Merging total synthesis and NMR technology for deciphering the realistic structure of natural 2,6-dideoxyglycosides.

The structural identification and efficient synthesis of bioactive 2,6-dideoxyglycosides are daunting challenges. Here, we report the total synthesis and structural revision of a series of 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx, which feature pregnane steroidal aglycones bearing an 18,20-lactone and glycans consisting of 2,6-dideoxy-3-O-methyl-ß-pyranose residues, including ecdysosides A, B, and F and ecdysantheroside A. All the eight possible 2,6-dideoxy-3-O-methyl-ß-pyranoside stereoisomers (of the proposed ecdysantheroside A) have been synthesized that testify the effective gold(I)-catalyzed glycosylation methods for the synthesis of various 2-deoxy-ß-pyranosidic linkages and lays a foundation via nuclear magnetic resonance data mapping to identify these sugar units which occur promiscuously in the present and other natural glycosides. Moreover, some synthetic natural compounds and their isomers have shown promising anticancer, immunosuppressive, anti-inflammatory, and anti-Zika virus activities.

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Assessing ammonium pollution and mitigation measures through a modified watershed non-point source model.

Watershed water quality modeling is a valuable tool for managing ammonium (NH4+) pollution. However, simulating NH4+ pollution presents unique challenges due to the inherent instability of NH4+ in natural environment. This study modified the widely-used Soil and Water Assessment Tool (SWAT) model to simulate non-point source (NPS) NH4+ processes, specifically incorporating the simulation of land-to-water NH4+ delivery. The Jiulong River Watershed (JRW) is the study area, a coastal watershed in Southeast China with substantial sewage discharge, livestock farming, and fertilizer application. The results demonstrate that the modified model can effectively simulate the NPS NH4+ processes. It is recommended to use multiple sets of observations to calibrate NH4+ simulation to enhance model reliability. Despite constituting a minor proportion (5.6 %), point source inputs significantly contribute to NH4+ load at watershed outlet (32.4∼51.9 %), while NPS inputs contribute 15.3∼17.3 % of NH4+ loads. NH4+ primarily enters water through surface runoff and lateral flow, with negligible leaching. Average NH4+ land-to-water delivery rate is about 2.35 to 2.90 kg N/ha/a. High delivery rates mainly occur at agricultural areas. Notably, proposed NH4+ mitigation measures, including urban sewage treatment enhancement, livestock manure management improvement, and fertilizer application reduction, demonstrate potential to collectively reduce the NH4+ load at watershed outlet by 1/4 to 1/3 and significantly enhance water quality standard compliance frequency. Insights gained from modeling experience in the JRW offer valuable implications for NH4+ modeling and management in regions with similar climates and significant anthropogenic nitrogen inputs.

[Effect and mechanism of Jiedu Huoxue Decoction in regulating YAP/ACSL4 pathway to inhibit ferroptosis in treatment of acute kidney injury].

