[Analysis on Driving Factors, Reduction Potential, and Environmental Effect of Inorganic Fertilizer Input in Chongqing].

In this study, we sought to quantify the effect of planting structure change on fertilizer input and environmental cost in Chongqing and develop scientific and rational strategies for chemical fertilizer reduction. Based on the crop fertilizer quota standard and large sample farmer survey data under the medium productivity level in Chongqing, we evaluated and analyzed the application reduction potential and environmental benefits of fertilizer with the difference method and life cycle assessment. The results showed that:① since Chongqing became a municipality directly under the central government (1997), Chongqing crop planting structure had greatly changed, and the proportion of food crop (rice, corn, wheat, bean, and potato) decreased by 21%. The area of fruits and vegetables increased from 3.36×105 hm2 to 1.05×106 hm2, and their proportion increased by 20%. ② Nearly 55% of fertilizers had been consumed by vegetable (37%) and citrus production systems, and 11%, 12%, and 12% of fertilizers were consumed by rice, corn, and potato, respectively. ③ The total fertilizer reduction of the Chongqing planting industry could reach up to 1.69×105 tons during the period of "the 14th Five-Year Plan," with a fertilizer reduction potential of 18.6%. The fertilizer reduction potential (reduction amount) of rice, corn, citrus, and vegetables would reach 0.3% (2.9×102 tons), 12% (1.45×104 tons), 21% (3.65×104 tons), and 30% (1.18×105 tons), respectively. On the other hand, the rape system was insufficient in phosphorus potassium fertilizers, and the corn tended to be insufficient in potash fertilizer. ④ The current production level was low, and the nitrogen loss, greenhouse gas emissions, and eutrophication potential in the planting industry of Chongqing reached 1.81×105 tons (N), 1.43×107 tons (CO2-eq), and 1.74×105 tons (PO4-eq). With the increase in the realization degree of the crop quota standard (60%-100%), the reactive nitrogen loss, greenhouse gas emissions, and eutrophication potential decreased by 14.9%-24.9%, 10.1%-16.7%, and 13.8%-23%, respectively. The structure of the planting industry in Chongqing significantly changed, the total fertilizer consumption in Chongqing tended to decline gradually, and the fertilization intensity of commercial crops stayed at a high level. The agricultural fertilizer reduction potential and the reactive nitrogen and greenhouse gas emission reduction potential were large, especially for citrus and vegetable production systems. However, it is also necessary to pay attention to insufficient corn potash fertilizer and rape phosphorus potassium fertilizer investment and carry out collaborative promotion of fertilizer reduction.

Holmium (III)-doped multifunctional nanotheranostic agent for ultra-high-field magnetic resonance imaging-guided chemo-photothermal tumor therapy.

Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Despite being the most commonly used MRI contrast agents, gadolinium chelates perform poorly in high magnetic fields, which significantly weakens their T1 intensity. In comparison, the rare element Holmium (Ho)-based nanoparticles (NPs) have demonstrated great potential as T2-weighted MRI contrast agents in UHF MRI due to their extremely short electron relaxation times (∼ 10-13s). In this study, a multifunctional nanotherapeutic probe was designed for UHF MRI-guided chemotherapy and photothermal therapy. The Ho (III)-doped mesoporous polydopamine (Ho-MPDA, HM) nanosphere was loaded with the chemotherapeutic drug mitoxantrone (MTO) and then coated with 4T1 cell membranes to enhance active targeting delivery to breast cancer. The prepared nanotherapeutic probe MTO@HMM@4T1 (HMM@T) exhibited good biocompatibility, high drug-loading capability and great potential as Ho (III)-based UHF MRI contrast agents. Moreover, the biodegradation of HMM@T in response to the intratumor pH and glutathione (GSH) promotes MTO release. Near-infrared (NIR) light irradiation of HM induced photothermal therapy and further enhanced drug release. Consequently, HMM@T effectively acted as an MRI-guided tumor-targeting chemo-photothermal therapy against 4T1 breast cancer. STATEMENT OF SIGNIFICANCE: Ultra-high-field (UHF) MRI has shown great advantages over low-field magnetic resonance imaging (MRI). Although gadolinium chelates are the most commonly used MRI contrast agents in clinical practice, they exhibit a significantly decreased T1 relaxivity at UHF. Holmium exhibits outstanding UHF magnetic resonance capabilities in comparison with gadolinium chelates currently used in clinic. Herein, a theranostic nanodrug (HMM@T) was designed for UHF MRI-guided chemo-photothermal therapy. The nanodrug possessed remarkable UHF T2 MRI properties (r2 = 152.13 mM-1s-1) and high drug loading capability of 18.4 %. The biodegradation of HMM@T NPs under triple stimulations of pH, GSH, and NIR led to an efficient release of MTO in tumor microenvironment. Our results revealed the potential of a novel UHF MRI-guided multifunctional nanosystem in cancer treatment.

