Metformin blocks BIK1-mediated CPK28 phosphorylation and enhances plant immunity.

INTRODUCTION: Metformin (MET), derived from Galega officinalis, stands as the primary first-line medication for the treatment of type 2 diabetes (T2D). Despite its well-documented benefits in mammalian cellular processes, its functions and underlying mechanisms in plants remain unclear. OBJECTIVES: This study aimed to elucidate MET's role in inducing plant immunity and investigate the associated mechanisms. METHODS: To investigate the impact of MET on enhancing plant immune responses, we conducted assays measuring defense gene expression, reactive oxygen species (ROS) accumulation, mitogen-activated protein kinase (MAPK) phosphorylation, and pathogen infection. Additionally, surface plasmon resonance (SPR) and microscale thermophoresis (MST) techniques were employed to identify MET targets. Protein-protein interactions were analyzed using a luciferase complementation assay and a co-immunoprecipitation assay. RESULTS: Our findings revealed that MET boosts plant disease resistance by activating MAPKs, upregulating the expression of downstream defense genes, and fortifying the ROS burst. CALCIUM-DEPENDENT PROTEIN KINASE 28 (CPK28) was identified as a target of MET. It inhibited the interaction between BOTRYTIS-INDUCED KINASE 1 (BIK1) and CPK28, blocking CPK28 threonine 76 (T76) transphosphorylation by BIK1, and alleviating the negative regulation of immune responses by CPK28. Moreover, MET enhanced disease resistance in tomato, pepper, and soybean plants. CONCLUSION: Collectively, our data suggest that MET enhances plant immunity by blocking BIK1-mediated CPK28 phosphorylation.

Potato calcium sensor modules StCBL3-StCIPK7 and StCBL3-StCIPK24 negatively regulate plant immunity.

BACKGROUND: Potato late blight, caused by Phytophthora infestans, is the most devastating disease on potato. Dissecting critical immune components in potato will be supportive for engineering P. infestans resistance. Upon pathogens attack, plant Ca2+ signature is generated and decoded by an array of Ca2+ sensors, among which calcineurin B-like proteins (CBLs) coupled with plant specific CBL-interacting protein kinases (CIPKs) are much less explored in plant immunity. RESULTS: In this study, we identified that two differential potato CBL-CIPK modules regulate plant defense responses against Phytophthora and ROS production, respectively. By deploying virus-induced gene silencing (VIGS) system-based pathogen inoculation assays, StCBL3 was shown to negatively regulate Phytophthora resistance. Consistently, StCBL3 was further found to negatively regulate PTI and ETI responses in Nicotiana benthamiana. Furthermore, StCIPK7 was identified to act together with StCBL3 to negatively regulate Phytophthora resistance. StCIPK7 physically interacts with StCBL3 and phosphorylates StCBL3 in a Ca2+-dependent manner. StCBL3 promotes StCIPK7 kinase activity. On the other hand, another StCBL3-interacting kinase StCIPK24 negatively modulating flg22-triggered accumulation of reactive oxygen species (ROS) by interacting with StRBOHB. CONCLUSIONS: Together, these findings demonstrate that the StCBL3-StCIPK7 complex negatively modulates Phytophthora resistance and StCBL3-StCIPK24 complex negatively regulate ROS production. Our results offer new insights into the roles of potato CBL-CIPK in plant immunity and provide valuable gene resources to engineer the disease resistance potato in the future.

Research on the causal mechanism of a rock burst accident in a longwall roadway and its prevention measures.

Based on the disaster characteristics and the geo-conditions at the scene, in this study, the occurrence mechanism of a serious rock burst accident that occurred in the Tangshan Coal Mine, China, was analysed. Ground stress measurements showed that the mine is in a high ground stress area dominated by horizontal tectonic stress around 33 MPa. Laboratory testing revealed that the coal was a hard seam of 8.3 MPa over bedded by a thick and hard roof stratum with uniaxial compressive strength of 66 MPa. The calculation results indicated that the accident occurred in the roof rebounding area. It is proposed that the hard roof and the hard coal seam formed a seesaw structure around the working face. The vertical pressure relief caused the rib coal mass to lose its clamping forces from the roof and floor and rush into the roadway, resulting in a rock burst accident. Based on the causality mechanism of the rock burst disaster developed in this study, pertinent coal bump prevention measures have been undertaken in practice. Large-diameter boreholes were drilled to eliminate the pivot effect of the seam. Roof blasting was undertaken to prevent the roof from forming a seesaw plank. To summarize, a new causality mechanism for rock burst in coal mines under hard roof and hard seam geo-conditions was developed.

