Melatonin, a phytohormone for enhancing the accumulation of high-value metabolites and stress tolerance in microalgae: Applications, mechanisms, and challenges.

High-value metabolites, such as carotenoids, lipids, and proteins, are synthesized by microalgae and find applications in various fields, including food, health supplements, and cosmetics. However, the potential of the microalgal industry to serve these sectors is constrained by low productivity and high energy consumption. Environmental stressors can not only stimulate the accumulation of secondary metabolites in microalgae but also induce oxidative stress, suppressing cell growth and activity, thereby resulting in a decrease in overall productivity. Using melatonin (MT) under stressful conditions is an effective approach to enhance the productivity of microalgal metabolites. This review underscores the role of MT in promoting the accumulation of high-value metabolites and enhancing stress resistance in microalgae under stressful and wastewater conditions. It discusses the underlying mechanisms whereby MT enhances metabolite synthesis and improves stress resistance. The review also offers new perspectives on utilizing MT to improve microalgal productivity and stress resistance in challenging environments.

Loke zupa decoction attenuates bronchial EMT-mediated airway remodelling in chronic asthma through the PI3K-Akt/HIF-1α signaling pathway.

CONTEXT: Loke zupa decoction (Lok) is a well-established classic Chinese folk remedy for asthma. OBJECTIVE: We sought to investigate the effect and mechanism of Lok on asthma airway remodelling and provide novel insights for the prevention and treatment of asthma. MATERIALS AND METHODS: For in vitro experiments, BEAS-2B cells were assigned into six groups: Control, TGF-ß1 (10 µM), TGF-ß1 + Lok-20, TGF-ß1 + Lok-40, TGF-ß1 + Lok-80 µg/mL and TGF-ß1 + SB431542 (5 µM). CCK8 and wound healing assays were performed. For in vivo experiments, 60 female BALB/c mice were randomly divided into 5 groups: Control, model, Lok-4.55, Lok-9.1, and DEX group. Lok was administrated by gavage during the challenge stage for 8 consecutive weeks (4.55 and 9.1 g/kg/day). We investigated airway inflammation and airway remodelling in the lungs and verified the activation status of EMT-related markers and the PI3K-Akt/HIF-1α signalling pathway. RESULTS: In vitro, Lok efficiently inhibited TGF-ß1-induced BEAS-2B cell proliferation ability (cell viability 165% vs. 105%) and migration (migration areas 85% vs. 35%) without affecting their normal growth (IC50 274.2 µg/mL at 48 h). In vivo, Lok effectively protected mice from asthma, as evidenced by decreased histological damage and level of cytokines in BALF (IL-4, IL-13 and TGF-ß1) by 17%-77%. Mechanistic research revealed that Lok reduced the levels of EMT-related molecules and significantly downregulated the PI3K-Akt/HIF-1α signalling pathway. DISCUSSION AND CONCLUSIONS: Our findings provide novel insights into the protective effect of Lok on asthma and the underlying mechanisms, providing a theoretical basis and potential treatment possibilities for this patient population.

Silicon composition and stoichiometric ratios with other nutrients in the lower Minjiang River, Southeast China.

Over the past decades, rivers have delivered imbalanced nutrient loads to coastal marine ecosystems due to human activities, which leads to serious regional or global eutrophication problems. The Minjiang River is heavily influenced by human activities. To understand the changing characteristics of nutrient transport ratios in the Minjiang River waters, we measured the seasonal variations of carbon, nitrogen, phosphorus and silicon nutrients in the lower surface waters of the Minjiang River between July 2019 and July 2020. The results showed that the annual average contents of dissolved silicon (DSi), lithogenic silicon (LSi) and biogenic silicon (BSi) in the surface waters of the lower Minjiang River were 5.30, 4.58 and 2.37 mg·L-1, respectively. There were large seasonal differences among these parameters, with higher content of DSi than LSi and BSi in summer, higher content of DSi than BSi and LSi in autumn and higher content of LSi than DSi and BSi in winter. The proportions of DSi in total silicon tended to decrease gradually from land to sea, while the proportion of BSi was on the contrary. In term of stoichiometric ratios, the Minjiang River mostly presented carbon or phosphorus limitation and was unlimited by silicon or nitrogen. About 1.03×1010 mol DSi and 0.46 ×1010 mol BSi were delivered via the Minjiang River to the ocean yearly, showing a decreasing trend year by year. Based on the data in recent years, the nutrient loads of carbon, nitrogen, and phosphorus transported by Minjiang River showed an increasing trend. The imbalanced nutrient loads may lead to changes in the structure and function of the river, estuary, and offshore ecosystems. The study of nutrient stoichiometric ratios can provide a theoretical basis for solving the problems in structural balance of nutrients and eutrophication in Minjiang River estuary and adjacent marine waters.

