Chromium(VI) Adsorption and Reduction in Soils under Anoxic Conditions: The Relative Roles of Iron (oxyhr)oxides, Iron(II), Organic Matters, and Microbes.

Chromium (Cr) transformation in soils mediated by iron (Fe) (oxyhr)oxides, Fe(II), organic matter (OM), and microbes is largely unexplored. Here, their coupling processes and mechanisms were investigated during anoxic incubation experiments of four Cr(VI) spiked soil samples with distinct physicochemical properties from the tropical and subtropical regions of China. It demonstrates that easily oxidizable organic carbon (EOC, 55-84%) and microbes (16-48%) drive Cr(VI) reduction in soils enriched with goethite and/or hematite, among which in dryland soils microbial sulfate reduction may also be involved. In contrast, EOC (38 ± 1%), microbes (33 ± 1%), and exchangeable and poorly crystalline Fe (oxyhr)oxide-associated Fe(II) (29 ± 3%) contribute to Cr(VI) reduction in paddy soils enriched with ferrihydrite. Additionally, exogenous Fe(II) and microbes significantly enhance Cr(VI) reduction in ferrihydrite- and goethite-rich soils, and Fe(II) greatly promotes but microbes slightly inhibit Cr passivation. Both Fe(II) and microbes, especially the latter, promote OM mineralization and result in the most substantial OM loss in ferrihydrite-rich paddy soils. During the incubation, part of the ferrihydrite converts to goethite but microbes may hinder the transformation. These results provide deep insights into the geochemical fates of redox-sensitive heavy metals mediated by the complicated effects of Fe, OM, and microbes in natural and engineered environments.

Solanapyrone analogues from endophytic Nigrospora sphaerica MZW-A associated with the endangered conifer Pinus wangii.

Eight previously undescribed solanapyrone analogues, sphasolanapyrones A-H (1-8), together with four structurally related known compounds (9-12) were obtained from the solid fermentation of Nigrospora sphaerica MZW-A, an endophytic fungus isolated from the fresh branches of the endangered conifer Pinus wangii. This study represents the first investigation on the secondary metabolites of endophytic fungus associated with this precious plant. The structures and absolute configurations of compounds 1-8 were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. 1 and 2 are first examples of 3,4-vic diol solanapyrone analogues, whereas 7 and 8 are rare 17-nor-solanapyrones. Among these isolates, 3, 4, 5, and 11 showed weak inhibitory against Staphylococcus aureus. In addition, compound 5 displayed weak cytotoxic effects against several tumor cell lines.

Combining Network Pharmacology and Transcriptomics to Investigate the Mechanisms of Yujiang Paidu Decoction in the Treatment of Chronic Rhinosinusitis with Nasal Polyps.

Background: Yujiang Paidu Decoction (YJPD) has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. Purpose: This study aimed to elucidate the potential mechanism of action of YJPD in the treatment of CRSwNP based on network pharmacology, transcriptomics and experiments. Methods: A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioral tests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation. Results: Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro. Conclusion: YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.

Bioactive polyketides and tryptophol alkaloids from the endophytic fungus Botryosphaeria dothidea LE-07 of Chinese tulip tree.

Two new tetraketide-derived phenol rhamnosides [botryrhamnosides A (1) and B (2)] and a new rhamnosylated tryptophol alkaloid (botryrhamnoside C, 3), along with seven related known compounds (4-10) were isolated from the solid culture of Botryosphaeria dothidea LE-07, an endophytic fungus residing in the leaves of the rare medicinal plant Chinese tulip tree (Liriodendron chinense). Their structures with the absolute configurations were determined by a combination of spectroscopy methods, comparing specific rotations, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compounds 1 and 2 are rare tetraketide-derived resorcinols incorporating a l-rhamnose moiety, while 3 represents the first example of rhamnose-bound tryptophol derivatives produced by microorganisms. These metabolites were evaluated in vitro for their antimicrobial and anti-neuroinflammation activities. The rhamnosylated derivatives 1-5 displayed potent antibacterial activity against Escherichia coli, with MIC values in the range of 8-16 µg/mL. Compound 2 attenuated neuroinflammation in lipopolysaccharide (LPS)-induced BV-2 microglial cells, by decreasing the level of pro-inflammatory mediators [nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6)] and down-regulating the mRNA expression of inducible nitric oxide synthase (iNOS). In addition, compound 8 exhibited remarkable inhibitory effect against the ATP-citrate lyase (ACL), an emerging drug target for hyperlipidemia and related glycolipid metabolic disorders, with an IC50 value of 5.32 µM.

