Autophagy-mediated degradation of integumentary tapetum is critical for embryo pattern formation.

Autophagy modulates the degradation and recycling of intracellular materials and contributes to male gametophyte development and male fertility in plants. However, whether autophagy participates in seed development remains largely unknown. Here, we demonstrate that autophagy is crucial for timely programmed cell death (PCD) in the integumentary tapetum, the counterpart of anther tapetum, influencing embryo pattern formation and seed viability. Inhibition of autophagy resulted in delayed PCD of the integumentary tapetum and defects in embryo patterning. Cell-type-specific restoration of autophagic activities revealed that the integumentary tapetum plays a non-autonomous role in embryo patterning. Furthermore, high-throughput, comprehensive lipidomic analyzes uncovered an unexpected seed-developmental-stage-dependent role of autophagy in seed lipid metabolism: it contributes to triacylglycerol degradation before fertilization and to triacylglycerol biosynthesis after fertilization. This study highlights the critical role of autophagy in regulating timely integumentary tapetum PCD and reveals its significance in seed lipid metabolism and viability.

Biosynthesis of Chryseno[2,1,c]oxepin-12-Carboxylic Acid from Glycyrrhizic Acid in Aspergillus terreus TMZ05-2, and Analysis of Its Anti-inflammatory Activity.

Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1ß (IL-1ß; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.

Auricularia auricula-judae Attenuates the Progression of Metabolic Syndrome in High-Fat Diet-Induced Obese Rats: Enzymatic Pre-Digestion Technology Is Superior to Superfine Grinding Method.

Auricularia auricula-judae (AAJ) has been cultivated for food in China for centuries, and is also used as a folk medicine for the regulation of glucose and lipid metabolism. However, there are few studies on the effects of different processing technologies on the therapeutic efficacy of AAJ to date. This study investigated the effectiveness of the AAJ made by using superfine grinding and enzymatic pre-digestion technologies, respectively, in a high-fat diet obese rat model. It was found that oral administrations of two AAJ products significantly alleviated dyslipidemia by decreasing serum lipid levels and restoring liver functions. AAJ products made by using pre-digestion technology have appreciable potential to ameliorate lipid metabolic disorders over other products, possibly due to the higher levels of dietary fiber, crude polysaccharides, and total flavonoids released from AAJ during processing. By analysis of transcriptome sequencing and protein expression, it was clear that starch and sucrose metabolism and glycerolipid metabolism-related factors involved in fatty acid synthesis and metabolism in the liver of obese rats were significantly improved. This study gives further evidence that AAJ significantly ameliorates the progression of glucose and lipid metabolism in obese rats. Moreover, this study demonstrated for the first time that the pre-digestion method may be a better and more efficient processing approach for the improvement of AAJ bioavailability.

A vertical-flow constructed wetland-microalgal membrane photobioreactor integrated system for treating high-pollution-load marine aquaculture wastewater: A lab-scale study.

Individual biological water treatment techniques often prove ineffective in removing accumulated high concentrations of nitrogen and phosphorus in the late stages of biofloc aquaculture. To address this issue, we integrated a previously developed autotrophic denitrification and nitrification integrated constructed wetland (ADNI-CW) with a microalgal membrane photobioreactor (MPBR). Under high nitrogen and phosphorus pollution loads in the influent, the standalone ADNI-CW system achieved removal rates of only 24.17 % ± 2.82 % for total nitrogen (TN) and 25.30 % ± 2.59 % for total phosphorus (TP). The optimal conditions for TN and TP degradation and microalgal biomass production in the Chlorella MPBR, determined using response surface methodology, were an inoculum OD680 of 0.394, light intensity of 161.583 µmol/m2/s, and photoperiod of 16.302 h light:7.698 h dark. Under the optimal operating conditions, the integrated ADNI-CW-MPBR system achieved remarkable TN and TP removal rates of 92.63 % ± 2.8 % and 77.46 % ± 8.41 %, respectively, and a substantial microalgal biomass yield of 54.58 ± 6.8 mg/L/day. This accomplishment signifies the successful achievement of efficient nitrogen and phosphorus removal from high-pollution-load marine aquaculture wastewater along with the acquisition of valuable microalgal biomass. A preliminary investigation of the microbial community composition and algal-bacterial interactions in different operational stages of the MPBR system revealed that unclassified_d__Bacteria, Chlorophyta, and Planctomycetes were predominant phyla. The collaborative relationships between bacteria and Chlorella surpassed competition, ensuring highly efficient nitrogen and phosphorus removal in the MPBR system. This study laid the foundation for the green and sustainable development of the aquaculture industry.

