Adverse childhood experience and depression: the role of gut microbiota.

Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the "microbe-gut-brain axis" and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.

GEO dataset mining analysis reveals novel Staphylococcus aureus virulence gene regulatory networks and diagnostic targets in mice.

Staphylococcus (S.) aureus infection is a serious, worldwide health concern, particularly in many communities and hospitals. Understanding the S. aureus pathogenetic regulatory network will provide significant insights into diagnostic target screening to improve clinical treatment of diseases caused by S. aureus. We screened differentially expressed genes between normal mice and S. aureus-infected mice. We used the Gene Expression Omnibus (GEO) DataSets database for functional analysis (GO-analysis) and the DAVID and KEGG databases for signaling pathway analyses. We next integrated the gene and pathway analyses with Transcriptional Regulatory Element Database (TRED) to build an antimicrobial resistance gene regulatory network of S. aureus. We performed association analysis of network genes and diseases using DAVID online annotation tools. We identified a total of 437 virulence genes and 15 transcription factors (TFs), as well as 444 corresponding target genes, in the S. aureus TF regulatory network. We screened seven key network nodes (Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl), four key transcription factors (Jun, C3, Spil, and Il6) and an important signaling pathway (TNF). We hypothesized that the cytokine activity and growth factor activity of S. aureus are combinatorically cross-regulated by Met, Mmp13, Il12b, Il4, Tnf, Ptgs2, and Ctsl genes, the TFs Jun, C3, Spi1, and Il6, as well as the immune response, cellular response to lipopolysaccharide, and inflammatory response. Our study provides information and reference values for the molecular understanding of the S. aureus pathogenetic gene regulatory network.

Protective Effect of Hop Ethyl Acetate Extract on Corticosterone-Induced PC12 and Improvement of Depression-like Behavior in Mice.

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.

A longitudinal study on the effects of social support on self-stigma, psychiatric symptoms, and personal and social functioning in community patients with severe mental illnesses in China.

BACKGROUND: Few studies have examined whether social support contributes to better consequences among chronic patients with severe mental illnesses (SMI) in their community recovery stage and whether self-stigma would be a mechanism through which social support impacts psychiatric symptoms and personal and social functioning. AIMS: This study aimed to examine prospective associations of social support with long-term self-stigma, psychiatric symptoms, and personal and social functioning, and to investigate whether self-stigma would mediate the associations of social support with psychiatric symptoms and personal and social functioning among patients with SMI. METHODS: A total of 312 persons with SMI (schizophrenia and bipolar disorder) in their community recovery stage participated in the study. Social support, self-stigma, psychiatric symptoms, and personal and social functioning were evaluated at baseline. The follow-up assessment was conducted at 6 months with the baseline measures except for social support. Hierarchical linear regression and mediation analysis were performed. RESULTS: The results showed that baseline social support predicted decreases in stigma (ß = -.115, p = .029) and psychiatric symptoms (ß = -.193, p < .001), and increases in personal and social functioning (ß = .134, p = .008) over 6 months, after adjusting for relevant covariates. Stigma at 6 months partially mediated the association between baseline social support and 6-month psychiatric symptoms (indirect effect: ß = -.043, CI [-0.074, -0.018]). Stigma and psychiatric symptoms at 6 months together mediated the association between baseline social support and 6-month personal and social functioning (indirect effect: ß = .084, 95% CI [0.029, 0.143]). CONCLUSION: It is necessary to provide comprehensive social support services and stigma reduction interventions at the community level to improve the prognosis of SMI.

Dipeptidase 1 promotes ferroptosis in renal tubular epithelial cells in diabetic nephropathy via inhibition of the GSH/GPX4 axis.

Renal tubular injury is an important pathological change associated with diabetic nephropathy (DN), in which ferroptosis of renal tubular epithelial cells is critical to its pathogenesis. Inhibition of the glutathione/glutathione peroxidase 4 (GSH/GPX4) axis is the most important mechanism in DN tubular epithelial cell ferroptosis, but the underlying reason for this is unclear. Our biogenic analysis showed that a zinc-dependent metalloproteinase, dipeptidase 1 (DPEP1), is associated with DN ferroptosis. Here, we investigated the role and mechanism of DPEP1 in DN tubular epithelial cell ferroptosis. DPEP1 upregulation was observed in the renal tubular epithelial cells of DN patients and model mice, as well as in HK-2 cells stimulated with high glucose. Furthermore, the level of DPEP1 upregulation was associated with the degree of tubular injury in DN patients and HK-2 cell ferroptosis. Mechanistically, knocking down DPEP1 expression could alleviate the inhibition of GSH/GPX4 axis and reduce HK-2 cell ferroptosis levels in a high glucose environment. HK-2 cells with stable DPEP1 overexpression also showed GSH/GPX4 axis inhibition and ferroptosis, but blocking the GSH/GPX4 axis could mitigate these effects. Additionally, treatment with cilastatin, a DPEP1 inhibitor, could ameliorate GSH/GPX4 axis inhibition and relieve ferroptosis and DN progression in DN mice. These results revealed that DPEP1 can promote ferroptosis in DN renal tubular epithelial cells via inhibition of the GSH/GPX4 axis.