MAB-DrNet: Bearing Fault Diagnosis Method Based on an Improved Dilated Convolutional Neural Network.

Rolling bearing fault diagnosis is of great significance to the safe and reliable operation of manufacturing equipment. In the actual complex environment, the collected bearing signals usually contain a large amount of noises from the resonances of the environment and other components, resulting in the nonlinear characteristics of the collected data. Existing deep-learning-based solutions for bearing fault diagnosis perform poorly in classification performance under noises. To address the above problems, this paper proposes an improved dilated-convolutional-neural network-based bearing fault diagnosis method in noisy environments named MAB-DrNet. First, a basic model called the dilated residual network (DrNet) was designed based on the residual block to enlarge the model's perceptual field to better capture the features from bearing fault signals. Then, a max-average block (MAB) module was designed to improve the feature extraction capability of the model. In addition, the global residual block (GRB) module was introduced into MAB-DrNet to further improve the performance of the proposed model, enabling the model to better handle the global information of the input data and improve the classification accuracy of the model in noisy environments. Finally, the proposed method was tested on the CWRU dataset, and the results showed that the proposed method had good noise immunity; the accuracy was 95.57% when adding Gaussian white noises with a signal-to-noise ratio of -6 dB. The proposed method was also compared with existing advanced methods to further prove its high accuracy.

Experimental Study of Mechanical Properties and Failure Characteristics of Coal-Rock-like Composite Based on 3D Printing Technology.

Coal contains cracks and has strong heterogeneity, so the data dispersion is large in laboratory tests. In this study, 3D printing technology is used to simulate hard rock and coal, and the rock mechanics test method is used to carry out the coal-rock combination experiment. The deformation characteristics and failure modes of the combination are analyzed and compared with the relevant parameters of the single body. The results show that the uniaxial compressive strength of the composite sample is inversely proportional to the thickness of the weak body and directly proportional to the thickness of the strong body. The Protodyakonov model or ASTM model can be used as a verification method for the results of a uniaxial compressive strength test of coal-rock combination. The elastic modulus of the combination is the equivalent elastic modulus, and the elastic modulus of the combination is between the elastic modulus of the two constituent monomers, which can be analyzed using the Reuss model. The failure of the composite sample occurs in the low-strength material, while the high-strength section is rebounding as an extra load on the low-strength body, which may cause a sharp increase in the strain rate of the weak body. The main failure mode of the sample with a small height-diameter ratio is splitting, and the failure mode of the sample with a large height-diameter ratio is shear fracturing. When the height-diameter ratio is not greater than 1, it shows pure splitting, and when the height-diameter ratio is 1~2, it shows a mixed mode of splitting and shear fracture. The shape has a significant effect on the uniaxial compressive strength of the composite specimen. For the impact propensity, it can be determined that the uniaxial compressive strength of the combination is higher than that of the single body, and the dynamic failure time is lower than that of the single body. It can hardly determine the elastic energy and the impact energy of the composite with the relationship to the weak body. The proposed methodology provides new cutting-edge test technologies in the study of coal and coal-like materials, with an exploration of their mechanical properties under compression.

HBcAb positivity increases the risk of postoperative complications after extended hemihepatectomy for hilar cholangiocarcinoma.

BACKGROUND: Hepatitis B core antibody (HBcAb) positivity is considered a prior hepatitis B virus (HBV) infection. However, little is known about the effect of HBcAb positivity on surgical safety for hilar cholangiocarcinoma (hCCA). The present study aims to investigate the role of HBcAb positivity on postoperative complications of hCCA. METHODS: A retrospective analysis was performed on the status of HBcAb positivity, liver fibrosis, perioperative surgical complications, and long-term outcomes of hCCA patients with Hepatitis B surface antigen (HBsAg) negativity who underwent surgical treatment in Tongji Hospital from April 2012 to September 2019. RESULTS: HBcAb positivity with negative HBsAg occurs in 137 hCCA patients (63.1%). A total of 99 hCCA patients with negative HBsAg underwent extended hemihepatectomy, of whom 69 (69.7%) and 30 (30.3%) were HBcAb-positive and HBcAb-negative, respectively. Significant fibrosis was detected in 63.8% of the patients with HBcAb-positive, which was markedly higher than those with HBcAb-negative (36.7%) (p = 0.016). The postoperative complications and 90-day mortality rates were 37.4% (37/99) and 8.1% (8/99), respectively. The incidence of postoperative complications in HBcAb-positive patients (44.9%) was significantly higher than that in HBcAb-negative patients (20.0%) (p = 0.018). All the patients who died within 30-day after surgery were HBcAb-positive. Multivariate analysis showed that the independent risk factors for complications were HBcAb positivity, preoperative cholangitis, portal occlusion >15 min, and significant fibrosis. There were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between HBcAb-positive and HBcAb-negative patients (p = 0.642 and p = 0.400, respectively). CONCLUSIONS: HBcAb positivity is a common phenomenon in hCCA patients from China, a country with highly prevalent HBcAb positivity. The status of HBcAb-positive markedly increases the incidence of postoperative complications after extended hemihepatectomy for hCCA patients.

