Untangling the influence of abiotic and biotic factors on leaf C, N, and P stoichiometry along a desert-grassland transition zone in northern China.

Plant elemental composition and stoichiometry are useful tools for understanding plant nutrient strategy and biogeochemical cycling in terrestrial ecosystems. However, no studies have examined how plant leaf carbon (C), nitrogen (N), and phosphorus (P) stoichiometry responds to abiotic and biotic factors in the fragile desert-grassland ecological transition zone in northern China. Then a systematically designed 400 km transect was established to investigate the C, N, and P stoichiometry of 870 leaf samples of 61 species from 47 plant communities in the desert-grassland transition zone. At the individual level, plant taxonomic groups and life forms rather than climate or soil factors determined the leaf C, N, and P stoichiometry. In addition, leaf C, N, and P stoichiometry (except leaf C) was significantly influenced by soil moisture content in the desert-grassland transition zone. At the community level, leaf C content showed a considerable interspecific variation (73.41 %); however, the variation in leaf N and P content, as well as C:N and C:P ratios, was mainly due to intraspecific variation, which was in turn driven by soil moisture. We suggested that intraspecific trait variation played a key role in regulating community structure and function to enhance the resistance and resilience of plant communities to climate change in the desert-grassland transition zone. Our results highlighted the role of soil moisture content as a critical parameter for modeling the biogeochemical cycling in dryland plant-soil systems.

A comprehensive study of alternative splicing in malignant pleural mesothelioma identifies potential therapeutic targets in a new cluster with poor survival.

BACKGROUND: Malignant pleural mesothelioma (MPM) is one of the most aggressive tumors with few effective treatments worldwide. It has been suggested that alternative splicing at the transcriptome level plays an indispensable role in MPM. METHODS: We analyzed the splicing profile of 84 MPM patients from the TCGA cohort by using seven typical splicing types. We classified MPM patients based on their splicing status and conducted a comprehensive analysis of the correlation between the splicing classification and clinical characteristics, genetic variation, pathway changes, immune heterogeneity, and potential therapeutic targets. RESULTS: The expression of the alternative splicing regulator SRPK1 is significantly higher in MPM tissues than in normal tissues, and correlates with poor survival. SRPK1 deficiency promotes MPM cell apoptosis and inhibits cell migration in vitro. We divided the MPM patients into four clusters based on their splicing profile and identified two clusters associated with the shortest (cluster 3) and longest (cluster 4) survival time. We present the different gene signatures of each cluster that are related to survival and splicing. Comprehensive analysis of data from the GDSC and TCGA databases revealed that cluster 3 MPM patients could respond well to the small-molecule inhibitor CHIR-99021, a small-molecule inhibitor of GSK-3. CONCLUSION: We performed unsupervised clustering of alternative splicing data from 84 MPM patients from the TCGA database and identified a cluster associated with the worst prognosis that was sensitive to a GSK-3 inhibitor.

Chlorogenic Acid Improves PTSD-like Symptoms and Associated Mechanisms.

Chlorogenic acid (CGA) is a kind of traditional Chinese medicine, abundant in honeysuckle and eucommia, and has a wide range of biological activities, and pharmacological effects. Previous studies have shown that CGA can regulate learning, memory, cognitive ability, coupled with improvement to anxiety, depression, and other post-traumatic stress disorder (PTSD)-like symptoms. This article explores the protective effects of CGA on neurons through its anti-apoptotic effect, inhibition of neuroinflammation and oxidative stress, which may be the mechanisms of its improvement of PTSD-like symptoms. It may provide a new therapeutic strategy for the treatment of PTSD and its comorbidities.

The Role of Nanoparticles-Mediated Ligustrazine in the Treatment of Knee Osteoarthritis and Its Effect on Matrix Metalloproteinases and Upstream NF-κB Signaling Pathway in Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a joint degenerative arthropathy, characterized by cartilage degeneration of knee joint. Ligustrazine is an effective component of traditional Chinese medicine chuanqiong. It is reported that ligustrazine is used as a kind of anti-inflammatory medicine in folk prescription, especially in the treatment of knee osteoarthritis. The study is aimed to study the therapeutic effect of ligustrazine mediated by nanoparticle on knee osteoarthritis and its impact on MMPs and upstream NF-κB signaling pathway in synovial fluid. Nanoparticle-mediated system is a kind of nano traditional Chinese medicine preparation, which is made by taking nanoparticle and combining with the effective components, effective parts, raw materials, and their compounds in a certain way. We found that the combination of nanoparticle and ligustrazine can improve its bioavailability and targeting, reduce the adverse reactions in the treatment of knee osteoarthritis. The ligustrazine mediated by nanoparticle can effectively alleviate knee osteoarthritis by reducing the level of MMPs in synovial fluid and the expression of NF-κB in upstream NF-κB signaling pathway.