Jiedu Huoxue Decoction(JDHX), first recorded in the Correction on Errors in Medical Works by WANG Qing-ren, is an effective formula screened out from ancient formulas by the traditional Chinese medicine(TCM) master ZHANG Qi to treat acute kidney injury(AKI) caused by heat, toxicity, stasis, and stagnation. This paper elucidated the therapeutic effect of JDHX on AKI and probed into the potential mechanism from ferroptosis. Thirty-two male C57BL/6 mice were randomized into four groups(n=8): normal, model, and low-and high-dose JDHX. Since the clinical treatment of AKI depends on supportive or alternative therapies and there is no specific drug, this study did not include a positive drug group. The low dose of JDHX corresponded to half of clinically equivalent dose, while the high dose corresponded to the clinically equivalent dose. Mice were administrated with JDHX by gavage daily for 7 consecutive days, while those in the normal group and the model group were administered with the corresponding volume of distilled water. On day 5 of drug administration, mice in other groups except the normal group were injected intraperitoneally with cisplatin solution at a dose of 20 mg·kg~(-1) to induce AKI, and the normal group was injected with saline. All of the mice were sacrificed 72 h after modeling, blood and kidney samples were collected for subsequent analysis. The levels of serum creatine(Scr) and blood urea nitrogen(BUN) were measured by the commercial kits. The expression level of kidney injury molecule 1(KIM-1) in the serum was measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin(HE) staining, periodic acid-Schiff(PAS) staining, and Prussian blue staining were employed to observe the pathological changes, glycogen deposition, and iron deposition, respectively, in the renal tissue. In addition, the levels of glutathione(GSH), superoxide dismutase(SOD), and catalase(CAT) in the renal tissue were examined by biochemical colorimetry. Western blot was performed to determine the protein levels of acyl-CoA synthetase long chain family member 4(ACSL4), lysophosphatidylcholine acyltransferase 3(LPCAT3), and Yes-associated protein(YAP, a key molecule in the Hippo pathway) in the renal tissue. Immunohistochemistry was then employed to detect the location and expression of YAP in the renal tissue. Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was performed to measure the mRNA levels of ACSL4 and glutathione peroxidase 4(GPX4). Compared with the normal group, the model group showed elevated serum levels of Scr, BUN, and KIM-1. In the AKI model group, the tubular epithelial cells underwent atrophy and necrotic detachment, disappearance of brush border, and some tubules became protein tubules or experienced vacuole-like degeneration. In addition, this group presented widening of the interstitium or even edema, increased renal tubule injury score, and obvious glycogen and iron deposition in parts of the renal tissue. Moreover, the model group had lower GSH, SOD, and CAT levels, higher ASCL4 and LPCAT3 levels, and lower GPX4 expression and higher YAP expression than the normal group. Compared with the model group, high dose of JDHX effectively protected renal function, lowered the levels of Scr, BUN and KIM-1, alleviated renal pathological injury, reduced glycogen and iron deposition, and elevated the GSH, SOD, and CAT levels in the renal tissue. Furthermore, JDHX down-regulated the protein levels of ACSL4, LPCAT3, and YAP and up-regulated the level of GPX4, compared with the model group. In conclusion, JDHX can protect mice from cisplatin-induced AKI by inhibiting ferroptosis via regulating the YAP/ACSL4 signaling pathway.

[Mechanism of acteoside in prevention and treatment of gouty arthritis based on liver metabolomics].

This study aims to reveal the effect of acteoside on gouty arthritis(GA) in rats based on liver metabolomics. The ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to search for the potential biomarkers and metabolic pathways. SD rats were randomly assigned into blank, model, colchicine(0.3 mg·kg~(-1)), and high-, medium-, low-dose(200, 100, and 50 mg·kg~(-1), respectively) acteoside groups(n=7). The rats were administrated once a day for 7 continuous days. Monosodium urate(MSU) was used to induce GA model in rats during administration. The degree of joint swelling and pathological changes of synovial tissue in rats were observed, and the levels of interleukin(IL)-1ß, IL-18 and tumor necrosis factor(TNF)-α in the synovial tissue of rats were measured. UPLC-Q-TOF-MS was employed to collect rat liver data, and Progenesis QI and EZ info were used for data analysis. Human Metabolomics Database(HMDB) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were employed to predict the potential biomarkers and metabolic pathways. The results showed that acteoside alleviated joint swelling, reduced synovial tissue damage, and lowered the levels of inflammatory cytokines in GA rats. A total of 19 common biomarkers were identified, 17 of which can be regulated by acteoside. Seven metabolic pathways were enriched, such as glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism, among which glycerophospholipid metabolism was strongly disturbed. The metabolomics analysis suggested that acteoside may down-regulate the expression of inflammatory cytokines and alleviate the symptoms of GA rats by regulating glycerophospholipid metabolism, linoleic acid metabolism, and taurine and hypotaurine metabolism. The findings provide a reference for future research and development of acteoside.

Multiclass classification of motor imagery tasks based on multi-branch convolutional neural network and temporal convolutional network model.

Motor imagery (MI) is a cognitive process wherein an individual mentally rehearses a specific movement without physically executing it. Recently, MI-based brain-computer interface (BCI) has attracted widespread attention. However, accurate decoding of MI and understanding of neural mechanisms still face huge challenges. These seriously hinder the clinical application and development of BCI systems based on MI. Thus, it is very necessary to develop new methods to decode MI tasks. In this work, we propose a multi-branch convolutional neural network (MBCNN) with a temporal convolutional network (TCN), an end-to-end deep learning framework to decode multi-class MI tasks. We first used MBCNN to capture the MI electroencephalography signals information on temporal and spectral domains through different convolutional kernels. Then, we introduce TCN to extract more discriminative features. The within-subject cross-session strategy is used to validate the classification performance on the dataset of BCI Competition IV-2a. The results showed that we achieved 75.08% average accuracy for 4-class MI task classification, outperforming several state-of-the-art approaches. The proposed MBCNN-TCN-Net framework successfully captures discriminative features and decodes MI tasks effectively, improving the performance of MI-BCIs. Our findings could provide significant potential for improving the clinical application and development of MI-based BCI systems.

