Incorporating carbon sequestration toward a water-energy-food-carbon planning with uncertainties.

Water-energy-food nexus (WEFN) is the core content in the United Nations 2030 Agenda for Sustainable Development. However, the value of soil and crops' carbon sink function has not yet been fully considered in the managment practices of WEFN system. Here, we developed a water-energy-food-carbon nexus (WEFCN) planning framework that incorporates carbon sequestration and multiple mathematical optimization methods into the practical WEFN management for Henan Province, which is one of major grain-producing areas in China. Uncertainties from multiple objectives, scenarios, and different stakeholder interests are captured. We found that wheat has the largest carbon sequestration, followed by corn and oil-bearing crops, while other crops have implicit carbon sequestration. Since chemical fertilizer produces the most carbon emissions, the usage of chemical fertilizer needs to be reasonably controlled. Overall, the proposed framework supports optimal decision-making for regional-scale WEFCN management and further unlocks the hidden value of agricultural carbon mitigation.

The mechanism of flavonoids from Cyclocarya paliurus on inhibiting liver cancer based on in vitro experiments and network pharmacology.

Introduction: Cyclocarya paliurus (Batal.) Iljinsk., a subtropical tree belonging to the family Juglandaceae, is rich in polysaccharides, flavonoids, and terpenoids. It has important pharmacological effects such as lowering blood lipids, blood sugar, and blood pressure. However, little has been discerned regarding anti tumor effects and their potential mechanisms. Method: In vitro cell culture experiments were used to test the effect of C. paliurus total flavonoids (CTFs) extract on apoptosis mechanisms in HepG2 cells. Network pharmacology was applied to further explore the effects of CTFs on liver cancer as well as the mechanisms through which these effects might be achieved. Both 3 hydroxyflavone and luteolin were randomly selected to verify the effect on inducing apoptosis and inhibiting the proliferation of HepG2 cells. Results and Discussion: Network pharmacological analysis was applied to these 62 compounds and their targets, and 13 flavonoids were further screened for their potential anti liver cancer activity. These 13 flavonoids included: tangeretin, baicalein, 7,3'-dihydroxyflavone, velutin, 3-hydroxyflavone, chrysin, kumatakenin, tricin, luteolin, chrysoeriol, apigenin, pinocembrin, and butin. Together, these flavonoids were predicted to interact with AKT1, MAPK3, PIK3CA, EGFR, MAP2K1, SRC, IGF1R, IKBKB, MET, and MAPK14. It was predicted that the inhibitory effect on hepatocellular carcinoma would be accomplished by regulation of core proteins relating to such KEGG pathways as cancer, PI3K-Akt, proteoglycans in cancer, microRNAs in cancer, and endocrine resistance via core target proteins. Both 3-hydroxyflavone and luteolin were demonstrated to induce apoptosis and inhibit the proliferation of HepG2 cells. Our study provides scientific evidence supporting the use of CTFs for the treatment of liver cancer.

The novel HLA-C*03:605 allele, identified using next-generation sequencing in a Chinese individual.

The HLA-C*03:605 allele differs from HLA-C*03:04:01:01 by a single nucleotide in exon 4, position 680.

The novel allele HLA-B*35:564, identified by next-generation sequencing in a Chinese individual.

The novel HLA-B*35:564 allele differs from the HLA-B*35:01:01:01 allele by one nucleotide in exon 3 at position 490.

A novel HLA-C allele, HLA-C*03:614, identified by next-generation sequencing in a Chinese individual.

HLA-C*03:614 has one nucleotide change compared with HLA-C*03:02:02:01 in exon 7, codon 336.

The mechanism of abscisic acid regulation of wild Fragaria species in response to cold stress.

