A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

Adipose stem cells control obesity-induced T cell infiltration into adipose tissue.

T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.

OTSUCNV: an adaptive segmentation and OTSU-based anomaly classification method for CNV detection using NGS data.

Copy-number variations (CNVs), which refer to deletions and duplications of chromosomal segments, represent a significant source of variation among individuals, contributing to human evolution and being implicated in various diseases ranging from mental illness and developmental disorders to cancer. Despite the development of several methods for detecting copy number variations based on next-generation sequencing (NGS) data, achieving robust detection performance for CNVs with arbitrary coverage and amplitude remains challenging due to the inherent complexity of sequencing samples. In this paper, we propose an alternative method called OTSUCNV for CNV detection on whole genome sequencing (WGS) data. This method utilizes a newly designed adaptive sequence segmentation algorithm and an OTSU-based CNV prediction algorithm, which does not rely on any distribution assumptions or involve complex outlier factor calculations. As a result, the effective detection of CNVs is achieved with lower computational complexity. The experimental results indicate that the proposed method demonstrates outstanding performance, and hence it may be used as an effective tool for CNV detection.

Water rights reform and water-saving irrigation: evidence from China.

As a market-based water resource management, the water rights reform (WRR) will allocate water rights to water users and allow water users to trade water rights, which can realize the reallocation across water users. In this context, the adoption of water-saving irrigation (WSI) is an important technical form to adapt to the reform. Based on this, this paper studies the impacts of the WRR on WSI using the difference-in-differences (DID) strategy. The results show that the WRR could increase the land area for WSI by an average of 13.63%. The WRR could promote the expansion of high-efficiency irrigation mainly because the WRR could promote the expansion of spray and drip irrigation areas, and micro-irrigation land areas, which are high-efficiency water-saving irrigation technologies. In addition, the WRR also could improve agricultural production by increasing agricultural water productivity and planting area (including the sown area of grain crops and cash crops), but the WRR does not reduce agricultural water extraction. Therefore, the WRR could increase agricultural production without increasing agricultural water extraction.

Multifunctional bisalkynylplatinum(II) bipyridine complexes with rhodamine-like ligands featuring near-infrared phosphorescence and delayed fluorescence.

A series of platinum(II) bipyridine complexes with two rhodamine-like alkynyl (Rhodyne) ligands were developed to show chemo-induced "ON-OFF" switching capabilities with exceptional near-infrared phosphorescence and delayed fluorescence. This study contributes to the design of versatile photosensitizers with multiple functionalities, including metal ion and biomolecule sensing, photodynamic therapy, and optoelectronics.

DHT-Net: Dynamic Hierarchical Transformer Network for Liver and Tumor Segmentation.

Automatic segmentation of liver tumors is crucial to assist radiologists in clinical diagnosis. While various deep learningbased algorithms have been proposed, such as U-Net and its variants, the inability to explicitly model long-range dependencies in CNN limits the extraction of complex tumor features. Some researchers have applied Transformer-based 3D networks to analyze medical images. However, the previous methods focus on modeling the local information (eg. edge) or global information (eg. morphology) with fixed network weights. To learn and extract complex tumor features of varied tumor size, location, and morphology for more accurate segmentation, we propose a Dynamic Hierarchical Transformer Network, named DHT-Net. The DHT-Net mainly contains a Dynamic Hierarchical Transformer (DHTrans) structure and an Edge Aggregation Block (EAB). The DHTrans first automatically senses the tumor location by Dynamic Adaptive Convolution, which employs hierarchical operations with the different receptive field sizes to learn the features of various tumors, thus enhancing the semantic representation ability of tumor features. Then, to adequately capture the irregular morphological features in the tumor region, DHTrans aggregates global and local texture information in a complementary manner. In addition, we introduce the EAB to extract detailed edge features in the shallow fine-grained details of the network, which provides sharp boundaries of liver and tumor regions. We evaluate DHT-Net on two challenging public datasets, LiTS and 3DIRCADb. The proposed method has shown superior liver and tumor segmentation performance compared to several state-of-the-art 2D, 3D, and 2.5D hybrid models.

Citrus aurantium 'Changshan-huyou'-An ethnopharmacological and phytochemical review.