A pair of G-type lectin receptor-like kinases modulates nlp20-mediated immune responses by coupling to the RLP23 receptor complex.

Plant cells recognize microbial patterns with the plasma-membrane-localized pattern-recognition receptors consisting mainly of receptor kinases (RKs) and receptor-like proteins (RLPs). RKs, such as bacterial flagellin receptor FLS2, and their downstream signaling components have been studied extensively. However, newly discovered regulatory components of RLP-mediated immune signaling, such as the nlp20 receptor RLP23, await identification. Unlike RKs, RLPs lack a cytoplasmic kinase domain, instead recruiting the receptor-like kinases (RLKs) BAK1 and SOBIR1. SOBIR1 specifically works as an adapter for RLP-mediated immunity. To identify new regulators of RLP-mediated signaling, we looked for SOBIR1-binding proteins (SBPs) in Arabidopsis thaliana using protein immunoprecipitation and mass spectrometry, identifying two G-type lectin RLKs, SBP1 and SBP2, that physically interacted with SOBIR1. SBP1 and SBP2 showed high sequence similarity, were tandemly repeated on chromosome 4, and also interacted with both RLP23 and BAK1. sbp1 sbp2 double mutants obtained via CRISPR-Cas9 gene editing showed severely impaired nlp20-induced reactive oxygen species burst, mitogen-activated protein kinase (MAPK) activation, and defense gene expression, but normal flg22-induced immune responses. We showed that SBP1 regulated nlp20-induced immunity in a kinase activity-independent manner. Furthermore, the nlp20-induced the RLP23-BAK1 interaction, although not the flg22-induced FLS2-BAK1 interaction, was significantly reduced in sbp1 sbp2. This study identified SBPs as new regulatory components in RLP23 receptor complex that may specifically modulate RLP23-mediated immunity by positively regulating the interaction between the RLP23 receptor and the BAK1 co-receptor.

Functional Diversification Analysis of Soybean Malectin/Malectin-Like Domain-Containing Receptor-Like Kinases in Immunity by Transient Expression Assays.

Plants have responded to microbial pathogens by evolving a two-tiered immune system, involving pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI). Malectin/malectin-like domain-containing receptor-like kinases (MRLKs) have been reported to participate in many biological functions in plant including immunity and resistance. However, little is known regarding the role of MRLKs in soybean immunity. This is a crucial question to address because soybean is an important source of oil and plant proteins, and its production is threatened by various pathogens. Here, we systematically identified 72 Glycine max MRLKs (GmMRLKs) and demonstrated that many of them are transcriptionally induced or suppressed in response to infection with microbial pathogens. Next, we successfully cloned 60 GmMRLKs and subsequently characterized their roles in plant immunity by transiently expressing them in Nicotiana benthamiana, a model plant widely used to study host-pathogen interactions. Specifically, we examined the effect of GmMRLKs on PTI responses and noticed that a number of GmMRLKs negatively regulated the reactive oxygen species burst induced by flg22 and chitin, and cell death triggered by XEG1 and INF1. We also analyzed the microbial effectors AvrB- and XopQ-induced hypersensitivity response and identified several GmMRLKs that suppressed ETI activation. We further showed that GmMRLKs regulate immunity probably by coupling to the immune receptor complexes. Furthermore, transient expression of several selected GmMRLKs in soybean hairy roots conferred reduced resistance to soybean pathogen Phytophthora sojae. In summary, we revealed the common and specific roles of GmMRLKs in soybean immunity and identified a number of GmMRLKs as candidate susceptible genes that may be useful for improving soybean resistance.

