The correlation of obesity status with serum 25-hydroxyvitamin D in US Asian adults: NHANES 2011-2018.

BACKGROUND: There is a correlation between obesity and 25-hydroxyvitamin D (25OHD) that tends to be negative. However, this relationship varies among different races. In this study, Asian adults with and without obesity were compared in terms of their levels of 25OHD. METHODS: We carried out a cross-sectional analysis on 2664 non-Hispanic Asian adults who participated in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. To examine the connection between obese status, body mass index (BMI), waist circumference (WC) and weight, and 25OHD, we ran multivariate linear regression models and multivariate logistic regression models. RESULTS: After adjusting for all confounding factors, obesity status shows a significant positive correlation with vitamin D deficiency (model 3: OR = 2.318, 95% CI:1.317, 4.082). This positive correlation remains significant in males (males: OR = 2.713, 95% CI: -13.398, 5.217). In all three models, a negative association was observed between obesity status and 25OHD (model 1: ß = -4.535, 95% CI: -6.987, -2.083; model 2 ß = -4.249, 95% CI: -6.549, -2.039; model 3 ß = -1.734, 95% CI: -7.285, 3.816). After controlling for covariates, there was a significant negative correlation between WC and 25OHD when stratified by gender and obesity status in both males with and without obesity (males with obesity: ß = -1.461, 95% CI: -2.485, -0.436; males without obesity: ß = -0.855. 95% CI: -1.499, -0.210). In males with obesity, there was a very strong positive connection between body weight and 25OHD (ß = 0.912, 95% CI: 0.227, 1.597). In addition, neither gender's obese individuals showed a significant link between BMI and 25OHD. CONCLUSION: This study demonstrated a positive correlation between obesity and vitamin D deficiency and a negative correlation between obesity and 25OHD in Asian American adults. Additionally, among male obese individuals, there was a significant negative correlation between WC and 25OHD, an observation that needs to be validated in further prospective studies.

bHLH121 and clade IVc bHLH transcription factors synergistically function to regulate iron homeostasis in Arabidopsis thaliana.

Iron is an essential micronutrient for plant growth and development. In Arabidopsis thaliana, an intricate regulatory network involving several bHLH transcription factors (TFs) controls the homeostasis of iron. Among these TFs, bHLH121 plays a crucial role. bHLH121 interacts in vivo with clade IVc bHLH TFs and activates the expression of FIT and clade Ib bHLH TFs to stimulate the uptake of iron. How bHLH121 and clade IVc bHLH TFs function collectively and efficiently to maintain iron homeostasis is still unclear. Herein, we found that double loss-of-function mutants involving bhlh121 and one of the clade IVc bHLH displayed more severe iron deficiency associated growth defects than each of the single ones. We also found that among the four clade IVc bHLH TFs, solely bHLH34 and bHLH105 could partially complement the iron-associated growth defects of bhlh121 when overexpressed. These data, together with protein localization analysis, support that bHLH121 and clade IVc bHLH TFs act synergistically to regulate iron homeostasis and that different bHLH121/clade IVc and clade IVc/clade IVc protein complexes are involved in this process.

Causal association of obesity with epigenetic aging and telomere length: a bidirectional mendelian randomization study.