BACKGROUND: Abiotic stresses have increasingly serious effects on the growth and yield of crops. Cold stress, in particular, is an increasing problem. In this study, Fragaria daltoniana and F. vesca were determined to be cold-resistant and cold-sensitive species, respectively. Integrated transcriptomics and metabolomics methods were used to analyze the regulatory mechanism of abscisic acid (ABA) in F. daltoniana and F. vesca in their response to low temperature stress. RESULTS: F. daltoniana and F. vesca increased their ABA content under low temperature stress by upregulating the expression of the ABA biosynthetic pathway gene NCED and downregulating the expression of the ABA degradative gene CYP707A. Both types of regulation increased the accumulation of glucose and fructose, resulting in a reduction of damage under low temperature stress. Twelve transcription factors were found to be involved in the ABA regulatory pathway. The strong cold tolerance of F. daltoniana could be owing to its higher levels of ABA that accumulated compared with those in F. vesca under low temperature stress. In addition, the gene ABF2, which is related to the transduction of glucose signaling, was significantly upregulated in the leaves of F. daltoniana, while it was downregulated in the leaves of F. vesca under low temperature stress. This could contribute to the higher levels of glucose signal transduction in F. daltoniana. Thus, this could explain the higher peroxidase activity and lower damage to cell membranes in the leaves of F. daltoniana compared with F. vesca under low temperature stress, which endows the former with stronger cold tolerance. CONCLUSIONS: Under low temperature stress, the differences in the accumulation of ABA and the expression trends of ABF2 and ABF4 in different species of wild strawberries may be the primary reason for their differences in cold tolerance. Our results provide an important empirical reference and technical support for breeding resistant cultivated strawberry plants.

A general approach to S-rhodamines from diaryl thioethers and their application in constructing pH probes.

A general strategy for the efficient preparation of S-rhodamines from the condensation of diaryl thioether and 2-carboxybenzaldehydes was reported. We further took a morpholine containing spirolactam structure as an example to illustrate that these S-rhodamine dyes could be utilized to construct fluorescent probes based on the ring-opening process. This work provided a general approach for the synthesis of novel S-rhodamine dyes, thus possibly facilitating the development of fluorescence imaging.

Clinical Potential of lncRNA PPP1R26-AS1 in Breast Cancer and Its Contribution to Cancer Progression.

Breast cancer has become the most leading diagnosed tumor worldwide in 2020. In this study, the biomarker potential and influence on the cellular function of lncRNA PPP1R26-AS1 was investigated in breast cancer. Expression levels of lncRNA PPP1R26-AS1 in breast tissues and cells were detected by RT-qPCR. Association between lncRNA PPP1R26-AS1 level and clinical parameters was investigated by Chi-square analysis. The prognostic potential was assessed by Kaplan-Meier and multivariate Cox regression analysis. Knockdown of lncRNA PPP1R26-AS1 was subjected to study the effect on cell proliferation, invasion, and migration by CCK-8 and transwell assay. The bind between PPP1R26-AS1 and miR-1226-3p was investigated. LncRNA PPP1R26-AS1 was highly expressed in breast tissues and cell lines. This upregulation was correlated with pTNM, positive ER status, luminal B subtype, positive nodal status, and shorter overall survival in breast cancer patients. Significant decreases in proliferation, migration, and invasion activity were observed upon knockdown of lncRNA PPP1R26-AS1. lncRNA PPP1R26-AS1 could act as ceRNA to bind with miR-1226-3p in breast cancer. LncRNA PPP1R26-AS1, as oncogenic lncRNA, could provide a new perspective on the development of prognostic biomarkers and a new approach in tailoring the treatment personalized in breast cancer.

Amino acid sequence identification of goji berry cyclic peptides and anticervical carcinoma activity detection.

The goji berry is widely used as tonics; however, the antihuman cervical carcinoma effect and underlying mechanism of goji berry peptide remain to be elucidated. The cyclic peptides are appealing targets in antitumor agent development, and in current study, three novel goji berry cyclic peptides (GCPs) were isolated and amino acid sequence identified. Among them, GCP-1 (Cycle-(Trp-Glu-His-Thr)) inhibited proliferation and induced human cervical cancer (HeLa) cells apoptosis and blocked the HeLa cells in G0/G1 phase significantly. Furthermore, the GCP-1 also inhibited the cervical carcinoma growth in vivo. Moreover, GCP-1 suppressed the cyclin expression and activated the caspase cascade and poly(ADP-ribose) polymerase. Of note, GCP-1 may be a promising novel inhibitor of human cervical cancer.

Multi-Head Self-Attention Model for Classification of Temporal Lobe Epilepsy Subtypes.