Citrus fruits are composed of oil cells layer, white membrane layer, pulp and seeds. The cultivar Citrus aurantium 'Changshan-huyou' (CACH) is a hybridization of Citrus grandis Osbeck and C. sinensis Osbeck. It is a rutaceae plant, and mainly grows in Changshan, Zhejiang, China. With the exploration of its high traditional values, it has been paid more and more attention by the scientific community in recent years. At present, one hundred and two chemical constituents have been identified from the pulp and peel of CACH, including volatile oils, terpenoids, phenols, limonins, sugars, etc., As the representative active component of CACH, phenols have been widely investigated. Studies have shown that CACH shows a variety of significant pharmacological activities, such as anti-inflammatory, antioxidant, hepatoprotective activity, respiratory system protection and intestinal regulation activity. This review mainly introduces the chemical constituents and pharmacological activities of CACH, and discusses its future research and development directions. It will provide theoretical basis for further research of its pharmacodynamic substances, functional mechanism and rational utilization.

Identification of Sorafenib as a Treatment for Type 1 Diabetes.

Th1 cell activation is considered a key mediator of the pathogenesis of type 1 diabetes. Targeting IL-12-induced Th1 cell differentiation seems to be an effective way to block the development of type 1 diabetes. However, given the critical function of Th1 in the immune system, the potential side effects hinder the application of anti-Th1 therapy in the treatment of type 1 diabetes. To identify safe anti-Th1 treatment(s), we screened the FDA-approved tyrosine kinase inhibitor (TKI) drug library using an IL-12-induced Th1 differentiation cell model. We found that among the TKIs with little effect on T cell viability, sorafenib is the top contender for the inhibition of Th1 differentiation. Treatment of NOD mice with sorafenib significantly impeded the development of type 1 diabetes and ameliorated insulitis, which coincided with a specifically decreased accumulation of Th1 cell population in the pancreas but not in peripheral immune organs. Mechanistically, sorafenib indirectly inhibited janus kinase 2 (JAK2) activity and blocked IL-12-induced phosphorylations of JAK2 and signal transducer and activator of transcription 4 (STAT4). Since sorafenib is classified as an FDA-approved drug, it serves as a preliminary lead point for additional experimentation and may be a promising therapy for type 1 diabetes in humans.

Metabolic effects of CCL5 deficiency in lean and obese mice.

Accumulation and activation of immunocytes in adipose tissues are essential to obesity-induced inflammation and insulin resistance. Chemokines are pivotal for the recruitment of immunocytes in adipose tissue during obesity. Chemokine (C-C motif) ligand 5 (CCL5) plays a vital role in the recruitment of immunocytes to sites of inflammation. CCL5 expression level is increased in obese adipose tissue from humans and mice. However, the role of CCL5 in obesity-induced adipose inflammation remains unclear. Our study found that the CCL5 expression level was increased in the epididymal white adipose tissue (eWAT) of obese mice, particularly in CD8+ T cells. CCL5 knockout (KO) mice exhibited better glucose tolerance than wild-type (WT) mice under lean conditions. In contrast, CCL5 KO mice were more insulin resistant and had severe hepatic steatosis than WT mice under obese conditions. Increased T cells in adipose tissue heaven adipose inflammation in obese CCL5 KO mice. The compensatory increased T cell-associated chemokines may account for increased T cell content in the eWAT of obese CCL5 KO mice. These findings imply that CCL5 deficiency exacerbates adipose inflammation and impairs insulin sensitivity in the metabolic tissues of obese mice.

MiR-34a-3p suppresses pulmonary vascular proliferation in acute pulmonary embolism rat by targeting DUSP1.

BACKGROUND: Acute pulmonary embolism (APE) is a prevalent reason of cardiovascular morbidity and mortality. Recent studies have underscored the positive effects of microRNAs (miRNAs) on many diseases. The present study aimed to identify the critical miRNA with differential expressions and explore its role in APE. METHODS: The critical miRNA with its target gene was screened by bioinformatics analysis. Their binding relationship was analyzed by TargetScan, Dual-luciferase reporter and RNA pull-down assays. A rat model of APE was established by self-blood coagulum. Human pulmonary artery smooth muscle cells (PASMCs) were exposed to platelet-derived growth factor (PDGF-BB) for excessive proliferation, and transfected with miR-34a-3p mimic. Mean pulmonary arterial pressure (mPAP) of rat was measured, and the pulmonary tissues were used for the pathological observation by Hematoxylin-Eosin (H&E) staining. Cell viability and proliferation were detected by Cell Counting Kit-8 (CCK-8) and EdU assays. The expressions of miR-34a-3p with its target genes (including dual-specificity phosphatase-1 (DUSP1)), neuron-derived orphan receptor-1 (NOR-1) and proliferating cell nuclear antigen (PCNA) were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) or/and Western blot. RESULTS: MiR-34a-3p expression was down-regulated in APE patients, which attenuated the increment of mPAP and thickening of the pulmonary arterial walls in APE rats, accompanied with regulation of NOR-1 and PCNA levels. MiR-34a-3p suppressed DUSP1 expression by directly binding to its 3'-untranslated region (UTR), and attenuated cell viability, proliferation, and the expressions of NOR-1 and PCNA in PDGF-BB-induced PASMCs by inhibiting DUSP1 expression. CONCLUSION: Up-regulated miR-34a-3p negatively regulates DUSP1 expression to inhibit PASMC proliferation, which, thus, may act on APE treatment by negatively regulating pulmonary vascular proliferation.