BACKGROUND: In observational studies, there exists an association between obesity and epigenetic age as well as telomere length. However, varying and partially conflicting outcomes have notably arisen from distinct studies on this topic. In the present study, two-way Mendelian randomization was used to identify potential causal associations between obesity and epigenetic age and telomeres. METHODS: A genome-wide association study was conducted using data from individuals of European ancestry to investigate bidirectional Mendelian randomization (MR) regarding the causal relationships between obesity, as indicated by three obesity indicators (body mass index or BMI, waist circumference adjusted for BMI or WCadjBMI, and waist-to-hip ratio adjusted for BMI or WHRadjBMI), and four epigenetic age measures (HannumAge, HorvathAge, GrimAge, PhenoAge), as well as telomere length. To assess these causal associations, various statistical methods were employed, including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode. To address the issue of multiple testing, we applied the Bonferroni correction. These methods were used to determine whether there is a causal link between obesity and epigenetic age, as well as telomere length, and to explore potential bidirectional relationships. Forest plots and scatter plots were generated to show causal associations between exposures and outcomes. For a comprehensive visualization of the results, leave-one-out sensitivity analysis plots, individual SNP-based forest plots for MR analysis, and funnel plots were included in the presentation of the results. RESULTS: A strong causal association was identified between obesity and accelerated HannumAge, GrimAge, PhenoAge and telomere length shrinkage. The causal relationship between WCadjBMI and PhenoAge acceleration (OR: 2.099, 95%CI: 1.248-3.531, p = 0.005) was the strongest among them. However, only the p-values for the causal associations of obesity with GrimAge, PhenoAge, and telomere length met the criteria after correction using the Bonferroni multiple test. In the reverse MR analysis, there were statistically significant causal associations between HorvathAge, PhenoAge and GrimAge and BMI, but these associations exhibited lower effect sizes, as indicated by their Odds Ratios (ORs). Notably, sensitivity analysis revealed the robustness of the study results. CONCLUSIONS: The present findings reveal a causal relationship between obesity and the acceleration of epigenetic aging as well as the reduction of telomere length, offering valuable insights for further scientific investigations aimed at developing strategies to mitigate the aging process in humans.

Network Reorganization for Neurophysiological and Behavioral Recovery Following Stroke.

Stroke continues to be the main cause of motor disability worldwide. While it has been promised to improve recovery after stroke, efficacy in clinical trials has been mixed. We need to understand the cortical recombination framework to understand how biomarkers for neurophysiological reorganized neurotechnologies alter network activity. Here, we summarize the principles of the movement network, including the current evidence of changes in the connections and function of encephalic regions, recovery from stroke and the therapeutic effects of rehabilitation. Overall, improvements or therapeutic effects in limb motor control following stroke are correlated with the effects of interhemispheric competition or compensatory models of the motor supplementary cortex. This review suggests that future research should focus on cross-regional communication and provide fundamental insights into further treatment and rehabilitation for post-stroke patients.

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An EEG motor imagery dataset for brain computer interface in acute stroke patients.

The brain-computer interface (BCI) is a technology that involves direct communication with parts of the brain and has evolved rapidly in recent years; it has begun to be used in clinical practice, such as for patient rehabilitation. Patient electroencephalography (EEG) datasets are critical for algorithm optimization and clinical applications of BCIs but are rare at present. We collected data from 50 acute stroke patients with wireless portable saline EEG devices during the performance of two tasks: 1) imagining right-handed movements and 2) imagining left-handed movements. The dataset consists of four types of data: 1) the motor imagery instructions, 2) raw recording data, 3) pre-processed data after removing artefacts and other manipulations, and 4) patient characteristics. This is the first open dataset to address left- and right-handed motor imagery in acute stroke patients. We believe that the dataset will be very helpful for analysing brain activation and designing decoding methods that are more applicable for acute stroke patients, which will greatly facilitate research in the field of motor imagery-BCI.

Carotenoids synthesis affects the salt tolerance mechanism of Rhodopseudomonas palustris.

Rhodopseudomonas palustris CGA009 is a Gram-negative, purple non-sulfur, metabolically diverse bacterium with wide-ranging habitats. The extraordinary ability of R. palustris to decompose a variety of raw materials and convert them into high-value products makes it an attractive host for biotechnology and industrial applications. However, being a freshwater bacterium R. palustris has limited application in highly-saline environments. Therefore, it is of great significance to obtain the salt-tolerant strain of R. palustris and understand its tolerance mechanism. In this study, R. palustris CGA009 was successfully evolved into eight salt-tolerant strains using an adaptive laboratory evolution technique. RPAS-11 (R. palustris anti-salt strain 11) was selected as the best salt-tolerant strain and was used in further studies to explore the salt-tolerance mechanism. The expression of most genes associated with the carotenoid synthesis in RPAS-11 increased significantly under high concentration of salt stress, suggesting that carotenoid synthesis is one of the reasons for the salt tolerance of RPAS-11. Gene overexpression and knockout experiments were performed to get clear about the role of carotenoids in salt stress tolerance. RPAS-11-IDI, the mutant with overexpression of IDI (Isopentenyl diphosphate isomerase) exhibited enhanced salt tolerance, whereas the knockout mutant CGA009-∆crtI showed a decline in salt tolerance. In addition, the results indicated that rhodopin, a carotenoid compound, was the key pigment responsible for the salt tolerance in R. palustris. Furthermore, the production of lycopene, a widely-used carotenoid, was also increased. Taken together, our research helps to deepen the understanding of the salt tolerance mechanism of R. palustris and also widens the application of R. palustris in highly-saline environments.