Developing Ganoderma lucidum as a next-generation cell factory for food and nutraceuticals.

Ganoderma lucidum holds a colossal reservoir of hydrolytic enzymes and therapeutic compounds and can be a sustainable source of proteins and bioactive compounds. Its metabolic versatility, propelled by its rich genome content, provides excellent biosynthetic machinery for innovation-driven pathway engineering. However, robust regulatory networks and low frequency of homologous recombination are critical bottlenecks that limit the development of molecular tools and precise genetic markers for biomanufacturing innovations in this organism. Modern synthetic biology provides tools that could help to accelerate precise multiple gene targeting and editing and untangling the biosynthetic machinery of G. lucidum. This review provides insight into molecular strategies to unwind the regulatory bottlenecks and transform G. lucidum into efficient cell factories for food and nutraceuticals.

The Causal Association between Alcohol, Smoking, Coffee Consumption, and the Risk of Arthritis: A Meta-Analysis of Mendelian Randomization Studies.

Objective: To evaluate the genetic causality between alcohol intake, smoking, coffee consumption, and arthritis. Methods: Mendelian randomization (MR) studies with alcohol, smoking, and coffee consumption behaviors as exposures, and osteoarthritis (OA) and rheumatoid arthritis (RA) as outcomes were retrieved from up to July 2023. Two researchers with relevant professional backgrounds independently assessed the quality and extracted data from the included studies. Meanwhile, we applied MR analyses of four lifestyle exposures and five arthritis outcomes (two for OA and three for RA) with gene-wide association study (GWAS) data that were different from the included studies, and the results were also included in the meta-analysis. Statistical analyses were performed using Stata 16.0 and R software version 4.3.1. Results: A total of 84 studies were assessed. Of these, 11 were selected for meta-analysis. As a whole, the included studies were considered to be at a low risk of bias and were of high quality. Results of the meta-analysis showed no significant genetic causality between alcohol intake and arthritis (odds ratio (OR): 1.02 (0.94-1.11)). Smoking and arthritis had a positive genetic causal association (OR: 1.44 (1.27-1.64)) with both OA (1.44 (1.22-1.71)) and RA (1.37 (1.26-1.50)). Coffee consumption and arthritis also had a positive genetic causal association (OR: 1.02 (1.01-1.03)). Results from the subgroup analysis showed a positive genetic causality between coffee consumption and both OA (OR: 1.02 (1.00-1.03)) and RA (OR: 1.56 (1.19-2.05)). Conclusion: There is positive genetic causality between smoking and coffee consumption and arthritis (OA and RA), while there is insufficient evidence for genetic causality between alcohol intake and arthritis.

Dysregulated neural activity between the thalamus and cerebral cortex mediates cortical reorganization in cervical spondylotic myelopathy.

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM.

Improving bridge effect to overcome interspecific hybrid sterility by pyramiding hybrid sterile loci from Oryza glaberrima.

In order to evaluate the genetic effect caused by hybrid sterile loci, NILs with O. glaberrima fragment at six hybrid sterile loci under O. sativa genetic background (single-locus-NILs) were developed; two lines harboring two hybrid sterile loci, one line harboring three hybrid sterile loci were further developed. A total of nine NILs were used to test cross with O. sativa recurrent parent, and O. glaberrima accessions respectively. The results showed that the sterility of pollen grains in F1 hybrids deepened with the increase of the number of hybrid sterile loci, when the nine lines test crossed with O. sativa recurrent parent. The F1 hybrids were almost completely sterile when three hybrid sterile loci were heterozygeous. On the other hand, the single-locus-NILs had limited bridge effect on improving pollen grain fertility of interspecific hybrids. Compared single-locus-NILs, the multiple-loci-NILs showed increasing effect on pollen fertility when test crossing with O. glaberrima accessions. Further backcrossing can improve the fertility of pollen grain and spikelet of interspecific hybrids. The optimal solution to improve the fertility of interspecific hybrid can be utilization of pyramiding bridge parent plus backcrossing. This report has potential for understanding the nature of interspecific hybrid sterility, and overcoming the interspecific hybrid F1 pollen grain sterility between O. sativa and O. glaberrima.

Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer.

In this case report, a 53-year-old woman was diagnosed with severe NE after receiving chemotherapy for breast cancer. The patient with breast cancer was treated with a single cycle of docetaxel (140 mg) + epirubicin (130 mg) + cyclophosphamide (0.9 g) chemotherapy. However, the woman presented with symptoms of fatigue and diarrhea 5 days later accompanied with severe neutropenia according to the routine blood test. The computed tomography examination displayed the thickening and swelling of the colorectal wall. After the diagnosis of NE, the woman received antibiotics and supportive treatment, but her symptoms were not improved. The Chinese herbal medicine (CHM) diagnostic pattern was then designed for the patient. The patient was administered with two CHM decoctions. One decoction contained 24 kinds of herbal materials, and the other one was called pure ginseng decoction. These two decoctions were administered to the patient 2 or 3 times per day to tonify the spleen, nourish Qi and blood, and remove phlegm and damp heat symptoms. After the CHM treatment lasting for 10 days, the symptoms of the patient were improved, and she was discharged. In conclusion, CHM treatment played an indispensable role in curing the woman with chemotherapy-induced NE.

The long-term effect of modulated acoustic stimulation on alteration in EEG brain network of chronic tinnitus patients: An exploratory study.

Acoustic stimulation is one of the most influential techniques for distressing tinnitus, while how it functions to reverse neural changes associated with tinnitus remains undisclosed. In this study, our objective is to investigate alterations in brain networks to shed light on the enigma of acoustic intervention for tinnitus. We designed a 75-day long-term acoustic intervention experiment, during which chronic tinnitus patients received daily modulated acoustic stimulation with each session lasting 15 days. Every 15 days, professional tinnitus assessments were conducted, collecting both electroencephalogram (EEG) and tinnitus handicap inventory (THI) data from the patients. Thereafter, we investigated the changes in EEG network organizations during continuous acoustic stimulation and their progressive evolution throughout long-term therapy, alongside exploring the associations between the evolving changes of the network alterations and THI. Our current study findings reveal reorganization in alpha/beta long-range frontal-parietal-occipital connections as well as local frontal and parietal-occipital regions induced by acoustic stimulation. Furthermore, we observed a decrease in modulation effects as therapy sessions progressed. These alterations in brain networks reflect the reversal of tinnitus-related neural activities, particularly distress and perception; thus contributing to tinnitus rehabilitation through long-term modulation effects. This study provides unique insights into how long-term acoustic intervention affects the network organizations of tinnitus patients and deepens our understanding of the pathophysiological mechanisms underlying tinnitus rehabilitation.

Study on Efficacy of Non-cutting Traction Seton Technique on Perianal Abscess.

Objective: Investigating the therapeutic effect of the non-cutting traction seton technique on perianal abscess. Methods: The clinical data of 70 patients with perianal abscesses diagnosed and treated by the Department of Anorectal Surgery of University Affiliated Hospital from January 2020 to December 2021 were collected, and conducted a retrospective study on them, of which 40 cases were treated with non-cut traction seton in the study group, and other 30 cases were treated with perianal abscess incision and drainage in the control group. The perioperative indexes (operation time, intraoperative bleeding volume, time of postoperative dressing change, time of postoperative granulation tissue formation, postoperative defecation-control ability, postoperative pain score, postoperative wound cleanliness) and follow-up indexes (wound healing time, incontinence Wexner score, recurrence rate, patient satisfaction) were compared between these two groups. Results: The operation time of the study group was more than that of the control group, and the difference was not statistically significant (P > .05). The intraoperative bleeding volume, time of postoperative dressing change, time of postoperative granulation tissue formation, the scores on postoperative defecation-control ability, the scores on postoperative wound cleanliness, postoperative complication rate, postoperative pain score, time of wound healing, incontinence Wexner score, and recurrence rate all from the study group were better than those in the control group. The patient satisfaction from the study group was higher than that in the control group, and the above differences were statistically significant (P < .05). Conclusion: Non-cutting traction suture technique has obvious advantages in the treatment of perianal abscess, shortening wound healing time and granulation tissue formation time, reducing intraoperative blood loss and postoperative complication rate, etc. It provides a reference for clinical treatment of perianal abscess.

Comprehensive genomic analysis of puerarin in inhibiting bladder urothelial carcinoma cell proliferation and migration.

