Selective production of methylindan and tetralin with xylose or hemicellulose.

Indan and tetralin are widely used as fuel additives and the intermediates in the manufacture of thermal-stable jet fuel, many chemicals, medicines, and shockproof agents for rubber industry. Herein, we disclose a two-step route to selectively produce 5-methyl-2,3-dihydro-1H-indene (abbreviated as methylindan) and tetralin with xylose or the hemicelluloses from agricultural or forestry waste. Firstly, cyclopentanone (CPO) was selectively formed with ~60% carbon yield by the direct hydrogenolysis of xylose or hemicelluloses on a non-noble bimetallic Cu-La/SBA-15 catalyst. Subsequently, methylindan and tetralin were selectively produced with CPO via a cascade self-aldol condensation/rearrangement/aromatization reaction catalyzed by a commercial H-ZSM-5 zeolite. When we used cyclohexanone (another lignocellulosic cycloketone) in the second step, the main product switched to dimethyltetralin. This work gives insights into the selective production of bicyclic aromatics with lignocellulose.

Optimal surgical population for cervical lymph node dissection in PTC.

Objective: There is still controversy about whether cervical lymph node dissection should be performed in surgical treatment of PTC. Based on the data of thyroid cancer patients from Liaocheng People's Hospital from 2015 to 2018, this study focused on appropriate indications for cervical lymph node dissection surgery. Methods: The clinical and pathological data of patients with initial treatment of PTC in thyroid surgery department from 2015 to 2018 were collected. In all cases, 1001 patients underwent total thyroidectomy + central lymph node dissection, and 1107 patients underwent total thyroidectomy + central + cervical lymph node dissection. Results: The average metastasis rate of all cases was 57.23%, and even the metastasis rate of PTMC was as high as 48.97%. The total metastasis rate of central and lateral cervical lymph nodes was 74.44%, and the cervical lymph nodes were present in 49.32% of the metastatic cases. In 55.56% of the cases, the tumor diameter was more than 1 cm, and the metastasis rate of cervical lateral area was 56%. With the increase of tumor diameter, the cervical metastasis rate increased from 22.54% to 73.33%. Conclusion: The metastasis rate of PTC is more than 50%, and nearly half of them have cervical metastasis, especially in patients with high risk factors. We observed that PTC 1 cm or greater has significant rates of metastasis.

Elucidation of active components and target mechanism in Jinqiancao granules for the treatment of prostatitis and benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases. MATERIALS AND METHODS: Jinqiancao granules were commercially available and purchased. Database-driven data mining and networking were utilized to establish a general correlation between Jinqiancao granules and the two diseases above. Ultra-performance liquid chromatography-mass spectrometry was used for compound separation and characterization. The characterized compounds were evaluated on four G-protein coupled receptors (GPCRs: GPR35, muscarinic acetylcholine receptor M3, alpha-1A adrenergic receptor α1A and cannabinoid receptor CB2). A dynamic mass redistribution technique was applied to evaluate compounds on four GPCRs. Nitric acid (NO) inhibition was tested on the macrophage cell line RAW264.7. Molecular docking was conducted on GPR35-active compounds and GPR35 crystal structure. Statistical analysis using GEO datasets was conducted. RESULTS: Seventy compounds were isolated and twelve showed GPCR activity. Three compounds showed potent GPR35 agonistic activity (EC50 < 10 µM) and the GPR35 agonism action of PAL-21 (Scutellarein) was reported for the first time. Docking results revealed that the GPR35-targeting compounds interacted at the key residues for the agonist-initiated activation of GPR35. Five compounds showed weak antagonistic activity on M3, which was confirmed to be a disease target by statistical analysis. Seventeen compounds showed NO inhibitory activity. Several compounds showed multi-target properties. An experiment-based network reflected a pharmacological relationship between Jinqiancao granules and the two diseases. CONCLUSIONS: This study identified active compounds in Jinqiancao granules that have synergistic mechanisms, contributing to anti-inflammatory effects. The findings provide scientific evidence for the potential use of Jinqiancao granules as a treatment for prostatitis and BPH.