Highly Reversible Zn-Air Batteries Enabled by Tuned Valence Electron and Steric Hindrance on Atomic Fe-N4-C Sites.

The bifunctional oxygen electrocatalyst is the Achilles' heel of achieving robust reversible Zn-air batteries (ZABs). Herein, durable bifunctional oxygen electrocatalysis in alkaline media is realized on atomic Fe-N4-C sites reinforced by NixCo3-xO4 (NixCo3-xO4@Fe1/NC). Compared with that of pristine Fe1/NC, the stability of the oxygen evolution reaction (OER) is increased 10 times and the oxygen reduction reaction (ORR) performance is also improved. The steric hindrance alters the valence electron at the Fe-N4-C sites, resulting in a shorter Fe-N bond and enhanced stability of the Fe-N4-C sites. The corresponding solid-state ZABs exhibit an ultralong lifespan (>460 h at 5 mA cm-2) and high rate performance (from 2 to 50 mA cm-2). Furthermore, the structural evolution of NixCo3-xO4@Fe1/NC before and after the OER and ORR as well as charge-discharge cycling is explored. This work develops an efficient strategy for improving bifunctional oxygen electrocatalysis and possibly other processes.

Sub-pixel marking and depth-based correction methods for the elimination of voxel drifting in integral imaging display.

Integral imaging is a kind of true three-dimensional (3D) display technology that uses a lens array to reconstruct vivid 3D images with full parallax and true color. In order to present a high-quality 3D image, it's vital to correct the axial position error caused by the misalignment and deformation of the lens array which makes the reconstructed lights deviate from the correct directions, resulting in severe voxel drifting and image blurring. We proposed a sub-pixel marking method to measure the axial position error of the lenses with great accuracy by addressing the sub-pixels under each lens and forming a homologous sub-pixel pair. The proposed measurement method relies on the geometric center alignment of image points, which is specifically expressed as the overlap between the test 3D voxel and the reference 3D voxel. Hence, measurement accuracy could be higher. Additionally, a depth-based sub-pixel correction method was proposed to eliminate the voxel drifting. The proposed correction method takes the voxel depth into consideration in the correction coefficient, and achieves accurate error correction for 3D images with different depths. The experimental results well confirmed that the proposed measuring and correction methods can greatly suppress the voxel drifting caused by the axial position error of the lenses, and greatly improve the 3D image quality.

Blood Management in a Liver Transplant Recipient with Kidd (Jka) and Rhesus (D) Antibodies: A Case Report.

A 67-year-old man presented for urgent liver transplantation (LT). Screening revealed the rare combination of antiRhesus (D) and antiKidd Jk(a) antibodies, requiring antigen-negative red blood cells (RBC) for both phenotypes. This combination has not been reported during LT. Compatible RBCs were initially limited, requiring continued communication between the blood bank/blood supplier to obtain more, including frozen, units. Additional strategies included the use of cell salvage and intentional management of coagulopathy to limit bleeding and RBC requirement. This case highlights blood management during LT when D and Jk(a) antibodies may limit RBC supply and emphasizes the need for effective communication with the blood bank.

Mucin alleviates colonic barrier dysfunction by promoting spermine accumulation through enhanced arginine metabolism in Limosilactobacillus mucosae.

