A constrained maximum likelihood approach to developing well-calibrated models for predicting binary outcomes.

The added value of candidate predictors for risk modeling is routinely evaluated by comparing the performance of models with or without including candidate predictors. Such comparison is most meaningful when the estimated risk by the two models are both unbiased in the target population. Very often data for candidate predictors are sourced from nonrepresentative convenience samples. Updating the base model using the study data without acknowledging the discrepancy between the underlying distribution of the study data and that in the target population can lead to biased risk estimates and therefore an unfair evaluation of candidate predictors. To address this issue assuming access to a well-calibrated base model, we propose a semiparametric method for model fitting that enforces good calibration. The central idea is to calibrate the fitted model against the base model by enforcing suitable constraints in maximizing the likelihood function. This approach enables unbiased assessment of model improvement offered by candidate predictors without requiring a representative sample from the target population, thus overcoming a significant practical challenge. We study theoretical properties for model parameter estimates, and demonstrate improvement in model calibration via extensive simulation studies. Finally, we apply the proposed method to data extracted from Penn Medicine Biobank to inform the added value of breast density for breast cancer risk assessment in the Caucasian woman population.

Research progress in the ethnopharmacology, phytochemistry, pharmacology, toxicology, and quality control of Valeriana jatamansi Jones.

ETHNOPHARMACOLOGIC RELEVANCE: Valeriana jatamansi Jones, belongs to the Valerianaceae family, is widely used in traditional Chinese medicine (TCM) and Ayurveda, traditional Indian medicine (TIM). This traditional herb has been officially listed in the pharmacopoeia of sixteen countries. Its usage was first described in Diannan Bencao, also known as "Zhizhuxiang", is a famous folk medicine herb with a long history of medicinal usage in China, and it was used to treat indigestion, flu, and mental disorders in the Han, Achang, Bai, Blang, Dai, Jingpo, Naxi, and Wa ethnic groups. In recent years, V. jatamansi has attracted worldwide attention as an important medicinal due to its pharmacological activity especially in nervous and digestive systems, and multiple uses. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, and quality control of V. jatamansi. MATERIALS AND METHODS: The relevant information of V. jatamansi was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D. and MSc dissertations, using "Valeriana jatamansi Jones", "Valeriana jatamansi", and "" as keywords. After eliminating repetitive and low-quality reports, the remaining reports were analyzed and summarized to prepare this review. Plant information was retrieved by www.worldfloraonline.org and www.gbif.org using "Valeriana jatamansi Jones" as keyword. RESULTS: V. jatamansi has been historically utilized as a traditional medicine to treat various diseases, including infectious, inflammatory, neurological, and gastrointestinal disorders. More than 400 compounds have been identified in V. jatamansi including iridoids, volatile oils, lignans, flavonoids, phenolic acids, phenylpropanoids, sesquiterpenes, sesquiterpene hydrocarbons, triterpenes as well as other compounds. The plant extracts and compounds showed various pharmacological activities such as antitumor, cytotoxic, antivirus, etc. In addition, V. jatamansi has found various applications in the agricultural, food, and cosmetics industry. CONCLUSION: A review of literature shows V. jatamansi has pharmacological properties valuable in treating diseases, particularly for antianxiety and gastrointestinal disorders. Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and in vivo, with a lack of pharmacokinetics, clinical trials and underlying mechanisms. Consequently, it becomes important to embark on additional researchs to elucidate the pharmacokinetics, material basis and mechanisms of V. jatamansi, thereby realizing the aspiration of its comprehensive utilization and sustainable development.

Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

[Retracted] Reduced miR­202 levels enhanced oral cancer development via targeting Sp1.

[This retracts the article DOI: 10.3892/etm.2019.7603.].

iJAZ-based approach to engineer lepidopteran pest resistance in multiple crop species.

The fall armyworm (FAW) poses a significant threat to global crop production. Here we showed that overexpression of jasmonate ZIM-domain (JAZ) protein GhJAZ24 confers resistance to cotton bollworm and FAW, while also causing sterility in transgenic cotton by recruiting TOPLESS and histone deacetylase 6. We identified the NGR motif of GhJAZ24 that recognizes and binds the aminopeptidase N receptor, enabling GhJAZ24 to enter cells and disrupt histone deacetylase 3, leading to cell death. To overcome plant sterility associated with GhJAZ24 overexpression, we developed iJAZ (i, induced), an approach involving damage-induced expression and a switch from intracellular to extracellular localization of GhJAZ24. iJAZ transgenic cotton maintained fertility and showed insecticidal activity against cotton bollworm and FAW. In addition, iJAZ transgenic rice, maize and tobacco plants showed insecticidal activity against their lepidopteran pests, resulting in an iJAZ-based approach for generating alternative insecticidal proteins with distinctive mechanisms of action, thus holding immense potential for future crop engineering.