Cost-effectiveness analysis of combining traditional Chinese medicine in the treatment of hypertension: compound Apocynum tablets combined with Nifedipine sustained-release tablets vs Nifedipine sustained-release tablets alone.

BACKGROUND: We evaluated the long-term cost-effectiveness of antihypertensive traditional Chinese medicines (TCMs) and to compare the cost-effectiveness of a combined treatment consisting of compound Apocynum tablets and Nifedipine sustained-release tablets with the cost-effectiveness of treatment with Nifedipine sustained-release tablets alone. METHODS: A Markov model was used to simulate the potential incremental cost-effectiveness per quality-adjusted life year (QALY) to be gained from compound Apocynum tablets and Nifedipine sustained-release tablets compared with Nifedipine sustained-release tablets alone. Model parameter estimates were informed by previously published studies. The direct medical costs of outpatients with hypertension were estimated from the health care provider's perspective. A 5% annual discount rate was applied to both costs and QALYs. RESULTS: TCMs combined with Nifedipine sustained-release tablets group generated a total 20-year cost of 11,517.94 RMB (US $1739.87), whereas Nifedipine sustained-release tablets alone group resulted in a 20-year cost of 7253.71 RMB (US $1095.73). TCMs combined with Nifedipine sustained-release tablets group resulted in a generation of 12.69 QALYs, whereas Nifedipine sustained-release tablets alone group resulted in 12.50. The incremental cost-utility ratio was 22,443.32 RMB (US $3390.23) per QALY. Considering the threshold of 1 GDP per capita in China in 2018 (US $9764.95), the combination of compound Apocynum tablets and Nifedipine sustained-release tablets was a cost-effective strategy. One-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. CONCLUSIONS: Combining Traditional Chinese Medicines with chemical medicines is more cost-effective strategy in the treatment of hypertension.

Salvianolic Acid A Exhibits Anti-Inflammatory and Antiarthritic Effects via Inhibiting NF-κB and p38/MAPK Pathways.

INTRODUCTION: Osteoarthritis (OA), a chronic joint disease, combines with massive inflammation and plays a vital role in cartilage degeneration. The main strategy in clinic is controlling inflammation, thereby treating osteoarthritis. Salvianolic acid A (SAA) is a type of phenolic acid, derived from a traditional chinese herbal medicine Danshen that is extensively used clinically. METHODS AND RESULTS: We observed the anti-inflammatory and antiarthritic effects of SAA in IL-1ß-stimulated cells. We found that SAA evidently decreased the expression of mainly inflammatory factors, exerted the remarkable effects of anti-inflammation and anti-arthritis. Furthermore, SAA inhibited the expression of Matrix metalloproteinases (MMP1, MMP13), and ADAMTS-5 and raised the synthesis of collagen II and aggrecan. Additionally, the results indicated that SAA gave rise to the effects by down-regulation of NF-κB and p38/MAPK pathways. DISCUSSION: Our study demonstrates that SAA may be a promising anti-inflammatory for the treatment of OA in clinic.

Mesoporous Carbon Nanoparticles as Multi-functional Carriers for Cancer Therapy Compared with Mesoporous Silica Nanoparticles.

Mesoporous carriers have been widely used to deliver anticancer drugs due to their unique characteristics. In this work, mesoporous silica nanoparticles (MSN) and mesoporous carbon nanoparticles (MCN) with substantially similar and uniform particle size, specific surface area, and pore size were prepared to compare the photothermal effect, drug loading efficiencies (LE), and drug release properties. In order to improve the dispersion stability and biocompatibility of the carriers, MSN and MCN were grafted with PEG, respectively. The NIR-induced photothermal effect results indicated that MCN had a brilliant photothermal conversion efficiency due to its strong near-infrared absorption capacity, while MSN had no photothermal conversion capability. Moreover, LE of DOX in DOX/MCN-PEG reached 36.58%, higher than that in DOX/MSN-PEG, which was ascribed to non-covalent interaction of π-π stacking and electrostatic attraction. In addition, compared to DOX/MSN-PEG, DOX/MCN-PEG had a significantly increased release rate under NIR laser irradiation due to excellent photothermal conversion capability of MCN-PEG. Furthermore, cell viability assay and cellular uptake experiment results demonstrated that DOX/MCN-PEG showed a synergistic therapeutic effect in the combination of chemotherapy and phototherapy, with a combination index (CI) of 0.238.