As a long-standing chronic disease, Temporal Lobe Epilepsy (TLE), resulting from abnormal discharges of neurons and characterized by recurrent episodic central nervous system dysfunctions, has affected more than 70% of drug-resistant epilepsy patients across the world. As the etiology and clinical symptoms are complicated, differential diagnosis of TLE mainly relies on experienced clinicians, and specific diagnostic biomarkers remain unclear. Though great effort has been made regarding the genetics, pathology, and neuroimaging of TLE, an accurate and effective diagnosis of TLE, especially the TLE subtypes, remains an open problem. It is of a great importance to explore the brain network of TLE, since it can provide the basis for diagnoses and treatments of TLE. To this end, in this paper, we proposed a multi-head self-attention model (MSAM). By integrating the self-attention mechanism and multilayer perceptron method, the MSAM offers a promising tool to enhance the classification of TLE subtypes. In comparison with other approaches, including convolutional neural network (CNN), support vector machine (SVM), and random forest (RF), experimental results on our collected MEG dataset show that the MSAM achieves a supreme performance of 83.6% on accuracy, 90.9% on recall, 90.7% on precision, and 83.4% on F1-score, which outperforms its counterparts. Furthermore, effectiveness of varying head numbers of multi-head self-attention is assessed, which helps select the optimal number of multi-head. The self-attention aspect learns the weights of different signal locations which can effectively improve classification accuracy. In addition, the robustness of MSAM is extensively assessed with various ablation tests, which demonstrates the effectiveness and generalizability of the proposed approach.

Predicting the potential distribution of the parasitic Cuscuta chinensis under global warming.

BACKGROUND: The climate is the dominant factor that affects the distribution of plants. Cuscuta chinensis is a stem holoparasitic plant without leaves or roots, which develops a haustorium and sucks nutrients from host plants. The potential distribution of the parasitic plant C. chinensis has not been predicted to date. This study used Maxent modeling to predict the potential global distribution of C. chinensis, based on the following six main bioclimatic variables: annual mean temperature, isothermality, temperature seasonality, precipitation seasonality, precipitation of the warmest quarter, and precipitation of the coldest quarter. RESULTS: The optimal annual average temperature and isothermality of C. chinensis ranged from 4 to 37 °C and less than 45, respectively, while the optimal temperature seasonality and precipitation seasonality ranged from 4000 to 25,000 and from 50 to 130, respectively. The optimal precipitation of the warmest season ranged from 300 to 1000 mm and from 2500 to 3500 mm, while that of the coldest season was less than 2000 mm. In Asia, C. chinensis is mainly distributed at latitudes ranging from 20° N to 50° N. During three specific historical periods (last glacial maximum, mid-Holocene, and 1960-1990) the habitats suitable for C. chinensis were concentrated in the central, northern, southern, and eastern parts of China. From the last glacial maximum to the mid-Holocene, the total area with suitability of 0.5-1 increased by 0.0875 million km2; however, from the mid-Holocene to 1960-1990, the total area with suitability of 0.5-1 decreased by 0.0759 million km2. The simulation results of habitat suitability in the two representative concentration pathways (RCP) 2.6 (i.e., the low greenhouse gas emissions pathway) and 8.5 (i.e., the high greenhouse gas emissions pathway) indicate that the habitat suitability of C. chinensis decreased in response to the warming climate. Compared with RCP2.6, areas with averaged suitability and high suitability for survival (RCP8.5) decreased by 0.18 million km2. CONCLUSION: Suitable habitats of C. chinensis are situated in central, northern, southern, and eastern China. The habitat suitability of C. chinensis decreased in response to the warming climate. These results provide a reference for the management and control of C. chinensis.

Smart Soft Sensor Design with Hierarchical Sampling Strategy of Ensemble Gaussian Process Regression for Fermentation Processes.

Accurate and real-time quality prediction to realize the optimal process control at a competitive price is an important issue in Industrial 4.0. This paper shows a successful engineering application of how smart soft sensors can be combined with machine learning technique to significantly save human resources and improve performance under complex industrial conditions. Ensemble learning based soft sensors succeed in capturing complex nonlinearities, frequent dynamic changes, as well as time-varying characteristics in industrial processes. However, local model regions under traditional ensemble modelling methods are highly dependent on labeled data samples and, hence, their prediction accuracy might get affected when labeled samples are limited. A novel active learning (AL) framework upon the ensemble Gaussian process regression (GPR) model is proposed for smart soft sensor design in order to overcome this drawback. Firstly, to iteratively select the most informative unlabeled samples for labeling with hierarchical sampling based AL strategy, to then apply Gaussian mixture model (GMM) technique to autonomously identify operation phases, to further construct local GPR models without human involvement, and finally to integrate the base predictors by applying the Bayesian fusion strategy. Comparative studies for the penicillin fermentation process demonstrate the reliability and superiority of the recommended smart soft sensing. The cost of human annotation can be dramatically reduced by at least half while the prediction performance simultaneously keeps high.