Generic phosphate affinity constants of the CD-MUSIC-eSGC model to predict phosphate adsorption and dominant speciation on iron (hydr)oxides.

Estimating the availability of phosphorus in soils and sediments is complicated by the diverse mineralogical properties of iron (hydr)oxides that control the environmental fate of phosphorus. Despite various surface complexation models have been developed, lack of generic phosphate affinity constants (logKPO4s) for iron (hydr)oxides hinders the prediction of phosphate adsorption to iron (hydr)oxides in nature. The aim of this work is to derive generic logKPO4s for the Charge Distribution-Multisite Complexation extended-Stern-Gouy-Chapman (CD-MUSIC-eSGC) model using a large phosphate adsorption database and previously derived generic protonation parameters. The optimized logKPO4s of goethite, hematite and ferrihydrite are located in a much narrower range than those in the RES3T database. Specifically, the logKPO4 ranges of FeOPO3, FeOPO2OH, FeOPO(OH)2, (FeO)2PO2, and (FeO)2POOH complexes were 17.40-18.00, 24.20-27.40, 27.90-29.80, 26.50-29.60, and 30.70-33.40, respectively. A simplified CD-MUSIC-eSGC model with species FeOPO2OH and (FeO)2PO2 and generic logKPO4 values 26.0 ± 0.9 and 27.9 ± 0.8, respectively, provides an accurate prediction of phosphate adsorption and dominant speciation to the iron (hydr)oxides at environmental pH and phosphate levels. For ferrihydrite at low pH and high phosphate levels the species FeOPO(OH)2 and (FeO)2POOH cannot be neglected. The simplified model expands the application boundaries of CD-MUSIC-eSGC model in predicting the phosphate adsorption on natural iron (hydr)oxides without laborious characterization.

Shizukaol C alleviates trimethylamine oxide-induced inflammation through activating Keap1-Nrf2-GSTpi pathway in vascular smooth muscle cell.

BACKGROUND: Cardiovascular disease is one of the main causes of global mortality, and there is an urgent need for effective treatment strategies. Gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) promotes the development of cardiovascular diseases, and shizukaol C, a natural sesquiterpene isolated from Chloranthus multistachys with various biological activities, might exhibit beneficial role in preventing TMAO-induced vascular inflammation. PURPOSE: The purpose of this study was to investigate the anti-inflammatory effects and the underlying mechanisms of shizukaol C on TMAO-induced vascular inflammation. METHODS: The effect and underlying mechanism of shizukaol C on TMAO-induced adhesion molecules expression, bone marrow-derived macrophages (BMDM) adhesion to VSMC were evaluated by western blot, cell adhesion assay, co-immunoprecipitation, immunofluorescence assay, and quantitative Real-Time PCR, respectively. To verify the role of shizukaol C in vivo, TMAO-induced vascular inflammation model were established using guidewire-induced injury on mice carotid artery. Changes in the intima area and the expression of GSTpi, VCAM-1, CD68 were examined using haematoxylin-eosin staining, and immunofluorescence assay. RESULTS: Our data demonstrated that shizukaol C significantly suppressed TMAO-induced adhesion molecule expression and the bone marrow-derived macrophages (BMDM) adhesion in vascular smooth muscle cells (VSMC). Mechanically, shizukaol C inhibited TMAO-induced c-Jun N-terminal kinase (JNK)-nuclear factor-kappa B (NF-κB)/p65 activation, and the JNK inhibition was dependent on the shizukaol C-mediated glutathione-S-transferase pi (GSTpi) expression. By further molecular docking and protein-binding analysis, we demonstrated that shizukaol C directly binds to Keap1 to induce Nrf2 nuclear translocation and upregulated GSTpi expression. Consistently, our in vivo experiment showed that shizukaol C elevated the expression level of GSTpi in carotid arteries and alleviates TMAO-induced vascular inflammation. CONCLUSION: Shizukaol C exerts anti-inflammatory effects in TMAO-treated VSMC by targeting Keap1 and activating Nrf2-GSTpi signaling and resultantly inhibits the downstream JNK-NF-κB/p65 activation and VSMC adhesion, and alleviates TMAO-induced vascular inflammation in vivo, suggesting that shizukaol C may be a potential drug for treating TMAO-induced vascular diseases.