Dietary fiber deprivation is linked to probiotic extinction, mucus barrier dysbiosis, and the overgrowth of mucin-degrading bacteria. However, whether and how mucin could rescue fiber deprivation-induced intestinal barrier defects remains largely unexplored. Here, we sought to investigate the potential role and mechanism by which exogenous mucin maintains the gut barrier function. The results showed that dietary mucin alleviated fiber deprivation-induced disruption of colonic barrier integrity and reduced spermine production in vivo. Importantly, we highlighted that microbial-derived spermine production, but not host-produced spermine, increased significantly after mucin supplementation, with a positive association with upgraded colonic Lactobacillus abundance. After employing an in vitro model, the microbial-derived spermine was consistently dominated by both mucin and Lactobacillus spp. Furthermore, Limosilactobacillus mucosae was identified as an essential spermine-producing Lactobacillus spp., and this isolated strain was responsible for spermine accumulation, especially after adhering to mucin in vitro. Specifically, the mucin-supplemented bacterial supernatant of Limosilactobacillus mucosae was verified to promote intestinal barrier functions through the increased spermine production with a dependence on enhanced arginine metabolism. Overall, these findings collectively provide evidence that mucin-modulated microbial arginine metabolism bridged the interplay between microbes and gut barrier function, illustrating possible implications for host gut health. IMPORTANCE: Microbial metabolites like short-chain fatty acids produced by dietary fiber fermentation have been demonstrated to have beneficial effects on intestinal health. However, it is essential to acknowledge that certain amino acids entering the colon can be metabolized by microorganisms to produce polyamines. The polyamines can promote the renewal of intestinal epithelial cell and maintain host-microbe homeostasis. Our study highlighted the specific enrichment by mucin on promoting the arginine metabolism in Limosilactobacillus mucosae to produce spermine, suggesting that microbial-derived polyamines support a significant enhancement on the goblet cell proliferation and barrier function.

What's the preferences of medical staff for providing health education service? - A discrete choice experiment in Beijing, China.

OBJECTIVE: To quantify medical staff preferences for providing health education service in hospitals. METHODS: This study took medical staff in the department of internal medicine of hospitals in Beijing, China as the research subjects, and designed a discrete choice experiment (DCE) to investigate the health education service provision preferences of them. Through various methods, 8 attributes and corresponding levels were determined. An online survey was conducted among the medical staff of the sample hospitals from May to June 2023. Participants' preferences were analyzed using conditional logit and mixed logit models. RESULTS: Finally, 831 respondents completed the questionnaire, among which 600 cases passed the consistency test. All the attributes included in this study had an impact on medical staff' health education service preferences (P < 0.001). The most important one with the greatest impact on the health education service delivery behavior of the respondents was "department working atmosphere-encouraging health education" (ß = 4.062, P < 0.001). CONCLUSION: In this study, the departmental work atmosphere and performance bonuses emerged as crucial factors influencing the engagement of medical staff in health education work. PRACTICAL IMPLICATIONS: Hospitals should prioritize measures to improve the health education working atmosphere in departments to increase the enthusiasm of medical staff to provide services.

Integrated transcriptomic and metabolomic analysis reveals the regulation mechanism of early bolting and flowering in two cultivars of Angelica sinensis.

The root of Angelica sinensis is utilized in Traditional Chinese medicine to enhance blood replenishment and facilitate blood circulation. The early bolting and flowering (EBF) of A. sinensis, however, compromises the quality of the roots and restricts the yield of medicinal substances. The study was conducted to compare the transcriptomic and metabolomic profiles between EBF plants and normal plants of two cultivars of A. sinensis, followed by validation of the transcriptome results using qRT-PCR. There were 3677 DEGs in EBF plants compared to normal plants of cultivar 2 (Mingui No.2), and cultivar 4 (Mingui No.4) was 3354. The main differential metabolites in the EBF and normal plants were phenolic acids, flavonoids, lignans, and coumarins. The analysis of 5 EBF-related pathways revealed 28 genes exhibiting differential expression and 5 metabolites showing differential accumulation. The expression of the Lhcb5, Lhcb2, Lhcb6, Lhcb1, Lhca4, ATPG1, EGLC, CELB, AMY, glgA, CYCD3, SnRK2, PYL, AHK2, AUX1, BSK, FabI/K, ACACA and FabV decreased and the expression of the PsbR, PsbA, LHY, FT, CO, malQ, HK, GPI and DELLA increased in EBF plants. In addition, the Abscisic acid, d-Glucose-6P, α-d-Glucose-1P, NADP+, and ADP were more significantly enriched in EBF plants. The findings offer novel perspectives on the EBF mechanisms in A. sinensis and other medicinal plants of the Apiaceae family.

Mesenchymal stem cells for repairing glaucomatous optic nerve.

Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Currently, there is no effective method to address the cause of RGCs degeneration. However, studies on neuroprotective strategies for optic neuropathy have increased in recent years. Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy. Regenerative medicine research into the repair of optic nerve damage using stem cells has received considerable attention. Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGC-friendly microenvironments through paracrine effects. This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury, raising the controversies and unresolved issues surrounding the future of stem cells.

Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/ß-catenin pathway.

Renal fibrosis (RF) is an important pathogenesis for renal function deterioration in chronic kidney disease. Secreted frizzled-related protein 5 (SFRP5) is an anti-fibrotic adipokine but its direct role on RF remains unknown. It was aimed to study the protective effect of SFRP5 against RF and interference with Wnt/ß-catenin signaling pathway for the first time. First, the therapeutic efficacy of SFRP5 was evaluated by adenovirus overexpression in rats with unilateral ureteral obstruction (UUO) in vivo. Thirty-six rats were randomly divided into the sham, UUO, and SFRP5 (UUO + Ad-SFRP5) groups. Half rats in each group were selected at random for euthanasia at 7 days and the others until 14 days. Then, the transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) was established in HK-2 cells in vitro. The cells were divided into four groups: the control group, the TGF-ß1 group, the TGF-ß1 + SFRP5 group, and the TGF-ß1 + SFRP5 + anti-SFRP5 group. The makers of EMT and Wnt/ß-catenin pathway proteins were investigated. In the UUO model, expression of SFRP5 showed compensatory upregulation, and adenoviral-mediated SFRP5 over-expression remarkably attenuated RF, as demonstrated by maintenance of E-cadherin and suppression of α-smooth muscle actin (SMA). In vitro, SFRP5 was shown to inhibit TGF-ß1-mediated positive regulation of α-SMA, fibronectin, collagen I but negative regulation of E-cadherin. Furthermore, SFRP5 abrogated activation of Wnt/ß-catenin, which was the essential pathway in EMT and RF pathogenesis. The changes after a neutralizing antibody to SFRP5 confirmed the specificity of SFRP5 for inhibition. These findings suggest that SFRP5 can directly ameliorate EMT and protect against RF by inhibiting Wnt/ß-catenin pathway.

E93 is indispensable for reproduction in ametabolous and hemimetabolous insects.

Ecdysone-induced protein 93 (E93), known as the "adult-specifier" transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. While E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discovered that in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNAs are broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we revealed that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

Constructing polynomial libraries for reservoir computing in nonlinear dynamical system forecasting.

Reservoir computing is an effective model for learning and predicting nonlinear and chaotic dynamical systems; however, there remains a challenge in achieving a more dependable evolution for such systems. Based on the foundation of Koopman operator theory, considering the effectiveness of the sparse identification of nonlinear dynamics algorithm to construct candidate nonlinear libraries in the application of nonlinear data, an alternative reservoir computing method is proposed, which creates the linear Hilbert space of the nonlinear system by including nonlinear terms in the optimization process of reservoir computing, allowing for the application of linear optimization. We introduce an implementation that incorporates a polynomial transformation of arbitrary order when fitting the readout matrix. Constructing polynomial libraries with reservoir-state vectors as elements enhances the nonlinear representation of reservoir states and more easily captures the complexity of nonlinear systems. The Lorenz-63 system, the Lorenz-96 system, and the Kuramoto-Sivashinsky equation are used to validate the effectiveness of constructing polynomial libraries for reservoir states in the field of state-evolution prediction of nonlinear and chaotic dynamical systems. This study not only promotes the theoretical study of reservoir computing, but also provides a theoretical and practical method for the prediction of nonlinear and chaotic dynamical system evolution.

Estimating Rotational Acceleration in Shoulder and Elbow Joints Using a Transformer Algorithm and a Fusion of Biosignals.

In the present study, we used a transformer model and a fusion of biosignals to estimate rotational acceleration in elbow and shoulder joints. To achieve our study objectives, we proposed a mechanomyography (MMG) signal isolation technique based on a variational mode decomposition (VMD) algorithm. Our results show that the VMD algorithm delivered excellent performance in MMG signal extraction compared to the commonly used technique of empirical mode decomposition (EMD). In addition, we found that transformer models delivered estimates of joint acceleration that were more precise than those produced by mainstream time series forecasting models. The average R2 values of transformer are 0.967, 0.968, and 0.935, respectively. Finally, we found that using a fusion of signals resulted in more precise estimation performance compared to using MMG signals alone. The differences between the average R2 values are 0.041, 0.053, and 0.043, respectively. Taken together, the VMD isolation method, the transformer algorithm and the signal fusion technique described in this paper can be seen as supplying a robust framework for estimating rotational acceleration in upper-limb joints. Further study is warranted to examine the effectiveness of this framework in other musculoskeletal contexts.