Correlation Between Doppler Ultrasound Blood Flow Parameters and Angiogenesis and Proliferation Activity in Breast Cancer.

BACKGROUND The aim of this study was to assess the correlation between Doppler ultrasound blood flow parameters and angiogenesis and proliferation activity in breast cancer. MATERIAL AND METHODS We enrolled breast cancer patients (n=55) and benign tumor patients (n=40) from Tengzhou Central People's Hospital from Mar 2014 to Dec 2016. Doppler ultrasound examination was conducted to determine blood flow parameters, and immunohistochemistry (IHC) experiments were performed to determine the protein expression of angiogenesis genes, cell proliferation genes, and tumor-suppressor genes. RESULTS Compared with benign tumors, the maximum velocity (Vmax) and resistance index (RI) were significantly different in I-II stage and III-IV stage breast cancer (P<0.01 and P<0.001, respectively). IHC assay showed that VEDGF165, NRP-1, SphK1, CD31, YAP, CTGF, and Gli2 proteins expressions were significantly higher in breast cancer patients (P<0.01 and P<0.001, respectively). PTEN and MFN2 protein expressions of breast cancer patients were significantly lower (P<0.01 or P<0.001, respectively) compared with those of benign tumor patients. VEDGF165, NRP-1, SphK1, CD31, YAP, CTGF, and Gli2 proteins expressions were positively correlated with Vmax and negatively correlated with RI in breast cancer. PTEN and MFN2 protein expressions were negative correlated with Vmax and positively correlated with RI in breast cancer patients. CONCLUSIONS Decreased RI and increased Vmax are correlated with angiogenesis, proliferation, and tumor suppression in breast cancer.

[Efficacy, Prognosis and Safety of Decitabine Combined with Low-Dose Cytarabine in the Treatment of Elderly Patients with Relapsed/Refractory Acute Myeloid Leukemia].

OBJECTIVE: To investigate the efficacy, prognosis and safety of decitabine combined with low-dose CAG regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS: The clinical data of 40 elderly patients with relapsed/refractory AML （69-85 years old） admitted to our hospital from January 2014 to August 2016 were analyzed retrospectively. 40 patients were divided into combination therapy group and CAG group according to different treatment methods. 20 patients of the combination therepy group were treated with decitabine combined with low-dose CAG （decitabine, 15 mg/m2, d 1; aclarithromycin, 10 mg/m2, d 3-6; Cytidine, 10 mg/m2, d 1-14; recombinant human granulocyte macrophage colony-stimulating factor （G-CSF） for injection, 200 µg/（m2·d）, d 1-14）. 20 patients of CAG group were treated by the standard CAG protocol （acralmycin 20 mg/m2, d 1-4; cytarabine for injection, 15 mg/m2, d 1-14; G-CSF 400 µg/（m2·d）, d 1-14）. One course of treatment lasted for 2 weeks, after 2 courses of continuous medication, the complete remission rate （CR）, overall remission rate （ORR）, overall survival （OS）, 1-year survival rate, hemoglobin, white blood cells, platelets improvement, and incidence of adverse reactions were compared. RESULTS: In combination therapy group the CR was 55.00% （11/20）, OR was 85.00% （17/20）, but in the CAG group CR was 30.00% （6/20）, and OR was 50.00% （10/20）. Till to February 2018, out of 40 patients 17 survived, 20 died, and 3 failed to be followed-up. The median follow-up time was 12 （2 to 35） months; the median survival time in the comtination therapy group was 13 （2-35） months, and the 1-year OS rate was 70.00%, and the median survival time of the CAG group was 10 （2-31） months, and the 1-year OS rate was 50.00%, without staistical significance between the 2 groups （P>0.05）. After treatment, the WBC and Plt counts in the combination therapy group were higher than those in the CAG group, but the Hb level was lower than that in the CAG group with statistically significant difference （P<0.05）. In the combination therapy group, the incidence of lung infection, nausea and vomiting was higher than that of the CAG group （65.00% vs 25.00%, 50.00% vs 20.00%）, with statistically significant difference （P<0.05）. CONCLUSION: Decitabine combined with low-dose CAG regimen is effective for the treatment of relapsed/refractory AML in the elderly. Compared with the standard CAG regimen, the long-term efficacy of this regimen is not different significantly, but its adverse reactions are increase, thus the preventive treatment should be given in time.