Menisperdaurines A-W, structurally diverse isoquinoline alkaloids from Menispermum dauricum and their dopamine D1 receptor activities.

A total of 33 structurally diverse isoquinoline alkaloids were isolated from the rhizomes of Menispermum dauricum, including seventeen benzylisoquinoline analogues (menisperdaurines A-Q, 1-17), five protoberberine analogues (menisperdaurines R-V, 18-22), a quaternary phenanthrene alkaloid (menisperdaurine W, 23) and ten known compounds (24-33). Compound structures, including absolute configurations, were determined by extensive spectroscopic methods, quantum chemical calculations of chemical shifts, and calculated and experimental electronic circular dichroism (ECD) data. Compounds 1-5 were glycosidic benzylisoquinolines with glucose moieties attached at the C-12 position. Compound 8 was the first example that was isolated from the rhizomes of Menispermum dauricum, benzylisoquinoline and an aromatic unit connected by a sugar bridge. Compounds were evaluated for their inhibitory effects on the dopamine D1 receptor. Compounds 1, 8, 21, 24 and 29 showed potent D1 antagonistic activities, with IC50 values ranging from 1.0 to 4.5 µM. Compound 1 exhibited the highest antagonistic activity with an IC50 value of 1.0 ± 0.2 µM.

Isoquinoline alkaloid dimers with dopamine D1 receptor activities from Menispermum dauricum DC.

A phytochemical investigation on chemical constituents from the rhizomes of Menispermum dauricum DC. identified eight undescribed dimeric alkaloids with structurally diverse monomeric isoquinoline. Alkaloid structures were elucidated by a combination of spectroscopic data analyses and time-dependent density functional theory (TDDFT) ECD calculation. The isolates were evaluated for inhibitory effect on dopamine D1 receptor and compound 1 exhibited potent D1 receptor antagonistic activity with an IC50 value of 8.4 ± 2.0 µM.

Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies: a real-world study.

BACKGROUND: Chemotherapy-induced neutropenia is commonly encountered in clinical practice. The management of neutropenia has been evolving from short-acting granulocyte colony-stimulating factors (G-CSFs) to long-acting G-CSFs. However, an evaluation of the safety and effectiveness of long-acting G-CSFs in clinical practice is still lacking. METHODS: This multicenter, non-interventional study was aimed at exploring the safety and effectiveness of mecapegfilgrastim in different cancer patients in China. All patients provided written informed consent prior to the study and were treated according to routine clinical practice. Different prophylactic strategies (primary or secondary prophylaxis) were also compared. RESULTS: This study included 638 patients from May 2019 to November 2020. More than half of the participants were breast cancer patients. The mean age of all the patients was 56 years. White blood cell increase (6.2%) was the most frequently reported adverse event (AE) possibly related to the study drug. No unexpected AEs were reported. Grade ≥3 neutropenia in chemotherapy treatment cycle 1 was reported in 36 (5.6%) patients. Incidence of grade ≥3 neutropenia in cycle 1 in the primary and secondary prophylaxis subgroups were of 4.3% and 9.2%, respectively. A decreasing trend of severe neutropenia incidence was observed from cycle 1 to cycle 4. CONCLUSIONS: Mecapegfilgrastim was generally well tolerated, and no unexpected AEs were observed in this study. Primary administration of mecapegfilgrastim led to a lower incidence of neutropenia than did secondary administration. Continuous administration of mecapegfilgrastim could keep the incidence of neutropenia to a relatively low level.

Anti-rheumatoid arthritis potential of diterpenoid fraction derived from Rhododendron molle fruits.