Scrutinizing a Lactococcus lactis mutant with enhanced capacity for extracellular electron transfer reveals a unique role for a novel type-II NADH dehydrogenase.

Lactococcus lactis, a lactic acid bacterium used in food fermentations and commonly found in the human gut, is known to possess a fermentative metabolism. L. lactis, however, has been demonstrated to transfer metabolically generated electrons to external electron acceptors, a process termed extracellular electron transfer (EET). Here, we investigated an L. lactis mutant with an unusually high capacity for EET that was obtained in an adaptive laboratory evolution (ALE) experiment. First, we investigated how global gene expression had changed, and found that amino acid metabolism and nucleotide metabolism had been affected significantly. One of the most significantly upregulated genes encoded the NADH dehydrogenase NoxB. We found that this upregulation was due to a mutation in the promoter region of NoxB, which abolished carbon catabolite repression. A unique role of NoxB in EET could be attributed and it was directly verified, for the first time, that NoxB could support respiration in L. lactis. NoxB, was shown to be a novel type-II NADH dehydrogenase that is widely distributed among gut microorganisms. This work expands our understanding of EET in Gram-positive electroactive microorganisms and the special significance of a novel type-II NADH dehydrogenase in EET.IMPORTANCEElectroactive microorganisms with extracellular electron transfer (EET) ability play important roles in biotechnology and ecosystems. To date, there have been many investigations aiming at elucidating the mechanisms behind EET, and determining the relevance of EET for microorganisms in different niches. However, how EET can be enhanced and harnessed for biotechnological applications has been less explored. Here, we compare the transcriptomes of an EET-enhanced L. lactis mutant with its parent and elucidate the underlying reason for its superior performance. We find that one of the most significantly upregulated genes is the gene encoding the NADH dehydrogenase NoxB, and that upregulation is due to a mutation in the catabolite-responsive element that abolishes carbon catabolite repression. We demonstrate that NoxB has a special role in EET, and furthermore show that it supports respiration to oxygen, which has never been done previously. In addition, a search reveals that this novel NoxB-type NADH dehydrogenase is widely distributed among gut microorganisms.

Assisted reproductive technologies and postpartum depressive symptoms: A meta-analysis.

BACKGROUND: Assisted reproductive technologies (ARTs) have become the main treatment for infertility. ART treatment can be a stressful life event for infertile females. Whether there is an association between ARTs and postpartum depressive symptoms (PDS) has not been established. METHODS: PubMed, MEDLINE, EMBASE, PsycINFO, and CNKI were searched. The pooled outcome was the difference in incidence of PDS within 1 year postpartum between ARTs and the spontaneous pregnancy group. RESULTS: A total of 12 cohort studies, which were conducted in eight developed countries and two developing countries, were involved. In total, 106,338 pregnant women, including 4990 infertile females with ARTs treatment and 101,348 women with spontaneous pregnancy, were enrolled in our final analysis. ARTs women had a lower incidence of PDS compared to the spontaneous pregnancy group according to a random effect model (OR = 0.83, 95 % CI: 0.71-0.97, p = 0.022, I2 = 62.0 %). Subgroup analyses indicated that studies on late PDS (follow-up: 3-12 months postpartum) were more heterogeneous than those on early PDS (follow-up: <3 months postpartum) (I2 = 24.3 % vs. I2 = 0 %, interaction p-value < 0.001). There was a strong relationship between ARTs and late PDS (OR = 0.65, 95 % CI: 0.55-0.77, p < 0.001). Therefore, the possible source of heterogeneity was the postpartum evaluation time, which was confirmed by post-hoc meta-regression. LIMITATIONS: Some underlying confounders, such as previous psychiatric illness, the limited availability of ARTs, and ethnic disparities, cannot be ignored and may have biased interpretation of the results. CONCLUSION: The available data suggested that ARTs were associated with lower incidence of PDS, especially when follow-up lasted over 3 months. However, these findings should be interpreted with caution. Better-designed trials are needed to confirm this association.

