Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

Smilax China L. polysaccharide prevents HFD induced-NAFLD by regulating hepatic fat metabolism and gut microbiota.

BACKGROUND: The increasing incidence of nonalcoholic fatty liver disease (NAFLD) has urged the development of new therapeutics. NAFLD is intimately linked to gut microbiota due to the hepatic portal system, and utilizing natural polysaccharides as prebiotics has become a prospective strategy for preventing NAFLD. Smilax china L. polysaccharide (SCP) possesses excellent hepatoprotective and anti-inflammatory activity. However, its protective effects on NAFLD remains unclear. PURPOSE: The goal of this study was to explore the protective effects of SCP on high-fat diet (HFD)-induced NAFLD mice by regulating hepatic fat metabolism and gut microbiota. METHODS: Extraction and isolation from Smilax china L. rhizome to obtain SCP. C57BL/6 J mice were distributed to six groups: Control (normal chow diet), HFD-fed mice were assigned to HFD, simvastatin (SVT), and low-, medium-, high-doses of SCP for 12 weeks. The body, liver, and different adipose tissues weights were detected, and lipids in serum and liver were assessed. RT-PCR and Western blot were used to detect the hepatic fat metabolism-related genes and proteins. Gut microbiota of cecum contents was profiled through 16S rRNA gene sequencing. RESULTS: SCP effectively reversed HFD-induced increase weights of body, liver, and different adipose tissues. Lipid levels of serum and liver were also significantly reduced after SCP intervention. According to the results of RT-PCR and western blot analysis, SCP treatment up-regulated the genes and proteins related to lipolysis were up-regulated, while lipogenesis-related genes and proteins were down-regulated. Furthermore, the HFD-induced dysbiosis of intestinal microbiota was similarly repaired by SCP intervention, including enriching beneficial bacteria and depleting harmful bacteria. CONCLUSION: SCP could effectively prevent HFD-induced NAFLD, might be considered as a prebiotic agent due to its excellent effects on altering hepatic fat metabolism and maintaining gut microbiota homeostasis.

Application Evaluation of Fluorouracil Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy in Patients after Radical Resection of Colorectal Cancer.

BACKGROUND: Colorectal cancer stands as one of the most prevalent malignant tumors affecting the digestive tract, posing a significant threat to human health. Its incidence and fatality rates rank third and second, respectively, among malignant tumors. This study seeks to analyze the efficacy of combining fluorouracil intraperitoneal perfusion chemotherapy with intravenous chemotherapy in patients following radical resection of colorectal cancer. METHODS: This retrospective study analyzed the medical records of 65 patients who underwent radical resection of colorectal cancer at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2011 to January 2013. These patients were divided into two groups based on their treatment methods: the control group (CG, n = 31, receiving intravenous chemotherapy) and the observation group (OG, n = 32, receiving fluorouracil intraperitoneal perfusion chemotherapy + intravenous chemotherapy). After 6 cycles of treatment, the study compared clinical symptoms, Karnofsky score, body weight, adverse reactions, local recurrence, and liver metastasis between the two groups. RESULTS: The OG demonstrated superior efficacy in controlling recurrence and metastasis compared to the CG (p < 0.05). However, there were no significant differences observed in clinical symptoms, quality of life, body weight, and drug safety between the two groups (p > 0.05). CONCLUSION: Intraperitoneal infusion chemotherapy with fluorouracil significantly impacts the control of recurrence and metastasis following radical resection of colorectal cancer. It also offers valuable references for developing clinical treatment protocols for these patients.

Potential causal association between gut microbiome and posttraumatic stress disorder.

BACKGROUND: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). METHODS: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome. RESULTS: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. CONCLUSION: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation.