Rhododendron molle G. Don is first recorded in Shengnong's Herbal Classic, and its fruits, which are termed as Liuzhouzi, are often used to treat rheumatoid arthritis in Chinese folk. During our ongoing investigation to develop a safer and potential new arthritis therapy, a process for the preparation of diterpenoid fraction from Rhododendron mollefruits was established. In order to evaluate the main components and the anti-rheumatoid arthritis effect of the diterpenoid fraction, phytochemical and pharmacological experiments were used. As the result, the main components of diterpenoid fraction were identified as rhodojaponin III (1), rhodojaponin VI (2), 2-O-methylrhodojaponin (3), and 5'-ß-D-glucopyranosy-loxyjasmonic acid (4). These four components constitute greater than 95% of diterpenoid fraction using area normalization method of HPLC-ELSD. The results of CIA rat experiment showed that high dose of diterpenoid fraction (0.6 mg·kg-1·d-1) significantly alleviated the symptoms of rheumatoid arthritis, similar to tripterygium polyglycosides, an effective RA therapy. Preliminary mechanism studies indicated that diterpenoid fraction significantly inhibited the abnormal proliferation of T and B lymphocytes, and remarkably reduced the levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α. Overall, our findings may provide a more effective and safe alternative treatment for RA using common clinical Chinese medicines like tripterygium polyglycosides.

Which is preferred for initial treatment of papillary thyroid cancer, total thyroidectomy or lobotomy?

PURPOSES: The incidence of thyroid cancer has increased annually, and has a heavy psychological and economic burden on society and individuals. Based thyroid cancer data from patients treated in Liaocheng People's Hospital from 2015 to 2018, with Chinese national and regional characteristics, in this study, we addressed the controversy of which initial thyroid surgical mode, lobectomy or total thyroidectomy, is most effective. METHODS: Clinical and pathological data from 2108 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, there were 1001 cases who underwent open operation with total thyroidectomy + central lymph node dissection; meanwhile, 1107 cases were treated with neck lateral lymph node dissection at the same time. RESULTS: The overall metastasis rate of all patients was 57.23%. Even the lymph node metastasis of papillary thyroid microcarcinoma (PTMC) was as high as 48.97%. When the mass rose above 2 cm, the proportion of metastasis increased to 77.22%. When the tumor was complicated with bilateral and multiple high-risk factors, the proportion of metastasis was 65.27% and 72.21%, respectively. When the tumor breaks through the capsule, the metastasis rate was 67.08%. With the increase of tumor diameter, the metastasis of cervical lymph nodes ranged from 22.54% to 73.33%, which showed positive correlation. 49.32% of patients had lymph node metastasis in the lateral cervical region. When the diameter of the tumor reached T1c level, the metastasis of the cervical lymph nodes was 56.91%, and the number of metastatic cases above T1c level accounted for 69.96% of the total metastatic cases. CONCLUSION: The degree of malignancy of thyroid cancer depends on tumor genome evolution. Rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. It is recommended that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, to avoid the risks associated with secondary surgery and effects on patient quality of life. When the tumor diameter exceeds 1 cm, the risk of cervical lymph node metastasis is high, and we recommended lateral lymph node dissection.

Analgesic bisbenzylisoquinoline alkaloids from the rhizoma of Menispermum dauricum DC.

Fifteen new bisbenzylisoquinoline alkaloids (1-15) were isolated from the rhizome of Menispermum dauricum DC. Compounds 1-9 were new N-oxides of dauricine-type alkaloids. Compounds 10-14 were rare tail-to-tail quaternary alkaloids. Their structures were characterized by comprehensive analysis of spectroscopic data, and absolute configurations were established from electronic circular dichroism (ECD) data and ECD calculations. Compounds were assayed on analgesic-related G-protein coupled receptors (GPCRs) including dopamine D1 and D2 receptors, opioid Mu receptor and muscarinic M3 receptor. Compound 1 showed high affinity and selective antagonistic activity on the M3 receptor with an IC50 value of 2.2 ± 0.5 µM; compound 15 exhibited the highest antagonistic affinity among the evaluated compounds on Mu (IC50 = 1.1 ± 0.6 µM) and it also acted as a D1 receptor antagonist (IC50 = 8.8 ± 2.9 µM). These findings expanded the existing library of bisbenzylisoquinoline alkaloids and provided new structures for the related future drug design and synthesis.