[Potential targets for traditional Chinese medicine treatment of chronic inflammation in obesity: macrophage polarization].

Obesity has been identified as a chronic low-grade systemic inflammation and a key risk factor for diseases such as diabetes, hypertension, and malignancies, and has become an urgent global health burden. Adipose tissue macrophages play a significant role in adipose immune homeostasis and inflammatory responses. Under different conditions, they can be polarized into pro-inflammatory M1 phenotype or anti-inflammatory M2 phenotype. In obese individuals, there is abnormal polarization of macrophages in adipose tissue, leading to an imbalance in the M1/M2 phenotype dynamic equilibrium and the development of pathological inflammation. Therefore, restoring the balance of M1/M2 macrophage polarization is an important potential target for the treatment of chronic inflammation in obesity. Studies have shown that traditional Chinese medicine(TCM) can positively modulate macrophage polarization and produce beneficial effects on obesity. Based on existing evidence, this paper systematically reviewed the potential mechanisms of TCM in improving chronic inflammation in obesity from the perspective of macrophage polarization, in order to provide evidence for the clinical diagnosis and treatment of chronic inflammation in obesity with TCM and offer new insights for related research design and the development of new TCM.

Development of lycopene-based whole-cell biosensors for the visual detection of trace explosives and heavy metals.

Residual explosives in conflicting zones have caused irreversible damage to human safety and the environment. Whole-cell biosensors can to detect remnants of buried explosives, such as 2,4-dinitrotoluene (DNT), a stable and highly volatile compound in explosives. However, all the reported whole-cell biosensors utilize fluorescence or luminescence as the biological markers, making their detection difficult in real minefields. Here, we presented a lycopene-based whole-cell biosensor in Escherichia coli to output visible signals in response to DNT, which can help in the visual detection of buried explosives. To construct the whole-cell biosensor, the DNT-responsive promoter yqjF was used as the sensing element, and the lycopene synthetic gene cassette crtEBI was served as the reporting element. Then, the metabolic flux for lycopene production was enhanced to improve the output signal of the whole-cell biosensor, and a terminator was utilized to reduce the background interference. The optimized biosensor LSZ05 could perceive at least 1 mg/L DNT. The DNT-specificity and robust performance of the biosensor under different environmental factors were confirmed. Our results showed that converting the biosensor into a lyophilized powder was an effective storage method. The biosensor LSZ05 could effectively detect DNT in two kinds of soil samples. The lycopene-based whole-cell biosensor could also be used to visually detect heavy metals. Our findings laid the foundation for visually detecting buried explosives in minefields, which was a valuable supplement to the reported biosensors. The methods used for optimizing the lycopene-based whole-cell biosensor, including the improvement of the output signal and reduction of background interference, were quite effective.

Optimization of IspSib stability through directed evolution to improve isoprene production.

