Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

Recurrent Tuberous Sclerosis Complex​​​​​/Mammalian Target of Rapamycin Mutations Define Primary Renal Hemangioblastoma as a Unique Entity Distinct From Its Central Nervous System Counterpart.

ABSTRACT: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 (TSC1, 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification.

Etiological analysis of 167 cases of drug-resistant epilepsy in children.

BACKGROUND: To analyze the etiological distribution characteristics of drug-resistant epilepsy (DRE) in children, with the aim of providing valuable perspectives to enhance clinical practice. METHODS: In this retrospective study, clinical data were collected on 167 children with DRE who were hospitalized between January 2020 and December 2022, including gender, age of onset, seizure types, video electroencephalogram(VEEG) recordings, neuroimaging, and genetic testing results. Based on the etiology of epilepsy, the enrolled children were categorized into different groups. The rank-sum test was conducted to compare the age of onset for different etiologies. RESULTS: Of the 167 cases, 89 (53.3%) had a clear etiology. Among them, structural factors account for 23.4%, genetic factors for 19.2%, multiple factors for 7.2%, and immunological factors for 3.6%. The age of onset was significantly earlier in children with genetic causes than those with structural (P < 0.001) or immunological (P = 0.001) causes. CONCLUSIONS: More than half of children with DRE have a distinct underlying cause, predominantly attributed to structural factors, followed by genetic factors. Genetic etiology primarily manifests at an early age, especially among children aged less than one year. This underscores the need for proactive enhancements in genetic testing to unveil the underlying causes and subsequently guide treatment protocols.

Experimental study on the full cycle evolution of high-intensity atmospheric dc arc discharge from breakdown to extinguishment.

In this study, the spatiotemporal evolution of full cycle of high-intensity dc argon arc discharge at atmospheric pressure is investigated by using a transferred arc device, which is easy to be directly observed in the experiment. Combining the voltage and current waveforms with high-speed images, the full cycle evolution process of high-intensity atmospheric dc arc can be divided into five different stages: breakdown pulse stage, cathode heating stage, current climbing stage, stable arc discharge stage, and finally arc extinguishing stage. The characteristics of each different stage are analyzed in detail through the electrical properties, high-speed pictures, and spectroscopic measurements. The results show that the strong luminescence region develops from the vicinity of cathode and anode to the middle in the breakdown pulse stage, which is explained from the spatiotemporal evolution of distributions of excited argon atom and ions. The development velocity of emission intensity of argon ions is mainly determined by the dominant stepwise ionization process. Then the cathode heating stage appears with many bright and nonuniformly distributed light spots on the cathode surface, and the electron emission mechanism of cathode gradually changes to the thermionic emission as the surface temperature rises. With the increase of arc current, the discharge channel significantly expands, then becomes stable due to the increment of the Lorentz force. The characteristics of arc extinguishing stage are clarified in terms of the decay of charged particles density.

Study on the correlation between IL-12p70, IL-17A and migraine in children.

Objective: To compare the serum levels of 12 cytokines in migraine group, encephalitis with headache symptoms group, pneumonia without headache symptoms group and migraine subgroups to explore the cytokines associated with migraine in children and their levels. Methods: A total of 44 children with migraine, 27 children in the encephalitis group with headache symptoms and 44 children in the pneumonia group without headache symptoms were selected from January 2022 to August 2023 in Hebei Children's Hospital. They were all tested for serum cytokines by immunofluorescence assay. The migraine group was further divided into subgroups according to different age, gender, course of disease, and presence of coinfection. The differences of serum cytokine levels among the above groups were compared, and the correlation analysis was carried out. Results: Except IL-5, there were no significant differences in the expression levels of other 11 inflammatory cytokines between migraine subgroups. Compared with encephalitis with headache symptoms group and pneumonia without headache symptoms group the serum levels of IL-4, TNF-α, IL-17A, and IL-12p70 were higher in migraine group than in pneumonia group, and the levels of IL-12p70 were higher than those in encephalitis group (p < 0.05). An increase in serum IL-12p70 (OR = 1.267, 95%CI 1.054-1.523, p = 0.012) and IL-17A (OR = 1.066, 95%CI 1.016-1.119, p = 0.010) levels had a significant effect on migraine. Conclusion: Elevated serum levels of IL-12p70 and IL-17A may increase the risk of migraine in children, which has certain diagnostic and predictive value.