Halofantrine Hydrochloride Acts as an Antioxidant Ability Inhibitor That Enhances Oxidative Stress Damage to Candida albicans.

Candida albicans, a prominent opportunistic pathogenic fungus in the human population, possesses the capacity to induce life-threatening invasive candidiasis in individuals with compromised immune systems despite the existence of antifungal medications. When faced with macrophages or neutrophils, C. albicans demonstrates its capability to endure oxidative stress through the utilization of antioxidant enzymes. Therefore, the enhancement of oxidative stress in innate immune cells against C. albicans presents a promising therapeutic approach for the treatment of invasive candidiasis. In this study, we conducted a comprehensive analysis of a library of drugs approved by the Food and Drug Administration (FDA). We discovered that halofantrine hydrochloride (HAL) can augment the antifungal properties of oxidative damage agents (plumbagin, menadione, and H2O2) by suppressing the response of C. albicans to reactive oxygen species (ROS). Furthermore, our investigation revealed that the inhibitory mechanism of HAL on the oxidative response is dependent on Cap1. In addition, the antifungal activity of HAL has been observed in the Galleria mellonella infection model. These findings provide evidence that targeting the oxidative stress response of C. albicans and augmenting the fungicidal capacity of oxidative damage agents hold promise as effective antifungal strategies.

Liriogerphines E-U, further unique sesquiterpene-alkaloid hybrids from the rare Chinese tulip tree.

Seventeen undescribed sesquiterpene-alkaloid hybrids (liriogerphines E-U, 1-17) were isolated and identified during a further phytochemical investigation on the branches and leaves of Chinese tulip tree (Liriodendron chinense), a rare medicinal and ornamental plant endemic to China. These unique heterodimers are conjugates of germacranolide-type sesquiterpenoids with structurally diverse alkaloids [i.e., aporphine- (1-15), proaporphine- (16), and benzyltetrahydroisoquinoline-type (17)] via the formation of a C-N bond. The previously undescribed structures were elucidated by comprehensive spectroscopic data analyses and electronic circular dichroism calculations. Such a class of sesquiterpene-alkaloid hybrids presumably biosynthesized via an aza-Michael addition is quite rare from terrestrial plants. In particular, the sesquiterpene-benzyltetrahydroisoquinoline hybrid skeleton has never been reported until the present study. All the isolates were evaluated for their cytotoxic effects against a small panel of leukemia cell lines (Raji, Jeko-1, Daudi, Jurkat, MV-4-11 and HL-60), and some of them exhibited considerable activities.

Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation.