Enzyme stability is often a limiting factor in the microbial production of high-value-added chemicals and commercial enzymes. A previous study by our research group revealed that the unstable isoprene synthase from Ipomoea batatas (IspSib) critically limits isoprene production in engineered Escherichia coli. Directed evolution was, therefore, performed in the present study to improve the thermostability of IspSib. First, a tripartite protein folding system designated as lac'-IspSib-'lac, which could couple the stability of IspSib to antibiotic ampicillin resistance, was successfully constructed for the high-throughput screening of variants. Directed evolution of IspSib was then performed through two rounds of random mutation and site-saturation mutation, which produced three variants with higher stability: IspSibN397V A476V, IspSibN397V A476T, and IspSibN397V A476C. The subsequent in vitro thermostability test confirmed the increased protein stability. The melting temperatures of the screened variants IspSibN397V A476V, IspSibN397V A476T, and IspSibN397V A476C were 45.1 ± 0.9°C, 46.1 ± 0.7°C, and 47.2 ± 0.3°C, respectively, each of which was higher than the melting temperature of wild-type IspSib (41.5 ± 0.4°C). The production of isoprene at the shake-flask fermentation level was increased by 1.94-folds, to 1,335 mg/L, when using IspSibN397V A476T. These findings provide insights into the optimization of the thermostability of terpene synthases, which are key enzymes for isoprenoid production in engineered microorganisms. In addition, the present study would serve as a successful example of improving enzyme stability without requiring detailed structural information or catalytic reaction mechanisms.IMPORTANCEThe poor thermostability of IspSib critically limits isoprene production in engineered Escherichia coli. A tripartite protein folding system designated as lac'-IspSib-'lac, which could couple the stability of IspSib to antibiotic ampicillin resistance, was successfully constructed for the first time. In order to improve the enzyme stability of IspSib, the directed evolution of IspSib was performed through error-PCR, and high-throughput screening was realized using the lac'-IspSib-'lac system. Three positive variants with increased thermostability were obtained. The thermostability test and the melting temperature analysis confirmed the increased stability of the enzyme. The production of isoprene was increased by 1.94-folds, to 1,335 mg/L, using IspSibN397V A476T. The directed evolution process reported here is also applicable to other terpene synthases key to isoprenoid production.

TCF4 Mutations Disrupt Synaptic Function Through Dysregulation of RIMBP2 in Patient-Derived Cortical Neurons.

BACKGROUND: Genetic variation in the TCF4 (transcription factor 4) gene is associated with risk for a variety of developmental and psychiatric conditions, which includes a syndromic form of autism spectrum disorder called Pitt-Hopkins syndrome (PTHS). TCF4 encodes an activity-dependent transcription factor that is highly expressed during cortical development and in animal models has been shown to regulate various aspects of neuronal development and function. However, our understanding of how disease-causing mutations in TCF4 confer pathophysiology in a human context is lacking. METHODS: To model PTHS, we differentiated human cortical neurons from human induced pluripotent stem cells that were derived from patients with PTHS and neurotypical individuals. To identify pathophysiology and disease mechanisms, we assayed cortical neurons with whole-cell electrophysiology, Ca2+ imaging, multielectrode arrays, immunocytochemistry, and RNA sequencing. RESULTS: Cortical neurons derived from patients with TCF4 mutations showed deficits in spontaneous synaptic transmission, network excitability, and homeostatic plasticity. Transcriptomic analysis indicated that these phenotypes resulted in part from altered expression of genes involved in presynaptic neurotransmission and identified the presynaptic binding protein RIMBP2 as the most differentially expressed gene in PTHS neurons. Remarkably, TCF4-dependent deficits in spontaneous synaptic transmission and network excitability were rescued by increasing RIMBP2 expression in presynaptic neurons. CONCLUSIONS: Taken together, these results identify TCF4 as a critical transcriptional regulator of human synaptic development and plasticity and specifically identifies dysregulation of presynaptic function as an early pathophysiology in PTHS.

A common thalamic hub for general and defensive arousal control.

The expression of defensive responses to alerting sensory cues requires both general arousal and a specific arousal state associated with defensive emotions. However, it remains unclear whether these two forms of arousal can be regulated by common brain regions. We discovered that the medial sector of the auditory thalamus (ATm) in mice is a thalamic hub controlling both general and defensive arousal. The spontaneous activity of VGluT2-expressing ATm (ATmVGluT2+) neurons was correlated with and causally contributed to wakefulness. In sleeping mice, sustained ATmVGluT2+ population responses were predictive of sensory-induced arousal, the likelihood of which was markedly decreased by inhibiting ATmVGluT2+ neurons or multiple downstream pathways. In awake mice, ATmVGluT2+ activation led to heightened arousal accompanied by excessive anxiety and avoidance behavior. Notably, blocking their neurotransmission abolished alerting stimuli-induced defensive behaviors. These findings may shed light on the comorbidity of sleep disturbances and abnormal sensory sensitivity in specific brain disorders.

Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

Objective: The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS). Methods: A comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk. Results: A total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54, p = 0.009, seven studies), FBS (MD = -8.6, 95% CI: -15.45 to -1.75, p = 0.01, nine studies), DBP (MD = -2.8, 95% CI: -4.53 to - 1.06, p = 0.002, five studies), HDL-C (MD = 4.98, 95% CI: 2.58 to 7.38, p < 0.0001, eight studies), TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, p < 0.00001, two studies), CRP (MD = - 1.24, 95% CI: -1.71 to -0.77, p < 0.00001, two studies), and MDA (MD = -2.35, 95% CI: -4.47 to -0.24, p = 0.03, three studies). These improvements were statistically significant. Meanwhile, there was no significant improvement in SBP (MD = -4.82, 95% CI: -9.98 to 0.35, p = 0.07, six studies), TG (MD = 1.28, 95% CI: -3.75 to 6.30, p = 0.62, eight studies), IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, p = 0.23, two studies), or hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, p < 0.51, two studies). FBS, SBP, HDL-C, IL-6, CRP, hsCRP, and MDA had a relatively high heterogeneity. Conclusion: Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022362553.

Iron Nutrition in Plants: Towards a New Paradigm?

Iron (Fe) is an essential micronutrient for plant growth and development. Fe availability affects crops' productivity and the quality of their derived products and thus human nutrition. Fe is poorly available for plant use since it is mostly present in soils in the form of insoluble oxides/hydroxides, especially at neutral to alkaline pH. How plants cope with low-Fe conditions and acquire Fe from soil has been investigated for decades. Pioneering work highlighted that plants have evolved two different strategies to mine Fe from soils, the so-called Strategy I (Fe reduction strategy) and Strategy II (Fe chelation strategy). Strategy I is employed by non-grass species whereas graminaceous plants utilize Strategy II. Recently, it has emerged that these two strategies are not fully exclusive and that the mechanism used by plants for Fe uptake is directly shaped by the characteristics of the soil on which they grow (e.g., pH, oxygen concentration). In this review, recent findings on plant Fe uptake and the regulation of this process will be summarized and their impact on our understanding of plant Fe nutrition will be discussed.

TCF4 mutations disrupt synaptic function through dysregulation of RIMBP2 in patient-derived cortical neurons.

Genetic variation in the transcription factor 4 ( TCF4) gene is associated with risk for a variety of developmental and psychiatric conditions, which includes a syndromic form of ASD called Pitt Hopkins Syndrome (PTHS). TCF4 encodes an activity-dependent transcription factor that is highly expressed during cortical development and in animal models is shown to regulate various aspects of neuronal development and function. However, our understanding of how disease-causing mutations in TCF4 confer pathophysiology in a human context is lacking. Here we show that cortical neurons derived from patients with TCF4 mutations have deficits in spontaneous synaptic transmission, network excitability and homeostatic plasticity. Transcriptomic analysis indicates these phenotypes result from altered expression of genes involved in presynaptic neurotransmission and identifies the presynaptic binding protein, RIMBP2 as the most differentially expressed gene in PTHS neurons. Remarkably, TCF4-dependent deficits in spontaneous synaptic transmission and network excitability were rescued by increasing RIMBP2 expression in presynaptic neurons. Together, these results identify TCF4 as a critical transcriptional regulator of human synaptic development and plasticity and specifically identifies dysregulation of presynaptic function as an early pathophysiology in PTHS.

Co-biosynthesis of germacrene A, a precursor of ß-elemene, and lycopene in engineered Escherichia coli.