Influenza is an acute viral respiratory illness with high morbidity rates worldwide. Excessive pulmonary inflammation is the main characteristic of lethal influenza A virus (IAV) infections. Therapeutic options for managing influenza are limited to vaccines and some antiviral medications. Phillyrin is one of the major bioactive components of the Chinese herbal medicine Forsythia suspensa, which has the functions of sterilization, heat clearing and detoxification. In this work, the effect and mechanism of phillyrin on H1N1 influenza (PR8)-induced pneumonia were investigated. We reported that phillyrin (15 mg/kg) treatment after viral challenge significantly improved the weight loss, ameliorated pulmonary inflammation and inhibited the accumulation of multiple cytokines and chemokines in bronchoalveolar lavage fluid on 7 days post infection (dpi). In vitro, phillyrin suppressed influenza viral replication (Matrixprotein and nucleoprotein messenger RNA level) and reduced influenza virus-induced cytopathic effect (CPE). Furthermore,chemokine receptor CXCR2 was confirmed to be markedly inhibited by phillyrin. Surface plasmon resonance results reveal that phillyrin exhibits binding affinity to CXCR2, having a binding affinity constant (KD) value of 1.858e-5 M, suggesting that CXCR2 is a potential therapeutic target for phillyrin. Moreover, phillyrin inhibited the mRNA and protein expression levels of Caspase1, ASC and NLRP3 in the lungs of mice with H1N1-induced pneumonia.This study reveals that phillyrin ameliorates IAV-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation partly.

Discovery of pyranonaphthoquinones and an eighteen-membered ring macrolide from the rhizospheric soil-derived fungus Phialocephala sp. YUD18001 by OSMAC strategy.

Two new pyranonaphthoquinones, phialoyxinones A (1) and B (2), a new eighteen-membered ring lactone, phialoyxtone (3), and five known pyranonaphthoquinone derivatives were identified from the fungus Phialocephala sp. YUD18001, which was isolated from the rhizospheric soil associated with Gastrodia elata. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1-3 was defined by a combination of TDDFT calculations, and the DP4+ probability analysis based on NMR chemical shift calculations. All of the new compounds 1-3 were evaluated for cytotoxicity and acetylcholinesterase inhibitory, compound 2 exhibited in vitro cytotoxic activities against five human cancer cell lines (HL-60, SMMC-7721, A549, MCF-7 and SW480) with IC50 values ranging from 11.80 to 19.32 µM. Compounds 2 and 3 exhibited moderate AChE inhibitory activities. A putative biosynthetic pathway for the pyranonaphthoquinones was proposed.

[LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis].

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Qualitative analysis on the transdermal absorption from the dichloromethane extract of the Sambucus adnata wall. based on UPLC-Q-Exactive Orbitrap/MS.

Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.

Toxicity, formation, contamination, determination and mitigation of acrylamide in thermally processed plant-based foods and herbal medicines: A review.

Thermal processing is one of the important techniques for most of the plant-based food and herb medicines before consumption and application in order to meet the specific requirement. The plant and herbs are rich in amino acids and reducing sugars, and thermal processing may lead to Maillard reaction, resulting as a high risk of acrylamide pollution. Acrylamide, an organic pollutant that can be absorbed by the body through the respiratory tract, digestive tract, skin and mucous membranes, has potential carcinogenicity, neurological, genetic, reproductive and developmental toxicity. Therefore, it is significant to conduct pollution determination and risk assessment for quality assurance and security of medication. This review demonstrates state-of-the-art research of acrylamide focusing on the toxicity, formation, contamination, determination, and mitigation in taking food and herb medicine, to provide reference for scientific processing and ensure the security of consumers.

An injectable multifunctional hydrogel for eradication of bacterial biofilms and wound healing.