Brain Structural Connectivity Guided Vision Transformers for Identification of Functional Connectivity Characteristics in Preterm Neonates.

Preterm birth is the leading cause of death in children under five years old, and is associated with a wide sequence of complications in both short and long term. In view of rapid neurodevelopment during the neonatal period, preterm neonates may exhibit considerable functional alterations compared to term ones. However, the identified functional alterations in previous studies merely achieve moderate classification performance, while more accurate functional characteristics with satisfying discrimination ability for better diagnosis and therapeutic treatment is underexplored. To address this problem, we propose a novel brain structural connectivity (SC) guided Vision Transformer (SCG-ViT) to identify functional connectivity (FC) differences among three neonatal groups: preterm, preterm with early postnatal experience, and term. Particularly, inspired by the neuroscience-derived information, a novel patch token of SC/FC matrix is defined, and the SC matrix is then adopted as an effective mask into the ViT model to screen out input FC patch embeddings with weaker SC, and to focus on stronger ones for better classification and identification of FC differences among the three groups. The experimental results on multi-modal MRI data of 437 neonatal brains from publicly released Developing Human Connectome Project (dHCP) demonstrate that SCG-ViT achieves superior classification ability compared to baseline models, and successfully identifies holistically different FC patterns among the three groups. Moreover, these different FCs are significantly correlated with the differential gene expressions of the three groups. In summary, SCG-ViT provides a powerfully brain-guided pipeline of adopting large-scale and data-intensive deep learning models for medical imaging-based diagnosis.

Effects of Enterococcus faecium (R8a) on nonspecific immune gene expression, immunity and intestinal flora of giant tiger shrimp (Penaeus monodon).

In this study, Penaeus monodon were gave basic feed supplemented with three levels of Enterococcus faecium. Then, the expression of non-specific immunity-related genes, and the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), malondialdehyde (MDA), acid phosphatase (ACP), alkaline phosphatase (AKP), phenol oxidase (PO) were evaluated. Meanwhile, the disease resistance test and intestinal flora determination were conducted. The results showed that the MDA levels of 2% and 5% E. faecium groups were significantly lower than that of the control group (P < 0.05). While the SOD and T-AOC and ACP and AKP of experimental groups were significantly higher (P < 0.05), the PO of experimental groups were significantly lower than that of the control group (P < 0.05). In addition, the expressions of immunity-related genes (tlr22, dorsal, lysozyme, crustin, imd, and relish) in the 2% and 5% E. faecalis groups were significantly greater than those in the control group (P < 0.05). After P. monodon was challenged with Vibrio parahaemolyticus for 7 days, the average cumulative mortality of P. monodon in the 2% and 5% groups were significantly lower than that in the 0% group (P < 0.05). With the increase of feeding time, the number of effective OTUs in each group showed a downward trend. At the 14th d, Proteobacteria, Bacteroidetes and Firmicutes, the dominant flora in the intestinal tract of P. monodon. In summary, supplied with E. faecium could increase the expression of non-specific immunity-related genes, enhance the immune capacity of P. monodon.

Characterization of the metabolites of Eucommiae Cortex in rats provides a further insight into its estrogen-like effective substances.

Eucommiae Cortex is one of important traditional Chinese medicines (TCMs) used in Asia for preventing and treating osteoporosis induced by estrogen deficiency. However, the low exposure of prototype components in Eucommiae Cortex in vivo is difficult to interpret its efficacy. Under the guidance of UPLC-Q/TOF-MS, 42 metabolites including 32 lignans and 10 phenolics, 21 of which were new compounds, were isolated from rat urine and feces after oral administration of aqueous extract of E. ulmoides Oliv. by various chromatographic techniques. Their structures were determined based on extensive physicochemical analyses and spectral data. Their absolute configurations were determined by experimental and calculated ECD spectra, along with the calculated NMR with DP4 evaluation. Additionally, all isolated metabolites were evaluated for their estrogen-like activities, and there are 15 metabolites having estrogen-like effects after assessing influences in MCF-7 cells. Further, Dual Luciferase Reporter Gene Assay was used to determine their activation with estrogen receptor, M10 and M11 mixtures, M14, M19, M33, M27, M31, M38-M41 could activate ERα, and M19 and M41 could activate ERß. These results not only clarify the pharmacological substances of Eucommiae Cortex, but also provide a basis for guiding its clinical application.