Systemic Diclofenac Sodium Reduces Postoperative rhBMP-2 Induced Neuroinflammation: A Rodent Model Study.

STUDY DESIGN: This is a basic science, animal research study. OBJECTIVE: This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation. SUMMARY OF BACKGROUND DATA: rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis. MATERIALS AND METHODS: Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups. RESULTS: The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant ( P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively ( P < 0.05). CONCLUSION: This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2-induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2-induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2-induced inflammation.

UVA1 irradiation attenuates collagen production via Ficz/AhR/MAPK signaling activation in scleroderma.

Scleroderma is an autoimmune disease mainly characterized by progressive fibrosis of the skin. There are two types of scleroderma, namely localized scleroderma (LS) and systemic sclerosis (SSc); skin lesions in both types of scleroderma are histologically identical. Progressive skin sclerosis induces psychological and ecological burden for scleroderma patients. However, there is no effective treatment for scleroderma due to its unclear etiology. Aryl hydrocarbon receptor (AhR) is recognized as an environmental chemical effector that can respond to ultraviolet radiation, which has been demonstrated to participate in the pathogenesis of SSc in our previous study. In this study, we verify whether the anti-fibrosis effect of ultraviolet A1 (UVA1) phototherapy could be partially induced through Ficz/AhR/MAPK signaling activation for fibrotic lesions in both SSc and LS patients. This is the first study to show the association between the AhR pathway and the anti-fibrotic mechanism of UVA1 phototherapy, which provides additional evidence of the role of AhR in the fibrotic mechanism of systemic scleroderma from different perspectives. Ficz and other AhR agonists may replace UVA1 phototherapy as anti-fibrotic agents in scleroderma.

Inspiratory muscle training improves cardiopulmonary function in patients after transcatheter aortic valve replacement: a randomized clinical trial.

AIMS: Inspiratory muscle training (IMT) can increase the strength or endurance of the diaphragm and accessory muscles of inspiration, yet there is no evidence that endorses the role of IMT in patients of transcatheter aortic valve replacement (TAVR). This study for the first time tested the effects of IMT plus usual cardiac rehabilitation (CR) function in patients after TAVR. METHODS AND RESULTS: A double-blinded, randomized controlled, single-centre clinical trial was undertaken. Participants who had a confirmed diagnosis of valve heart disease and were clinically stable after TAVR were recruited and received a CR programme during the hospital stay. A total of 96 patients were recruited and randomly assigned to the IMT + CR group (n = 48) or the CR group (n = 48) in a 1:1 ratio. The group difference in the primary outcome, the 6-min walk distance at the discharge of the hospital, significantly favoured the IMT + CR group (mean difference -33.52, 95% CI: -64.42 to -2.62, P = 0.034). The significant difference was maintained at the 1-month and 3-month follow-ups (mean difference: 41.51, 95% CI: 1.82-81.21, P = 0.041). In addition, the mean hospital stays of subjects in the IMT + CR group was 11 days, which was significantly shorter than the 12.5 days in the CR group (P = 0.016). Sensitivity analysis using per-protocol analysis supported these findings. No adverse treatment-related events were reported. CONCLUSION: Compared with usual CR, IMT plus CR can effectively improve exercise endurance, pulmonary ventilation function, and inspiratory muscle strength in patients after TAVR and shorten the length of hospital stay.

First Report of Achromobacter Xylosoxidans Causing Stem Soft Rot on Amorphophallus Konjac in China.