Elucidating immune cell dynamics in chronic lung allograft dysfunction: A comprehensive single-cell transcriptomic study.

Chronic Lung Allograft Dysfunction (CLAD) is a critical post-transplant complication that predominantly determines the long-term survival rates and quality of life of patients undergoing lung transplantation. The limited efficacy of current immunosuppressive strategies underscores our incomplete understanding of the immunological aspects of CLAD. Hence, there is an urgent need for more comprehensive and targeted research to unravel the complex interplay of immune cells in the development and progression of CLAD. This study conducts an in-depth analysis of the immune environment in CLAD. By examining the gene expression profiles of T cells, natural killer cells, B cells, macrophages, and monocytes, we have elucidated a unique immunological landscape in CLAD compared to healthy controls. We highlight the heterogeneity within the immune populations and provide a comprehensive understanding of the immune mechanisms driving CLAD. Enrichment analysis identified specific pathways that are either overactive or suppressed in CLAD, revealing potential molecular targets for therapeutic intervention. Our findings emphasize the crucial role of T cells in the pathophysiology of CLAD, coordinating the immune response and revealing an amplified immune cell network, potentially leading to maladaptive tissue responses. By integrating a comprehensive cellular and molecular portrait of the immune environment, our research not only deepens our understanding of the pathogenesis of CLAD but also lays a foundational approach for the development of targeted therapies.

The PKA-CREB1 axis regulates coronavirus proliferation by viral helicase nsp13 association.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a worldwide threat in the past 3 years. Although it has been widely and intensively investigated, the mechanism underlying the coronavirus-host interaction requires further elucidation, which may contribute to the development of new antiviral strategies. Here, we demonstrated that the host cAMP-responsive element-binding protein (CREB1) interacts with the non-structural protein 13 (nsp13) of SARS-CoV-2, a conserved helicase for coronavirus replication, both in cells and in lung tissues subjected to SARS-CoV-2 infection. The ATPase and helicase activity of viral nsp13 were shown to be potentiated by CREB1 association, as well as by Protein kinase A (PKA)-mediated CREB1 activation. SARS-CoV-2 replication is significantly suppressed by PKA Cα, cAMP-activated protein kinase catalytic subunit alpha (PRKACA), and CREB1 knockdown or inhibition. Consistently, the CREB1 inhibitor 666-15 has shown significant antiviral effects against both the WIV04 strain and the Omicron strain of the SARS-CoV-2. Our findings indicate that the PKA-CREB1 signaling axis may serve as a novel therapeutic target against coronavirus infection. IMPORTANCE: In this study, we provide solid evidence that host transcription factor cAMP-responsive element-binding protein (CREB1) interacts directly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helicase non-structural protein 13 (nsp13) and potentiate its ATPase and helicase activity. And by live SARS-CoV-2 virus infection, the inhibition of CREB1 dramatically impairs SARS-CoV-2 replication in vivo. Notably, the IC50 of CREB1 inhibitor 666-15 is comparable to that of remdesivir. These results may extend to all highly pathogenic coronaviruses due to the conserved nsp13 sequences in the virus.

Built-in Electric Field Promotes Interfacial Adsorption and Activation of CO2 for C1 Products over a Wide Potential Window.

The unsatisfactory adsorption and activation of CO2 suppress electrochemical reduction over a wide potential window. Herein, the built-in electric field (BIEF) at the CeO2/In2O3 n-n heterostructure realizes the C1 (CO and HCOO-) selectivity over 90.0% in a broad range of potentials from -0.7 to -1.1 V with a maximum value of 98.7 ± 0.3% at -0.8 V. In addition, the C1 current density (-1.1 V) of the CeO2/In2O3 heterostructure with a BIEF is about 2.0- and 3.2-fold that of In2O3 and a physically mixed sample, respectively. The experimental and theoretical calculation results indicate that the introduction of CeO2 triggered the charge redistribution and formed the BIEF at the interfaces, which enhanced the interfacial adsorption and activation of CO2 at low overpotentials. Furthermore, the promoting effect was also extended to CeO2/In2S3. This work gives a deep understanding of BIEF engineering for highly efficient CO2 electroreduction over a wide potential window.

Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.