The Rice Malectin Regulates Plant Cell Death and Disease Resistance by Participating in Glycoprotein Quality Control.

In animals, malectin is well known to play an essential role in endoplasmic reticulum quality control (ERQC) by interacting with ribophorin I, one unit of the oligosaccharyltransferase (OST) complex. However, the functions of malectin in plants remain largely unknown. Here, we demonstrate the rice OsMLD1 is an ER- and Golgi-associated malectin protein and physically interacts with rice homolog of ribophorin I (OsRpn1), and its disruption leads to spontaneous lesion mimic lesions, enhanced disease resistance, and prolonged ER stress. In addition, there are many more N-glycosites and N-glycoproteins identified from the mld1 mutant than wildtype. Furthermore, OsSERK1 and OsSERK2, which have more N-glycosites in mld1, were demonstrated to interact with OsMLD1. OsMLD1 can suppress OsSERK1- or OsSERK2-induced cell death. Thus, OsMLD1 may play a similar role to its mammalian homologs in glycoprotein quality control, thereby regulating cell death and immunity of rice, which uncovers the function of malectin in plants.

Ubiquitination of Receptorsomes, Frontline of Plant Immunity.

Sessile plants are constantly exposed to myriads of unfavorable invading organisms with different lifestyles. To survive, plants have evolved plasma membrane-resident pattern recognition receptors (PRRs) and intracellular nucleotide-binding domain leucine-rich repeat receptors (NLRs) to initiate sophisticated downstream immune responses. Ubiquitination serves as one of the most important and prevalent posttranslational modifications (PTMs) to fine-tune plant immune responses. Over the last decade, remarkable progress has been made in delineating the critical roles of ubiquitination in plant immunity. In this review, we highlight recent advances in the understanding of ubiquitination in the modulation of plant immunity, with a particular focus on ubiquitination in the regulation of receptorsomes, and discuss how ubiquitination and other PTMs act in concert to ensure rapid, proper, and robust immune responses.

A tale of many families: calcium channels in plant immunity.

Plants launch a concerted immune response to dampen potential infections upon sensing microbial pathogen and insect invasions. The transient and rapid elevation of the cytosolic calcium concentration [Ca2+]cyt is among the essential early cellular responses in plant immunity. The free Ca2+ concentration in the apoplast is far higher than that in the resting cytoplasm. Thus, the precise regulation of calcium channel activities upon infection is the key for an immediate and dynamic Ca2+ influx to trigger downstream signaling. Specific Ca2+ signatures in different branches of the plant immune system vary in timing, amplitude, duration, kinetics, and sources of Ca2+. Recent breakthroughs in the studies of diverse groups of classical calcium channels highlight the instrumental role of Ca2+ homeostasis in plant immunity and cell survival. Additionally, the identification of some immune receptors as noncanonical Ca2+-permeable channels opens a new view of how immune receptors initiate cell death and signaling. This review aims to provide an overview of different Ca2+-conducting channels in plant immunity and highlight their molecular and genetic mode-of-actions in facilitating immune signaling. We also discuss the regulatory mechanisms that control the stability and activity of these channels.

Comparison of the Distinct, Host-Specific Response of Three Solanaceae Hosts Induced by Phytophthora infestans.

Three Solanaceae hosts (TSHs), S. tuberosum, N. benthamiana and S. lycopersicum, represent the three major phylogenetic clades of Solanaceae plants infected by Phytophthora infestans, which causes late blight, one of the most devastating diseases seriously affecting crop production. However, details regarding how different Solanaceae hosts respond to P. infestans are lacking. Here, we conducted RNA-seq to analyze the transcriptomic data from the TSHs at 12 and 24 h post P. infestans inoculation to capture early expression effects. Macroscopic and microscopic observations showed faster infection processes in S. tuberosum than in N. benthamiana and S. lycopersicum under the same conditions. Analysis of the number of genes and their level of expression indicated that distinct response models were adopted by the TSHs in response to P. infestans. The host-specific infection process led to overlapping but distinct in GO terms and KEGG pathways enriched for differentially expressed genes; many were tightly linked to the immune response in the TSHs. S. tuberosum showed the fastest response and strongest accumulation of reactive oxygen species compared with N. benthamiana and S. lycopersicum, which also had similarities and differences in hormone regulation. Collectively, our study provides an important reference for a better understanding of late blight response mechanisms of different Solanaceae host interactions.