Amorphophallus konjac is one of the important commercial crops cultivated in south China and has long been used as a food source and a traditional medicine, because it is the only species with glucomannan and other trace elements (Ban et al. 2009; Melinda et al. 2010). In June of 2021, an outbreak of stem soft rot disease was observed on A. konjac plants in more than 2,000 square meters of agricultural planting fields in the Fuyuan country (25°34'50″N, 104°04'21″E), Qujing City, Yunnan Province, China. The disease incidence ranged from 30 to 35% in severely infested fields. The diseased plants displayed the first symptoms were damp brown spots. As the brown spots expanded, dark brown water stains appeared at the basal part of the stem and the bulbs were rotting with a foul smell, gradually extending to the underground parts. Progressively, the whole plants wilted and collapsed, and even the plants ultimately died. To identify the pathogen, symptomatic stems were cut into pieces, surface sterilized with 75% (v/v) ethanol, and placed on LB (tryptone/yeast extract/NaCl) medium for 24 to 48 hours at 28 ± 2°C. Six single-colony isolates were obtained from the diseased stems. The colonies on LB present a raised milky white opaque colonies moisture on the surface, round and convex in shape, with neat edges. Scanning electron microscopy showed that the cells were short rods (0.3∼0.5) × (1.9∼2.1)µm in size without any flagellum and were often arranged in pairs or clusters at certain angles. The 16S rDNA sequence of the randomly selected strain MY-G1 with primers 27F/1492R (Ying et al. 2012) and the housekeeping genes nusA, eno, lepA and nuoL (Spilker et al. 2012) were amplified and sequenced. The 16S rDNA sequence of the 1326 bp product was deposited in GenBank (accession no. ON786717) and showed a 99.77% similarity to A. xylosoxidans strain E2 (accession no. MK849863.1). The nusA (OP680477), eno (OP680479), lepA (OP680481) and nuoL (OP680482) sequences showed 94.71%, 97.24%, 94.64% and 95.95% similarity to A. xylosoxidans strain DN002 (accession no. CP045222.1), respectively. The phylogenetic trees built based on 16S rRNA and the nusA-eno-lepA-nuoL multilocus analysis showed the isolate MY-G1 to cluster with A. xylosoxidans. Based on morphological and molecular analysis, the isolated MY-G1 was identified as A. xylosoxidans, which indicates that MY-G1 is a new strain of A. xylosoxidans. Pathogenicity tests were confirmed on the stem and petiole of one-year-old A. konjac. The wounds were made by puncturing with a MY-G1 bacteria suspension containing 108 CFU/ml (15ul/inoculation site). As a negative control, control seedlings were injected with the same amount of sterilized distilled water. Control and inoculated seedlings (each six) were kept in greenhouses and watered as needed in controlled conditions: 28°C, 75% relative humidity. Inoculated seedlings presented similar symptoms of stem soft rot, inner medulla disintegration, and wilt of leaves on developed within 3 to 9 days. The bacterial pathogen was re-isolated from inoculated seedlings and identified by morphological and molecular methods to fulfill Koch's postulates test. According to previous research, A. xylosoxidans can cross-kingdom infect animals and plants (Aisenberg et al.,2004; Ye et al.,2018). To the best of our knowledge, this is the first report of A. xylosoxidans causing stem soft rot of A. konjac in China, expanding the known pathogen for the soft rot of A. konjac, and also the host range of A. xylosoxidans.

Combined metabolomics and proteomics to reveal beneficial mechanisms of Dendrobium fimbriatum against gastric mucosal injury.

As a dietary and medicinal plant, Dendrobium fimbriatum (DF) is widely utilized in China for improving stomach disease for centuries. However, the underlying mechanisms against gastric mucosal injury have not been fully disclosed. Here, metabolomics and proteomics were integrated to clarify the in-depth molecular mechanisms using cyclophosphamide-induced gastric mucosal injury model in mice. As a result, three metabolic pathways, such as creatine metabolism, arginine and proline metabolism, and pyrimidine metabolism were hit contributing to DF protective benefits. Additionally, γ-L-glutamyl-putrescine, cytosine, and thymine might be the eligible biomarkers to reflect gastric mucosal injury tatus, and DF anti-gastric mucosal injury effects were mediated by the so-called target proteins such as Ckm, Arg1, Ctps2, Pycr3, and Cmpk2. This finding provided meaningful information for the molecular mechanisms of DF and also offered a promising strategy to clarify the therapeutic mechanisms of functional foods.