BACKGROUND: Cyclic-dependent kinase (CDK) 4/6 kinases, as the critical drivers of the cell cycle, are involved in the tumor progression of various malignancies. Pharmacologic inhibitors of CDK4/6 have shown significant clinical prospects in treating hormone receptor-positive and human epidermal growth factor receptor-negative (HR + /HER2-) breast cancer (BC) patients. However, acquired resistance to CDK4/6 inhibitors (CDK4/6i), as a common issue, has developed rapidly. It is of great significance that the identification of novel therapeutic targets facilitates overcoming the CDK4/6i resistance. PARP1, an amplified gene for CDK4/6i-resistant patients, was found to be significantly upregulated during the construction of CDK4/6i-resistant strains. Whether PARP1 drives CDK4/6i resistance in breast cancer is worth further study. METHOD: PARP1 and p-YB-1 protein levels in breast cancer cells and tissues were quantified using Western blot (WB) analysis, immunohistochemical staining (IHC) and immunofluorescence (IF) assays. Bioinformatics analyses of Gene Expression Profiling Interactive Analysis (GEPIA), Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) datasets were applied to explore the relationship between YB-1/PARP1 protein levels and CDK4/6i IC50. Cell Counting Kit-8 (CCK-8) and crystal violet staining assays were performed to evaluate cell proliferation rates and drug killing effects. Flow cytometry assays were conducted to assess apoptosis rates and the G1/S ratio in the cell cycle. An EdU proliferation assay was used to detect the DNA replication ratio after treatment with PARP1 and YB-1 inhibitors. A ChIP assay was performed to assess the interaction of the transcription factor YB-1 and associated DNA regions. A double fluorescein reporter gene assay was designed to assess the influence of WT/S102A/S102E YB-1 on the promoter region of PARP1. Subcutaneous implantation models were applied for in vivo tumor growth evaluations. RESULTS: Here, we reported that PARP1 was amplified in breast cancer cells and CDK4/6i-resistant patients, and knockdown or inhibition of PARP1 reversed drug resistance in cell experiments and animal models. In addition, upregulation of transcription factor YB-1 also occurred in CDK4/6i-resistant breast cancer, and YB-1 inhibition can regulate PARP1 expression. p-YB-1 and PARP1 were upregulated when treated with CDK4/6i based on the WB and IF results, and elevated PARP1 and p-YB-1 were almost simultaneously observed during the construction of MCF7AR-resistant strains. Inhibition of YB-1 or PAPR1 can cause decreased DNA replication, G1/S cycle arrest, and increased apoptosis. We initially confirmed that YB-1 can bind to the promoter region of PARP1 through a ChIP assay. Furthermore, we found that YB-1 phosphorylated at S102 was crucial for PARP1 transcription according to the double fluorescein reporter gene assay. The combination therapy of YB-1 inhibitors and CDK4/6i exerted a synergistic antitumor effect in vitro and in vivo. The clinical data suggested that HR + /HER2- patients with low expression of p-YB-1/PARP1 may be sensitive to CDK4/6i in breast cancer. CONCLUSION: These findings indicated that a ''YB-1/PARP1'' loop conferred resistance to CDK4/6 inhibitors. Furthermore, interrupting the loop can enhance tumor killing in the xenograft tumor model, which provides a promising strategy against drug resistance in breast cancer.

[Interaction and Transport Characteristics of Lead and Cadmium in Different Soil-wheat Systems].

In this study, four groups of lead(Pb) and cadmium(Cd) combined treatments with different concentration ratios were set up in Hailun black soil, Xianning brown-red soil, and Changwu Heilu soil, and wheat(Zhengmai 9023) was planted for a five-month pot experiment to analyze the Pb-Cd interaction behavior on heavy metal bioaccumulation in wheat under three soil-wheat systems. The low pH brown-red soil had the highest water-soluble Cd and Pb contents with significant Pb-Cd interactions in the soil, whereas the black soil with high organic matter and Heilu soil with high calcium carbonate content exhibited lower Cd and Pb activities. Among the three soils, wheat height and dry weight showed the poorest growth performance in the Heilu soil, but the wheat height increased by 2.68-8.49 cm compared with that in the control under the Pb-Cd combined treatment, whereas Pb-Cd interaction had the least effect on wheat height and dry weight in black soil and inhibited the growth of wheat in the brown-red soil. In the transport process of Cd or Pb in wheat, Pb-Cd interaction showed quite different effects in the three soil-wheat systems. Under the 125 mg·kg-1 and 250 mg·kg-1 Pb treatments, the Pb content in wheat grain planted in brown-red soil significantly increased by 73.2% and 19.1% with the addition of Cd, respectively, and therefore there was a synergistic effect between Pb and Cd. Under the 0.3 mg·kg-1 and 0.6 mg·kg-1 Cd treatments, the Cd content in wheat grains planted in black soil decreased by 51% and 33% with the addition of Pb, respectively; therefore, there was an antagonist effect between Pb and Cd. In the Heilu soil, a synergistic effect of Cd on Pb transport in wheat leaves was only observed under high Pb treatment. Therefore, pH and organic matter content were the key factors that determined the interaction behavior of Pb and Cd. The wheat food security risk of Pb and Cd combined pollution was higher than that of single metal pollution in acidic brown-red soil and lower in high organic matter black soil, whereas the interaction of Pb and Cd had little impact on the wheat food security risk of alkaline Heilu soil.