Triple stimuli-responsive ZnO quantum dots-conjugated hollow mesoporous carbon nanoplatform for NIR-induced dual model antitumor therapy.

Aiming at the inefficiency and toxicity in traditional antitumor therapy, a novel multifunctional nanoplatform was constructed based on hollow mesoporous carbon (HMC) to achieve triple stimuli response and dual model antitumor therapy via chemo-photothermal synergistic effect. HMC was used as an ideal nanovehicle with a high drug loading efficiency as well as a near-infrared (NIR) photothermal conversion agent for photothermal therapy. Acid-dissoluble, luminescent ZnO quantum dots (QDs) were used as the proper sealing agents for the mesopores of HMC, conjugated to HMC via disulfide linkage to prevent drug (doxorubicin, abbreviated as Dox) premature release from Dox/HMC-SS-ZnO. After cellular endocytosis, the Dox was released in a pH, GSH and NIR laser triple stimuli-responsive manner to realize accurate drug delivery. Moreover, the local hyperthermia effect induced by NIR irradiation could promote the drug release, enhance cell sensitivity to chemotherapeutic agents, and also directly kill cancer cells. As expected, Dox/HMC-SS-ZnO exhibited a high drug loading capacity of 43%, well response to triple stimuli and excellent photothermal conversion efficiency η of 29.7%. The therapeutic efficacy in 4T1 cells and multicellular tumor spheroids (MCTSs) demonstrated that Dox/HMC-SS-ZnO + NIR had satisfactory chemo-photothermal synergistic effect with a combination index (CI) of 0.532. The cell apoptosis rate of the combined treatment group was more than 95%. The biodistribution and pharmacodynamics studies showed its biosecurity to normal tissues and synergistic inhibition effect to tumor cells. These distinguished results indicated that the Dox/HMC-SS-ZnO nanoplatform is potential to realize efficient triple stimuli-responsive drug delivery and dual model chemo-photothermal synergistic antitumor therapy.

Moderate intensity low frequency rotating magnetic field inhibits breast cancer growth in mice.

Moderate intensity low frequency rotating magnetic field (LF-RMF) has been shown to inhibit melanoma, liver and lung cancer growth in mice. However, its effects on other types of cancers have not been investigated in vivo. Here, we show that 0-0.15T moderate intensity 4.2 Hz LF-RMF can inhibit tumor growth in mice bearing MDA-MB231 and MCF7 human breast cancer cells by over 30%. In contrast, the human gastrointestinal stromal tumor GIST-T1 growth was not inhibited by LF-RMF. In all RMF treatments, there were no apparent adverse effects on mice organs, body weight or water/food consumptions. However, the alanine aminotransferase (ALT) level was decreased in LF-RMF-treated mice bearing MCF7 and GIST-T1 cells, which indicated alleviated liver damage. Therefore, our study shows that moderate intensity LF-RMF might be a safe physical method that has clinical potentials to be used to inhibit breast cancer growth in the future.

Fatty Acid Metabolism is Associated With Disease Severity After H7N9 Infection.

BACKGROUND: Human infections with the H7N9 virus could lead to lung damage and even multiple organ failure, which is closely associated with a high mortality rate. However, the metabolic basis of such systemic alterations remains unknown. METHODS: This study included hospitalized patients (n = 4) with laboratory-confirmed H7N9 infection, healthy controls (n = 9), and two disease control groups comprising patients with pneumonia (n = 9) and patients with pneumonia who received steroid treatment (n = 10). One H7N9-infected patient underwent lung biopsy for histopathological analysis and expression analysis of genes associated with lung homeostasis. H7N9-induced systemic alterations were investigated using metabolomic analysis of sera collected from the four patients by using ultra-performance liquid chromatography-mass spectrometry. Chest digital radiography and laboratory tests were also conducted. FINDINGS: Two of the four patients did not survive the clinical treatments with antiviral medication, steroids, and oxygen therapy. Biopsy revealed disrupted expression of genes associated with lung epithelial integrity. Histopathological analysis demonstrated severe lung inflammation after H7N9 infection. Metabolomic analysis indicated that fatty acid metabolism may be inhibited during H7N9 infection. Serum levels of palmitic acid, erucic acid, and phytal may negatively correlate with the extent of lung inflammation after H7N9 infection. The changes in fatty acid levels may not be due to steroid treatment or pneumonia. INTERPRETATION: Altered structural and secretory properties of the lung epithelium may be associated with the severity of H7N9-infection-induced lung disease. Moreover, fatty acid metabolism level may predict a fatal outcome after H7N9 virus infection.

