Evolution and stability of complex microbial communities driven by trade-offs.

Microbial communities are ubiquitous in nature and play an important role in ecology and human health. Cross-feeding is thought to be core to microbial communities, though it remains unclear precisely why it emerges. Why have multi-species microbial communities evolved in many contexts and what protects microbial consortia from invasion? Here, we review recent insights into the emergence and stability of coexistence in microbial communities. A particular focus is the long-term evolutionary stability of coexistence, as observed for microbial communities that spontaneously evolved in the E. coli long-term evolution experiment (LTEE). We analyze these findings in the context of recent work on trade-offs between competing microbial objectives, which can constitute a mechanistic basis for the emergence of coexistence. Coexisting communities, rather than monocultures of the 'fittest' single strain, can form stable endpoints of evolutionary trajectories. Hence, the emergence of coexistence might be an obligatory outcome in the evolution of microbial communities. This implies that rather than embodying fragile metastable configurations, some microbial communities can constitute formidable ecosystems that are difficult to disrupt.

FUT11 expression in gastric cancer: its prognostic significance and role in immune regulation.

BACKGROUND: Gastric cancer (GC) is a malignant digestive tract tumor with a high recurrence rate and poor prognosis. Fucosylation is important in tumor glycosylation, in which the key enzyme is fucosyltransferase (FUT). FUT11 is a member of the fucosyltransferase family and has been closely associated with the development of multiple cancers. However, the specific relationship between FUT11 and GC prognosis and its molecular mechanism has not been fully studied. This study explored FUT11 expression, clinical correlation, and its role in GC occurrence and development to deepen understanding of its function. METHODS: FUT11 expression in 33 cancers was preliminarily analyzed using the Tumor Immunoassay Resource (TIMER2.0) database. FUT11 expression in GC was evaluated using The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) and Gene Expression Profiling Interactive Analysis (GEPIA2) data and verified using the Gene Expression Omnibus (GEO) GSE65801 dataset. Furthermore, we studied the survival prognosis of FUT11 in GC and analyzed its effect on the survival rate of patients with GC using the KM-plotter. We also performed COX regression analysis on TCGA GC clinical data and analyzed FUT11 expression in the pathway using the STRING and LinkedOmics databases. Moreover, the relationship between FUT11 and GC immune infiltration level was examined, and the Kaplan-Meier survival analysis diagram was constructed. The FUT11 genetic variation information was retrieved using cBioPortal, and its drug sensitivity was analyzed using CellMiner. Finally, differential FUT11 expression in GC tissues was verified using immunohistochemistry. RESULTS: The data mining and analysis demonstrated that FUT11 expression was abnormally elevated in GC tissues and correlated with poor patient prognosis. The FUT11 expression level was an independent prognostic factor for GC. The difference in FUT11 expression level resulted in different degrees of immune cell infiltration in the patients with GC, which might regulate the tumor microenvironment. FUT11 affected GC development by participating in cancer pathways such as PI3K-AKT, neuroactive ligand-receptor, and MAPK. Immunohistochemical staining revealed that FUT11 was highly expressed in GC. CONCLUSIONS: This study revealed that FUT11 expression is significantly increased in GC tissues. This increase is associated with poor prognosis and might affect immune regulation. FUT11 might have immunological and targeted therapeutic value, providing a new approach to GC treatment.

Effects of geographical, soil and climatic factors on the two marker secondary metabolites contents in the roots of Rubia cordifolia L.

The growth and quality of medicinal plants depend heavily on environmental variables. The quality of Rubia cordifolia, an important medicinal plant, is determined by the two main secondary metabolites of the root, purpurin and mollugin. However, their relationship with environmental factors has not been studied. In this study, the purpurin and mollugin contents of R. cordifolia roots from different sampling sites in China were measured using ultra-high-performance liquid chromatography, and the correlations between the two secondary metabolites and environmental variables were analyzed. The results showed that there were significant differences in the contents of purpurin and mollugin in the roots of R. cordifolia at different sampling points. The content of purpurin ranged from 0.00 to 3.03 mg g-1, while the content of mollugin ranged from 0.03 to 10.09 mg g-1. The quality of R. cordifolia in Shanxi, Shaanxi and Henan border areas and southeastern Liaoning was higher. Liaoning is expected to become a R. cordifolia planting area in Northeast China. Correlation and regression analysis revealed that the two secondary metabolites were affected by different environmental factors, the two secondary metabolites contents were positively correlated with longitude and latitude, and negatively correlated with soil nutrients. In addition, higher temperature and shorter sunshine duration facilitated the synthesis of purpurin. Annual precipitation might be the main factor limiting the quality of R. cordifolia because it had opposite effects on the synthesis of two major secondary metabolites. Therefore, this study is of great significance for the selection of R. cordifolia planting areas and the improvement of field planting quality.