Systematic Review and Meta-analysis: Macrolide in the Treatment of Chronic Rhinosinusitis After Endoscopic Sinus Surgery.

OBJECTIVES: To evaluate the efficacy and safety of macrolide antibiotics therapy in patients with chronic rhinosinusitis (CRS) receiving endoscopic sinus surgery. DATA SOURCES: PubMed, Web of Science, Embase, and Cochrane Library. REVIEW METHODS: The electronic databases were comprehensively searched on June 2, 2022, for randomized controlled trials on macrolide antibiotics in the treatment of patients undergoing CRS endoscopic surgery. The primary outcome measures were the sinonasal outcome test (SNOT) score and the visual analog scale (VAS) score. The secondary outcome measures were the nasal endoscopy score (NES), the sinus computed tomography score, and adverse events. RESULTS: A total of 8 studies were included, involving 606 patients who used macrolide for a long time. Meta-analysis showed that no significant difference was observed in SNOT (standardized mean difference [SMD] = -0.13; 95% confidence interval [CI]: -0.38 to 0.13, I2 = 0%) and VAS (SMD = -0.10; 95% CI, -0.88 to 0.68, I2 = 81%) between the macrolide and placebo groups. However, macrolide outperformed the placebo in improving NES (SMD = -0.32; 95% CI, -0.62 to -0.03, I2 = 21%). The use of macrolide did not increase the incidence of adverse events. CONCLUSION: Long-term use of macrolide after CRS surgery may not significantly improve the quality of life and disease severity of the patients but may play a role in improving postoperative NES in patients with CRS. There is still no sufficient evidence to determine whether the disease phenotype of CRS or the patient's race will affect the efficacy of long-term use of macrolide after CRS.

Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma.

We aimed to characterize the stomach adenocarcinoma (STAD) microbiota and its clinical value using an integrated analysis of the microbiome and transcriptome. Microbiome and transcriptome data were downloaded from the Cancer Microbiome Atlas and the Cancer Genome Atlas databases. We identified nine differentially abundant microbial genera, including Helicobacter, Mycobacterium, and Streptococcus, which clustered patients into three subtypes with different survival rates. In total, 74 prognostic genes were screened from 925 feature genes of the subtypes, among which five genes were identified for prognostic model construction, including NTN5, MPV17L, MPLKIP, SIGLEC5, and SPAG16. The prognostic model could stratify patients into different risk groups. The high-risk group was associated with poor overall survival. A nomogram established using the prognostic risk score could accurately predict the 1, 3, and 5 year overall survival probabilities. The high-risk group had a higher proportion of histological grade 3 and recurrence samples. Immune infiltration analysis showed that samples in the high-risk group had a higher abundance of infiltrating neutrophils. The Notch signaling pathway activity showed a significant difference between the high- and low-risk groups. In conclusion, a prognostic model based on five feature genes of microbial subtypes could predict the overall survival for patients with STAD.

Effect of online interventions on reducing anxiety and depression for women with breast cancer: a systematic review and network meta-analysis protocol.