BACKGROUND: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms. METHODS: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation. RESULTS: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218µmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients. CONCLUSION: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

Physiological and metabolomic analyses reveal that Fe3O4 nanoparticles ameliorate cadmium and arsenic toxicity in Panax notoginseng.

Heavy metal(loid)-contaminated available arable land seriously affects crop development and growth. Engineered nanomaterials have great potential in mitigating toxic metal(loid) stress in plants. However, there are few details of nanoparticles (NPs) involved in Panax notoginseng response to cadmium (Cd) and arsenic (As). Herein, integrating physiological and metabolomic analyses, we investigated the effects of Fe3O4 NPs on plant growth and Cd/As responses in P. notoginseng. Cd/As treatment caused severe growth inhibition. However, foliar application of Fe3O4 NPs increased beneficial elements in the roots and/or leaves, decreased Cd/As content by 10.38% and 20.41% in the roots, reduced membrane damage and regulated antioxidant enzyme activity, thereby alleviating Cd/As-induced growth inhibition, as indicated by increased shoot fresh weight (FW), the rootlet length and root FW by 40.14%, 15.74%, and 46.70% under Cd stress and promoted the shoot FW by 27.00% under As toxicity. Metabolomic analysis showed that 227 and 295 differentially accumulated metabolites (DAMs) were identified, and their accumulation patterns were classified into 8 and 6 clusters in the roots and leaves, respectively. Fe3O4 NPs altered metabolites significantly involved in key pathways, including amino sugar and nucleotide sugar metabolism, flavonoid biosynthesis and phenylalanine metabolism, thus mediating the trade-off between plant growth and defense under stress. Interestingly, Fe3O4 NPs recovered more Cd/As-induced DAMs to normal levels, further supporting that Fe3O4 NPs positively affected seedling growth under metal(loid)s stress. In addition, Fe3O4 NPs altered terpenoids when the seedlings were subjected to Cd/As stress, thus affecting their potential medicinal value. This study provides insights into using nanoparticles to improve potential active ingredients of medicinal plants in metal(loid)-contaminated areas.

Clerodendranthus spicatus inhibits epithelial-mesenchymal transition of renal tubular cells through the NF-κB/Snail signalling pathway in hyperuricaemia nephropathy.

CONTEXT: Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN). OBJECTIVE: To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN. RESULTS: HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 µg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function. DISCUSSION AND CONCLUSIONS: These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.

Advanced low-strength wastewater treatment, side-stream phosphorus recovery, and in situ sludge reduction with aerobic granular sludge.

Modern paradigm has upgraded wastewater treatment plants (WWTPs) to water resources recovery facilities (WRRFs), where aerobic granular sludge (AGS) is a sewage treatment technology with promising phosphorus recovery (PR) potential. Herein, the AGS-based simultaneous nitrification, denitrification, and phosphorus removal coupling side-stream PR process (AGS-SNDPRr) was developed with municipal wastewater. Results revealed that AGS always maintained good structural stability, and pollutant removal was unaffected and effective after 40 days of anaerobic phosphorus-rich liquid extraction (fixed rate of 30%). The AGS-SNDPRr achieved a stable phosphorus recovery efficiency of 63.40%, and the side-stream PR further exaggerated in situ sludge reduction by 7.7-10%. Apart from responses of extracellular polymeric substances (EPS), the Matthew effect of typical denitrifying glycogen accumulating organisms (DGAOs) Candidatus_Competibacter up to 67.40% mainly contributed to enhanced performance of this new process. This study demonstrated a new approach for simultaneous advanced wastewater treatment, phosphorus recovery, and excess sludge minimization.

Unsupervised Noise Reductions for Gravitational Reference Sensors or Accelerometers Based on the Noise2Noise Method.

Onboard electrostatic suspension inertial sensors are important applications for gravity satellites and space gravitational-wave detection missions, and it is important to suppress noise in the measurement signal. Due to the complex coupling between the working space environment and the satellite platform, the process of noise generation is extremely complex, and traditional noise modeling and subtraction methods have certain limitations. With the development of deep learning, applying it to high-precision inertial sensors to improve the signal-to-noise ratio is a practically meaningful task. Since there is a single noise sample and unknown true value in the measured data in orbit, odd-even sub-samplers and periodic sub-samplers are designed to process general signals and periodic signals, and adds reconstruction layers consisting of fully connected layers to the model. Experimental analysis and comparison are conducted based on simulation data, GRACE-FO acceleration data, and Taiji-1 acceleration data. The results show that the deep learning method is superior to traditional data smoothing processing solutions.