Homeostasis of cytoplasmic crowding by cell wall fluidization and ribosomal counterions.

In bacteria, algae, fungi, and plant cells, the wall must expand in concert with cytoplasmic biomass production, otherwise cells would experience toxic molecular crowding1,2 or lyse. But how cells achieve expansion of this complex biomaterial in coordination with biosynthesis of macromolecules in the cytoplasm remains unexplained3, although recent works have revealed that these processes are indeed coupled4,5. Here, we report a striking increase of turgor pressure with growth rate in E. coli, suggesting that the speed of cell wall expansion is controlled via turgor. Remarkably, despite this increase in turgor pressure, cellular biomass density remains constant across a wide range of growth rates. By contrast, perturbations of turgor pressure that deviate from this scaling directly alter biomass density. A mathematical model based on cell wall fluidization by cell wall endopeptidases not only explains these apparently confounding observations but makes surprising quantitative predictions that we validated experimentally. The picture that emerges is that turgor pressure is directly controlled via counterions of ribosomal RNA. Elegantly, the coupling between rRNA and turgor pressure simultaneously coordinates cell wall expansion across a wide range of growth rates and exerts homeostatic feedback control on biomass density. This mechanism may regulate cell wall biosynthesis from microbes to plants and has important implications for the mechanism of action of antibiotics6.

Factors associated with SARS-CoV-2 vaccine hesitancy after stroke: a cross-sectional study.

BACKGROUND: The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. METHODS: This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. RESULTS: Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36-2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82-0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32-2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51-5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. CONCLUSION: We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.

Atherosclerosis, gut microbiome, and exercise in a meta-omics perspective: a literature review.

Background: Cardiovascular diseases are the leading cause of death worldwide, significantly impacting public health. Atherosclerotic cardiovascular diseases account for the majority of these deaths, with atherosclerosis marking the initial and most critical phase of their pathophysiological progression. There is a complex relationship between atherosclerosis, the gut microbiome's composition and function, and the potential mediating role of exercise. The adaptability of the gut microbiome and the feasibility of exercise interventions present novel opportunities for therapeutic and preventative approaches. Methodology: We conducted a comprehensive literature review using professional databases such as PubMed and Web of Science. This review focuses on the application of meta-omics techniques, particularly metagenomics and metabolomics, in studying the effects of exercise interventions on the gut microbiome and atherosclerosis. Results: Meta-omics technologies offer unparalleled capabilities to explore the intricate connections between exercise, the microbiome, the metabolome, and cardiometabolic health. This review highlights the advancements in metagenomics and metabolomics, their applications in research, and examines how exercise influences the gut microbiome. We delve into the mechanisms connecting these elements from a metabolic perspective. Metagenomics provides insight into changes in microbial strains post-exercise, while metabolomics sheds light on the shifts in metabolites. Together, these approaches offer a comprehensive understanding of how exercise impacts atherosclerosis through specific mechanisms. Conclusions: Exercise significantly influences atherosclerosis, with the gut microbiome serving as a critical intermediary. Meta-omics technology holds substantial promise for investigating the gut microbiome; however, its methodologies require further refinement. Additionally, there is a pressing need for more extensive cohort studies to enhance our comprehension of the connection among these element.

A green aqueous binder to enhance the electrochemical performance of Li-rich disordered rock salt cathode material.