Risk factors and prediction score for new-onset diabetes mellitus after liver transplantation.

AIM: New-onset diabetes mellitus is a frequent and severe complication arising after liver transplantation (LT). We aimed to identify the risk factors for new-onset diabetes mellitus after liver transplantation (NODALT) and to develop a risk prediction score system for relevant risks. METHODS: We collected and analyzed data from all recipients who underwent liver transplantation at the First Affiliated Hospital of Xi'an Jiaotong University. The OR derived from a multiple logistic regression predicting the presence of NODALT was used to calculate the risk prediction score. The performance of the risk prediction score was externally validated in patients who were from the CLTR (China Liver Transplant Registry) database. RESULTS: A total of 468 patients met the outlined criteria and finished the follow-up. Overall, NODALT was diagnosed in 115 (24.6%) patients. Age, preoperative impaired fasting glucose (IFG), postoperative fasting plasma glucose (FPG), and the length of hospital stay were significantly associated with the presence of NODALT. The risk prediction score includes age, preoperative IFG, postoperative FPG, and the length of hospital stay. The risk prediction score of the area under the receiver operating curve was 0.785 (95% CI: 0.724-0.846) in the experimental population and 0.782 (95% CI: 0.708-0.856) in the validation population. CONCLUSIONS: Age at the time of transplantation, preoperative IFG, postoperative FPG, and length of hospital stay were independent predictive factors of NODALT. The use of a simple risk prediction score can identify the patients who have the highest risk of NODALT and interventions may start early.

Upregulated ATF1 Promotes Lipopolysaccharide Induced Inflammatory Response and Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Regulating NF-κB Pathway.

BACKGROUND: Periodontitis is a chronic inflammatory disease resulting from bacterial plaque infection. While the involvement of activating transcription factor 1 (ATF1) has been extensively explored in various human diseases, its specific role in periodontitis remains unclear. This study aims to elucidate the expression and biological function of ATF1 in the context of periodontitis. METHODS: Primary human periodontal ligament cells (hPDLCs) were procured from clinical samples and subsequently characterized. Following treatment with P. gingivalis lipopolysaccharide (LPS, 10 µg/mL), hPDLCs underwent transfection with either ATF1 vector or siRNA. The expression levels of ATF1 in LPS-treated hPDLCs or transfected cells were evaluated through real-time quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Inflammatory factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1ß), were quantified using Enzyme-linked Immunosorbent Assay (ELISA). The assessment of osteogenic proteins, such as runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteoprotegerin (OPG), as well as noncanonical nuclear factor-kappaB (NF-κB) pathway-related proteins (p65, p-p65, IkBα, p-IkBα), was conducted using western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry assays were employed to detect cell viability. RESULTS: LPS induced an inflammatory response and hindered the osteogenic differentiation of hPDLCs (p < 0.05, p < 0.01). Furthermore, ATF1 silencing enhanced cell proliferation and suppressed apoptosis in LPS-stimulated hPDLCs (p < 0.05, p < 0.01). ATF1 silencing not only restrained the inflammatory response but also promoted the osteogenic differentiation of LPS-stimulated hPDLCs (p < 0.05, p < 0.01). Importantly, ATF1 silencing effectively blocked the LPS-induced activation of the NF-κB signaling pathway (p < 0.05, p < 0.01, p < 0.001). CONCLUSIONS: ATF1 emerges as a promising treatment option, inhibiting the osteogenic differentiation of hPDLCs and mitigating the inflammatory response by preventing the phosphorylation of the NF-κB signaling pathway.

Outpatient cervical ripening with balloon catheters: A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: One in four labors are induced. The process of cervical ripening can be lengthy and pre-labor hospitalization is required. Outpatient cervical ripening can be an attractive alternative. OBJECTIVES: To evaluate the efficacy and safety of outpatient cervical ripening with a balloon catheter compared with inpatient balloon catheter or prostaglandin E2 (PGE2 ). SEARCH STRATEGY: The PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases were searched from their inception to October 15, 2022. SELECTION CRITERIA: Randomized controlled trials comparing the outpatient balloon catheter with inpatient balloon catheter or inpatient PGE2 for term cervical ripening. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis was performed. The primary outcome was the cesarean delivery rate. The secondary outcomes included instrumental delivery, the time from intervention-to-birth, oxytocin augmentation, total hospital duration, and maternal/neonatal adverse events. MAIN RESULTS: Twenty-nine randomized controlled trials with a total of 6004 participants were identified. No difference in the cesarean delivery rate was revealed among the three interventions. Compared with inpatient balloon catheter, outpatient balloon catheter had shorter total hospital duration (mean difference -8.58, 95% confidence interval -17.02 to -1.10). No differences were revealed in the time from intervention-to-birth, instrumental delivery, postpartum hemorrhage, 5-min Apgar score less than 7, umbilical cord arterial pH less than 7.1, and neonatal intensive care unit admission among the three interventions. CONCLUSIONS: Outpatient balloon catheter in low-risk term pregnancies is an available option that could be considered for cervical ripening. The safety and effectiveness are comparable to inpatient cervical ripening methods.