[Antitumor activity and structure-activity relationship of seven lanostane-type triterpenes from Fomitopsis pinicola and F. officinalis].

Seven lanostane-type triterpenes including fomitopsin C(1),3-keto-dehydrosulfurenic acid(2),dehydroeburiconic acid(3),3-acetyloxylanosta-8, 24-dien-21-oic acid(4),pinicolic acid A(5),trametenolic acid B(6),and eburicoic acid(7),were isolated from the fruitbodies of Fomitopsis pinicola and F. officinalis. In vitro assay, all compounds were evaluated against MCF-7, HeLa, HepG2 and A549 cells lines using the MTT assay and the structure-activity relationship of antitumor activity was discussed. The results showed that the seven compounds were more sensitive to MCF-7 cells.The IC50 value for MCF-7 was 2<5<4<1<3<6<7. H22 tumor mouse model was used to assay compounds 2, 3, 4 and 5 in vivo. Compounds 2 and 4 had obvious effect and the necrosis area and measurement were positively correlated. The results showed that compounds 2, 4 and 5 had significant antitumor activities at a dose of 20 mg•L⁻¹ with 65.31%, 56.71%, 58.72% suppression, respectively, approaching to CTX group with 69.19% suppression in subcutaneous H22-implanted mice.The results showed that these compounds had significant against the expression of VEGF, cytokines IL-4 and IFN-γ tumor, additionally, the structure-activity relationship of lanostane-type triterpenes indicated that the acetoxyl or carbonyl at C-3 and hydroxy at C-15 can enhance the antitumor activity.

[Study on the relationship between tone burst ABR and CE-Chirp ASSR in infants with profound sensorineural hearing loss].

OBJECTIVE: To analyse the correlation between tone burst auditory brainstem response (tone burst auditory brainstem response, tb-ABR) and CE-Chirp voice evoked auditory steady-state response (auditory steady-state response, CE-Chirp ASSR) in infants with profound sensorineural hearing loss. METHODS: A total of 45 infants with profound sensorineural hearing loss underwent threshold tone burst ABR and CE-Chirp ASSR of the frequency response test, response thresholds were recorded in 0.5, 1.0, 2.0 and 4.0 kHz. Whether there was correlation or not existed between two methods were analyzed, SPSS 11.0 statistics software was used. RESULTS: Tone burst ABR and CE-Chirp ASSR could lead to different degrees of threshold in each frequency. Response e elicited threshold percentage mainly concentrated in the 91-100 dBnHL, correlation coefficient between 500-4 000 Hz response threshold elicited rate were: 0.837, 0.913, 0.909, and 0.919, respectively (P < 0.001). The difference of the frequency response threshold test between CE-Chirp ASSR and tone burst ABR were not significant (P > 0.05, Chi square). CONCLUSIONS: The tone burst ABR and CE-Chirp ASSR each frequency have different levels of residual hearing in infants with profound sensorineural hearing loss diagnosed by Click ABR, good correlation exists between tone burst ABR and CE-Chirp ASSR.

Primary and secondary drug screening assays for Friedreich ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the protein frataxin. Frataxin chaperones iron in the mitochondrial matrix for the assembly of iron-sulfur clusters (ISCs), which are prosthetic groups critical for the function of the Krebs cycle and the mitochondrial electron transport chain (ETC). Decreased expression of frataxin or the yeast frataxin orthologue, Yfh1p, is associated with decreased ISC assembly, mitochondrial iron accumulation, and increased oxidative stress, all of which contribute to mitochondrial dysfunction. Using yeast depleted of Yfh1p, a high-throughput screening (HTS) assay was developed in which mitochondrial function was monitored by reduction of the tetrazolium dye WST-1 in a growth medium with a respiration-only carbon source. Of 101 200 compounds screened, 302 were identified that effectively rescue mitochondrial function. To confirm activities in mammalian cells and begin understanding mechanisms of action, secondary screening assays were developed using murine C2C12 cells and yeast mutants lacking specific complexes of the ETC, respectively. The compounds identified in this study have potential relevance for other neurodegenerative disorders associated with mitochondrial dysfunction, such as Parkinson disease.