Li-rich disordered rock-salt oxides (DRX) are considered an attractive cathode material in the future battery field due to their excellent energy density and specific capacity. Nevertheless, anionic redox provides high capacity while causing O2 over-oxidation to O2, resulting in voltage hysteresis and capacity decay. Herein, the crystal structure of Li1.3Mn0.4Ti0.3O1.7F0.3 (LMTOF) cathode is stabilized by using sodium carboxymethylcellulose (CMC) binders replacing traditional polyvinylidene difluoride (PVDF) binders. The electrochemical impedance spectroscopy (EIS) and galvanostatic intermittent titration technique (GITT) reveal that the CMC-based LMTOF electrode has higher electronic conductivity and lithium-ion diffusion kinetics. Moreover, CMC has been demonstrated to improve the O2- reversibility, reduce the amounts of byproducts from electrolyte decomposition and suppress transition metal dissolution by Na+/Li+ exchange reaction. Furthermore, the CMC-based LMTOF electrode also exhibits less volume change upon lithiation/delithiation processes compared to the PVDF-based electrode, resulting in enhanced structural stability during cycling. Benefiting from these features, the CMC binders can effectively improve the cycling life and rate performance of the LMTOF cathode, and the CMC-based LMTOF electrode shows good capacity retention of 94.5 % after 30 cycles at 20 mA/g and 66.7 % after 100 cycles at 200 mA/g. This finding indicates that CMC as a binder can efficiently stabilize the structure and improve the electrochemical performance of Li-rich disordered rock-salt oxides cathode, making it possible for practical Li-ion battery applications.

Physiological and transcriptomic analysis revealed the alleviating effect of 1,25(OH)2D3 on environmental iron overloading induced ferroptosis in zebrafish.

Iron overload in the aquatic environment can cause damage in fish bodies. Vitamin D3 (VD3) has been proven to have antioxidant and regulatory effects on iron transport. The current research investigated the effects of environmental iron overload on larval zebrafish and explored the effects of 1,25(OH)2D3 on ferroptosis in zebrafish larvae and zebrafish liver cells (ZFL) caused by iron overload in the environment and its possible regulatory mechanisms. The results showed that 1,25(OH)2D3 alleviated liver damage in zebrafish larvae and mitochondrial damage in ZFL after excessive ammonium ferric citrate (FAC) treatment, and improved the survival rate of ZFL. 1,25(OH)2D3 cleared and inhibited excessive FAC induced abnormal accumulation of ROS, lipid ROS, MDA, and Fe2+ in zebrafish larvae and ZFL, as well as enhanced the activity of antioxidant enzyme GPx4. Transcriptomic analysis showed that 1,25(OH)2D3 can regulate ferroptosis in ZFL by regulating signaling pathways related to oxidative stress, iron homeostasis, mitochondrial function, and ERS, mainly including ferroptosis, neoptosis, p53 signaling pathway, apoptosis, FoxO signaling pathway. Validation of transcriptome data showed that 1,25(OH)2D3 inhibits ferroptosis in zebrafish larvae and ZFL caused by excessive FAC via promoting the expression of slc40a1 and hmox1a genes and increasing SLC40A1 protein levels. In summary, 1,25(OH)2D3 can resist ferroptosis in zebrafish caused by iron overload in the environment mainly via regulating antioxidant capacity and iron ion transport.