Relief of Residual Stress in Bulk Thermosets in the Glassy State by Local Bond Exchange.

The covalently cross-linked network gives thermosets superior thermal, mechanical, and electrical properties, which, however, squarely makes the large residual stress that is inevitably induced during preparation hardly relieved in the glassy state. In this work, an incredible reduction in residual stress is successfully achieved in bulk thermosets in the glassy state through introducing highly dynamic thiocarbamate bonds by "click" reactions of thiols and isocyanates. Due to the excellent dynamic behaviors of thiocarbamate bonds, local network rearrangement is achieved through thermal stimulation, while the strong 3D cross-linked network is well maintained. Ultimately, a decrease by 44% in residual stress is detected by simply annealing samples at 30 °C below glass transition temperature (Tg), during which they could well maintain more than 98.4% of the storage modulus. After the annealing, more uniform residual stress distribution is also observed, showing a 32% decline in sample standard deviation. However, the residual stress of epoxy resin, a typical thermoset as a reference, changes little even after annealing at Tg. The results prove it a feasible strategy to reduce residual stress in bulk thermosets in the glassy state by introducing proper dynamic covalent bonds.

Quantitative Risk Assessment of Salmonella in Breaded Pork Products in China.

Pork products were the most common media of Salmonella in China, breaded pork products as a very popular meat presently, whose Salmonella risk should be drawn to attention. Given that quantitative risk assessment is a more scientific method for risk evaluation, a quantitative risk assessment model of Salmonella in breaded pork products was first constructed from processing to consumption, and was used for assessing the risk and the effective interventions in this study. The data of Salmonella contamination in breaded pork products during processing were obtained from the actual detection data of samples from a representative meat processing plant. With combining the predictive microbial modeling and dose-response relationship, the risk of Salmonella in breaded pork products was charactered, and the probability of Salmonella infection per meal was found to be 5.585 × 10-9. Based on the results of sensitivity analysis, the curing and seasoning process was found to be the key control point for Salmonella contamination during the processing, and consumer behavior was the key control point affecting the probability of Salmonella infection from processing to consumption. The model was also applied for assessing the effectiveness of risk interventions, and among the nine interventions given, control of thawing temperature before cooking such as microwave thawing could reduce the risk of infection by 30.969-fold, while cooking the products thoroughly, Salmonella would not pose a pathogenic hazard to consumers. The model and the assessed results in this study may provide guidance on microbial control in producing process and safety consumption of breaded pork products.