Genome sequencing as a generic diagnostic strategy for rare disease.

BACKGROUND: To diagnose the full spectrum of hereditary and congenital diseases, genetic laboratories use many different workflows, ranging from karyotyping to exome sequencing. A single generic high-throughput workflow would greatly increase efficiency. We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease. METHODS: We performed short-read GS (NovaSeq™6000; 150 bp paired-end reads, 37 × mean coverage) on 1000 cases with 1271 known clinically relevant variants, identified across different workflows, representative of our tertiary diagnostic centers. Variants were categorized into small variants (single nucleotide variants and indels < 50 bp), large variants (copy number variants and short tandem repeats) and other variants (structural variants and aneuploidies). Variant calling format files were queried per variant, from which workflow-specific true positive rates (TPRs) for detection were determined. A TPR of ≥ 98% was considered the threshold for transition to GS. A GS-first scenario was generated for our laboratory, using diagnostic efficacy and predicted false negative as primary outcome measures. As input, we modeled the diagnostic path for all 24,570 individuals referred in 2022, combining the clinical referral, the transition of the underlying workflow(s) to GS, and the variant type(s) to be detected. RESULTS: Overall, 95% (1206/1271) of variants were detected. Detection rates differed per variant category: small variants in 96% (826/860), large variants in 93% (341/366), and other variants in 87% (39/45). TPRs varied between workflows (79-100%), with 7/10 being replaceable by GS. Models for our laboratory indicate that a GS-first strategy would be feasible for 84.9% of clinical referrals (750/883), translating to 71% of all individuals (17,444/24,570) receiving GS as their primary test. An estimated false negative rate of 0.3% could be expected. CONCLUSIONS: GS can capture clinically relevant germline variants in a 'GS-first strategy' for the majority of clinical indications in a genetics diagnostic lab.

Sustainable production of bacterial flocculants by nylon-6,6 microplastics hydrolysate utilizing Brucella intermedia ZL-06.

Nylon-6,6 microplastics (NMPs) in aquatic systems have emerged as potential contaminants to the global environment and have garnered immense consideration over the years. Unfortunately, there is currently no efficient method available to eliminate NMPs from sewage. This study aims to address this issue by isolating Brucella intermedia ZL-06, a bacterium capable of producing a bacterial polysaccharide-based flocculant (PBF). The PBF generated from this bacterium shows promising efficacy in effectively flocculating NMPs. Subsequently, the precipitated flocs (NMPs + PBF) were utilized as sustainable feedstock for synthesizing PBF. The study yielded 6.91 g/L PBF under optimum conditions. Genome sequencing analysis was conducted to study the mechanisms of PBF synthesis and nylon-6,6 degradation. The PBF exhibited impressive flocculating capacity of 90.1 mg/g of PBF when applied to 0.01 mm NMPs, aided by the presence of Ca2+. FTIR and XPS analysis showed the presence of hydroxyl, carboxyl, and amine groups in PBF. The flocculation performance of PBF conformed to Langmuir isotherm and pseudo-first-order adsorption kinetics model. These findings present a promising approach for reducing the production costs of PBF by utilizing NMPs as sustainable nutrient sources.

Comprehensive assessment of fine motor movement and cognitive function among older adults in China: a cross-sectional study.

BACKGROUND: Fine motor skills are closely related to cognitive function. However, there is currently no comprehensive assessment of fine motor movement and how it corresponds with cognitive function. To conduct a complete assessment of fine motor and clarify the relationship between various dimensions of fine motor and cognitive function. METHODS: We conducted a cross-sectional study with 267 community-based participants aged ≥ 60 years in Beijing, China. We assessed four tests performance and gathered detailed fine motor indicators using Micro-Electro-Mechanical System (MEMS) motion capture technology. The wearable MEMS device provided us with precise fine motion metrics, while Chinese version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. We adopted logistic regression to analyze the relationship between fine motor movement and cognitive function. RESULTS: 129 (48.3%) of the participants had cognitive impairment. The vast majority of fine motor movements have independent linear correlations with MoCA-BJ scores. According to logistic regression analysis, completion time in the Same-pattern tapping test (OR = 1.033, 95%CI = 1.003-1.063), Completion time of non-dominant hand in the Pieces flipping test (OR = 1.006, 95%CI = 1.000-1.011), and trajectory distance of dominant hand in the Pegboard test (OR = 1.044, 95%CI = 1.010-1.068), which represents dexterity, are related to cognitive impairment. Coordination, represented by lag time between hands in the Same-pattern tapping (OR = 1.663, 95%CI = 1.131-2.444), is correlated with cognitive impairment. Coverage in the Dual-hand drawing test as an important indicator of stability is negatively correlated with cognitive function (OR = 0.709, 95%CI = 0.6501-0.959). Based on the above 5-feature model showed consistently high accuracy and sensitivity at the MoCA-BJ score (ACU = 0.80-0.87). CONCLUSIONS: The results of a comprehensive fine-motor assessment that integrates dexterity, coordination, and stability are closely related to cognitive functioning. Fine motor movement has the potential to be a reliable predictor of cognitive impairment.