Identification of DEAD-Box RNA Helicase DDX41 as a Trafficking Protein That Involves in Multiple Innate Immune Signaling Pathways in a Zebrafish Model.

DDX41 is an important sensor for host recognition of DNA viruses and initiation of nuclear factor-κB (NF-κB) and IFN signaling pathways in mammals. However, its occurrence and functions in other vertebrates remain poorly defined. Here, a DDX41 ortholog [Danio rerio DDX41 (DrDDX41)] with various conserved structural features to its mammalian counterparts was identified from a zebrafish model. This DrDDX41 was found to be a trafficking protein distributed in the nucleus of resting cells but transported into the cytoplasm under DNA stimulation. Two nuclear localization signal motifs were localized beside the coiled-coil domain, whereas one nuclear export signal motif existed in the DEADc domain. DrDDX41 acts as an initiator for the activation of NF-κB and IFN signaling pathways in a Danio rerio STING (DrSTING)-dependent manner through its DEADc domain, which is a typical performance of mammalian DDX41. These observations suggested the conservation of DDX41 proteins throughout the vertebrate evolution, making zebrafish an alternative model in understanding DDX41-mediated immunology. With this model system, we found that DrDDX41 contributes to DrSTING-Danio rerio STAT6 (DrSTAT6)-mediated chemokine (Danio rerio CCL20) production through its DEADc domain. To the best of our knowledge, this work is the first report showing that DDX41 is an upstream initiator in this newly identified signaling pathway. The DrDDX41-mediated signaling pathways play important roles in innate antibacterial immunity because knockdown of either DrDDX41 or DrSTING/DrSTAT6 significantly reduced the survival of zebrafish under Aeromonas hydrophilia or Edwardsiella tarda infection. Our findings would enrich the current knowledge of DDX41-mediated immunology and the evolutionary history of the DDX41 family.

A new method for water quality assessment: by harmony degree equation.

Water quality assessment is an important basic work in the development, utilization, management, and protection of water resources, and also a prerequisite for water safety. In this paper, the harmony degree equation (HDE) was introduced into the research of water quality assessment, and a new method for water quality assessment was proposed according to the HDE: by harmony degree equation (WQA-HDE). First of all, the calculation steps and ideas of this method were described in detail, and then, this method with some other important methods of water quality assessment (single factor assessment method, mean-type comprehensive index assessment method, and multi-level gray correlation assessment method) were used to assess the water quality of the Shaying River (the largest tributary of the Huaihe in China). For this purpose, 2 years (2013-2014) dataset of nine water quality variables covering seven monitoring sites, and approximately 189 observations were used to compare and analyze the characteristics and advantages of the new method. The results showed that the calculation steps of WQA-HDE are similar to the comprehensive assessment method, and WQA-HDE is more operational comparing with the results of other water quality assessment methods. In addition, this new method shows good flexibility by setting the judgment criteria value HD0 of water quality; when HD0 = 0.8, the results are closer to reality, and more realistic and reliable. Particularly, when HD0 = 1, the results of WQA-HDE are consistent with the single factor assessment method, both methods are subject to the most stringent "one vote veto" judgment condition. So, WQA-HDE is a composite method that combines the single factor assessment and comprehensive assessment. This research not only broadens the research field of theoretical method system of harmony theory but also promotes the unity of water quality assessment method and can be used for reference in other comprehensive assessment.

XdhR negatively regulates actinorhodin biosynthesis in Streptomyces coelicolor M145.

The xdhR gene encodes a TetR-family regulator in Streptomyces coelicolor. However, little is known about the function of XdhR in regulating actinorhodin production. Here, we report that XdhR negatively regulates actinorhodin biosynthesis in S. coelicolor. Deletion of xdhR resulted in overproduction of actinorhodin by approximately 2.5-fold compared to the wild-type strain. Complementation of the xdhR deletion strain restored actinorhodin production to normal levels. In addition, the relative expression levels of actinorhodin cluster genes were all significantly increased in the xdhR deletion strain compared to the wild-type strain. XdhR can specifically bind the promoters of actII-4 and actII-1, two pathway-specific regulators of actinorhodin biosynthesis. These results suggest that xdhR negatively controls actinorhodin biosynthesis by directly regulating actII-4 and actII-1 in S. coelicolor.