Direct-current generators based on conductive polymers for self-powered flexible devices.

Direct-current generators, especially those based on the Schottky contacts between conductive polymers and metal electrodes, are efficient in converting mechanical stimuli into electrical energy. In contrast to triboelectric and piezoelectric generators, direct-current generators readily produce direct-current outputs and high currents that are crucial for integrating multiple energy-harvesting units in large scale and driving some types of devices. We are focusing on the relationship between Schottky barrier height and performance, systematically investigating the effects of various conductive polymers and electrodes on the outputs by both theoretical simulation and experiments. Tailoring the Schottky barrier height between conductive polymers and metal electrodes is demonstrated a significant approach to design the new DC generators. The preparation method of electrochemical deposition endows the generators flexibility, the linear relationship of current/voltage output vs. strain applied on the generators, combined with the large outputs offer advantages for the generator to work as flexible sensors. Furthermore, a mechanosensation-active matrix array based on direct-current generator for the strain monitoring demonstrated its promising prospects in flexible electronics. The direct-current generators with improved performance could serve as a stream new blood for versatile sensory systems and human-machine interactive interfaces.

A Phytophthora capsici RXLR effector targets and inhibits the central immune kinases to suppress plant immunity.

Receptor-like cytoplasmic kinase subfamily VII (RLCK-VII) proteins are the central immune kinases in plant pattern-recognition receptor (PRR) complexes, and they orchestrate a complex array of defense responses against bacterial and fungal pathogens. However, the role of RLCK-VII in plant-oomycete pathogen interactions has not been established. Phytophthora capsici is a notorious oomycete pathogen that infects many agriculturally important vegetables. Here, we report the identification of RXLR25, an RXLR effector that is required for the virulence of P. capsici. In planta expression of RXLR25 significantly enhanced plants' susceptibility to Phytophthora pathogens. Microbial pattern-induced immune activation in Arabidopsis was severely impaired by RXLR25. We further showed that RXLR25 interacts with RLCK-VII proteins. Using nine rlck-vii high-order mutants, we observed that RLCK-VII-6 and RLCK-VII-8 members are required for resistance to P. capsici. The RLCK-VII-6 members are specifically required for Phytophthora culture filtrate (CF)-induced immune responses. RXLR25 directly targets RLCK-VII proteins such as BIK1, PBL8, and PBL17 and inhibits pattern-induced phosphorylation of RLCK-VIIs to suppress downstream immune responses. This study identified a key virulence factor for P. capsici, and the results revealed the importance of RLCK-VII proteins in plant-oomycete interactions.

Efficiency of chitosan application against Phytophthora infestans and the activation of defence mechanisms in potato.

Late blight, caused by the oomycete Phytophthora infestans, is one of the most devastating diseases that results in huge losses of potato crops worldwide. Chitosan as a defence elicitor can induce plant innate immunity against pathogen infection, but the efficiency and specific defence mechanism of chitosan against late blight in potato have not been elaborated. In this study, we demonstrated that the application of chitosan significantly enhanced potato resistance and reduced P. infestans infection in potted potato and in the field. Large-scale transcriptomic analysis suggested that chitosan preferentially activated several important pathways related to the plant defence response. Notably, we revealed that chitosan triggered pattern-triggered immunity responses in potato. Chitosan could trigger pattern recognition receptors to initiate intracellular signalling, and gradually amplify the immune signal. qRT-PCR verification showed that chitosan induced the expression of defence-related genes in potato. Moreover, treatment with chitosan result in Induced Systemic Resistance (ISR) in potato, including an accumulation of plant hormone salicylic acid, increase in the level of phenylalanine ammonia lyase activity and a content decrease of malondialdehyde. These findings help elucidate chitosan-mediated activation of the immune system in potato and provide a potential ecofriendly strategy to control potato late blight in the field.

High-Performance Phototransistors Based on MnPSe3 and Its Hybrid Structures with Au Nanoparticles.