INTRODUCTION: Breast cancer has becoming the most common malignancy in women globally. Various online interventions have been conducted to help women with breast cancer to manage their psychological symptoms. However, there has been not yet a network meta-analysis that has synthesised scientific evidence about online intervention on reducing anxiety and depression for women with breast cancer. To fill the literature gap, this protocol aims to generate a systematic review and network meta-analysis to assess the effectiveness of online interventions on reducing anxiety and depression for these women with breast cancer. The study results may inform the recommendations for clinical guidelines and facilitate the decision-making process to improve psychological health of women with breast cancer. METHODS AND ANALYSIS: The protocol is in compliance with the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols and for Systematic Reviews and Network Meta-Analysis. The electronic databases of Pubmed, EMBASE, CINAHL, PsycINFO, Web of Science, Cochrane Central Registry of Controlled Trials and OpenGrey will be used for searching of related randomised controlled trials from their inception. No restrictions on publication date and language will be applied. The primary outcomes are the symptoms of anxiety and depression, and the secondary outcome is the satisfaction with the received healthcare. Two reviewers independently evaluate the risk of bias using the Cochrane Collaboration's Risk of Bias tool. The assessment of heterogeneity, inconsistency, subgroup analysis, sensitivity analysis and publication bias will be conducted. The netmeta package of R software will be used to perform the network meta-analysis. ETHICS AND DISSEMINATION: This study will be based on previous research findings, so that ethics approval is not required. Data searching commences in July 2023 and expects to complete in January, 2024. The findings will be disseminated through peer-reviewed journals and academic conferences. PROSPERO REGISTRATION NUMBER: CRD42022318530.

Structurally Diverse Triterpene-26-oic Acids as Potential Dual ACL and ACC1 Inhibitors from the Vulnerable Conifer Keteleeria fortunei.

A preliminary phytochemical investigation on the 90% MeOH extract from the twigs and needles of the vulnerable conifer Keteleeria fortunei led to the isolation and characterization of 17 structurally diverse triterpen-26-oic acids, including nine previously undescribed ones (fortunefuroic acids A-I, 1-9) featuring a rare furoic acid moiety in the lateral chain. Among them, 1-5 are uncommon 9ßH-lanostane-type triterpenoic acids. Friedo-rearranged triterpenoids 6 and 7 feature a unique 17,14-friedo-lanostane skeleton, whereas 9 possesses a rare 17,13-friedo-cycloartane-type framework. Their structures and absolute configurations were elucidated by extensive spectroscopic (e.g., detailed 2D NMR) and computational (NMR/ECD) calculations and the modified Mosher's method. In addition, the absolute structure of compound 1 was ascertained by single-crystal X-ray diffraction analyses. Fortunefuroic acids B (2), G (7), and I (9), along with isomangiferolic acid (12) and 3α,27-dihydroxycycloart-24E-en-26-oic acid (14), exhibited dual inhibitory effects against the adenosine triphosphate (ATP)-citrate lyase (ACL, IC50s: 5.7-11.4 µM) and acetyl-CoA carboxylase 1 (ACC1, IC50s: 7.5-10.5 µM), both of which are key enzymes for glycolipid metabolism. The interactions of the bioactive triterpenoids with both enzymes were examined by molecular docking studies. The above findings reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics for ACL-/ACC1-associated diseases.

Efficacy and safety of low concentration hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy: a pilot cohort study.

Purpose: This study aimed to evaluate and analyze the efficacy and safety of low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy. Methods: Patients with nasopharyngeal carcinoma from Jiangxi cancer hospital were randomly divided into two cohorts. The training cohort (n= 50) received low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma radiotherapy, and the control cohort (n= 50) received 0.02% nitrofurazone lavage fluid. The primary endpoint of the study was result of short-term efficacy. Second endpoints were assessment of the linear visual analogue scale score and the incidences rate of nasopharyngeal radiation related toxicity. Results: All patients had completed the scheduled nasopharyngeal radiotherapy except two patients in control cohort. The complete response, partial response, stable disease and disease objective response of nasopharyngeal primary tumor observed in the training cohort included 18 cases, 23 cases, 9 cases and 41 cases respectively, while in the control cohort 20 cases, 25 cases, 5 cases and 45 cases were recorded, respectively. The study showed a significant discrepancy in the incidence rate of radiation-related mucosa damage between the two. Specifically, Grade 1 and 2 included 37 cases (74.0%) in the training cohort, while in the control cohort the cases were 20 (40.0%). Grade 3 and 4 damage however reported an incidence of 26.0% and 60%, respectively, which clearly constitutes a significant statistical difference (P = 0.002). The assessment of linear visual analogue scale showed that the patients self-conscious comfortable feeling in the training cohort were significantly higher than in the control cohort (P = 0.003). Conclusions: low concentration (0.15%) hydrogen peroxide as nasopharyngeal lavage fluid in the treatment for nasopharyngeal carcinoma patients is effective and safe, and can reduce nasopharyngeal local mucosa radiation related toxicity after radiotherapy.