Biotemplated fabrication of N/O co-doped porous carbon confined spinel NiFe2O4 heterostructured mimetics for triple-mode sensing of antioxidants and ameliorating packaging properties.

In this work, shrimp shell-derived magnetic NiFe2O4/N, O co-doped porous carbon nanozyme with superior oxidase (OXD)-like activity was prepared and used for colorimetric/photothermal/smartphone dual-signal triple-mode detection of antioxidants in fruits and beverages. The magnetic NiFe2O4/N, O co-doped porous carbon (MNPC) material was triumphantly fabricated using a combined in-situ surface chelation and pyrolysis method. The resultant MNPC composite exhibits a superior OXD-like activity, which can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) for yielding colorimetric/temperature dual-signal (CTDS) in absence of H2O2. This CTDS output sensor was successfully used for the determination of ascorbic acid and tannic acid. The proposed CTDS sensor with good specificity and high sensitivity can satisfy different on-site analysis requirements. Interestingly, the MNPC as a sustainable filler was further used for improving packaging properties of polyvinyl alcohol film. In short, this work offers a large-scale and cheap method to fabricate magnetic carbon-based nanozyme for monitoring antioxidants and ameliorating packaging properties.

Diosmetin alleviates neuropathic pain by regulating the Keap1/Nrf2/NF-κB signaling pathway.

BACKGROUND: Neuropathic pain, a chronic condition with a high incidence, imposes psychological burdens on both patients and society. It is urgent to improve pain management and develop new analgesic drugs. Traditional Chinese medicine has gained popularity as a method for pain relief. Diosmetin (Dio) is mainly found in Chinese herbal medicines with effective antioxidant, anti-cancer, and anti-inflammatory properties. There are few known mechanisms underlying the effectiveness of Dio in treating neuropathic pain. However, the complete understanding of its therapeutic effect is missing. PURPOSE: This study aimed to evaluate Dio's therapeutic effects on neuropathic pain models and determine its possible mechanism of action. We hypothesized that Dio may activate antioxidants and reduce inflammation, inhibit the activation of Kelch-like epichlorohydrin-associated protein 1 (Keap1) and nuclear factor-k-gene binding (NF-κB), promote the metastasis of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of heme oxygenase 1 (HO-1), thus alleviating the neuropathic pain caused by spinal nerve ligation. METHODS: Chronic nociceptive pain mouse models were established in vivo by L4 spinal nerve ligation (SNL). Different dosages of Dio (10, 50, 100 mg/kg) were intragastrically administered daily from the third day after the establishment of the SNL model. Allodynia, caused by mechanical stimuli, and hyperalgesia, caused by heat, were assessed using the paw withdrawal response frequency (PWF) and paw withdrawal latency (PWL), respectively. Cold allodynia were assessd by acetone test. RT-PCR was used to detect the content of interleukin-(IL)- 1ß, IL-6 and tumor necrosis factor (TNF)-a. Immunofluorescence and western blotting were employed to assess the expression levels of Glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule (Iba1), Keap1, Nrf2, HO-1, and NF-κB p-p65 protein. RESULTS: Dio administration relieved SNL-induced transient mechanical and thermal allodynia in mice. The protective effect of Dio in the SNL model was associated with its anti-inflammatory and anti-glial responses in the spinal cord. Dio inhibited both inflammatory factors and macrophage activation in the DRG. Furthermore, Dio regulated the Keap1/Nrf2/NF-κB signaling pathway. HO-1 and Nrf2 were upregulated following Dio administration, which also decreased the levels of Keap1 and NF-κB p65 protein. CONCLUSION: Mice with SNL-induced neuropathic pain were therapeutically treated with Dio. Dio may protect against pain by inhibiting inflammatory responses and improved Keap1/Nrf2/NF-κB pathway. These results highlight the potential therapeutic effect of Dio for the development of new analgesic drugs.

Using Traditional Chinese Medicine to Alleviate Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high incidence in the world. Its main feature is that the lungs are affected by airflow obstruction. The disease can lead to impaired lung function in adults and cannot be completely cured. This paper expounds the pathogenesis of COPD, which can be alleviated by chemical methods and TCM methods. TCM treatment of COPD has the advantage of overall regulation, which can improve airway remodeling and alleviate the development of the disease. According to their structure, TCM therapeutic drugs can be divided into flavonoids, terpenoids, phenylpropanoids and alkaloids. On this basis, the article summarizes the advantages and disadvantages of common Chinese medicine administration methods, aiming to provide some reference and help when alleviating the disease.