Saikosaponin a activates tet1/dll3/notch1 signalling and promotes hippocampal neurogenesis to improve depression-like behavior in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Bupleuri, also named "Chaihu" in Chinese, is a substance derived from the dry roots of Bupleurum chinense DC. [Apiaceae] and Bupleurum scorzonerifolium Willd. [Apiaceae]. Radix Bupleuri was initially recorded as a medicinal herb in Shen Nong Ben Cao Jing, the earliest monograph concerning traditional Chinese medicine (TCM). Ever since, Radix Bupleuri has been broadly used to alleviate exterior syndrome, disperse heat, modulate the liver-qi, and elevate yang-qi in TCM. Radix Bupleuri has also been utilized as an important component in Xiaoyaosan, a classical formula for relieving depression, which was originated from the famous Chinese medical book called "Tai Ping Hui Min He Ji Ju Fang" in Song Dynasty. Currently, many valuable pharmacological effects of Radix Bupleuri have been explored, such as antidepressant, neuroprotective activities, antiinflammation, anticancer, immunoregulation, etc. Former studies have illustrated that Saikosaponin A (SSa), one of the primary active components of Radix Bupleuri, possesses potential antidepressant properties. However, the underlying mechanisms still remain unknown. AIM OF THE STUDY: We used a chronic social defeat stress (CSDS) mouse model to explore the ameliorative effects and potential mechanisms of SSa in depressive disorder in vivo. MATERIALS AND METHODS: The CSDS mouse model was established and mice underwent behavioral studies using assays such as the social interaction test (SIT), sucrose preference test (SPT), forced-swim test (FST), tail suspension test (TST), and open field test (OFT). Western blotting, immunofluorescence, and Golgi staining were performed to investigate signaling pathway activity, and alterations in synaptic spines in the hippocampus. To model the anticipated interaction between SSa and Tet1, molecular docking and microscale thermophoresis (MST) techniques were employed. Finally, sh-RNA Tet1 was employed for validation via lentiviral transfection in CSDS mice to confirm the requirement of Tet1 for SSA efficacy. RESULTS: SSa dramatically reduced depressed symptoms, boosted the expression of Tet1, Notch, DLL3, and BDNF, encouraged hippocampus development, and enhanced the dendritic spine density of hippocampal neurons. In contrast, Tet1 knockdown in CSDS mice dampened the beneficial effects of SSa on depressive symptoms. CONCLUSIONS: Therefore, our results suggest that SSa significantly activates the Tet1/Notch/DLL3 signaling pathways and promotes hippocampal neurogenesis to exert antidepressant effects in the CSDS mouse model in vivo. The present results also provide new insight into the importance of the Tet1/DLL3/Notch pathways as potential targets for novel antidepressant development.

Association of Fine Particulate Matter Constituents with the Predicted 10-Year Atherosclerotic Cardiovascular Disease Risk: Evidence from a Large-Scale Cross-Sectional Study.

Little is known concerning the associations of fine particulate matter (PM2.5) and its constituents with atherosclerotic cardiovascular disease (ASCVD). A total of 31,162 participants enrolled from the Henan Rural Cohort were used to specify associations of PM2.5 and its constituents with ASCVD. Hybrid machine learning was utilized to estimate the 3-year average concentration of PM2.5 and its constituents (black carbon [BC], nitrate [NO3-], ammonium [NH4+], inorganic sulfate [SO42-], organic matter [OM], and soil particles [SOIL]). Constituent concentration, proportion, and residual models were utilized to examine the associations of PM2.5 constituents with 10-year ASCVD risk and to identify the most hazardous constituent. The isochronous substitution model (ISM) was employed to analyze the substitution effect between PM2.5 constituents. We found that each 1 µg/m3 increase in PM2.5, BC, NH4+, NO3-, OM, SO42-, and SOIL was associated with a 3.5%, 49.3%, 19.4%, 10.5%, 21.4%, 14%, and 28.5% higher 10-year ASCVD risk, respectively (all p < 0.05). Comparable results were observed in proportion and residual models. The ISM found that replacing BC with other constituents will generate the greatest health benefits. The results indicated that long-term exposure to PM2.5 and its constituents were associated with increased risks of ASCVD, with BC being the most attributable constituent.

mRNA-based Vaccines Targeting the T-cell Epitope-rich Domain of Epstein Barr Virus Latent Proteins Elicit Robust Anti-Tumor Immunity in Mice.

Epstein-Barr virus (EBV) is associated with various malignancies and infects >90% of the global population. EBV latent proteins are expressed in numerous EBV-associated cancers and contribute to carcinogenesis, making them critical therapeutic targets for these cancers. Thus, this study aims to develop mRNA-based therapeutic vaccines that express the T-cell-epitope-rich domain of truncated latent proteins of EBV, including truncatedlatent membrane protein 2A (Trunc-LMP2A), truncated EBV nuclear antigen 1 (Trunc-EBNA1), and Trunc-EBNA3A. The vaccines effectively activate both cellular and humoral immunity in mice and show promising results in suppressing tumor progression and improving survival time in tumor-bearing mice. Furthermore, it is observed that the truncated forms of the antigens, Trunc-LMP2A, Trunc-EBNA1, and Trunc-EBNA3A, are more effective than full-length antigens in activating antigen-specific immune responses. In summary, the findings demonstrate the effectiveness of mRNA-based therapeutic vaccines targeting the T-cell-epitope-rich domain of EBV latent proteins and providing new treatment options for EBV-associated cancers.