Wound treatment is largely influenced by pre-existing hypoxic microenvironments and biofilms, which can severely diminish the efficacy of phototherapy, suggesting the importance of multifunctional nanoplatforms for synergistic treatment of wound infections. Here, we developed a multifunctional injectable hydrogel (PSPG hydrogel) by loading photothermal sensitive sodium nitroprusside (SNP) into Pt-modified porphyrin metal organic framework (PCN) and in situ modification of gold particles to form a near-infrared (NIR) light-triggered all-in-one phototherapeutic nanoplatform. The Pt-modified nanoplatform exhibits a remarkable catalase-like behavior and promotes the continuous decomposition of endogenous H2O2 into O2, thereby enhancing the photodynamic therapy (PDT) effect under hypoxia. Under dual NIR irradiation, PSPG hydrogel can not only produce hyperthermia (η=89.21%) but also generate reactive oxygen species and trigger NO release, contributing jointly to removal of biofilms and disruption of the cell membranes of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). In vivo experiments demonstrated a 99.9% reduction in bacterial burden on wounds. Additionally, PSPG hydrogel can accelerate MRSA-infected and Pseudomonas aeruginosa-infected (P. aeruginosa-infected) wound healing by promoting angiogenesis, collagen deposition, and suppressing inflammatory responses. Furthermore, in vitro and in vivo experiments revealed that PSPG hydrogel has good cytocompatibility. Overall, we proposed an antimicrobial strategy to eliminate bacteria through the synergistic effects of gas-photodynamic-photothermal killing, alleviating hypoxia in the bacterial infection microenvironment, and inhibiting biofilms, offering a new way against antimicrobial resistance and biofilm-associated infections. STATEMENT OF SIGNIFICANCE: The NIR light-triggered multifunctional injectable hydrogel nanoplatform (PSPG hydrogel) based on Pt-decorated gold nanoparticles with sodium nitroprusside (SNP)-loading porphyrin metal organic framework (PCN) as inner templates can efficiently perform photothermal conversion (η=89.21%) to trigger NO release from SNP, while continuously regulating the hypoxic microenvironment at the bacterial infection site through Pt-induced self-oxygenation, achieving efficient sterilization and removal of biofilm by synergistic PDT and PTT phototherapy. In vivo and in vitro experiments demonstrated that the PSPG hydrogel has significant anti-biofilm, antibacterial, and inflammatory regulatory functions. This study proposed an antimicrobial strategy to eliminate bacteria through the synergistic effects of gas-photodynamic-photothermal killing, alleviating hypoxia in the bacterial infection microenvironment, and inhibiting biofilms.

Feasibility of soil and sludge standards for freshwater sediment pollutant determination and quality judgment.

The environmental standards of soil and sludge have been typically referenced for freshwater sediment determination and quality assessment, especially in some areas without sediment standards. The feasibility of determination method and quality standard of soils and sludge for freshwater sediment was investigated in this study. Fractions of heavy metals, nitrogen, phosphorus, and reduced inorganic sulfur (RIS) in different type of samples were determined, including freshwater sediments, dryland and paddy soils, and sludge with air-drying (AD) and freeze-drying (FD) treatment, respectively. Results showed fraction distributions of heavy metals, nitrogen, phosphorus, and RIS in sediments markedly differed from those of soils and sludge. Fraction redistributions of heavy metals, nitrogen, phosphorus, and RIS in sediments were observed with AD compared to those treated by FD. The proportions of heavy metals, nitrogen, and phosphorus associated with organic matter (or sulfide) in FD sediments decreased by 4.8-74.2%, 9.5-37.5%, and 16.1-76.3%, respectively, compared to those in AD sediments, while those associated with Fe/Mn oxides increased by 6.3-39.1%, 50.9-226.9%, and 6.1-31.0%, respectively. The fraction proportions of RIS in sediments with AD also sharply decreased. Determination of standard methods for sludge and soil caused the distortion of pollutant fraction analysis in sediment. Similarly, the quality standard of sludge and soil was inappropriate for sediment quality assessment due to the differences in pollutant fraction pattern between sediment and soils/sludge. Totally, soil and sludge standards are inapplicable for freshwater sediment pollutant determination and quality judgment. This study would greatly advance the establishment of freshwater sediment determination methods and quality standards.

In Situ Deposition of Gold Nanoparticles and L-Cysteine on Screen-Printed Carbon Electrode for Rapid Electrochemical Determination of As(III) in Water and Tea.