Robust superhydrophobic silicone/epoxy functional coating with excellent chemical stability and self-cleaning ability.

Superhydrophobic surfaces have attracted broad attention because of their unique water repellency but are restricted by poor wear resistance, weak adhesion to the substrate, and complex fabrication processes. Herein, a double-layer coating strategy consisting of the amino fluorine-silicone resin/epoxy resin (AFSR/EP) system is created. The system features a high hardness and transparent hydrophobic interface adhesive layer through the amine-epoxy "click" chemical reaction. The environmentally friendly resin system and low-cost nano-silica particles (n-SiO2) are composited and sprayed onto the substrate surface to form a superhydrophobic layer with outstanding robustness and excellent environmental stability. The prepared AFSR/EP@n-SiO2 composite coatings have a water contact angle of 161.1° and a sliding angle of 3.4°, demonstrating high superhydrophobic properties. Benefitting from the complementary advantages of silicone/epoxy resin, the prepared composite coatings maintain remarkable water repellency after various harsh environmental tests, including cyclic mechanical abrasion and tape-stripping, acid-base (pH 1 and pH 14) treatment, 10 wt% NaCl (pH 7) salt solution immersion, temperature treatment, knife scratching, and long-term ultraviolet radiation treatment, showing reinforced mechanical robustness and durable anti-corrosion stability. Notably, surface hardness of 5H and optical transparency over 80% can be achieved. The simple method offers a novel approach for the large-scale preparation of multifunctional superhydrophobic coatings.

Bimetallic capture sites on porous La/Bi hydroxyl double salts for efficient phosphate adsorption: Multiple active centers and excellent selective properties.

The rapid development of modern agriculture aggravated water eutrophication. Therein, efficient and selective removal of phosphorus in water is the key to alleviating eutrophication. It is well known that lanthanum (La)-based material is a kind of outstanding phosphorus-locking agent. Therefore, improving the property of La-based adsorbents is a hot topic in this field. Herein, novel porous hydroxyl double salts (La/Bi-HDS) with bimetallic capture sites were prepared. The experimental result shows that La/Bi-HDS could maintain the high removal rate in the solution with a higher concentration of competing ions and the maximum P adsorption quantity of La/Bi-HDS attains 168.12 mg/g. Mechanistic studies supported by density functional theory (DFT) calculation demonstrate that introducing Bi3+ optimizes the electronic structure of La, reducing adsorption energy. In addition, the surface analysis shows that the introduction of Bi, which increases the pore size and volume of the material, improves the utilization efficiency of the active site. In a word, the introduction of Bi element as a strategy of killing two birds with one stone successfully improved the performance of La-based adsorbent. It provided a new direction for developing an efficient phosphorus-locking agent.

Chinese mini percutaneous nephrolithotomy for upper urinary calculi under local infiltration anesthesia.

Percutaneous nephrolithotomy is generally performed under general or regional anesthesia; however, it is rarely performed under local infiltration anesthesia (LIA). This study aimed to assess the safety and effectiveness of Chinese mini percutaneous nephrolithotomy (MPCNL) for upper urinary calculi under LIA. A retrospective analysis of 52 patients with upper urinary stones who underwent MPCNL under LIA from April 2019 to May 2022 was performed. Pethidine and Phenergan were intramuscularly injected 30 minutes preoperatively. Oxybuprocaine hydrochloride gel was applied to the urethra for lubricating and mucosal anesthesia. Ropivacaine hydrochloride and lidocaine were injected into the whole percutaneous channel for local anesthesia. An 8/9.8F ureteroscope and an 18F vacuum-assisted access sheath were applied in MPCNL. All 52 patients tolerated procedures and underwent operations successfully; none of them converted the anesthesia method or required additional analgesia. The mean visual analogue scale scores intraoperatively and at 6 hours, 24 hours, and 48 hours after surgery were 3.25 ± 0.52, 3.13 ± 0.69, 2.25 ± 0.56, and 1.58 ± 0.50, respectively. The stone free rate was 84.6%. Complications were seen in 6 (11.5%) patients, including fever in 2 patients (Clavien I), renal colic in 1 patient (Clavien I), clinically insignificant bleeding in 2 patients (Clavien I), and urinary tract infection in 1 patient (Clavien II). No severe complications were observed in any patients. Chinese MPCNL under LIA was a feasible option and achieved good outcomes in appropriately selected patients, and it may become the routine procedure for general patients.

Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Probiotic Fermentation of Herbal Medicine: Progress, Challenges, and Opportunities.

Fermentation is a processing method used in traditional Chinese medicine (TCM). However, traditional fermentation methods suffer from poor production control. In contrast, probiotic fermented herbal medicine (PFHM) offers advantages such as the use of pure strains, a controllable process, and the ability to produce a variety of active enzymes during fermentation. As a result, PFHM has become a research hotspot. This review focuses on the progress, challenges, and opportunities in the research of PFHM. The use of probiotic enzymes during fermentation alters the active ingredients of TCM, resulting in positive pharmacological effects such as increased active ingredients, reduced toxicity, new pharmacological effects, and the reuse of herbal residues. PFHM has the potential to transfer the metabolic transformation of the effective components of TCM by intestinal flora outside the body during production and preparation, which has a broad application prospect. However, due to the complexity of the chemical composition of TCM, the mechanism of PFHM requires further investigation. Finally, we discuss the prospects of industrializing PFHM, which is essential for promoting the innovation and modernization of TCM.

Hydrogen Protection Boosts the Bioactivity of Chrysanthemum morifolium Extract in Preventing Palmitate-Induced Endothelial Dysfunction by Restoring MFN2 and Alleviating Oxidative Stress in HAEC Cells.

As the most important natural antioxidants in plant extracts, polyphenols demonstrate versatile bioactivities and are susceptible to oxidation. The commonly used ultrasonic extraction often causes oxidation reactions involving the formation of free radicals. To minimize the oxidation effects during the ultrasonic extraction process, we designed a hydrogen (H2)-protected ultrasonic extraction method and used it in Chrysanthemum morifolium extraction. Hydrogen-protected extraction improved the total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and polyphenol content of Chrysanthemum morifolium water extract (CME) compared with air and nitrogen (N2) conditions. We further investigated the protective effects and mechanisms of CME on palmitate (PA)-induced endothelial dysfunction in human aorta endothelial cells (HAECs). We found that hydrogen-protected CME (H2-CME) best-prevented impairment in nitric oxide (NO) production, endothelial NO synthase (eNOS) protein level, oxidative stress, and mitochondrial dysfunction. In addition, H2-CME prevented PA-induced endothelial dysfunction by restoring mitofusin-2 (MFN2) levels and maintaining redox balance.

Patrinia villosa treat colorectal cancer by activating PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: At present, the colorectal cancer (CRC) is a malignant tumor of the colon and rectum that is often found at the junction of the two, and it will invade many visceral organs and organizations, causing very serious damage to the body of the patient. Patrinia villosa Juss. (P.V), is a well-known traditional chinese medicine (TCM), and is recorded in the Compendium of Materia Medica as a necessary article for the treatment of intestinal carbuncle. It has been incorporated into traditional cancer treatment prescriptions in modern medicine. While the mechanism of action of P.V in the treatment of CRC remains unclear. AIM OF THE STUDY: To investigate P.V in treating CRC and clarify the underlying mechanism. MATERIALS AND METHODS: This study was based on Azoxymethane (AOM) combined with the Dextran Sulfate Sodium Salt (DSS)-induced CRC mouse model to clarify the pharmacological effects of P.V. The mechanism of action was found by metabolites and metabolomics. The rationality of metabolomics results was verified through the clinical target database of network pharmacology, and find the upstream and downstream target information of relevant action pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using quantitative PCR (q-PCR) and Western blot. RESULTS: The number and the diameter of tumors were decreased when mice were treated with P.V. P.V group section results showed newly generated cells which improved the degree of colon cell injury. Pathological indicators presented a trend of recovery to normal cells. Compared to the model group, P.V groups had significantly lower levels of the CRC biomarkers CEA, CA19-9, and CA72-4. Through the evaluation of metabolites and metabolomics, it was found that a total of 50 endogenous metabolites had significant changes. Most of these are modulated and recovered after P.V treatment. It alters glycerol phospholipid metabolites, which are closely related to PI3K target, suggesting that P.V can treat CRC though the PI3K target and PI3K/Akt signaling pathway. q-PCR and Western blot results also verified that the expression of VEGF, PI3K, Akt, P38, JNK, ERK1/2, TP53, IL-6, TNF-α and Caspase-3 were significantly decreased, whereas that of Caspase-9 was increased after treatment. CONCLUSION: P.V is dependent on PI3K target and PI3K/Akt signaling pathway for CRC treatment.