ß-Elemene is the major component of a traditional Chinese medicine (Rhizoma Curcumae) for cancer treatment, and plant extraction is the major methods currently. Biosynthesis of ß-elemene is a promising and attractive route due to its advantages, including environmentally friendly processes, renewable resources, and sustainable development. In this research, biosynthesis of germacrene A, direct precursor of ß-elemene, in Escherichia coli was successfully performed and 11.99 mg/L germacrene A was obtained. Thereafter, a cobiosynthesis system for germacrene A and lycopene, another kind of isoprenoid, was constructed. Furthermore, the cultivation conditions were optimized. The germacrene A production was increased to the highest level reported to date, 364.26 mg/L, threefold increase to the strain with only germacrene A production. The cobiosynthesis system was suggested to promote the metabolic flux for germacrene A production. This research enabled germacrene A production in E. coli, and it highlights the promoting mechanism of the cobiosynthesis system for two chemicals which are both belonging to isoprenoids. KEY POINTS : • Co-production of germacrene A and lycopene in E. coli. • Promoting mechanism of cobiosynthesis of two isoprenoid compounds in E. coli. • Shake-flask production of germacrene A reached to the highest 364.26 mg/L in E. coli.

Disruption of mTORC1 rescues neuronal overgrowth and synapse function dysregulated by Pten loss.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of AKT/mTOR signaling pathway. Mutations in PTEN are found in patients with autism, epilepsy, or macrocephaly. In mouse models, Pten loss results in neuronal hypertrophy, hyperexcitability, seizures, and ASD-like behaviors. The underlying molecular mechanisms of these phenotypes are not well delineated. We determined which of the Pten loss-driven aberrations in neuronal form and function are orchestrated by downstream mTOR complex 1 (mTORC1). Rapamycin-mediated inhibition of mTORC1 prevented increase in soma size, migration, spine density, and dendritic overgrowth in Pten knockout dentate gyrus granule neurons. Genetic knockout of Raptor to disrupt mTORC1 complex formation blocked Pten loss-mediated neuronal hypertrophy. Electrophysiological recordings revealed that genetic disruption of mTORC1 rescued Pten loss-mediated increase in excitatory synaptic transmission. We have identified an essential role for mTORC1 in orchestrating Pten loss-driven neuronal hypertrophy and synapse formation.

Rapid structural characterization of human milk oligosaccharides and distinction of their isomers using trapped ion mobility spectrometry time-of-flight mass spectrometry.

Oligosaccharides have multiple functions essential for health. Derived from the condensation of two to several monosaccharides, they are structurally diverse with many co-occurring structural isomer families, which make their characterization difficult. Thanks to its ability to separate small molecules based on their mass, size, shape, and charge, ion mobility-mass spectrometry (IM-MS) has emerged as a powerful tool for separating glycan isomers. Here, the potential of such a technique for the rapid characterization of main human milk oligosaccharides (HMOs) was investigated. Our study focused on 18 HMO standards. The IM-MS analysis enabled to distinguish almost all the HMOs studied, in particular thanks to the single ion mobility monitoring acquisition using the trapped ion mobility spectrometry device, providing high ion mobility resolution and enhanced ion mobility separation. Alternatively, the combination of IM-MS separation with MS/MS experiments has proven to increase performance in identifying HMOs and especially isomers poorly separated by ion mobility alone. Finally, collision cross-section values are provided for each species generated from the 18 HMOs standards, which can serve as an additional identifier to characterize HMOs.

Progesterone Reduces ATP-Induced Pyroptosis of SH-SY5Y Cells.

Aim: To investigate the mechanism of progesterone inhibiting the scorch death of SH-SY5Y cells induced by exogenous adenosine triphosphate (ATP). Methods: SH-SY5Y cells with good logarithmic growth were used in the experiment. The cells were randomly divided into 5 groups: normal control group, DMSO group, BBG group, ATP group, and ATP+progesterone group. The cell survival rate of each group was measured by CCK-8 method. The expressions of P2X7 receptor, caspase-1, caspase-11, and IL-1ß were detected by western blotting. Results: (1) After SH-SY5Y cells were treated with ATP at different concentrations (1, 3, 6, and 9 mmol/L) for 2 hours, the cell survival rate decreased in a concentration-dependent manner compared with the normal blank group. The results showed that the optimal lethal concentration of ATP was 6 mmol/L. SH-SY5Y cells were preincubated with progesterone at different concentrations (3, 10, 30, and 100 nmol/L) for 30 minutes and then incubated with 6 mmol/L ATP. The cell survival rate of this group was significantly improved (P < 0.01). The optimal concentration of progesterone to improve cell survival and inhibit cell death was 30 nmol/L. (2) Compared to the control group, there was no significant difference (P > 0.05) in P2X7 receptor, caspase-1, caspase-11, and IL-1ß with the DMSO group (0.001% DMSO, 24 h) and BBG group (bbg1 mmol/L, 24 h). (3) In the ATP group, the expression of P2X7 receptor and caspase-1 (the key protein of classical cell death pathway) increased significantly (P < 0.01), which was related to inflammatory factor IL-1ß with consistent performance (P < 0.01). There was no significant change in caspase-11 (the key protein of nonclassical focal death pathway) (P > 0.05). (4) The expression of P2X7 receptor, caspase-1, and inflammatory factor IL-1ß in the progesterone+ATP group was significantly downregulated (P < 0.01). There was no significant change in caspase-11 (P > 0.05). Conclusion: Certain dose of progesterone can inhibit the focal death of SH-SY5Y cells induced by extracellular high concentration ATP. It can reduce the expression of P2X7 receptor, inhibit the conduction pathway of cell death, reduce the release of inflammatory factor IL-1ß, and improve cell survival.