Prediction of EGFR mutation status in lung adenocarcinoma based on 18F-FDG PET/CT radiomic features.

The earlier identification of EGFR mutation status in lung adenocarcinoma patients is crucial for treatment decision-making. Radiomics, which involves high-throughput extraction of imaging features from medical images for quantitative analysis, can quantify tumor heterogeneity and assess tumor biology non-invasively. This field has gained attention from researchers in recent years. The aim of this study is to establish a model based on 18F-FDG PET/CT radiomic features to predict the epidermal growth factor receptor (EGFR) mutation status of lung adenocarcinoma and evaluate its performance. 155 patients with lung adenocarcinoma who underwent 18F-FDG PET/CT scans and EGFR gene detection before treatment were retrospectively analyzed. The LIFEx packages was used to perform 3D volume of interest (VOI) segmentation manually on DICOM images and extract 128 radiomic features. The Wilcoxon rank sum test and least absolute shrinkage and selection operator (LASSO) regression algorithm were applied to filter the radiomic features and establish models. The performance of the models was evaluated by the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Among the models we have built, the radiomic model based on 18F-FDG PET/CT has the best prediction performance for EGFR gene mutation status, with an AUC of 0.90 (95% CI 0.84~0.96) in the training set and 0.79 (95% CI 0.64~0.94) in the test set. In conclusion, we have established a radiomics model based on 18F-FDG PET/CT, which has good predictive performance in identifying EGFR gene mutation status in lung adenocarcinoma patients.

Clinical efficacy of low-dose aspirin combined with calcium in preventing preeclampsia: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of low-dose aspirin combined with calcium supplements for the prevention of preeclampsia. METHODS: China National Knowledge Infrastructure, VIP, Wanfang, PubMed, EMBASE, and Cochrane Library databases were searched from inception until December 2022. Randomized controlled trials investigating the preventive use of aspirin in combination with calcium supplementation for preeclampsia in high-risk pregnant women were included. The quality of the literature was evaluated, and a meta-analysis was conducted using RevMan 5.3 software to analyze the clinical efficacy of low-dose aspirin combined with calcium supplementation in preventing preeclampsia. RESULTS: Seven randomized controlled trials were included in this meta-analysis, and compared with the control group, the experimental group had lower incidence rates of preeclampsia with gestational hypertension (odds ratios [OR]: 0.17, 95% confidence interval [CI]: 0.11-0.28), preeclampsia (OR: 0.20, 95% CI: 0.10-0.37), gestational hypertension (OR: 0.15, 95% CI: 0.07-0.31), preterm birth (OR: 0.26, 95% CI: 0.16-0.44), postpartum hemorrhage (OR: 0.15, 95% CI: 0.08-0.27), and fetal growth restriction (OR: 0.16, 95% CI: 0.08-0.33). CONCLUSION: Compared with aspirin alone, low-dose aspirin combined with calcium supplementation was more effective in preventing preeclampsia, reduced the risk of preterm birth and postpartum hemorrhage, and promoted fetal growth. This intervention has clinical value and should be considered for high-risk pregnant women.

[Characteristics of sympathetic skin response in children with Guillain-Barré syndrome]. / å„¿ç«¥å‰å °-巴雷综合征交感皮肤反应的特点分析.