Synthesis of polyaspartic acid-capped 2-aminoethylamino acid as a green water treatment agent and study of its inhibition performance and mechanism for calcium scales.

Polyaspartic acid (PASP), a well-known green scale inhibitor for industrial water treatment, might be decomposed with prolonged duration, and its anti-scaling performance against CaCO3 and CaSO4 is diminished at a low concentration (<10 mg L-1) and a high temperature. With semi-ethylenediaminetetraacetic acid (EDTA) tetrasodium salt as the mimicking model, novel phosphorus-free PASP-capped 2-aminoethylamino acid (PASP-ED2A) containing side chains bearing multi-functional groups is rationally designed and successfully prepared via the ring-opening reaction of cheap poly(succinimide) under mild reaction conditions with the assistance of readily available 2-aminoethyl amino acid. The static scale inhibition method is used to evaluate the scale inhibition performance of the as-synthesized PASP derivative. Scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy are utilized to monitor the crystallization process of calcium carbonate and calcium sulfate scales, and density functional theory calculations are conducted to shed light on the relationship between the molecular structure and scale inhibition mechanism of PASP-ED2A. Results show that the as-prepared PASP-ED2A shows better scale inhibition performance for CaCO3 and CaSO4 than PASP with a low concentration, a high temperature, and an extended duration. Particularly, PASP-ED2A with a concentration of 10 mg L-1 exhibits the best scale inhibition performance for CaCO3; its scale inhibition capacity is about two times as much as that of PASP. The reason lies in that the coordination atoms in the molecular structure of PASP-ED2A can chelate with Ca2+ to inhibit the combination of Ca2+ with anions and prevent the generation of CaCO3 and CaSO4 scales. The PASP-ED2A derivative can more efficiently retard the formation and growth of CaCO3 and CaSO4 crystal nuclei and exerts better inhibition performance against CaCO3 and CaSO4 scales than PASP.

Functionalized 2D Nb2C nanosheets for primary and recurrent cancer photothermal/immune-therapy in the NIR-II biowindow.

Near-infrared-II (NIR-II) cancer photothermal therapy (PTT) has become more and more attractive as the NIR-II light shows a higher tissue penetrating depth, which leads to better anti-cancer effects. Recently, the members of the MXene family have been reported as NIR-II photothermal agents, possessing a high specific surface area and a fascinating light-to-heat conversion rate at the same time. Herein, we reported a combination of NIR-II photothermal therapy and immune therapy based on the MXene family member niobium carbide (Nb2C). First, Nb2C nanosheets (NSs) under 50 nm were prepared. They showed a high photothermal conversion efficiency under a 1064-nm laser, and the NIR-II light showed a deeper tissue penetration depth. Then, a nanoplatform with high R837 stability and a high loading rate was obtained after modification with a polydopamine (PDA) layer on the surface of Nb2C. With the R837 modification, the percentage of mature dendritic cells (DCs) increased and the immune response enhanced, compared with the immune response caused by PTT only. Finally, a red blood cell (RBC) membrane was applied as a coat over the nanoplatform in order to avoid excessive blood clearance. During in vivo experiments, blood circulation of Nb2C@PDA-R837@RBC nanoparticles (NPs) was prolonged, and all primary tumors were eliminated. Secondary tumors were also inhibited effectively due to the strengthened immune response, proving that Nb2C@PDA-R837@RBC NPs could inhibit tumor recurrence. All the results above indicated Nb2C@PDA-R837@RBC NPs as a potential RBC camouflaged nanoplatform for the combination of effective PTT and immune therapy towards tumor treatment.