ITGA11, a Prognostic Factor Associated with Immunity in Gastric Adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) presents a challenge given its advanced stage at diagnosis and poor prognosis. Integrin subunit alpha 11 (ITGA11) encodes alpha integrin and has been implicated in promoting tumorigenesis and development by participating in cell proliferation and invasion. However, the precise mechanism of ITGA11 in STAD remains unclear. Methods: The differences in ITGA11 expression levels between 375 gastric cancer samples and 32 paracancerous tissue samples from the Cancer Genome Atlas (TCGA) database were examined. The relationship between ITGA11 expression and clinical features and ITGA11 diagnostic and prognostic value were evaluated using the chi-square test and receiver operating characteristic (ROC) assay. Differentially expressed genes were identified based on ITGA11 expression. Subsequently, functional enrichment analyses were conducted using Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis. Furthermore, immune infiltration and the expression of ITGA11-associated immune checkpoints in patients with tumors were assessed using CIBERSORT, single-sample gene set enrichment analysis, and the TIMER database. Drug sensitivity associated with ITGA11 expression was analyzed using the R oncoPredict package to guide treatment decisions. Finally, the difference in ITGA11 expression between cancer tissue and the adjacent tissues was validated using quantitative PCR (qPCR) and immunohistochemistry. Results: The gastric cancer tissue had significantly upregulated ITGA11 expression compared to paracancerous tissues. ITGA11 demonstrated robust diagnostic and prognostic value in gastric cancer (GC) and was an independent risk factor for adverse outcomes. The patients with STAD with elevated ITGA11 expression levels had heightened immune cell infiltration and increased immune checkpoint marker expression. Notably, patients with increased ITGA11 expression demonstrated reduced responsiveness to oxaliplatin and afatinib. Conclusion: The results indicated the pivotal role of ITGA11 in shaping the tumor immune microenvironment, ultimately establishing ITGA11 as an immune-related prognostic predictor within the intricate landscape of STAD.

Plasticity of growth laws tunes resource allocation strategies in bacteria.

Bacteria like E. coli grow at vastly different rates on different substrates, however, the precise reason for this variability is poorly understood. Different growth rates have been attributed to 'nutrient quality', a key parameter in bacterial growth laws. However, it remains unclear to what extent nutrient quality is rooted in fundamental biochemical constraints like the energy content of nutrients, the protein cost required for their uptake and catabolism, or the capacity of the plasma membrane for nutrient transporters. Here, we show that while nutrient quality is indeed reflected in protein investment in substrate-specific transporters and enzymes, this is not a fundamental limitation on growth rate, at least for certain 'poor' substrates. We show that it is possible to turn mannose, one of the 'poorest' substrates of E. coli, into one of the 'best' substrates by reengineering chromosomal promoters of the mannose transporter and metabolic enzymes required for mannose degradation. This result falls in line with previous observations of more subtle growth rate improvement for many other carbon sources. However, we show that this faster growth rate comes at the cost of diverse cellular capabilities, reflected in longer lag phases, worse starvation survival and lower motility. We show that addition of cAMP to the medium can rescue these phenotypes but imposes a corresponding growth cost. Based on these data, we propose that nutrient quality is largely a self-determined, plastic property that can be modulated by the fraction of proteomic resources devoted to a specific substrate in the much larger proteome sector of catabolically activated genes. Rather than a fundamental biochemical limitation, nutrient quality reflects resource allocation decisions that are shaped by evolution in specific ecological niches and can be quickly adapted if necessary.

Peer victimization and non-suicidal self-injury among high school students: the mediating role of social anxiety, mobile phone addiction, and sex differences.

BACKGROUND: Peer victimization (PV) is one of the major causes of non-suicidal self-injury. Non-suicidal self-injury (NSSI), peer victimization, social anxiety, and mobile phone addiction are significantly related; however, the interaction mechanism and effect of sex differences remain to be determined. OBJECTIVE: Herein, we investigated the relationship between peer victimization and NSSI among Chinese high school students. We also explored the chain mediating roles of social anxiety and mobile phone addiction and the regulatory role of sex. The findings of this study provide insights for theoretical interventions based on internal mechanisms. METHOD: A self-reported survey of 14,666 high school students from Sichuan County was conducted using a peer victimization scale, NSSI scale, social anxiety scale, and mobile phone addiction scale. A self-administered questionnaire was used to capture sociodemographic information. RESULTS: Peer victimization, social anxiety, and mobile phone addiction were positively correlated with NSSI. Peer victimization had significant direct predictive effects on NSSI (95% CI: 0.341, 0.385) and significant indirect predictive effects on NSSI through social anxiety (95% CI: 0.008, 0.019) or mobile phone addiction (95% CI: 0.036, 0.053). Peer victimization had significant indirect predictive effects on NSSI through social anxiety as well as mobile phone addiction (95% CI: 0.009, 0.014). The first stage (predicting the effect of peer victimization on NSSI) and the third stage (predicting the effect of mobile phone addiction on NSSI) were both moderated by sex. CONCLUSIONS: Peer victimization could directly predict NSSI and indirectly predict NSSI through social anxiety and mobile phone addiction. Thus, social anxiety and mobile phone addiction exhibited chain mediating effects between peer victimization and NSSI in high school students; moreover, sex might be involved in the regulation of the mediation process.