Deep Learning-Based Pathology Image Analysis Enhances Magee Feature Correlation With Oncotype DX Breast Recurrence Score.

Background: Oncotype DX Recurrence Score (RS) has been widely used to predict chemotherapy benefits in patients with estrogen receptor-positive breast cancer. Studies showed that the features used in Magee equations correlate with RS. We aimed to examine whether deep learning (DL)-based histology image analyses can enhance such correlations. Methods: We retrieved 382 cases with RS diagnosed between 2011 and 2015 from the Emory University and the Ohio State University. All patients received surgery. DL models were developed to detect nuclei of tumor cells and tumor-infiltrating lymphocytes (TILs) and segment tumor cell nuclei in hematoxylin and eosin (H&E) stained histopathology whole slide images (WSIs). Based on the DL-based analysis, we derived image features from WSIs, such as tumor cell number, TIL number variance, and nuclear grades. The entire patient cohorts were divided into one training set (125 cases) and two validation sets (82 and 175 cases) based on the data sources and WSI resolutions. The training set was used to train the linear regression models to predict RS. For prediction performance comparison, we used independent variables from Magee features alone or the combination of WSI-derived image and Magee features. Results: The Pearson's correlation coefficients between the actual RS and predicted RS by DL-based analysis were 0.7058 (p-value = 1.32 × 10-13) and 0.5041 (p-value = 1.15 × 10-12) for the validation sets 1 and 2, respectively. The adjusted R 2 values using Magee features alone are 0.3442 and 0.2167 in the two validation sets, respectively. In contrast, the adjusted R 2 values were enhanced to 0.4431 and 0.2182 when WSI-derived imaging features were jointly used with Magee features. Conclusion: Our results suggest that DL-based digital pathological features can enhance Magee feature correlation with RS.

Characteristics and Application of Rhodopseudomonas palustris as a Microbial Cell Factory.

Rhodopseudomonas palustris, a purple nonsulfur bacterium, is a bacterium with the properties of extraordinary metabolic versatility, carbon source diversity and metabolite diversity. Due to its biodetoxification and biodegradation properties, R. palustris has been traditionally applied in wastewater treatment and bioremediation. R. palustris is rich in various metabolites, contributing to its application in agriculture, aquaculture and livestock breeding as additives. In recent years, R. palustris has been engineered as a microbial cell factory to produce valuable chemicals, especially photofermentation of hydrogen. The outstanding property of R. palustris as a microbial cell factory is its ability to use a diversity of carbon sources. R. palustris is capable of CO2 fixation, contributing to photoautotrophic conversion of CO2 into valuable chemicals. R. palustris can assimilate short-chain organic acids and crude glycerol from industrial and agricultural wastewater. Lignocellulosic biomass hydrolysates can also be degraded by R. palustris. Utilization of these feedstocks can reduce the industry cost and is beneficial for environment. Applications of R. palustris for biopolymers and their building blocks production, and biofuels production are discussed. Afterward, some novel applications in microbial fuel cells, microbial electrosynthesis and photocatalytic synthesis are summarized. The challenges of the application of R. palustris are analyzed, and possible solutions are suggested.