Study on the mechanism of active components of Liupao tea on 3CLpro based on HPLC-DAD fingerprint and molecular docking technique.

Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were determined using SARS-COV-2 3-chymotrypsin-like protease (3CLpro ), and an in vitro drug screening model based on fluorescence resonance energy transfer was used to evaluate its inhibitory activity in vitro. The fingerprint results showed that the alcohol extract of Liupao tea contained gallic acid, epigallocatechin gallate (EGCG), caffeine, epicatechin gallate, rutin, and ellagic acid. The molecular docking binding energies of the six index components of SARS-CoV-2 3Clpro were all less than -5.0 kJ/mol and showed strong binding affinity. The results of in vitro activity showed that the IC50 of EGCG was 8.84 µmol/L, which could inhibit SARS-CoV-2 3Clpro to a certain extent. This study unleashed that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , and Liupao tea has a certain significance as a tea drink for the prevention of COVID-19. PRACTICAL APPLICATIONS: The objective of this study was to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor. We predicted that the understandings gained in the current research may evidence that Liupao tea has a certain significance as a tea drink for the prevention of COVID-19.

Synergistic Antitumor Effect of 5-Fluorouracil Combined with Constituents from Pleurospermum lindleyanum in Hepatocellular Carcinoma SMMC-7721 Cells.

BACKGROUND: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. OBJECTIVE: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. METHODS: Sequential chromatographic techniques were conducted for the isolation studies. The isolate's structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. RESULTS: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. CONCLUSION: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.

Effectiveness of theta and gamma electroacupuncture for post-stroke patients on working memory and electrophysiology: study protocol for a double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial.

BACKGROUND: Practitioners of complementary and alternative medicine have suggested that electroacupuncture (EA) could improve post-stroke cognitive impairment, based on the clinical evidence. This study protocol is aimed at showing the effectiveness of theta and gamma EA for post-stroke patients on working memory (WM) and electrophysiology. METHODS: After assessing their eligibility, 66 patients with stroke will be enrolled from two Chinese medicine hospitals and randomly divided into theta frequency EA group, gamma frequency EA group, and sham-EA group according to the ratio of 1:1:1. All patients will receive 20 sessions of EA procedures for 4 weeks. Patients in three groups will receive EA at two same acupoints in the head: Baihui (GV20) and Shenting (GV24). The frequency of the three groups of EA is set as follows: 6 Hz (theta-EA group), 40 Hz (gamma-EA group), and no current through the electrodes (sham EA). Patients and assessors will be blinded throughout the entire study. The primary outcome is the performance accuracy of 1-back task which is a frequently used measure of WM in cognitive neuroscience research contexts. Secondary outcome measures will include the response time of 1-back task, the Rivermead Behavioral Memory Test, Trail Making Test, Loewenstein Occupational Therapy Cognitive Assessment Scale, modified Barthel Index, and electroencephalogram (EEG) signals during 1-back tasks. A blinding index will be assessed. Data will be statistically analyzed by one-way ANOVA, at 5% of significance level. DISCUSSION: We expect this double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial to explore the effectiveness of theta and gamma EA therapy, compared with sham EA, for post-stroke WM. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031995 . Registered on 17 April 2020.

Catalytic rhodium (Rh)-based (mesoporous polydopamine) MPDA nanoparticles with enhanced phototherapeutic efficiency for overcoming tumor hypoxia.