Squamabietenols A-F, undescribed abietane-O-abietane dimeric diterpenoids from the ornamental conifer Juniperus squamata and their ATP-citrate lyase inhibitory activities.

Six undescribed naturally occurring abietane-O-abietane dimers (squamabietenols A-F) together with one 3,4-seco-totarane-type, a pimarane-type, and 17 related known mono-/dimeric diterpenoids were isolated and characterized from the needles and twigs of the ornamental conifer Juniperus squamata. The undescribed structures and their absolute configurations were established by extensive spectroscopic methods, GIAO NMR calculations with DP4+ probability analyses, and ECD calculations. Squamabietenols A and B showed significant inhibitory effects against ATP-citrate lyase (ACL, a novel drug target for hyperlipidemia and other metabolic disorders), with IC50 values of 8.82 and 4.49 µM, respectively. A molecular docking study corroborated the findings by highlighting the interactions between the bioactive compounds and the ACL enzyme (binding affinities: -7.1 to -9.0 kcal/mol). The unique abietane-O-abietane dimeric diterpenoids are quite rare in the vegetable kingdom, and they are of chemotaxonomic significance for the Cupressaceae family.

How different is the remediation effect of biochar for cadmium contaminated soil in various cropping systems? A global meta-analysis.

Cadmium (Cd) poses great threats to human health as a major contaminant in agricultural soil. Biochar shows great potential in the remediation of agricultural soil. However, it remains unclear whether the remediation effect of biochar on Cd pollution is affected by various cropping systems. Here, this study used 2007 paired observations from 227 peer-reviewed articles and employed hierarchical meta-analysis to investigate the response of three types of cropping systems to the remediation of Cd pollution by using biochar. As a result, biochar application significantly reduced the Cd content in soil, plant roots and edible parts of various cropping systems. The decrease in Cd level ranged from 24.9% to 45.0%. The feedstock, application rate, and pH of biochar as well as soil pH and cation exchange capacity were dominant factors for Cd remediation effect of biochar, and their relative importance all exceeded 37.4%. Lignocellulosic and herbal biochar were found to be suitable for all cropping systems, while the effects of manure, wood and biomass biochar were limited in cereal cropping systems. Furthermore, biochar exhibited a more long-lasting remediation effect on paddy soils than on dryland. This study provides new insights into the sustainable agricultural management of typical cropping systems.

Prediction of cadmium bioavailability in the rice-soil system on a county scale based on the multi-surface speciation model.

Relative to total cadmium (Cd) content, bioavailable Cd in paddy soil is regarded as a more reasonable indicator for the risk of Cd bioaccumulation in rice. However, there is still a lack of approach to accurately predict the content of bioavailable Cd in paddy soil due to its heterogeneity and complexity. Here, multi-surface speciation model (MSM) was employed to predict the bioavailable Cd and Cd immobilization effect. Moreover, a precise remediation strategy was designed based on screening and scenario simulation of the sensitive factors with MSM. The results demonstrated that MSM can well predict Cd bioaccumulation risk in rice. The contribution of pH to Cd bioavailability was quantified under three analysis scenarios, accounting for 87.51% of the total variance of bioavailable Cd. In addition, the pH alert value (6.31 ± 0.52) for Cd risk was acquired for each rice field on a county scale. A precise map for the application amount of lime materials was constructed by taking CaCO3 (3.38-15.75 t ha-1) as a recommended economical and green immobilization agent. This study provides a potentially effective approach for risk assessment of Cd contamination in rice and important reference for precise Cd remediation in paddy soil.