Application of KHSO5 for remediation of soils polluted by organochlorides: A comprehensive study on the treatment's efficacy, environmental implications, and phytotoxicity.

Soil pollution caused by complex organochloride mixtures has been increasing in many parts of the world in recent years; as a result, countless numbers of people are exposed to dangerous pollutions; hence, the treatment of organochlorides-polluted soils is gaining considerable attention. In this study, the potential of unactivated peroxymonosulfate (KHSO5) in remediating soil co-contaminated with trichlorophenol, para-dichlorobenzene, and para-chloro-meta-cresol was investigated. In addition, the treatment's collateral effect on critical soil properties was explored. The result revealed that treating 10 g of soil with 20 mL of 5 mM KHSO5 for 60 min could oxidize 70.49% of the total pollutants. The pH of the soil was decreased following the treatment. The significant decrease, (p < 0.05), in the soil organic matter following the remediation has affected cation exchange capacity, and available nitrogen. It was also observed that the treatment reduced the ß-glucosidase, urease, invertase, and cellulase activities significantly, (p < 0.05). The treatment, on the other hand, brought negligible effects on available phosphorus, available potassium, and particle size distribution. The phytotoxicity tests, which included seed germination and root elongation and soil respiration tests revealed that the treatment did not leach toxins into the treated soil. The treatment method was found to be relatively ecofriendly and cost effective.

Method for real-time prediction of cutter wear during shield tunnelling: A new wear rate index and MCNN-GRU.

Cutter wear is one of the key factors influencing construction efficiency during shield tunnelling. Prediction of cutter wear can improve construction efficiency by reducing the times of cutter inspections in engineering practice. Evaluation of cutter life is vital for cutter wear prediction, however, existing cutter life indices can only estimate the health condition of all cutters on cutterhead on a holistic basis. A new index was proposed to evaluate cutter wear located at a specific installation position on cutterhead. A deep learning model integrating the index was developed for the estimation of accumulated cutter wear during real time shield tunnelling. The new index can be obtained by monitored field parameters and can predict cutter wear with historical wear patterns. The input and output data samples were reshaped for multi-step prediction. A shield tunnelling section in Guangzhou weathered granite was used for validation. The proposed method can help reduce the cost of cutter replacement by reducing the times of machine interventions. The method article is a companion paper to the original article [1].•Proposed index for prediction of cutter wear rate.•Deep learning model of 1D-CNN and GRU.•Multi-step cutter wear prediction.

Qing-Xin-Jie-Yu Granule inhibits ferroptosis and stabilizes atherosclerotic plaques by regulating the GPX4/xCT signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Xin-Jie-Yu Granule (QXJYG) is an integrated traditional Chinese medicine formula used to treat atherosclerotic (AS) cardiovascular diseases. A randomized controlled trial found that QXJYG reduced cardiovascular events and experiments also verified that QXJYG attenuated AS by remodeling the intestinal flora. AIM OF THE STUDY: To determine whether QXJYG would attenuate AS and plaque vulnerability by regulating ferroptosis in high-fat diet-induced atherosclerotic ApoE-/- mice and to investigate the effects of QXJYG on macrophage ferroptosis in RAS-selective lethal 3 (RSL3)-induced J744A.1 cells. METHODS: AS models in ApoE-/- mice and RSL3-induced ferroptosis in J744A.1 cells were established to measure the protective and anti-ferroptotic effects of QXJYG in vivo and in vitro. The glutathione peroxidase 4 (GPX4)/cystine glutamate reverse transporter (xCT) signal pathway was examined by immunohistochemistry and western blotting. RESULTS: QXJYG attenuated AS progression and plaque vulnerability. Characteristic morphological changes of ferroptosis in the QXJYG-treated animals were rare. Total iron was significantly lower in the QXJYG group than in the model group (P < 0.05); QXJYG suppressed the lipid peroxidation (LPO) levels (malondialdehyde), enhanced the antioxidant capacity (superoxide dismutase and glutathione), and reduced inflammatory factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor-α) associated with ferroptosis. Expression of GPX4/xCT in aorta tissues was remarkably increased in the QXJYG group. QXJYG inhibited ferroptosis in J744A.1 macrophages disturbed using RSL3. The Fe2+, LPO, and reactive oxygen species levels were lower in the QXJYG group than in the RSL3 group (P < 0.05). The QXJYG group showed higher expression of the GPX4/xCT signal pathway. CONCLUSION: QXJYG inhibits ferroptosis in vulnerable AS plaques partially via the GPX4/xCT signaling pathway.