Lu3+-based nanoprobe for virtual non-contrast CT imaging of hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE), the mainstream treatment for hepatocellular carcinoma (HCC), is a method of blocking tumor blood vessels with a mixture of lipiodol and chemotherapeutics. And the contrast-enhanced computed tomography (CT) is the commonly used way for follow-up of HCC after TACE. However, it is noteworthy that when lipiodol deposition plays an embolic effect, it also produces high-density artifacts in CT images. These artifacts usually conceal the enhancement effect of iodine contrast agents. As a result, the residual region is difficult to be visualized. To overcome this obstacle, we developed one kind of Lu3+/Gd3+ doped fluoride nanoprobe modified with Dp-PEG2000 to realize CT/MRI dual-modality imaging of HCC. Compared with lipiodol or ioversol, the obtained PEGylated product LG-PEG demonstrated a greater density value in high keV CT images. In vitro experiments showed the lipiodol artifacts can be removed in virtual non-contrast (VNC) imaging, but the density of ioversol was also removed at the same time. However, the LG-PEG synthesized in this work can still maintain a high density in VNC imaging, which indicates that LG-PEG can exploit its advantages to the full in VNC imaging. Furthermore, LG-PEG successfully exerted tumor enhancement effects in the in vivo VNC images of HCC with lipiodol deposition. In addition, LG-PEG exhibited a strong T2 enhancement effect with low biological toxicity and less side-effect on the main organ and blood. Thus, the LG-PEG reported in this research can serve as an effective and safe VNC contrast agent for HCC imaging after TACE.

Phenotype-Based HPLC-Q-TOF-MS/MS Coupled With Zebrafish Behavior Trajectory Analysis System for the Identification of the Antidepressant Components in Methanol Extract of Anshen Buxin Six Pills.

Phenotype screening has become an important tool for the discovery of active components in traditional Chinese medicine. Anshen Buxin Six Pills (ASBX) are a traditional Mongolian medicine used for the treatment of neurosis in clinical settings. However, its antidepressant components have not been explicitly identified and studied. Here, the antidepressant effect of ASBX was evaluated in adult zebrafish. High performance liquid chromatography-mass spectrometry (HPLC-Q-TOF-MS/MS) was combined with zebrafish behavior trajectory analysis to screen and identify the antidepressant-active extract fraction and active components of ASBX. Finally, the antidepressant effect of the active ingredients were verified by the behavior, pathology, biochemical indices and protein level of adult fish. The novel tank driving test (NTDT) showed that ASBX can effectively improve the depressive effect of reserpine on zebrafish. Petroleum ether and dichloromethane extracts of ASBX were screened as antidepressant active extracts. Costunolide (COS) and dehydrocostus lactone (DHE) were screened as the active components of ASBX. COS had been shown to significantly improve the depressive behavior, nerve injury and neurotransmitter levels (5-hydroxytryptamine (5-HT) and norepinephrine (NE)) of zebrafish by inhibiting the high expression of serotonin transporter and norepinephrine transporter induced by reserpine suggesting the antidepressant effect of COS may be related to its effect on 5-HT and NE pathways. This study provided a phenotype based screening method for antidepressant components of traditional Chinese medicines, so as to realize the separation, identification and activity screening of components at the same time.

Arsenite-loaded albumin nanoparticles for targeted synergistic chemo-photothermal therapy of HCC.

Arsenic trioxide (ATO, As2O3), an active ingredient of traditional Chinese medicine, has been approved by the U.S. Food and Drug Administration as an effective therapeutic agent for acute promyelocytic leukemia (APL). However, the application of ATO in treating advanced solid tumors like hepatocellular carcinoma (HCC) is still restricted by limited therapeutic efficacy and insufferable side effects. To solve this problem, we reported a general and facile strategy using human serum albumin (HSA) as a template for synthesizing a series of ATO-based nanoparticles with uniform single-albumin size. Then, we prepared a multifunctional drug delivery system (MDDS) based on MnAs/HSA termed MnAs/ICG/HSA-RGD, and tested its efficacy both in vitro and in vivo. Our results revealed that the photothermal effect of MnAs/ICG/HSA-RGD can not only cause irreversible damage to the tumor but also accelerate the discharge of As and Mn2+ ions, enabling responsive chemotherapy and magnetic resonance imaging. Interestingly, the expression of HSP90, vimentin, and MMP-9 in tumor cells was inhibited during the treatment, resulting in less metastasis and recurrence. Moreover, no apparent side effect has been observed during the treatment. Therefore, MnAs/ICG/HSA-RGD can be considered as a promising option for HCC with excellent therapeutic efficacy and minimum side effects.