In this study, a screen-printed carbon electrode (SPCE) based on in situ deposition modification was developed for the sensitive, rapid, easy and convenient determination of As(III) in water and tea by linear sweep anodic stripping voltammetry (LSASV). The screen-printed carbon electrodes were placed in a solution consisting of As(III) solution, chlorauric acid and L-cysteine. Under certain electrical potential, the chloroauric acid was reduced to gold nanoparticles (AuNPs) on the SPCE. L-cysteine was self-assembled onto AuNPs and promoted the enrichment of As(III), thus enhancing the determination specificity and sensitivity of As(III). The method achieved a limit of determination (LOD) of 0.91 ppb (µg L-1), a linear range of 1~200 µg L-1, an inter-assay coefficient of variation of 5.3% and good specificity. The developed method was successfully applied to the determination of As(III) in tap water and tea samples, with a recovery rate of 93.8%~105.4%, and further validated by inductively coupled plasma mass spectrometry (ICP-MS). The developed method is rapid, convenient and accurate, holding great promise in the on-site determination of As(III) in tap water and tea leaves, and it can be extended to the detection of other samples.

A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.

Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.

A Two-Pronged Strategy for Enhanced Deep-Tumor Penetration and NIR-II Multimodal Imaging-Monitored Photothermal Therapy.

The second near-infrared (NIR-II)-induced photothermal therapy (PTT) has attracted a great deal of attention in recent years due to its non-invasiveness and because it uses less energy. However, the penetration of photothermal agents into solid tumors is seriously impeded by the dense-tumor extracellular matrix (ECM) containing cross-linked hyaluronic acid (HA), thereby compromising the ultimate therapeutic effects. Herein, acid-labile metal-organic frameworks were employed as nanocarriers to efficiently mineralize hyaluronidase (HAase) and encapsulate Ag2S nanodots by a one-pot approach under mild conditions. The obtained nanocomposites (AHZ NPs) maintained enzyme activity and changed in size to prolong blood circulation and complete delivery of the cargo to the tumor. Moreover, the released HAase could specifically break out the HA to loosen ECM and enable the Ag2S nanodots to breeze through the tumor matrix space and gain access to the deep tumor. Under near-infrared laser irradiation, the AHZ NPs displayed remarkable fluorescence, outstanding photoacoustic signals, and excellent photothermal properties in the whole tumor. This work offers a promising two-pronged strategy via a decrease in nanoparticle size and the degradation of dense ECM for NIR-II multimodal imaging-guided PTT of deep tumors.

Antifungal and Antibiofilm In Vitro Activities of Ursolic Acid on Cryptococcus neoformans.

Ursolic acid (UA) exists in a variety of medicinal plants. UA exhibits antimicrobial activity against several microorganisms; however, little is known regarding the potential antifungal effect of UA on Cryptococcus neoformans (C. neoformans). The antifungal and antibiofilm activities of UA on C. neoformans H99 were evaluated in this study. Minimum inhibitory concentration (MIC) of UA against C. neoformans H99 was determined by microdilution technique, and its action mode was elucidated by clarifying the variations in cell membrane integrity, capsule, and melanin production. Moreover, the inhibition and dispersal effects of UA on biofilm formation and mature biofilms by C. neoformans H99 were evaluated using crystal violet (CV) assay, optical microscopy, field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that the MIC value of UA against C. neoformans H99 was 0.25 mg/mL. UA disrupted the cell membrane integrity, inhibited the capsule and melanin production of C. neoformans H99 in a concentration-dependent manner. Further, UA presented the inhibitory effect on biofilm formation and dispersed mature biofilms, as well as compromised the cell membrane integrity of C. neoformans H99 cells within biofilms. Together, these results indicate that UA might be a potential therapeutic option for the treatment of C. neoformans-related infections.

GhMYC2 activates cytochrome P450 gene CYP71BE79 to regulate gossypol biosynthesis in cotton.