Layered metal thiophosphates with a general formula MPX3 (M is a group VIIB or VIII element and X is a chalcogen) have emerged as a novel member in a two-dimensional (2D) family with fascinating physical and chemical properties. Herein, the photoelectric performance of the few-layer MnPSe3 was studied for the first time. The multilayer MnPSe3 shows p-type conductivity and its field-effect transistor delivers an ultralow dark current of about 0.1 pA. The photoswitching ratio reaches ∼103 at a wavelength of 375 nm, superior to that of other thiophosphates. A responsivity and detectivity of 392.78 mA/W and 2.19 × 109 Jones, respectively, have been demonstrated under irradiation of 375 nm laser with a power intensity of 0.1 mW/cm2. In particular, the photocurrent can be remarkably increased up to 30 times by integrating a layer of Au nanoparticle array at the bottom of the MnPSe3 layer. The metal-semiconductor interfacial electric field and the strain-induced flexoelectric polarization field caused by the underlying nanorugged Au nanoparticles are proposed to contribute together to the significant current improvement.

Differential Ubiquitination of BIK1 Fine-Tunes Plant Immunity.

Botrytis-Induced Kinase 1 (BIK1) is a convergent and central signaling component in plant immunity. Recent studies in Arabidopsis thaliana by Wang et al. and Ma et al. have revealed that polyubiquitination and monoubiquitination of BIK1 lead to the attenuation or activation of immune signaling, respectively.

A malectin-like receptor kinase regulates cell death and pattern-triggered immunity in soybean.

Plant cells can sense conserved molecular patterns through pattern recognition receptors (PRRs) and initiate pattern-triggered immunity (PTI). Details of the PTI signaling network are starting to be uncovered in Arabidopsis, but are still poorly understood in other species, including soybean (Glycine max). In this study, we perform a forward genetic screen for autoimmunity-related lesion mimic mutants (lmms) in soybean and identify two allelic mutants, which carry mutations in Glyma.13G054400, encoding a malectin-like receptor kinase (RK). The mutants exhibit enhanced resistance to both bacterial and oomycete pathogens, as well as elevated ROS production upon treatment with the bacterial pattern flg22. Overexpression of GmLMM1 gene in Nicotiana benthamiana severely suppresses flg22-triggered ROS production and oomycete pattern XEG1-induced cell death. We further show that GmLMM1 interacts with the flg22 receptor FLS2 and its co-receptor BAK1 to negatively regulate flg22-induced complex formation between them. Our study identifies an important component in PTI regulation and reveals that GmLMM1 acts as a molecular switch to control an appropriate immune activation, which may also be adapted to other PRR-mediated immune signaling in soybean.

RNA-Seq Analysis of the Liver Transcriptome Reveals the Networks Regulating Treatment of Sitagliptin Phosphate plus Fuzhujiangtang Granule in the Zucker Diabetic Fatty Rats.

Diabetes is one of the most serious chronic diseases. Numerous drugs including oral agents and traditional Chinese medicines, such as sitagliptin phosphate (SP) and Fuzhujiangtang granules (FJG), have been discovered to treat diabetes and used in combination in clinical practice. However, the exact effect and underlying mechanism of using combined medicine is not clear. In this study, we compared the antidiabetic effect of SP, FJG, and SP plus FJG (SP-FJG) using forty 8-week-old Zucker diabetic fatty (ZDF) rats and 10 age-matched Zucker lean rats as the normal control group. ZDF rats were treated with different therapies, respectively, for 6 weeks. The study showed that the fast blood glucose, random blood glucose (RBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index, triglyceride (TC), superoxide dismutase, and malondialdehyde of each treatment group were improved when compared with the diabetes mellitus (DM) control group. Using SP-FJG in combination had better improvements in OGTT, fast serum insulin levels, TNF-α, and IL-6 compared with using SP individually. Besides, the increased LDL and TC caused by using SP was attenuated by using FJG in combination. Meanwhile, compared with the DM group, 1781 differentially expressed genes (DEGs) (including 1248 mRNA, 211 ncRNA, 202 cirRNA, and 120 miRNA) were enriched in 58 pathways. Through analysis of ceRNA networks, we found that rno-miR-326-3p, rno-miR-423-5p, rno-miR-15b-5p, rno-let-7c-5p, and rno-let-7b-5p were related to pharmacodynamics in different groups. By analyzing the protein-protein interaction (PPI) and coexpression networks of the transcriptomes of different groups, it is inferred that Lrrk2 and Irak3 may be pharmacodynamic genes for type 2 diabetes mellitus (T2DM). Our research compared the treatment of SP, FJG, and SP-FJG and acquainted the PPI network, coexpression network, mutations, and pharmacodynamics genes, which reveals the new mechanisms of pathogenesis of T2DM.