Corrigendum: The Adipocyte and Adaptive Immunity.

[This corrects the article DOI: 10.3389/fimmu.2020.593058.].

Agricultural Water Use Efficiency and Rebound Effect: A Study for China.

Agricultural water use accounts for the largest proportion of water withdrawal, so improving agricultural water use efficiency is an important way to alleviate water shortage. However, the expected water saving by the improved agricultural water use efficiency may be offset by the rebound effect, which means the goal of water saving by improving agricultural water use efficiency is not achieved. Based on the definition of the rebound effect of agricultural water use, this paper first uses a fixed model to measure the causal effect of agricultural water use efficiency on agricultural water use to analyze the agricultural water rebound effect, then analyses the heterogeneity and mechanism of the effect of agricultural water use efficiency on agricultural water use with the panel data from 30 provinces or cities in China from 2000 to 2017. The results show that, firstly, the agricultural water use efficiency has a significant negative effect on agricultural water use, but the average agricultural water rebound effect is 88.81%. Secondly, the effect of agricultural water use efficiency on agricultural water use is heterogeneous, in which the improvement of agricultural water use efficiency in humid or major grain-producing areas will have a lower agricultural water rebound effect. Finally, agricultural water use efficiency can affect agricultural water use through planting area and planting structure. An increase in agricultural water use efficiency will expand the planting area to increase water use. However, this will change the planting structure to decrease water use. The implication for agricultural water management is that the irrigation agricultural scale has to be controlled under the condition of available water resource, while improving agricultural water use efficiency.

PERFORM: Pulmonary embolism risk score for mortality in computed tomographic pulmonary angiography-confirmed patients.

BACKGROUND: Current prognostic scores for pulmonary embolism (PE) were partly based on patients without PE confirmation via computed tomographic pulmonary angiography (CTPA), involving subjective parameters and complicated scoring methods. Therefore, we sought to develop an objective, accurate, and simple prognostic model in CTPA-confirmed patients to predict the risk of 30-day mortality. METHODS: We retrospectively evaluated 509 patients with objectively confirmed PE by CTPA from 2010 to 2017 in the Minhang Hospital, which is affiliated to Fudan University. Patients were randomly divided into the training and validation cohorts. The primary end point was 30-day mortality. The secondary end points were the time to recovery in 30 days and mortality in 15 days. We compared the predictive performance of Pulmonary Embolism Severity Index (PESI), simplified PESI (sPESI), and the PE risk score we developed, called PERFORM. FINDINGS: PERFORM (ranging from 0 to 12 score) is based on the patient's age, heart rate, and partial pressure of arterial oxygen. The area under the curve was 0.718 (95% confidence interval [CI], 0.627-0.809) for the training cohort and 0.906 (95% CI, 0.846-0.966) for the validation cohort. PERFORM was as good as PESI and sPESI in predicting mortality. Patients in the low-risk group (PERFORM score < 5) had a shorter time to recovery, whereas those in the high-risk group (PERFORM score ≥ 5) had a high mortality. INTERPRETATION: PERFORM in CTPA-confirmed patients is an objective, accurate, and simple tool to predict the risk of 30-day mortality. FUNDING: Research Project of Shanghai Municipal Commission of Health and Family Planning (201740127), Shanghai Medical Key Subject Construction Project (ZK2019B08).

A new antibacterial 3,5-dimethylorsellinic acid-based meroterpene from the marine fungus Aspergillus sp. CSYZ-1.

Chemical investigation of the extracts of Aspergillus sp. CSYZ-1 resulted in the identification of compound 1, aspergillactone, a new 3,5-dimethylorsellinic acid-based meroterpenoid, together with four known metabolites (2-5). The structure and relative configuration of 1 were unambiguously determined by nuclear magnetic resonance (NMR), mass spectrometry. The absolute configuration of 1 was defined by quantum chemical TDDFT calculated and the experimental ECD spectra. The possible biosynthetic pathway of compound 1 was also proposed. The new compound exhibited potent antimicrobial activity against Helicobacter pylori and Staphylococcus aureus with MIC values of around 1-4 and 2-16 µg/mL, respectively.

Operation of Three-Stage Process of Lithium Recovery from Geothermal Brine: Simulation.