[Research on in vivo metabolites of Longxue Tongluo Capsules by liquid chromatography coupled with hybrid ion trap/time-of-flight mass spectrometry].

Longxue Tongluo Capsules(LTC) has good efficacy against blood stasis syndrome during the recovery period of ischemic stroke. Its main active ingredient is the phenolic extract of Chinese dragon's blood. In our previous study, the primary mass fragmentation pathways of phenolic derivatives from LTC were clarified. Herein, the metabolites in rat plasma were characterized following the oral administration of loureirin A and loureirin C using liquid chromatography coupled with hybrid ion trap/time-of-flight mass spectro-metry(LC-IT-TOF-MS), with 18 and 55 metabolites identified, respectively. On this basis, with the help of the obtained accurate molecular weight, characteristic fragment ions, reference comparison, combined with LTC database and natural products database self-created in our group, 18 prototypes and 106 metabolites were tentatively identified in rat plasma after oral gavage of LTC at a dose of 500 mg·kg~(-1). Glucuronidation, sulfonation, and methylation were major biotransformation pathways of LTC. This study preliminarily clarified the LTC constituents absorbed into blood and laid the foundation for clarifying the effective substances of LTC.

Bi/Se-Based Nanotherapeutics Sensitize CT Image-Guided Stereotactic Body Radiotherapy through Reprogramming the Microenvironment of Hepatocellular Carcinoma.

The particular characteristics of hypoxia, immune suppression in the tumor microenvironment, and the lack of accurate imaging guidance lead to the limited effects of stereotactic body radiotherapy (SBRT) in reducing the recurrence rate and mortality of hepatocellular carcinoma (HCC). This research developed a novel theranostic agent based on Bi/Se nanoparticles (NPs), synthesized by a simple reduction reaction method for in vivo CT image-guided SBRT sensitization in mice. After loading Lenvatinib (Len), the obtained Bi/Se-Len NPs had excellent performance in reversing hypoxia and the immune suppression status of HCC. In vivo CT imaging results uncovered that the radiotherapy (RT) area could be accurately labeled after the injection of Bi/Se-Len NPs. Under Len's unique and robust properties, in vivo treatment was then carried out upon injection of Bi/Se-Len NPs, achieving excellent RT sensitization effects in a mouse HCC model. Comprehensive tests and histological stains revealed that Bi/Se-Len NPs could reshape and normalize tumor blood vessels, reduce the hypoxic situation of the tumor, and upregulate tumor-infiltrating CD4+ and CD8+ T lymphocytes around the tumors. Our work highlights an excellent proposal of Bi/Se-Len NPs as theranostic nanoparticles for image-guided HCC radiotherapy.

[Identification of active components of Dendrobium inhibit growth of gastric cancer cells based on component-activity relationship].

Three cancer cell lines including gastric cancer SGC-7901, HGC-27, and MGC-803 cells were employed to evaluate the bioactivity of seven Dendrobium species. Simultaneously, these Dendrobium species were assessed with UPLC-Q-TOF-MS, and 504 common peaks were found. Based on the hypothesis that biological effects varied with differences in components, multivariate relevance analysis for chemical component-activity relationship of Dendrobium, including grey relation(GRA) and partial least squares(PLS) analysis were performed to evaluate the contribution of each identified component. The target peaks were identified by standards toge-ther with databases of Dendrobium, Nature Chemistry, MassBank, etc. Finally, four active components, including 3,5,9-trihydroxy-23-methylergosta-7,22-dien-6-one, diacylglycerol(14∶1/22∶6/0∶0), pipercitine, and 22-tricosenoic acid, might have negative effect on the growth of gastric cancer cells.

First Report of Botryosphaeria dothidea Causing Stem Canker and Dieback of Gleditsia sinensis in China.