[Spatial Distribution of Nitrogen and Phosphorus Nutrients in the Main Stream and Typical Tributaries of Tuojiang River and Fujiang River].

The Tuojiang River and Fujiang River, two important tributaries of the upper reaches of the Yangtze River, have serious water pollution problems, among which nitrogen (N) and phosphorus (P) are the most important pollutants. Therefore, the aim of this study was to identify the influencing factors of water quality in different spaces and provide a scientific basis for the prevention and control of surface water pollution in the upper reaches of the Yangtze River and its tributaries. Water samples of trunk and tributaries in the Tuojiang River and Fujiang River were collected, and the spatial distribution characteristics of water N and P were analyzed. The results showed that the Tuojiang River and Fujiang River showed serious pollution of total nitrogen (TN), with a water quality worse Ⅴ-section proportion as high as 94% and 50%, respectively. Both rivers showed that TN and TP concentrations in the tributaries were higher than those in the main stream. For both rivers, total phosphorus (TP), with moderate pollution, was mainly concentrated in Ⅱ, Ⅲ, and Ⅳ class water quality, whereas the P pollution was more serious for the Fujiang River compared to that of the Fujiang River. For the Tuojiang River, nitrate nitrogen (NN) concentration from upstream to downstream showed a trend of decreasing after the first increase, with the maximum concentration of ammonium nitrogen (AN) exhibiting at the upstream site. In particular, TP concentration increased significantly after rivers flowed through a city. For the Fujiang River trunk stream, TN and NN concentration exhibited a gradually increasing trend from the middle to lower reaches. Generally, our study revealed that TN, TP, and NN in the rivers were affected by water pH and water temperature (T). Therefore, the control of N and P pollution in rivers should pay attention to the influence of water environmental factors.

Lycium ruthenicum Murr. anthocyanins inhibit hyperproliferation of synovial fibroblasts from rheumatoid patients and the mechanism study powered by network pharmacology.

BACKGROUND: Rheumatoid arthritis (RA), is a typical autoimmune disease affecting nearly 1% of the world's population. The dysfunctional hyperproliferation of synovial fibroblast (SF) in articular cartilage of RA patients is considered as the essential etiology. Traditional chemotherapeutic agents for RA treatment are imperfect for their high cost and unpredictable side-effects. L. ruthenicum anthocyanins (LRAC) is a natural product that of potential for therapeutic application against RA. METHODS: LRAC was characterized by UPLC-MS/MS. Bioinformatics analyses based on network pharmacology were applied to predict the potential targets of LRAC, and to select DEGs (differentially expressed genes) caused by RA pathogenesis from GSE77298. Interactions between LRAC and the predicted targets were evaluated by molecular docking. Effects of LRAC on SFs from RA patients were examined by in vitro assays, which were analyzed by flow cytometry and western blotting (WB). RESULTS: LRAC was able to inhibit the abnormal proliferation and aggressive invasion of SFs from RA patients. LRAC was mainly constituted by petunidin (82.7%), with small amount of delphinidin (12.9%) and malvidin (4.4%) in terms of anthocyanidin. Bioinformatics analyses showed that in 3738 RA-related DEGs, 58 of them were collectively targeted by delphinidin, malvidin and delphinidin. AR, CDK2, CHEK1, HIF1A, CXCR4, MMP2 and MMP9, the seven hub genes constructed a central network mediating the signal transduction. Molecular docking confirmed the high affinities between the LRAC ligands and the protein receptors encoded by the hub genes. The in vitro assays validated that LRAC repressed the growth of RASF by cell cycle arresting and cell invasion paralyzing (c-Myc/p21/CDK2), initiating cell apoptosis (HIF-1α/CXCR4/Bax/Bcl-2), and inducing pyroptosis via ROS-dependent pathway (NOX4/ROS/NLRP3/IL-1ß/Caspase-1). CONCLUSION: LRAC can selectively inhibit the proliferation of RASFs, without side-effecting immunosuppression that usually occurred for RA treatment using MTX (methotrexate). These findings demonstrate the potential application of LRAC as a phytomedicine for RA treatment, and provide a valid approach for exploring natural remedies against autoimmune diseases.