OBJECTIVES: To explore the value of sympathetic skin response (SSR) in the early diagnosis and prognostic evaluation of Guillain-Barre syndrome (GBS) in children. METHODS: A retrospective analysis was conducted on the clinical data of 25 children with GBS who were diagnosed from October 2018 to November 2022, and 30 children who were diagnosed with Tourette's syndrome during the same period were selected as the control group. The characteristics of SSR were compared between the two groups, and the association of SSR with autonomic dysfunction (AD), disease severity, and prognosis was analyzed. RESULTS: The GBS group had a significantly higher abnormal rate of SSR than the control group during the acute phase (P<0.001). SSR combined with early nerve conduction (within 2 weeks after onset) had a sensitivity of 84%, a specificity of 100%, and an accuracy of 93% in the diagnosis of GBS. There were no significant differences in the proportion of AD cases, as well as the Hughes scores during the disease peak, between the abnormal and normal SSR groups (P>0.05). All 7 children with poor short-term prognosis (at 1 month after onset) had abnormal SSR. CONCLUSIONS: SSR can be used for the early diagnosis of GBS and the monitoring of treatment response in children.

Lytic polysaccharide monooxygenase synergized with lignin-degrading enzymes for efficient lignin degradation.

Even though the discovery of lytic polysaccharide monooxygenases (LPMOs) has fundamentally shifted our understanding of biomass degradation, most of the current studies focused on their roles in carbohydrate oxidation. However, no study demonstrated if LPMO could directly participate to the process of lignin degradation in lignin-degrading microbes. This study showed that LPMO could synergize with lignin-degrading enzymes for efficient lignin degradation in white-rot fungi. The transcriptomics analysis of fungi Irpex lacteus and Dichomitus squalens during their lignocellulosic biomass degradation processes surprisingly highlighted that LPMOs co-regulated with lignin-degrading enzymes, indicating their more versatile roles in the redox network. Biochemical analysis further confirmed that the purified LPMO from I. lacteus CD2 could use diverse electron donors to produce H2O2, drive Fenton reaction, and synergize with manganese peroxidase for lignin oxidation. The results thus indicated that LPMO might uniquely leverage the redox network toward dynamic and efficient degradation of different cell wall components.

Effect of neoadjuvant therapy on serum transforming growth factor-ß, squamous cell carcinoma associated antigen, and prognosis in patients with locally advanced esophageal cancer.

It was to explore the effect of neoadjuvant therapy (NAT) on serum-related indicators and prognosis of patients with locally advanced esophageal cancer (EC). 400 EC patients were grouped as controls (295 cases, radical EC resection alone) and research group (105 cases, NAT plus radical EC resection). The levels of serum carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), programmed death-1 (PD-1), PD-2, transforming growth factor-ß1 (TGF-ß1), and squamous cell carcinoma (SCC) antigen were detected before and after treatment. The follow-up lasted for 3 years. The quality of life (QoL) was evaluated by QLQ-OES24. The recurrence rate, recurrence time, overall survival rate (SR), disease-free SR, and complication rate were compared. Compared with controls, the levels of serum CA19-9, CEA, CYFRA21-1, PD-1, PD-2, TGF-ß1, and SCC were decreased, the QoL score was increased 3 years post-treatment, and the recurrence time was prolonged in the research group (P<0.05). The R0 resection rate, recurrence rate, 3-year overall SR, and disease-free SR of the two groups were 67.12% vs 85.71%, 21.36% vs 6.67%, 56.27% vs 77.14%, 29.83% vs 45.71%, respectively (P<0.05). The complication rates of the two groups were 32.54% and 29.52%, respectively (P>0.05). NAT plus radical resection of EC can effectively reduce the level of serum oncology markers in patients with locally advanced EC, reduce the postoperative recurrence rate, improve QoL and SR, and has high safety.

The preoperative platelet to neutrophil ratio and lymphocyte to monocyte ratio are superior prognostic indicators compared with other inflammatory biomarkers in ovarian cancer.