HTS-driven discovery of new chemotypes with West Nile Virus inhibitory activity.

West Nile virus (WNV) is a positive sense, single-stranded RNA virus that can cause illness in humans when transmitted via mosquito vectors. Unfortunately, no antivirals or vaccines are currently available, and therefore efficient and safe antivirals are urgently needed. We developed a high throughput screen to discover small molecule probes that inhibit virus infection of Vero E6 cells. A primary screen of a 13,001 compound library at a 10 microM final concentration was conducted using the 384-well format. Z' values ranged from 0.54-0.83 with a median of 0.74. Average S/B was 17 and S/N for each plate ranged from 10.8 to 23.9. Twenty-six compounds showed a dose response in the HT screen and were further evaluated in a time of addition assay and in a titer reduction assay. Seven compounds showed potential as small molecule probes directed at WNV. The hit rate from the primary screen was 0.185% (24 compounds out of 13,001 compounds) and from the secondary screens was 0.053% (7 out of 13,001 compounds) respectively.

[Influence of therapeutic effect of acupoint sticking at Shenque (CV 8) for treatment of stroke patients].

OBJECTIVE: To observe the therapeutic effect of acupoint sticking therapy for treatment of stroke. METHODS: Two hundred and forty-six cases were randomly divided into a non-acupoint sticking group (control group, n=122) and an acupoint sticking group (n=124). The control group was treated with routine ward treatment of stroke (acupuncture combined with routine western medicine). The acupoint sticking group was treated with basis ward treatment of stroke (similar to the control group), and acupoint sticking therapy was applicated on Shenque (CV 8). The scores of Stroke-Specific Quality of Life (SS-QOL) and WHOQOL-100BREF were adopted to evaluate the therapeutic effects and the cysteine of patients were tested before and after treatment. RESULTS: There were significant differences in scores comparison of SS-QOL and WHOQOL-100BREF before and after treatment in both groups (both P < 0.001); there was no significant difference after treatment between two groups (P > 0.05); there was a significant difference in thinking items of SS-QOL after treatment between two groups (P < 0.05), the acupoint sticking group was superior to that of control group; SS-QOL score of patients with abnormal cysteine of acupoint sticking group was superior to that of the control group after treatment, with a significant difference between the two groups (P < 0.05). CONCLUSION: The acupoint sticking therapy can improve the thinking ability of stroke patients, and improve the life quality of high cysteine stroke patients.

Influence of therapeutic effect of acupoint sticking at Shenque (CV 8) for treatment of stroke patients / 中国针灸

<p><b>OBJECTIVE</b>To observe the therapeutic effect of acupoint sticking therapy for treatment of stroke.</p><p><b>METHODS</b>Two hundred and forty-six cases were randomly divided into a non-acupoint sticking group (control group, n=122) and an acupoint sticking group (n=124). The control group was treated with routine ward treatment of stroke (acupuncture combined with routine western medicine). The acupoint sticking group was treated with basis ward treatment of stroke (similar to the control group), and acupoint sticking therapy was applicated on Shenque (CV 8). The scores of Stroke-Specific Quality of Life (SS-QOL) and WHOQOL-100BREF were adopted to evaluate the therapeutic effects and the cysteine of patients were tested before and after treatment.</p><p><b>RESULTS</b>There were significant differences in scores comparison of SS-QOL and WHOQOL-100BREF before and after treatment in both groups (both P < 0.001); there was no significant difference after treatment between two groups (P > 0.05); there was a significant difference in thinking items of SS-QOL after treatment between two groups (P < 0.05), the acupoint sticking group was superior to that of control group; SS-QOL score of patients with abnormal cysteine of acupoint sticking group was superior to that of the control group after treatment, with a significant difference between the two groups (P < 0.05).</p><p><b>CONCLUSION</b>The acupoint sticking therapy can improve the thinking ability of stroke patients, and improve the life quality of high cysteine stroke patients.</p>