Gleditsia Sinensis Lam is a kind of legume perennial woody plant, which is a traditional Chinese medicine with high economic and ecological value. Its planting area is about 0.1 million ha. In July 2018, symptoms of stem blight were observed on G. sinensis in An shun (26.072311°N, 106.097433°E), Guizhou province (southwestern China). Symptoms included stem canker and dieback, twig blight and extensive vascular discoloration, with incidence rate of 45 to 70%. Samples from plants with symptoms were washed with running tap water, surface sterilized with 2% sodium hypochlorite and then 75% ethanol, rinsed in sterile distilled water, plated on potato dextrose agar (PDA) and incubated at 28°C. Fungal isolates developed copious white aerial mycelium that became dark grey after four to five days, and formed black pycnidia after 23 days. Single hyphal tip cultures of putative 27 isolates were stored in the culture collection (CMW) of the Urban Modern Agriculture Engineering Research Center at the Kunming University. Conidia forming on pycnidia were one-celled, hyaline, aseptate, and fusiform, with dimensions of 20.3-25.9 µm x 4.2-6.5 µm (average 22.5 x 5.5 µm) (sixty conidia were measured). DNA sequence analysis of the ribosomal internal transcribed spacer regions ITS1-5.8S-ITS4, ß-tubulin, and the translation elongation factor 1-alpha (EF1-α) were performed. BLAST searches at GenBank showed the highest nucleotide sequence identity with Botryosphaeria dothidea reference sequence (ITS: >99.82%, KR708996; EF1-α: 99.62%, KP183214; ß-tubulin: > 99.67%, KU306116). Representative sequences of isolates from these regions were deposited in GenBank (ITS: Accession No. MT449017; EF1-α: Accession No. MT454342; ß-tubulin: Accession No. MT454343). Morphological and molecular results confirmed this species as B. dothidea (Aguirre et al. 2018). Pathogenicity tests were conducted by stem inoculation of two-year-old G. sinensis seedlings. Mycelial plugs (2-3 mm in diameter) from actively growing colonies of B. dothidea (PDA) were applied to same-size bark wounds on the middle point of the stems. Inoculated wounds were wrapped with Parafilm. Control seedlings received sterile PDA plugs. Inoculated and control seedlings (9 each), and kept in the greenhouse (28℃, 80% humidity); After 10 days, all of the inoculated plants showed dark vascular stem tissue, and the controls remained healthy. After 30 days, all of the inoculated but none of the control G. sinensis seedlings showed leaf wilting and tissue discoloration. B. dothidea was re-isolated from symptomatic tissues, thus fulfilling Koch's postulates. No symptoms were visible in the control seedlings, and no B. dothidea was re-isolated from the control seedlings tissues. B. dothidea is a member of Botryosphaeriaceae, commonly associated with cankers and dieback of woody plants. B. dothidea has been reported as a pathogen causing stem dieback and branch canker on Malosma laurina (Aguirre et al. 2018), Helwingia chinensis (Yu et al. 2012), and blueberry (Choi 2011; Yu et al. 2012). To our knowledge, this is the first report of B. dothidea on G. sinensis in China.

Safety of Shujinjianyao pill in clinical real world: A prospective, observational, multicenter, large-sample study Protocol.

BACKGROUND: Low back pain is a common health problem worldwide, which also is a leading cause of long-term disability and has an important effect on the global economy and society. Usually, conservative therapies are used to treat low back pain. As a kind of Chinese patent medicine, Shujinjianyao pill (SJJYP) has a great curative effect on low back pain. However, its safety has not been studied yet. Therefore, we carried out this clinical trial to observe the safety of SJJYP in the real world. METHODS: First, participants need to meet the medication standards according to inclusion and exclusion criteria. Then, participants are conducted safety examination before taking SJJYP. After qualified screening, participants can be enrolled into the group. Second, all enrolled participants will receive SJJJYP for a period of 4 weeks. During the observation period, participants need to return to the hospital for a subsequent visit after 2 weeks of medication, and come to the hospital for safety check after 4 weeks of medication. Third, telephone follow-up is used to investigate any participants' physical discomfort after 6 to 8 weeks (2-4 weeks after medication withdrawal). After all these steps are completed, clinical observation is finished. If any adverse events occur during this process, we will record them in time. When serious adverse events occur, we will use nested case-control study to explore the causes and mechanisms. DISCUSSION: This study will obtain the safety results of SJJYP in clinical real world, which will offer a scientific basis for clinicians in the treatment of low back pain, and also provide a methodological basis for the safety study of other medicines. TRIAL REGISTRATION: ClinicalTrial.gov registration number is NCT03598153. This study was approved by the ethics committee of Wangjing hospital, China Academy of Chinese Medical Sciences (WJEC-KT-2018-012-P002).