Essential Roles of TIM-1 and TIM-4 Homologs in Adaptive Humoral Immunity in a Zebrafish Model.

TIM-1 and TIM-4 proteins have become increasingly attractive for their critical functions in immune modulation, particularly in CD4(+) Th2 cell activation. Thus, these proteins were hypothesized to regulate adaptive humoral immunity. However, further evidence is needed to validate this hypothesis. This study describes the molecular and functional characteristics of TIM-1 and TIM-4 homologs from a zebrafish (Danio rerio) model (D. rerio TIM [DrTIM]-1 and DrTIM-4). DrTIM-1 and DrTIM-4 were predominantly expressed in CD4(+) T cells and MHC class II(+) APCs under the induction of Ag stimulation. Blockade or knockdown of both DrTIM-1 and DrTIM-4 significantly decreased Ag-specific CD4(+) T cell activation, B cell proliferation, Ab production, and vaccinated immunoprotection against bacterial infection. This result suggests that DrTIM-1 and DrTIM-4 serve as costimulatory molecules required for the full activation of adaptive humoral immunity. DrTIM-1 was detected to be a trafficking protein located in the cytoplasm of CD4(+) T cells. It can translocate onto the cell surface under stimulation by TIM-4-expressing APCs, which might be a precise regulatory strategy for CD4(+) T cells to avoid self-activation before APCs stimulation. Furthermore, a unique alternatively spliced soluble DrTIM-4 variant was identified to exert a negative regulatory effect on the proliferation of CD4(+) T cells. The above findings highlight a novel costimulatory mechanism underlying adaptive immunity. This study enriches the current knowledge on TIM-mediated immunity and provides a cross-species understanding of the evolutionary history of costimulatory systems throughout vertebrate evolution.

Characterization of γδ T Cells from Zebrafish Provides Insights into Their Important Role in Adaptive Humoral Immunity.

γδ T cells represent an evolutionarily primitive T cell subset characterized by distinct T cell receptors (TCRs) and innate and adaptive immune functions. However, the presence of this T cell subset in ancient vertebrates remains unclear. In this study, γδ T cells from a zebrafish (Danio rerio) model were subjected to molecular and cellular characterizations. The constant regions of zebrafish TCR-γ (DrTRGC) and δ (DrTRDC) were initially identified. Zebrafish γδ T cells accounted for 7.7-20.5% of the total lymphocytes in spleen, head kidney, peripheral blood, skin, gill, and intestine tissues. They possess typical morphological features of lymphocytes with a surface phenotype of γ+δ+CD4-CD8+. Zebrafish γδ T cells functionally showed a potent phagocytic ability to both soluble and particulate antigens. They can also act as an antigen-presenting cell to initiate antigen (KLH)-specific CD4+ TKLH cell activation and to induce B cell proliferation and IgM production. Particularly, zebrafish γδ T cells also play a critical role in antigen-specific IgZ production in intestinal mucus. These findings demonstrated that γδ T cells had been originated as early as teleost fish, which providing valuable insights into the evolutionary history of T cell subset. It is anticipated that this study would be used as a guide to develop a zebrafish model for the cross-species investigation of γδ T cell biology.

Description and Application of a Mathematical Method for the Analysis of Harmony.

Harmony issues are widespread in human society and nature. To analyze these issues, harmony theory has been proposed as the main theoretical approach for the study of interpersonal relationships and relationships between humans and nature. Therefore, it is of great importance to study harmony theory. After briefly introducing the basic concepts of harmony theory, this paper expounds the five elements that are essential for the quantitative description of harmony issues in water resources management: harmony participant, harmony objective, harmony regulation, harmony factor, and harmony action. A basic mathematical equation for the harmony degree, that is, a quantitative expression of harmony issues, is introduced in the paper: HD = ai - bj, where a is the uniform degree, b is the difference degree, i is the harmony coefficient, and j is the disharmony coefficient. This paper also discusses harmony assessment and harmony regulation and introduces some application examples.