MAIN CONCLUSION: GhMYC2 regulates the gossypol biosynthesis pathway in cotton through activation of the expression of gossypol synthesis gene CYP71BE79, CDNC, CYP706B1, DH1, and CYP82D113. Cotton is one of the main cash crops globally. Cottonseed contains fiber, fat, protein, and starch, and has important economic value. However, gossypol in cottonseed seriously affects the development and utilization of cottonseed. Nonetheless, gossypol has great application potential in agriculture, medicine, and industry. Therefore, it is very important to study gossypol biosynthesis and its upstream regulatory pathways. It has been reported that the content of gossypol in hairy roots of cotton is regulated through jasmonic acid signaling; however, the specific molecular mechanism has not been revealed yet. We found that the expression of basic helix-loop-helix family transcription factor GhMYC2 was significantly upregulated after exogenous administration of methyl jasmonate to cotton seedlings, and the content of gossypol changed significantly with the variation of GhMYC2 expression. Further studies revealed that GhMYC2 could specifically bind to the G-Box in the promoter region of CDNC, CYP706B1, DH1, CYP82D113, CYP71BE79 to activate its expression and regulate gossypol synthesis, and its activation of CYP71BE79 promoter was inhibited by GhJAZ2. Not only that GhMYC2 could also interact with GoPGF. In this work, the molecular mechanisms of gossypol biosynthesis regulated by GhMYC2 were analyzed. The results provide a theoretical basis for cultivating new varieties of low-gossypol or high-gossypol cotton and creating excellent germplasm resources.

The potential role of betaine in enhancement of microbial-assisted phytoremediation of benzophenone-3 contaminated soil.

Benzophenone-3 (BP-3) is an emerging environmental pollutant used in personal care products, helping to reduce the risk of ultraviolet radiation to human skin. The BP-3 removal potential from soil by tobacco (Nicotiana tabacum) assisted with Methylophilus sp. FP-6 was explored in our previous study. However, the reduced BP-3 remediation efficiency by FP-6 in soil and the inhibited plant growth by BP-3 limited the application of this phytoremediation strategy. The aim of the present study was to reveal the potential roles of betaine, as the methyl donor of methylotrophic bacteria and plant regulator, in improving the strain FP-6-assisted phytoremediation capacity of BP-3 contaminated soil. The results revealed that strain FP-6 could use betaine as a co-metabolism substrate to enhance the BP-3 degradation activity. About 97.32% BP-3 in soil was effectively removed in the phytoremediation system using tobacco in combination with FP-6 and betaine for 40 d while the concentration of BP-3 in tobacco significantly reduced. Moreover, the biomass and photosynthetic efficiency of plants were remarkably improved through the combined treatment of betaine and strain FP-6. Simultaneously, inoculation of FP-6 in the presence of betaine stimulated the change of local microbial community structure, which might correlate with the production of a series of hydrolases and reductases involved in soil carbon, nitrogen and phosphorus cycling processes. Meantime, some of the dominant bacteria could secrete various multiple enzymes involved in degrading organic pollutants, such as laccase, to accelerate the demethylation and hydroxylation of BP-3. Overall, the results from this study proposed that the co-metabolic role of betaine could be utilized to strengthen microbial-assisted phytoremediation process by increasing the degradation ability of methylotrophic bacteria and enhancing plant tolerance to BP-3. The present results provide novel insights and perspectives for broadening the engineering application scope of microbial-assisted phytoremediation of organic pollutants without sacrificing economic crop safety.

Purification, structural characterization, and anticoagulant activity evaluation of chondroitin sulfate from codfish (Gadus macrocephalus) bones.

Chondroitin sulfate (CCS) was purified from discarded codfish (Gadus macrocephalus) bones, and its chemical structure and anticoagulant activity were assessed. CCS was obtained via enzymatic lysis and ion-exchange column chromatography, with a yield of approximately 0.15%. High-performance gel performance chromatography revealed CCS to be a largely homogeneous polysaccharide with a relatively low molecular weight of 12.3 kDa. FT-IR spectroscopy, NMR spectroscopy, and SAX-HPLC indicated that CCS was composed of monosulfated disaccharides (ΔDi4S 73.85% and ΔDi6S 19.06%) and nonsulfated disaccharides (ΔDi0S 7.09%). In vitro anticoagulation analyses revealed that CCS was able to significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) (p < 0.05). At a CCS concentration of 5 µg/mL and 25 µg/mL, APTT and TT were approximately 1.08 and 1.12 times higher, respectively, compared to the negative control group. The results indicated that CCS might offer value as a dietary fiber supplement with the potential to prevent the incidence of coagulation-related thrombosis.