Total thyroidectomy is superior for initial treatment of thyroid cancer.

PURPOSE: The incidence of thyroid cancer has increased annually, and has a heavy psychological and economic burden on the society and individuals. Based on thyroid cancer data from patients treated in Liaocheng People's Hospital in 2017, with Chinese national and regional characteristics, in this study we addressed the controversy of which initial thyroid surgical mode, lobectomy, or total thyroidectomy is the most effective. PATIENTS AND METHODS: Clinical and pathological data from 552 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, 40 patients underwent endoscopic surgery, with resection, including lobectomy + central lymph node dissection of the affected lobe, while 512 cases underwent total thyroidectomy + central lymph node dissection. RESULTS: The metastasis rate for all patients was 59.42%, with lymph node metastasis of papillary thyroid microcarcinoma of 46.92%; however, for patients with tumors >2 cm, the proportion developing metastasis was increased to 77.53%. CONCLUSION: In thyroid cancer, rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. Our data suggest that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, at least in tumors larger than 1 cm, to avoid the risks associated with secondary surgery and effects on patient quality of life.

With High-Risk Factors, Total Thyroidectomy is Preferred for Thyroid Cancer.

INTRODUCTION: Based on thyroid cancer data from patients treated in Liaocheng People's Hospital in 2017, with Chinese national and regional characteristics, in this study we addressed the controversy of which initial thyroid surgical mode, lobectomy or total thyroidectomy, is most effective. PATIENTS AND METHODS: Clinical and pathological data from 552 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, 40 patients underwent endoscopic surgery, with resection including lobectomy + central lymph node dissection of the affected lobe, while 512 cases underwent total thyroidectomy + central lymph node dissection. RESULTS: The metastasis rate for all patients was 59.42%. Further, among patients with bilateral or multiple tumors or capsule invasion, the proportions who developed metastatic disease were 63.54% and 71.19% and 67.46%, respectively. Meanwhile, the incidence of contralateral accidental malignancy was 7.25% after postoperative paraffin pathology. DISCUSSION: Rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. It is recommended that, among patients with risk factors, initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, to avoid the risks associated with secondary surgery and effects on patient quality of life.

Motion-to-BMI: Using Motion Sensors to Predict the Body Mass Index of Smartphone Users.

Obesity has become a widespread health problem worldwide. The body mass index (BMI) is a simple and reliable index based on weight and height that is commonly used to identify and classify adults as underweight, normal, overweight (pre-obesity), or obese. In this paper, we propose a hybrid deep neural network for predicting the BMI of smartphone users, based only on the characteristics of body movement captured by the smartphone's built-in motion sensors without any other sensitive data. The proposed deep learning model consists of four major modules: a transformation module for data preprocessing, a convolution module for extracting spatial features, a long short-term memory (LSTM) module for exploring temporal dependency, and a fully connected module for regression. We define motion entropy (MEn), which is a measure of the regularity and complexity of the motion sensor, and propose a novel MEn-based filtering strategy to select parts of sensor data that met certain thresholds for training the model. We evaluate this model using two public datasets in comparison with baseline conventional feature-based methods using leave-one-subject-out (LOSO) cross-validation. Experimental results show that the proposed model with the MEn-based filtering strategy outperforms the baseline approaches significantly. The results also show that jogging may be a more suitable activity of daily living (ADL) for BMI prediction than walking and walking upstairs. We believe that the conclusions of this study will help to develop a long-term remote health monitoring system.

Long noncoding RNA LINC00963 promotes breast cancer progression by functioning as a molecular sponge for microRNA-625 and thereby upregulating HMGA1.