Phenolic constituents, pharmacological activities, quality control, and metabolism of Dracaena species: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Dragon's blood (Chinese name: Xuejie), which comprises red resins obtained from several plants (27 species from 4 families), is drawing worldwide interests in medicinal applications owing to its broad pharmacological spectrum such as promoting blood circulation, regenerating muscle, relieving swelling and pain, maintaining hemostasis, etc. AIM OF THE STUDY: This work aims to evaluate current research progress on phenolic constituents, pharmacological activities, quality control, and metabolism of six Dracaena plants, namely, Dracaena cochinchinensis (Lour.) S.C.Chen, D. cambodiana Pierre ex Gagnep., D. cinnabari Balf. f., D. draco (L.) L., D. loureiroi Gagnep., and D. schizantha Baker, figure out the shortcomings of existing studies, and provide meaningful guidelines for future investigations. METHODS: Extensive database retrieval, such as SciFinder, PubMed, CNKI, ChemSpider, etc., was performed by using the keywords "Dracaena," "dragon's blood," as well as the Latin names of the six Dracaena species. In addition, relevant textbooks, patents, reviews, and documents were also employed to ensure sufficient information is collected. RESULTS: Flavonoids and their oligomers are the primary chemical clusters distributed in Dracaena plants. Pharmacological activities including analgesic, anti-inflammatory, antibacterial, hypolipidemic, hypoglycemic, and cytotoxic effects; bi-directional regulation effects on hemorheology; and cardiovascular and cerebrovascular effects have been disclosed by modern pharmacological evaluations. The chemical and metabolic profiles after oral administration of dragon's blood extract were preliminarily characterized. However, some of the pharmacological investigations reported only elementary methodologies and unreliable findings, and even worse, some important aspects were questionable or missing in these articles. CONCLUSIONS: Dragon's blood is a valuable source of bioactive compounds, mainly flavonoids and their oligomers. Its potential therapeutic effects on different diseases are attractive, such as the notable effect on cardiovascular diseases. In future studies, there is an urgent need to test the effect of this extract on appropriate cell lines and animal models to analyze its ethnopharmacological applications; moreover, "composition-effect correlation" methods and omics technologies are demanded for identifying the effective material basis and therapeutic mechanisms before entering into clinical trials. Moreover, attention should be paid to the chemical profiling and quality evaluation of this precious herbal medicine.

[Identification of active components in Longxue Tongluo Capsules against ischemic brain injury based on component-activity relationship].

Ten fractions(A-J) were prepared by separation of Longxue Tongluo Capsules(LTC) by using silica gel column chromatography and orthogonal experimental design,showing similar chemical profiles with different abundances of peaks.These ten samples were assessed with UHPLC-QE OrbitrapHRMS for 97 common peaks.For the pharmacological activity experiment,three kinds of in vitro cell models including lipopolysaccharide(LPS)-induced BV-2 microglial cells NO release model,oxygen-glucose deprivation/reoxygenation(OGD/R)-treated HUVEC vascular endothelial cells injury model,and OGD/R-treated PC-12 nerve cells injury model were employed to evaluated the bioactivity of each fraction.Based on the contribution of each identified component,grey relation analysis and partial least squares(PLS) analysis were performed to establish component-activity relationship of LTC,identify the potential active components.After that,validation of the potential active components in LTC was carried out by using the same models.The results indicated that 4 phenolic compounds including 7,4'-dihydroxyhomoisoflavanone,loureirin C,4,4'-dihydroxy-2,6-dimethoxydihydrochalcone,and homoisosocotrin-4'-ol,might be the active components for anti-neuroinflammation effect;five phenolic compounds such as 3,5,7,4'-tetrahydroxyhomoisoflavanone,loureirin D,7,4'-dihydroxyhomoisoflavane,and 5,7-dihydroxy-4'-methoxy-8-methyflavane,might have positive effects on the vascular endothelial injury;three phenolic compounds including 5,7,4'-trihydroxyflavanone,7,4'-dihydroxy-5-methoxyhomoisoflavane,and loureirin D,might be the active components in LTC against neuronal injury.