Simple & better - Accelerated cheese ripening using a mesophilic starter based on a single strain with superior autolytic properties.

In the manufacture of rennet-coagulated cheese, autolysis is a rate-limiting step for ripening. Previously, a highly autolytic and thermotolerant Lactococcus lactis strain, RD07, was generated, which in preliminary laboratory cheese trials demonstrated great potential as a cheese ripening accelerant. RD07 is proteinase positive (Prt+) and capable of metabolizing citrate (Cit+). In this study, we obtained two derivatives of RD07: EC8 lacking the citrate plasmid, and EC2 lacking the proteinase plasmid. EC2 and EC8 retained the autolytic properties of RD07, and autolyzed 20 times faster than Flora Danica (FD) and SD96, where the latter is the parent of RD07. The three strains EC2, EC8 and RD07 were used in a ratio of 90:8:2, to create a simple starter termed ERC. ERC was less sensitive to cooking when cultured in milk and autolyzed well after entering the stationary phase upon facing sugar starvation. The ERC starter was benchmarked against FD and SD96 in laboratory cheese trials. The free amino acid content in cheese prepared using the ERC culture was 31 % and 34 % higher than in cheese prepared using FD and SD96, respectively. Overall, the ERC culture resulted in a more rapid release of free amino acids. A large-scale (5000 L) Gouda cheese trial at a Danish dairy demonstrated that the single strain ERC starter was comparable in performance to FD + an adjunct Lactobacillus helveticus culture. Furthermore, a large-scale Danbo cheese trial demonstrated that ERC could reduce the ripening period by 50 % for long-term ripened (25 weeks) cheese, resulting in better cheese.

Environmental Applications of Electromembrane Extraction: A Review.

Electromembrane extraction (EME) is a miniaturized extraction technique that has been widely used in recent years for the analysis and removal of pollutants in the environment. It is based on electrokinetic migration across a supported liquid membrane (SLM) under the influence of an external electrical field between two aqueous compartments. Based on the features of the SLM and the electrical field, EME offers quick extraction, effective sample clean-up, and good selectivity, and limits the amount of organic solvent used per sample to a few microliters. In this paper, the basic devices (membrane materials and types of organic solvents) and influencing factors of EME are first introduced, and the applications of EME in the analysis and removal of environmental inorganic ions and organic pollutants are systematically reviewed. An outlook on the future development of EME for environmental applications is also given.

Transforming acid whey into a resource by selective removal of lactic acid and galactose using optimized food-grade microorganisms.

The presence of lactic acid and galactose makes spray drying of acid whey (AW) a significant challenge for the dairy industry. In this study, a novel approach is explored to remove these compounds, utilizing food-grade microorganisms. For removing lactic acid, Corynebacterium glutamicum was selected, which has an inherent ability to metabolize lactic acid but does so slowly. To accelerate lactic acid metabolism, a mutant strain G6006 was isolated through adaptive laboratory evolution, which metabolized all lactic acid from AW two times faster than its parent strain. To eliminate galactose, a lactose-negative mutant of Lactococcus lactis that cannot produce lactate was generated. This strain was then co-cultured with G6006 to maximize the removal of both lactic acid and galactose. The microbially "filtered" AW could readily be spray dried into a stable lactose powder. This study highlights the potential of utilizing food-grade microorganisms to process AW, which currently constitutes a global challenge.

Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity.

Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4+ T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-ß-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4+ cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-κB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases.

Development of Au8 nanocluster-based fluorescent strip immunosensor for sensitive detection of aflatoxin B1.

Gold clusters with intriguing chemical/physical properties have great promise in applications such as sensing and bio-imaging due to their fascinating photoluminescence character. In this study, an immunofluorescence sensor based on levonorgestrel protected atomically precise Au8 nanocluster (Au8NC) for aflatoxin B1 (AFB1) detection was fabricated due to its strong carcinogenic and mutagenic effect on humans. The prepared polymer-Au8NC nanospheres displayed bright luminescence and good stability in aqueous solution. The obtained AFB1 fluorescent strip immunosensor achieved quantitative point-of-care detection of AFB1 in less than 15 min, with high selectivity and detection limits down to 0.27 ng/mL. In addition, the recovery rates of AFB1 from tea soup ranged from 96% to 105% with relative standard deviations less than 10%. This work not only realized high-sensitively fluorescent sensing for AFB1, but also expanded the bio-applications of atomic-precise metal clusters.