Feasibility analysis and mechanism exploration of Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) against COVID-19.

Introduction. As a novel global epidemic, corona virus disease 2019 (COVID-19) caused by SARS-CoV-2 brought great suffering and disaster to mankind. Recently, although significant progress has been made in vaccines against SARS-CoV-2, there are still no drugs for treating COVID-19. It is well known that traditional Chinese medicine (TCM) has achieved excellent efficacy in the treatment of COVID-19 in China. As a treasure-house of natural drugs, Chinese herbs offer a promising prospect for discovering anti-COVID-19 drugs.Hypothesis/Gap Statement. We proposed that Rhei Radix et Rhizome-Schisandrae Sphenantherae Fructus (RS) may have potential value in the treatment of COVID-19 patients by regulating immune response, protecting the cardiovascular system, inhibiting the production of inflammatory factors, and blocking virus invasion and replication processes.Aim. We aimed to explore the feasibility and molecular mechanisms of RS against COVID-19, to provide a reference for basic research and clinical applications.Methodology. Through literature mining, it is found that a Chinese herbal pair, RS, has potential anti-COVID-19 activity. In this study, we analysed the feasibility of RS against COVID-19 by high-throughput molecular docking and molecular dynamics simulations. Furthermore, we predicted the molecular mechanisms of RS against COVID-19 based on network pharmacology.Results. We proved the feasibility of RS anti-COVID-19 by literature mining, virtual docking and molecular dynamics simulations, and found that angiotensin converting enzyme 2 (ACE2) and 3C-like protease (3 CL pro) were also two critical targets for RS against COVID-19. In addition, we predicted the molecular mechanisms of RS in the treatment of COVID-19, and identified 29 main ingredients, 21 potential targets and 16 signalling pathways. Rhein, eupatin, (-)-catechin, aloe-emodin may be important active ingredients in RS. ALB, ESR1, EGFR, HMOX1, CTSL, and RHOA may be important targets against COVID-19. Platelet activation, renin secretion, ras signalling pathway, chemokine signalling pathway, and human cytomegalovirus infection may be important signalling pathways against COVID-19.Conclusion. RS plays a key role in the treatment of COVID-19, which may be closely related to immune regulation, cardiovascular protection, anti-inflammation, virus invasion and replication processes.

N-acetylcysteine improves diabetic associated erectile dysfunction in streptozotocin-induced diabetic mice by inhibiting oxidative stress.

Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus erectile dysfunction (DMED). This study aimed to investigate the effect of N-acetylcysteine (NAC) on DMED in streptozotocin-induced diabetic mice and to explore potential mechanisms. In the present study, we show that an erectile dysfunction is present in the streptozotocin-induced mouse model of diabetes as indicated by decreases in intracavernous pressure responses to electro-stimulation as well as from results of the apomorphine test of erectile function. After treatment of NAC, the intracavernous pressure was increased. In these DMED mice, oxidative stress and inflammatory responses were significantly reduced within the cavernous microenvironment, while activity of antioxidant enzymes in this cavernous tissue was enhanced after NAC treatment. These changes protected mitochondrial stress damage and a significant decreased in apoptosis within the cavernous tissue of DMED mice. This appears to involve activation of the nuclear factor erythroid 2-like-2 (Nrf2) signalling pathway, as well as suppression of the mitogen-activated protein kinase (MAPK) p38/ NF-κB pathway within cavernous tissue. In conclusion, NAC can improve erectile function through inhibiting oxidative stress via activating Nrf2 pathways and reducing apoptosis in streptozotocin-induced diabetic mice. NAC might provide a promising therapeutic strategy for individuals with DMED.