Background: Previous studies have suggested that the ratios of immune-inflammatory cells could serve as prognostic indicators in ovarian cancer. However, which of these is the superior prognostic indicator in ovarian cancer remains unknown. In addition, studies on the prognostic value of the platelet to neutrophil ratio (PNR) in ovarian cancer are still limited. Methods: A cohort of 991 ovarian cancer patients was analyzed in the present study. Receiver operator characteristic (ROC) curves were utilized to choose the optimal cut-off values of inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and PNR. The correlation of inflammatory biomarkers with overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier methods and log-rank test, followed by Cox regression analyses. Results: Kaplan-Meier curves suggested that LMR<3.39, PLR≥181.46, and PNR≥49.20 had obvious associations with worse RFS (P<0.001, P=0.018, P<0.001). Multivariate analysis suggested that LMR (≥3.39 vs. <3.39) (P=0.042, HR=0.810, 95% CI=0.661-0.992) and PNR (≥49.20 vs. <49.20) (P=0.004, HR=1.351, 95% CI=1.103-1.656) were independent prognostic indicators of poor RFS. In addition, Kaplan-Meier curves indicated that PLR≥182.23 was significantly correlated with worse OS (P=0.039). Conclusion: Taken together, PNR and LMR are superior prognostic indicators compared with NLR, PLR, and SII in patients with ovarian cancer.

Boric acid group-functional ruthenium complex as a novel fluorescence probe for robust detection of propyl gallate and tert-butyl hydroquinone by tuning the pH.

This study reported a ruthenium complex-based fluorescence probe, achieving rapid and sequential detection of propyl gallate (PG) and tert-butyl hydroquinone (TBHQ) for the first time by tuning pH only. Under 480 nm excitation, probe exhibited intensive emission at 620 nm, which was selectively quenched by PG at pH 7.0 due to the covalent binding between the boric acid of probe and o-diphenol hydroxyl of PG. Then pH was tuned to 7.4, the emission was significantly quenched by TBHQ because of the π-π stacking between aromatic rings of probe and paraquinone of TBHQ. This probe realized specific and sensitive detection of PG and TBHQ with wide range and low detection limit (0.26 µM for PG and 0.66 µM for TBHQ). Furthermore, a portable visual test paper detection platform was built based on this probe for rapid and sensitive detection of antioxidants in food, which was of great significance for market regulation.

Intrinsic peroxidase-like activity of dissolved black carbon released from biochar.

Dissolved black carbon (DBC) is an important constituent of the natural organic carbon pool, influencing the global carbon cycling and the fate processes of many pollutants. In this work, we discovered that DBC released from biochar has intrinsic peroxidase-like activity. DBC samples were derived from four biomass stocks, including corn, peanut, rice, and sorghum straws. All DBC samples catalyze H2O2 decomposition into hydroxyl radicals, as determined by the electron paramagnetic resonance and the molecular probe. Similar to enzymes that exhibit saturation kinetics, the steady-state reaction rates follow the Michaelis-Menten equation. The peroxidase-like activity of DBC is controlled by the ping-pong mechanism, as suggested by parallel Lineweaver-Burk plots. Its activity increases with temperature from 10 to 80 °C and has an optimum at pH 5. The peroxidase-like activity of DBC is positively correlated with its aromaticity as aromatics can stabilize the reactive intermediates. The active sites in DBC also involve oxygen-containing groups, as inferred by increased activity after the chemical reduction of carbonyls. The peroxidase-like activity of DBC has significant implications for biogeochemical processing of carbon and potential health and ecological impacts of black carbon. It also highlights the need to advance the understanding of the occurrence and role of organic catalysts in natural systems.

Enhancing Biocidal Capability in Cuprite Coatings.

The SARS-CoV-2 global pandemic has reinvigorated interest in the creation and widespread deployment of durable, cost-effective, and environmentally benign antipathogenic coatings for high-touch public surfaces. While the contact-kill capability and mechanism of metallic copper and its alloys are well established, the biocidal activity of the refractory oxide forms remains poorly understood. In this study, commercial cuprous oxide (Cu2O, cuprite) powder was rapidly nanostructured using high-energy cryomechanical processing. Coatings made from these processed powders demonstrated a passive "contact-kill" response to Escherichia coli (E. coli) bacteria that was 4× (400%) faster than coatings made from unprocessed powder. No viable bacteria (>99.999% (5-log10) reduction) were detected in bioassays performed after two hours of exposure of E. coli to coatings of processed cuprous oxide, while a greater than 99% bacterial reduction was achieved within 30 min of exposure. Further, these coatings were hydrophobic and no external energy input was required to activate their contact-kill capability. The upregulated antibacterial response of the processed powders is positively correlated with extensive induced crystallographic disorder and microstrain in the Cu2O lattice accompanied by color changes that are consistent with an increased semiconducting bandgap energy. It is deduced that cryomilling creates well-crystallized nanoscale regions enmeshed within the highly lattice-defective particle matrix. Increasing the relative proportion of lattice-defective cuprous oxide exposed to the environment at the coating surface is anticipated to further enhance the antipathogenic capability of this abundant, inexpensive, robust, and easily handled material for wider application in contact-kill surfaces.