Lithium-rich geothermal waters are considered as an alternative source, and further concentration of lithium is required for its effective recovery. In this work, we have simulated a three-stage lithium recovery process including the brine softening by precipitation Ca2+/Mg2+ cations with sodium carbonate (calculated in PHREEQC), followed by an integrated system consisting of membrane distillation unit (water evaporation), crystallizer (NaCl precipitation), and membrane extraction (Li+ recovery), which was simulated in Simulink/MATLAB. It was shown that the deterioration of membrane performance in time due to scaling/fouling plays a critical role in the performance of the system resulting in the dramatic increase of the replaced membrane modules by a factor of 5. Low cost membranes are required. The process simulation based on the experimental and literature data on the high salinity solutions with the membrane distillation revealed that the specific productivity can be achieved in the range of 9.9-880 g (Li+) per square meter of membranes in the module used before its replacement. The increase of energy efficiency is needed. The mass-flow-rate of saline solution circulated to the crystallizer was set at its almost minimum value as 6.5 kg/min to enable its successful operation at the given parameters of the membrane distillation unit. In other words, the operation of the integrated system having 140 kg of saline solution in the loop and a membrane module of 2.5 m2 for concentration of lithium presence from 0.11 up to 2.3 g/kg would be associated with the circulation of about of 259 tons of saline solution per month between the distillation unit (60 °C) and the crystallizer (15 °C) to yield of up to 1.4 kg of lithium ions. The comprehensive summary and discussion are presented in the conclusions section.

Glucocorticoids Regulate the Activation of Neutrophils and Inhibit the Formation of Pulmonary Embolism.

BACKGROUND: There is a close relationship between neutrophil extracellular traps (NETs) and venous thromboembolism (VTE). The regulatory role and mechanism of glucocorticoids (GC) in the formation of NETs are unclear. OBJECTIVE: This study was conducted to assess the effect of GC on the formation of NETs. METHODS: We constructed a mouse VTE model and treated them with GC to observe the effect of GC on the formation of NETs. In this regard, peripheral blood neutrophils were isolated, and the effect and mechanism of GC in neutrophil activation were analyzed. RESULTS: Following LPS treatment, the colony-forming ability of neutrophils and their ability to form NETs increased significantly. The analysis of cytokine changes by RT-PCR combined with ELISA showed that the level of inflammatory factors in LPS-activated neutrophils increased significantly; however, these factors were significantly inhibited after GC treatment, and the inhibitory effect was positively correlated with the concentration of GC. LPS treatment was able to activate the production of ROS and lipid peroxides, however, this activation was significantly inhibited after GC treatment, and the inhibition increased with increasing doses of GC. Further examination of the changes in NF-κB signaling activation revealed that LPS-induced NF-κB signaling was significantly inhibited after GC treatment, and this inhibition increased with increasing the GC concentration. CONCLUSION: Glucocorticoids were able to inhibit neutrophil activation and reduce the formation of NETs. The research results provided a new research direction for clinical antithrombotic treatment.

The Adipocyte and Adaptive Immunity.

Not only do Adipocytes have energy storage and endocrine functions, but they also play an immunological role. Adipocytes are involved in adaptive immunity to mediate the pathological processes of a variety of chronic inflammatory diseases and autoimmune syndromes. The adaptive immune response consists of T cell-mediated cellular immunity and B cell-mediated humoral immunity. Obese adipocytes overexpress MHC class II molecules and costimulators to act as antigen-presenting cells (APCs) and promote the activation of CD4+ T cells. In addition, various adipokines secreted by adipocytes regulate the proliferation and differentiation of T cells. Adipokines are also involved in B cell generation, development, activation, and antibody production. Therefore, adipocytes play an important role in B cell-mediated adaptive immunity. This review describes how adipocytes participate in adaptive immunity from the perspective of T cells and B cells, and discusses their role in the pathogenesis of various diseases.

Long noncoding RNA colorectal neoplasia differentially expressed alleviates sepsis-induced liver injury via regulating miR-126-5p.