Exogenous 1,25(OH)2D3/VD3 counteracts RSL3-Induced ferroptosis by enhancing antioxidant capacity and regulating iron ion transport: Using zebrafish as a model.

RSL3 is a common inhibitor of glutathione peroxidase 4 (GPx4) that can induce ferroptosis. Ferroptosis is an iron ion-dependent, oxidative-type of programmed cell death. In this study, larval/adult zebrafish were stimulated with RSL3 to construct a ferroptosis model, and CYP2R1-/- zebrafish was used as a 1,25(OH)2D3 knock-down model to explore the regulatory effect and mechanism of 1,25(OH)2D3/VD3 on RSL3-induced ferroptosis. The results showed that 1,25(OH)2D3/VD3 alleviated RSL3 induced mitochondrial damage in liver of larval/adult zebrafish, reversed the decline of GPx4 activity, and reduced the accumulation of ROS, LPO and MDA. VD3 also inhibited hepcidin (HEPC) in adult fish liver, promoted the production of ferroportin (FPN), and reduced the aggregation of Fe2+. Exogenous 1,25(OH)2D3 increased the CYP2R1-/- survival and liver GPx4 activity after RSL3 treatment. At the gene level, 1,25(OH)2D3/VD3 activated Keap1-Nrf2-GPx4 and inhibited the NFκB-hepcidin axis. In the ferroptosis context, deletion of the cyp2r1 gene resulted in a more severe decline in gpx4 expression, but the exogenous 1,25(OH)2D3 increased the expression of the GPx4 gene and protein in CYP2R1-/- zebrafish liver after RSL3 treatment. The collective results indicated that 1,25(OH)2D3/VD3 can inhibit ferroptosis induced by RSL3 in liver of larval/adult zebrafish by improving the antioxidant capacity and regulating iron ion transport. Exogenous 1,25(OH)2D3 reverses the downregulation of GPx4 in the CYP2R1-/- zebrafish liver in the ferroptosis state. Compared with the ferroptosis inhibitor Fer-1, the mechanism of action of 1,25(OH)2D3/VD3 is diversified and nonspecific. This study demonstrated the resistance of VD3 to RSL3-induced ferroptosis at different developmental stages in zebrafish.

Vitamin D3 promotes fish oocyte development by directly regulating gonadal steroid hormone synthesis†.

Vitamin D receptors and vitamin D3-metabolizing enzymes have been found to be highly expressed in the ovaries and spermatophores of fish. However, the role of vitamin D3 on fish gonadal development has rarely been reported. In this study, 2-month-old female zebrafish were fed with different concentrations of vitamin D3 diets (0, 700, 1400, and 11 200 IU/kg) to investigate the effects of vitamin D3 on ovarian development. The diet with 0 IU/kg vitamin D3 resulted in elevated interstitial spaces, follicular atresia, and reproductive toxicity in zebrafish ovaries. Supplementation with 700 and 1400 IU/kg of vitamin D3 significantly increased the oocyte maturation rate; upregulated ovarian gonadal steroid hormone synthesis capacity; and elevated plasma estradiol, testosterone, and ovarian vitellogenin levels. Furthermore, the current study identified a vitamin D response element in the cyp19a1a promoter and demonstrated that 1.25(OH)2D3-vitamin D response directly activated cyp19a1a production through activating the vitamin D response element. In conclusion, this study shows that an appropriate concentration of vitamin D3 can promote zebrafish ovarian development and affect vitellogenin synthesis through the vdr/cyp19a1a/er/vtg gene axis.

Cultural-Responsiveness of the Mental Health First Aid Training for Asian Immigrant Populations in Greater Boston, Massachusetts.

