolescents, which will aid the development of effective interventions in this population.

Acute Exercise and Sustained Attention on Memory Function.

Objective: Sustained attention is critical for various activities of daily living, including engaging in health-enhancing behaviors and inhibition of health compromising behaviors. Sustained attention activates neural networks involved in episodic memory function, a critical cognition for healthy living. Acute exercise has been shown to activate these same neural networks. Thus, it is plausible that engaging in a sustained attention task and engaging in a bout of acute exercise may have an additive effect in enhancing memory function, which was the purpose of this experiment. Methods: 23 young adults (Mage = 20.7 years) completed 2 visits, with each visit occurring approximately 24 hours apart, in a counterbalanced order, including: (1) acute exercise with sustained attention, and (2) sustained attention only. Memory was assessed using a word-list paradigm and included a short- and long-term memory assessment. Sustained attention was induced via a sustained attention to response task (SART). Acute exercise involved a 15-minute bout of moderate-intensity exercise. Results: Short-term memory performance was significantly greater than long-term memory, Mdiff = 1.86, p < .001, and short-term memory for Exercise with Sustained Attention was significantly greater than short-term memory for Sustained Attention Only, Mdiff = 1.50, p = .01. Conclusion: Engaging in an acute bout of exercise before a sustained attention task additively influenced short-term memory function.

Engineering endogenous ABC transporter with improving ATP supply and membrane flexibility enhances the secretion of ß-carotene in Saccharomyces cerevisiae.

BACKGROUND: Product toxicity is one of the bottlenecks for microbial production of biofuels, and transporter-mediated biofuel secretion offers a promising strategy to solve this problem. As a robust microbial host for industrial-scale production of biofuels, Saccharomyces cerevisiae contains a powerful transport system to export a wide range of toxic compounds to sustain survival. The aim of this study is to improve the secretion and production of the hydrophobic product (ß-carotene) by harnessing endogenous ABC transporters combined with physiological engineering in S. cerevisiae. RESULTS: Substrate inducibility is a prominent characteristic of most endogenous transporters. Through comparative proteomic analysis and transcriptional confirmation, we identified five potential ABC transporters (Pdr5p, Pdr10p, Snq2p, Yor1p, and Yol075cp) for ß-carotene efflux. The accumulation of ß-carotene also affects cell physiology in various aspects, including energy metabolism, mitochondrial translation, lipid metabolism, ergosterol biosynthetic process, and cell wall synthesis. Here, we adopted an inducible GAL promoter to overexpress candidate transporters and enhanced the secretion and intracellular production of ß-carotene, in which Snq2p showed the best performance (a 4.04-fold and a 1.33-fold increase compared with its parental strain YBX-01, respectively). To further promote efflux capacity, two strategies of increasing ATP supply and improving membrane fluidity were following adopted. A 5.80-fold increase of ß-carotene secretion and a 1.71-fold increase of the intracellular ß-carotene production were consequently achieved in the engineered strain YBX-20 compared with the parental strain YBX-01. CONCLUSIONS: Overall, our results showcase that engineering endogenous plasma membrane ABC transporters is a promising approach for hydrophobic product efflux in S. cerevisiae. We also highlight the importance of improving cell physiology to enhance the efficiency of ABC transporters, especially energy status and cell membrane properties.