Catalytic nanomedicine with high oxygen-generation efficiency may find applications in alleviating tumor hypoxia and improving the efficiency of photodynamic therapy (PDT). In this study, a catalytic nanosystem (Ce6-Rh@MPDA) was developed using mesoporous polydopamine nanoparticles (MPDA) to encapsulate catalase-like rhodium nanoparticles (Rh NPs) and photosensitizer chlorine6 (Ce6) for photoacoustic/fluorescence dual imaging-guided tumor therapy. The Rh NPs can catalyze the production of O2 from tumor-enriched H2O2in situ, in which the mesoporous structure of MPDA plays an important role via improving the catalytic efficiency of Rh NPs. Moreover, the hyperthermia generated by both MPDA and Rh NPs under laser irradiation accelerates the O2 generation to promote the PDT. The Ce6-Rh@MPDA nanoparticles described herein represent a multifunctional metal-based catalytic nanomedicine which not only alleviates tumor hypoxia but also enables a synergistic antitumor treatment using PTT and PDT.

Mesoporous polydopamine carrying sorafenib and SPIO nanoparticles for MRI-guided ferroptosis cancer therapy.

Iron-based nanomaterials as the main ferroptosis-inducing platforms are more promising because iron itself is a key component in the Fenton reaction to produce ROS. However, the Fe dose needs to be very high in order to induce ferroptosis-based cancer treatment using the SPIO NPs. Therefore, it is still of great challenge to enhance the efficacy of ferroptosis-based cancer therapy by associating the iron-based nanomaterials with other components and therapeutic modalities. In this study, sorafenib (SRF) and ultrasmall SPIO nanoparticles were loaded into the mesopores and onto the surface of MPDA NPs to form SRF@MPDA-SPIO nanoparticles. SPIO loading endowed the system with iron-supply for ferroptosis and made the system MRI-visible. Meanwhile, SRF was able to induce ferroptosis in cancer cells with lower Fe dose. Furthermore, the heat generated by MPDA NPs upon laser irradiation offered a moderate PTT to boost the ferroptosis effect. The SRF@MPDA-SPIO exhibited biocompatibility highly desirable for in vivo application and superior anticancer therapy via the combination of ferroptosis and photothermal therapy.

Polydopamine-Encapsulated Perfluorocarbon for Ultrasound Contrast Imaging and Photothermal Therapy.

Biomedical nanoplatforms have been widely investigated for ultrasound (US) imaging and cancer therapy. Herein, perfluorocarbon (PFC) is encapsulated into biocompatible polydopamine (PDA) to form a theranostic nanosystem, followed by the modification of polyethylene glycol (PEG) to stabilize the nanoparticle via a facile one-pot method. Under 808 nm near-infrared laser irradiation, PDA can generate hyperthermia to transform PFC droplets to bubbles with high US imaging sensitivity. The US imaging detection of the PFC-PDA-PEG nanosystem is achievable in a time span of up to 25 min in vitro at a low US frequency and mechanical index, manifesting a US imaging performance for in vivo application. Moreover, tumor cells incubated with the nanosystem are ablated effectively under laser irradiation at 808 nm. The results illustrate the potential of the PDA-based theranostic agent in US imaging-guided photothermal therapy of tumor.

Theranostic Nanomedicine Carrying L-Menthol and Near-Infrared Dye for Multimodal Imaging-Guided Photothermal Therapy of Cancer.

Photothermal therapy (PTT) as an emerging technique for cancer treatment has drawn great attention owing to its minimally invasive nature. However, it is difficult to achieve a complete tumor regression due to the heterogeneous heat distribution over the tumor. Application of photothermal conversion agents may enhance PTT efficiency, and a multifunctional imaging may provide guidance for the implementation of PTT. Herein, an L-menthol/IR-780 loaded liposome (MIL) is prepared to achieve NIR-triggered cavitation for enhancing photothermal ablation. The synthesized MIL possesses outstanding colloidal stability and photoacoustic/near infrared fluorescence/ultrasound (PA/NIRF/US) imaging contrast to offer multimodal imaging-guided photothermal therapy of cancer. Upon irradiation, the IR-780 acts as the photoabsorber to convert NIR light into heat energy. More importantly, the produced hyperthermia can not only induce ablation of tumor cells but also trigger vaporization and bubbling of encapsulated L-menthol (menthol). Consequently, the generated menthol bubbles obviously enhance the US imaging signal and promote photothermal ablation of the tumor.