Efficient Azo Dye Biodecolorization System Using Lignin-Co-Cultured White-Rot Fungus.

The extensive use of azo dyes by the global textile industry induces significant environmental and human health hazards, which makes efficient remediation crucial but also challenging. Improving dye removal efficiency will benefit the development of bioremediation techniques for textile effluents. In this study, an efficient system for azo dye (Direct Red 5B, DR5B) biodecolorization is reported, which uses the white-rot fungus Ganoderma lucidum EN2 and alkali lignin. This study suggests that the decolorization of DR5B could be effectively enhanced (from 40.34% to 95.16%) within 48 h in the presence of alkali lignin. The dye adsorption test further confirmed that the alkali-lignin-enhanced decolorization of DR5B was essentially due to biodegradation rather than physical adsorption, evaluating the role of alkali lignin in the dye biodegradation system. Moreover, the gas chromatography/mass spectrometry analysis and DR5B decolorization experiments also indicated that alkali lignin carried an excellent potential for promoting dye decolorization and displayed a significant role in improving the activity of lignin-modifying enzymes. This was mainly because of the laccase-mediator system, which was established by the induced laccase activity and lignin-derived small aromatic compounds.

Tetrachlorobisphenol A and bisphenol AF induced cell migration by activating PI3K/Akt signaling pathway via G protein-coupled estrogen receptor 1 in SK-BR-3 cells.

Different subtypes of breast cancer express positively G protein-coupled estrogen receptor 1 (GPER1). Our previous studies found that tetrachlorobisphenol A (TCBPA) and bisphenol AF (BPAF) significantly promoted SK-BR-3 cell proliferation by activating GPER1-regulated signals. The present study further investigated the effects of TCBPA and BPAF on the migration of SK-BR-3 cells and examined the role of phosphatidylinositol 3-kinase-protein kinase B (PI3K/Akt) and its downstream signal targets in this process. We found that low-concentration BPAF and TCBPA markedly accelerated the migration of SK-BR-3 cells and elevated the mRNA levels of target genes associated with PI3K/Akt and mitogen-activated protein kinase (MAPK) signals. TCBPA- and BPAF-induced upregulation of target genes was significantly reduced by GPER1 inhibitor G15, the PI3K/Akt inhibitor wortmannin (WM), and the epidermal growth factor receptor (EGFR) inhibitor ZD1839 (ZD). G15 and WM also decreased cell migration induced by TCBPA and BPAF. The findings revealed that TCBPA and BPAF promoted SK-BR-3 cell migration ability by activating PI3K/Akt signaling pathway via GPER1-EGFR.

Population total and unbound pharmacokinetics and pharmacodynamics of ciprofol and M4 in subjects with various renal functions.

AIMS: The aim of this study was to develop a population pharmacokinetic (PK) model to simultaneously describe both total and unbound concentrations of ciprofol and its major glucuronide metabolite, M4, and to link it to the population pharmacodynamics (PD) model in subjects with various renal functions. METHODS: A total of 401 and 459 pairs of total and unbound plasma concentrations of ciprofol and M4, respectively, as well as 2190 bispectral index (BIS) data from 24 Chinese subjects with various renal functions were available. Covariates that may potentially contribute to the PK and PD variability of ciprofol were screened using a stepwise procedure. The optimal ciprofol induction dosing regimen was determined by model-based simulations. RESULTS: The PK of unbound ciprofol could best be described by a three-compartment model, while a two-compartment model could adequately describe unbound M4 PK. The concentrations of total and unbound ciprofol and M4 were linked using a linear protein binding model. The relationship between plasma concentrations of ciprofol and BIS data was best described by an inhibitory sigmoidal Emax model with a two-compartment biophase distribution compartment. Hemoglobin was the identified covariate determining the central compartment clearance of ciprofol; uric acid was a covariate affecting the central compartment clearance of M4 and protein binding rate, kB . The included covariates had no effect on the PD of ciprofol. Simulation results indicated that the label-recommended dose regimen was adequate for anaesthesia induction. CONCLUSIONS: The developed model fully characterized the population PK and PD profiles of ciprofol. No dose adjustment is required in patients with mild and moderate renal impairment.