In this study, we intended to determine the detailed function and mechanism of long noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in liver injury induced by sepsis. Cecal ligation and perforation (CLP) models were adopted to induce sepsis in vivo with rats, and hepatic epithelial cells L02 were treated with lipopolysaccharide (LPS) to mimic sepsis in vitro. Enzyme-linked immunosorbent assay was conducted to detect the levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-γ (IFN-γ) in the serum of rats. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expressions of CRNDE and microRNA-126-5p (miR-126-5p). Flow cytometry analysis and Cell Counting Kit-8 (CCK-8) method were carried out followed by the up- or downregulation of CRNDE and miR-126-5p to monitor the proliferation and apoptosis of L02 cells, respectively. Western blot was then applied to determine the expressions of cysteinyl aspartate specific proteinase 3 (caspase 3), poly(ADP-ribose)polymerase (PARP), cytochrome c, and BCL2-like 2 (BCL2L2). The interactions between CRNDE with miR-126-5p and miR-126-5p with BCL2L2 were determined through bioinformatics, qRT-PCR, dual luciferase reporter assay, and RNA immunoprecipitation assay. CRNDE was significantly decreased in liver tissues and hepatic cells in sepsis models. Upregulation of CRNDE promoted the viability of L02 cells and inhibited their apoptosis, while downregulation of CRNDE had opposite effects. The expression of CRNDE in liver tissues of septic rats was correlated with the expression miR-126-5p. It was also demonstrated that the transfection of miR-126-5p mimics reversed the inhibitory effect induced by CRNDE on apoptosis of L02 cells. CRNDE could specifically bind to miR-126-5p and reduce its expression, in turn promote the expression of BCL2L2. Additionally, CRNDE overexpression in rats ameliorated liver injury induced by sepsis. Downregulated CRNDE aggravates hepatic injury via regulating miR-126-5p and BCL2L2 during sepsis.

Down-regulation of LncRNA CRNDE aggravates kidney injury via increasing MiR-181a-5p in sepsis.

Long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is reported to be linked to inflammation and cell apoptosis. However its role in sepsis induced kidney injury remains unclear. This study aims to explore the possible mechanism of CRNDE in kidney injury induced by sepsis. In vivo urine-derived sepsis (US) rat model and in vitro LPS-induced HK-2 and HEK293 cells were established. Kidney function was measured in rats from different groups. Relative levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß(IL-1ß) in kidney tissue were detected via Enzyme-linked immune sorbent assay (ELISA). Then we up- or down-regulated CRNDE and miRNA-181a-5p expression in the cells. The biological influence of CRNDE and miR-181a-5p on cells was studied using CCK-8 assay and Annexin V assay. Interaction between CRNDE and miR-181a-5p was determined by bioinformatics analysis, RT-PCR, and dual luciferase reporter assay. Peroxisome proliferator-activated receptor-α (PPARα) and cell apoptosis related molecules were detected by western blot. We demonstrated that CRNDE was markedly down-regulated while miR-181a-5p was significantly up-regulated in sepsis models. CRNDE interacted with miR-181a-5p, and negatively regulated its expression level. CRNDE knockdown in rats increased the urea nitrogen and serum creatinine in plasma. Knockdown of CRNDE or transfection of miR-181a-5p significantly inhibited proliferation and promoted apoptosis of HK-2 and HEK293 cells, while overexpression of CRNDE and transfection of miR-181a-5p inhibitors had opposite effects. For mechanism, miR-181a-5p directly targeted the 3' untranslated region of PPARα, and depressed its protein level, and PPARα was regulated indirectly by CRNDE. We concluded that CRNDE protected renal cell from sepsis-induced injury via miR-181a-5p/PPARα pathway.

[Study on original plant species and geographical distribution of Fructus Aurantii].

The original plant species of Fructus Aurantii are multitudinous and complex, and their requirements to the growing environment is strict. In order to clarify the original plant species and geographical distribution of Fructus Aurantii which recorded in the standards and circulated, used in commodity. The national and local standards of Chinese medicinal materials were collected and the original plants of Fructus Aurantii recoded in standards were found. Ten original plant species of Fructus Aurantii (including varieties of cultivars, the same below) were recorded in the Chinese pharmacopoeia and six local standards of Zhejiang, Yunnan and Guizhou etc. The producing areas and commodity in markets of Fructus Aurantii were investigated. The growth environment and geographical distribution of them were analyzed. There are six types of Fructus Aurantii i.e., Fructus Aurantii Chuan, Fructus Aurantii Xiang, Fructus Aurantii Jiang, Fructus Aurantii Qu, Fructus Aurantii Su, Fructus Aurantii Wen, and nineteen species of original plants in the practical commodities. There are four major Fructus Aurantii producing areas: Sichuan Basin, Dongting Lake Plain, Poyang Lake Plain, Jinqu Basin and its surrounding hilly areas. All of them are located in the area of the east longitude 104° to 121° and the northern latitudes 27° to 31°. There is a certain difference between the actual commodity and the standards of medicinal materials. It is suggested that the traditional mainstream types of Fructus Aurantii with fine quality should be accepted into Chinese Pharmacopoeia, and the types with poor quality should be withdrawn from Chinese Pharmacopoeia.