Generic CD-MUSIC-eSGC model parameters to predict the surface reactivity of iron (hydr)oxides.

The surface reactivity of iron (hydr)oxides plays a crucial role in controlling their interfacial reactions, for which various surface complexation models have been developed. The diversity of mineralogical properties of iron (hydr)oxides has resulted in a redundancy of model parameters, which hampers the modeling of iron (hydr)oxides in soils and sediments, where goethite, hematite and ferrihydrite dominate the iron (hydr)oxide mass fraction. To capture their combined surface reactivity, optimized generic protonation parameters of the Charge Distribution-Multisite Complexation (CD-MUSIC) extended-Stern-Gouy-Chapman (eSGC) model were derived by reanalyzing literature datasets and tested with some newly synthesized iron (hydr)oxides. It was observed that the proton and monovalent ion affinity constants of the different iron (hydr)oxides were located in a narrow range. For the singly- and triply-coordinated hydroxyl sites the obtained generic log(affinity constants) were 8.3 and 11.7 for the protonation reaction and -0.5 for the reaction with the monovalent background ions. Their combination with fixed site densities of singly-/triply-coordinated hydroxyl sites of 3.45/2.70, 5.00/2.50, and 5.80/1.40 sites/nm2 for goethite, hematite, and ferrihydrite, respectively, provided good results. The Stern layer capacitances of the inner and outer Stern layers were set equal and could be acquired by an empirical correlation with the sample specific surface area (SSA). The CD-MUSIC-eSGC model with the generic model parameters enables good quality predictions of the proton reactivity of iron (hydr)oxides in 1:1 electrolyte solutions regardless of the sample heterogeneity. The advantages of the generic CD-MUSIC-eSGC model are twofold: (1) protonation of iron (hydr)oxides can be described without making use of spectroscopic measurements and proton titrations, and (2) the model calculations are greatly simplified.

Oral Hydroxychloroquine Mitigates Lipopolysaccharide-induced Lung Injury by Inhibiting Pyroptosis in Mice.

BACKGROUND AND OBJECTIVE: Hydroxychloroquine (HCQ) is a molecule derived from quinacrine; it displays a wide range of pharmacological properties, including anti-inflammatory, immunomodulatory, and antineoplastic. However, little is known about this molecule's role in lung injury. This study aimed to identify HCQ's regulatory role of HCQ in sepsis-induced lung injury and its molecular mechanism. METHODS: To test the protective properties of HCQ, we established an in vivo model of lipopolysaccharide (LPS)-induced lung injury in mice. The extent of the injury was determined by evaluating histopathology, inflammatory response, oxidative stress, and apoptosis. Mechanistically, conventional nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 (NLRP3) knockout mice were employed to investigate whether HCQ exerted pulmonary protection by inhibiting NLRP3-mediated pyroptosis. RESULTS: Our findings revealed that HCQ pretreatment significantly mitigated LPS-induced lung injury in mice in terms of histopathology, inflammatory response, oxidative stress, and apoptosis, while inhibiting LPS-induced NLRP3 inflammasome activation and pyroptosis. Additionally, the indicators of lung injury, including histopathology, inflammatory response, oxidative stress, and apoptosis, were still reduced drastically in LPS-treated NLRP3 (-/-) mice after HCQ pretreatment. Notably, HCQ pretreatment further decreased the levels of pyroptosis indicators, including IL-1ß, IL-18 and Cle-GSDMD, in LPS-treated NLRP3 (-/-) mice. CONCLUSION: Taken together, HCQ protects against lung injury by inhibiting pyroptosis, maybe not only through the NLRP3 pathway but also through non-NLRP3 pathway; therefore, it may be a new therapeutic strategy in the treatment of lung injury.