Background: The COVID-19 pandemic and rise in anti-Asian racism have had adverse mental health impacts in Asian communities. The lack of culturally-responsive and linguistically-accessible mental health trainings hinders access to mental health services for Asian populations. In this study, we assessed the mental health needs of Asian communities in Greater Boston and evaluated cultural responsiveness of the Mental Health First Aid (MHFA), a first-responder training teaching participants skills to recognize signs of mental health and substance use challenges, and how to appropriately respond. Methods: This community-based participatory research with the Boston Chinatown Neighborhood Center (BCNC), Asian Women For Health (AWFH), and the Addressing Disparities in Asian Populations through Translational Research (ADAPT) Coalition employed two phases. In phase 1, we conducted focus groups with BCNC and AWFH staff and peer educators to assess mental health priorities of Asian populations in Boston. Findings informed phase 2, which evaluated cultural responsiveness of the MHFA through pre- and post-training questionnaires and focus groups with community participants. The pre-training questionnaire asked about mental health needs and barriers, help-seeking behaviors, and literacy; and personal and Asian community stigma. The post-training questionnaire and focus group with community participants asked about cultural competence of MHFA training for Asian populations. Paired t-tests were used to evaluate questionnaire responses. Thematic analysis was used to analyze interviews. Results: In total, 10 staff/educators and 8 community members participated in focus groups. They identified common mental health needs and workforce and culturally-responsive community strategies to support persons with mental health issues. Twenty-four community participants completed pre- and post-training questionnaires. They reported the MHFA training reduced mental health care stigma and increased mental health literacy. Recommendations to increase cultural-responsiveness of the MHFA were to include mental health case studies common in Asian populations and provide the training in other languages (e.g., Chinese, Vietnamese). Conclusion: Cultural responsiveness of the MHFA for Asian populations could be improved with the inclusion of case studies specific to the Asian communities and accessibility of the training in other languages. Increasing the cultural relevance and language accessibility of these trainings could help reduce mental health stigma and gaps in mental health awareness and service utilization among Asian populations.

Membrane potential mediates an ancient mechano-transduction mechanism for multi-cellular homeostasis.

Membrane potential is a property of all living cells1. However, its physiological role in non-excitable cells is poorly understood. Resting membrane potential is typically considered fixed for a given cell type and under tight homeostatic control2, akin to body temperature in mammals. Contrary to this widely accepted paradigm, we found that membrane potential is a dynamic property that directly reflects tissue density and mechanical forces acting on the cell. Serving as a quasi-instantaneous, global readout of density and mechanical pressure, membrane potential is integrated with signal transduction networks by affecting the conformation and clustering of proteins in the membrane3,4, as well as the transmembrane flux of key signaling ions5,6. Indeed, we show that important mechano-sensing pathways, YAP, Jnk and p387-121314, are directly controlled by membrane potential. We further show that mechano-transduction via membrane potential plays a critical role in the homeostasis of epithelial tissues, setting tissue density by controlling proliferation and cell extrusion of cells. Moreover, a wave of depolarization triggered by mechanical stretch enhances the speed of wound healing. Mechano-transduction via membrane potential likely constitutes an ancient homeostatic mechanism in multi-cellular organisms, potentially serving as a steppingstone for the evolution of excitable tissues and neuronal mechano-sensing. The breakdown of membrane potential mediated homeostatic regulation may contribute to tumor growth.

A universal mechanism of biomass density homeostasis via ribosomal counterions.

In all growing cells, the cell envelope must expand in concert with cytoplasmic biomass to prevent lysis or molecular crowding. The complex cell wall of microbes and plants makes this challenge especially daunting and it unclear how cells achieve this coordination. Here, we uncover a striking linear increase of cytoplasmic pressure with growth rate in E. coli. Remarkably, despite this increase in turgor pressure with growth rate, cellular biomass density was constant across a wide range of growth rates. In contrast, perturbing pressure away from this scaling directly affected biomass density. A mathematical model, in which endopeptidase-mediated cell wall fluidization enables turgor pressure to set the pace of cellular volume expansion, not only explains these confounding observations, but makes several surprising quantitative predictions that we validated experimentally. The picture that emerges is that changes in turgor pressure across growth rates are mediated by counterions of ribosomal RNA. Profoundly, the coupling between rRNA and cytoplasmic pressure simultaneously coordinates cell wall expansion across growth rates and exerts homeostatic feedback control on biomass density. Because ribosome content universally scales with growth rate in fast growing cells, this universal mechanism may control cell wall biosynthesis in microbes and plants and drive the expansion of ribosome-addicted tumors that can exert substantial mechanical forces on their environment.