Cerasome-based gold-nanoshell encapsulating L-menthol for ultrasound contrast imaging and photothermal therapy of cancer.

Various nanoformulations of perfluorocarbon have been developed thus far, to achieve ultrasound imaging of tumors and tumor-targeted therapy. However, their application has been greatly limited by their short sonographic duration and large size distribution. A novel theranostic agent was constructed based on gold nanoshell cerasome-encapsulated L-menthol (GNC-LM). Owing to the sustained and controllable generation of L-menthol bubbles under near-infrared laser irradiation, GNC-LM showed good performance in contrast enhancement of ultrasound imaging in vivo. GNC-LM could be imaged for 30 min, which is much longer than the imaging time of SonoVue (commercially used microbubbles). Moreover, photothermal therapy (PTT) based on the light-to-heat conversion of the nanosystem effectively ablated the tumor. Our study demonstrated the promising potential of the obtained GNC-LM to serve as a therapeutic nanoprobe for ultrasound contrast imaging and PTT of tumors.

Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy.

Hepatocellular carcinoma (HCC) is one of the most common malignancies imposing a serious threat to human health worldwide. To date, the effect of HCC chemotherapy has been limited due to drug resistance. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy that may improve anticancer effects by synergistic actions. The current study was aimed at achieving better HCC treatment via combination therapy, in which PEI-modified liposomes prepared by a thin-film hydration method were used to codeliver sorafenib (SF) and siRNA targeting GPC3 gene (siGPC3). Under optimized experimental conditions, SF and siGPC3 were effectively loaded into liposomes (SF-PL/siGPC3). SF-PL/siGPC3 with selected sizes and zeta potentials effectively accumulated at tumor sites and entered HCC cells. The two codelivered therapeutic agents exerted good anticancer effects by jointly suppressing the expression of the anti-apoptotic GPC3 gene and the proliferative cyclin D1 gene in HCC. Consequently, the intravenous injection of SF-PL/siGPC3 into nude mice bearing subcutaneous human HepG2 xenografts effectively inhibited tumor growth and also increased the survival rates of animals. These results revealed the great potential of the PEI-modified liposomal nanomedicine carrying SF and siGPC3 to improve HCC treatment.

Dietary L-glutamine supplementation modulates microbial community and activates innate immunity in the mouse intestine.

This study was conducted to determine effects of dietary supplementation with 1 % L-glutamine for 14 days on the abundance of intestinal bacteria and the activation of intestinal innate immunity in mice. The measured variables included (1) the abundance of Bacteroidetes, Firmicutes, Lactobacillus, Streptococcus and Bifidobacterium in the lumen of the small intestine; (2) the expression of toll-like receptors (TLRs), pro-inflammatory cytokines, and antibacterial substances secreted by Paneth cells and goblet cells in the jejunum, ileum and colon; and (3) the activation of TLR4-nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), and phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt) signaling pathways in the jejunum and ileum. In the jejunum, glutamine supplementation decreased the abundance of Firmicutes, while increased mRNA levels for antibacterial substances in association with the activation of NF-κB and PI3K-Akt pathways. In the ileum, glutamine supplementation induced a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes, and enhanced mRNA levels for Tlr4, pro-inflammatory cytokines, and antibacterial substances participating in NF-κB and JNK signaling pathways. These results indicate that the effects of glutamine on the intestine vary with its segments and compartments. Collectively, dietary glutamine supplementation of mice beneficially alters intestinal bacterial community and activates the innate immunity in the small intestine through NF-κB, MAPK and PI3K-Akt signaling pathways.