Extensive research has shown that LINC00963 is aberrantly expressed in human cancers, and that dysregulation of LINC00963 is implicated in the initiation and progression of human cancers. The expression and functions of LINC00963 in breast cancer are still unclear. Our aims were to measure the expression of LINC00963 in breast cancer, determine its effects on malignant behaviors of tumor cells, and uncover the molecular events underlying the actions of LINC00963 in breast cancer. Herein, LINC00963 was found to be overexpressed in breast cancer samples, and its overexpression was correlated with lymph node metastasis, TNM stage and differentiation grade. Patients with breast cancer harboring higher LINC00963 expression showed shorter overall survival than did the patients with lower LINC00963 expression. Functional experiments revealed that depletion of LINC00963 inhibited breast cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro and impaired tumor growth in vivo. Mechanism investigation revealed that LINC00963 can interact with microRNA-625 (miR-625). LINC00963 worked as a competitive endogenous RNA for miR-625 to weaken the suppressive effect of miR-625 on high mobility group AT-hook 1 (HMGA1) in breast cancer cells. Furthermore, miR-625 inhibition and HMGA1 restoration both abrogated the effects of LINC00963 silencing on breast cancer cells. Our findings indicate that the LINC00963-miR-625-HMGA1 pathway plays an important role in the malignancy of breast cancer in vitro and in vivo. Hence, targeting this pathway may be a novel strategy against breast cancer.

Preparation and evaluation of duloxetine hydrochloride enteric-coated pellets with different enteric polymers.

The main purpose of the present study was to prepare duloxetine hydrochloride (DXH) enteric-coated pellets using different enteric polymers. Three layers (drug-loaded layer, barrier layer, and enteric-coated layer) were applied to the inert core pellets, successively. The optimal formulation was manufactured by employing suspension layering method in fluidized bed processor (FBP) with varieties of enteric polymers like Aqoat® AS-LF, Eudragit® L30D55 and HPMCP-HP55. The prepared pellets were measured for physical characterization and the in vitro dissolution profile. Scanning electron microscopy (SEM) was conducted to observe the morphology of pellets, and different kinetic models were applied to analyze the release mechanism of Cymbalta® and home-made pellets. The coating weight gain of enteric-coated layer containing Eudragit® L30D55, Aqoat® AS-LF and HP-55 were determined to be 35%, 26% and 24%, respectively. The similarity factors (f2 ) of self-made capsules with above polymers and commercially available capsules (Cymbalta®) were above 50 in the dissolution medium of pH 6.8 phosphate buffer solution (PBS). SEM figures showed the smooth surfaces of self-prepared pellets using Eudragit® L30D55 and Aqoat® AS-LF, whereas rough surface was found in the HP-55 pellets at day 0, and an impurity was appearing in the condition of 40 °C/75% relative humidity for 1 month. In conclusion, the pellets prepared by utilizing Eudragit® L30D55 and Aqoat® AS-LF were the optimal preparations based on the dissolution profile and stability.

Assessing the visual quality of green landscaping in rural residential areas: the case of Changzhou, China.

Changzhou is a typical waterside municipality with approximately 2,500 years of history located south of the Yangtze River. It was an agriculturally oriented region but is becoming an industrialized region. Rural green landscaping in this region possesses characteristics of traditional Chinese gardens. This paper presents a methodology for assessing the visual quality of green landscaping in rural residential areas through public perception-based and expert/design approaches. The former approach enables us to rank green landscaping based on a survey of public preference; the latter weighs the contributions of the attributes contained in a photograph to its overall scenic beauty via correlation, regression, and factor analyses. The photographs used in the survey included road greenways, riparian greenways, residential public gardens and green landscaping around houses, with each type of landscape represented by seven photographs. In total, 141 college students and 41 other participants ranked photographs of each landscaping type from highest to lowest preference. The results indicate that the preferences of students are similar to those of the general public. Examples of green landscaping depicted in the "best" four photographs possessed more attractive qualities regarding the variety of vegetation, richness of colors and a selection of human additions compared to those depicted in the "worst" photographs. The perceived visual quality was positively influenced by, in decreasing order of importance, the variety of vegetation, color contrast, the openness of green spaces, the area of vegetation, and positive man-made elements; conversely, it was negatively influenced by the type of topography. Moreover, some suggestions were offered for future rural greening regarding perceived visual beauty.