Changes in marker secondary metabolites revealed the medicinal parts, harvest time, and possible synthetic sites of Rubia cordifolia L.

Rubia cordifolia L. is a significant medicinal plant. To investigate the changes of marker metabolites of R. cordifolia, the purpurin, mollugin, carbon, nitrogen contents, and the expression of genes involved in anthraquinones synthesis were examined. The findings indicated that the two secondary metabolites were only detected in stems and roots. Root purpurin content was 5-26 times higher than in stems, and root mollugin content was 92 times higher than in stems in June. These findings suggest that the potential of the roots as a medicinal part. The roots were found to have highest purpurin content in October (2.406 mg g-1), whereas the mollugin content was highest in August (6.193 mg g-1). However, the purpurin content in August was only 0.029 mg g-1 lower than that in October, making August a suitable harvest period for R. cordifolia. The expression 1-deoxy-D-xylulose 5-phosphate synthase (dxs) and 1-deoxy-D-xylulose-5-phosphate reductorisomerase (dxr) genes in roots showed an upward trend. However, the expression level of dxr gene was significantly higher than dxs with the range of 60-518 times higher, indicating the important role of dxr gene. Through correlation and redundancy analyses, it was found that mollugin showed positive correlation with carbon contents and carbon-nitrogen ratio of aerial parts. Additionally, purpurin showed a positive correlation with the expression of both genes. As a result, mollugin is likely to be synthesized in the aerial parts and then stored in the roots, whereas purpurin might be synthesized in the stems and roots. These findings could provide cultivation guidelines for R. cordifolia.

Plasticity of growth laws tunes resource allocation strategies in bacteria.

Bacteria like E. coli grow at vastly different rates on different substrates, however, the precise reason for this variability is poorly understood. Different growth rates have been attributed to 'nutrient quality', a key parameter in bacterial growth laws. However, it remains unclear to what extent nutrient quality is rooted in fundamental biochemical constraints like the energy content of nutrients, the protein cost required for their uptake and catabolism, or the capacity of the plasma membrane for nutrient transporters. Here, we show that while nutrient quality is indeed reflected in protein investment in substrate-specific transporters and enzymes, this is not a fundamental limitation on growth rate. We show that it is possible to turn mannose, one of the 'poorest' substrates of E. coli, into one of the 'best' substrates by reengineering chromosomal promoters of the mannose transporter and metabolic enzymes required for mannose degradation. However, we show that this faster growth rate comes at the cost of diverse cellular capabilities, reflected in longer lag phases, worse starvation survival and lower motility. We show that addition of cAMP to the medium can rescue these phenotypes but imposes a corresponding growth cost. Based on these data, we propose that nutrient quality is largely a self-determined, plastic property that can be modulated by the fraction of proteomic resources devoted to a specific substrate in the much larger proteome sector of catabolically activated genes. Rather than a fundamental biochemical limitation, nutrient quality reflects resource allocation decisions that are shaped by evolution in specific ecological niches and can be quickly adapted if necessary.

METTL3-mediated m6A modification of pri-miR-148a-3p affects prostate cancer progression by regulating TXNIP.

OBJECTIVE: Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase-like 3 (METTL3) in affecting PCa development by regulating miR-148a-3p expression via N6-methyladenosine (m6A) modification was investigated. METHODS: METTL3, miR-148a-3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT-qPCR and Western blotting. The m6A modification level of miR-148a-3p was observed by Me-RIP assay. Bioinformatics website predicted miR-148a-3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual-luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK-8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry. RESULTS: METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up-regulated miR-148a-3p by promoting the m6A modification of pri-miR-148a-3p in PCa cells. miR-148a-3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR-148a-3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down-regulating miR-148a-3p and up-regulating TXNIP. CONCLUSION: METTL3 promoted miR-148a-3p by mediating the m6A modification of pri-miR-148a-3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.