The aberrant expression of microRNAs (miRNAs) has emerged as important hallmarks of cancer. However, the molecular mechanisms underlying the differences of miRNA expression remain unclear. Many studies have reported that miR-98-5p plays vital functions in the development and progression of multiple cancers. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown.

The health of informal caregivers of adults with chronic conditions is increasingly vital since caregivers comprise a large proportion of supportive care to family members living in the community. Due to efficiency and reach, internet-based interventions for informal caregivers have the potential to mitigate the negative mental health outcomes associated with caregiving.

In bacteria and eukaryotes alike, proper cellular physiology relies on robust subcellular organization. For the phototrophic purple nonsulfur bacteria (PNSB), this organization entails the use of a light-harvesting, membrane-bound compartment known as the intracytoplasmic membrane (ICM). Here we show that ICMs are spatially and temporally localized in diverse patterns among PNSB. We visualized ICMs in live cells of 14 PNSB species across nine genera by exploiting the natural autofluorescence of the photosynthetic pigment bacteriochlorophyll (BChl). We then quantitatively characterized ICM localization using automated computational analysis of BChl fluorescence patterns within single cells across the population. We revealed that while many PNSB elaborate ICMs along the entirety of the cell, species across as least two genera restrict ICMs to discrete, nonrandom sites near cell poles in a manner coordinated with cell growth and division. Phylogenetic and phenotypic comparisons established that ICM localization and ICM architecture are not strictly interdependent and that neither trait fully correlates with the evolutionary relatedness of the species. The natural diversity of ICM localization revealed herein has implications for both the evolution of phototrophic organisms and their light-harvesting compartments and the mechanisms underpinning spatial organization of bacterial compartments.IMPORTANCE Many bacteria organize their cellular space by constructing subcellular compartments that are arranged in specific, physiologically relevant patterns. The purple nonsulfur bacteria (PNSB) utilize a membrane-bound compartment known as the intracytoplasmic membrane (ICM) to harvest light for photosynthesis. It was previously unknown whether ICM localization within cells is systematic or irregular and if ICM localization is conserved among PNSB. Here we surveyed ICM localization in diverse PNSB and show that ICMs are spatially organized in species-specific patterns. Most strikingly, several PNSB resolutely restrict ICMs to regions near the cell poles, leaving much of the cell devoid of light-harvesting machinery. Our results demonstrate that bacteria of a common lifestyle utilize unequal portions of their intracellular space to harvest light, despite light harvesting being a process that is intuitively influenced by surface area. Our findings therefore raise fundamental questions about ICM biology and evolution.

The discovery of integrative conjugative elements (ICEs) in wall-less mycoplasmas and the demonstration of their role in massive gene flows within and across species have shed new light on the evolution of these minimal bacteria. Of these, the ICE of the ruminant pathogen Mycoplasma agalactiae (ICEA) represents a prototype and belongs to a new clade of the Mutator-like superfamily that has no preferential insertion site and often occurs as multiple chromosomal copies. Here, functional genomics and mating experiments were combined to address ICEA functions and define the minimal ICEA chassis conferring conjugative properties to M. agalactiae Data further indicated a complex interaction among coresident ICEAs, since the minimal ICEA structure was influenced by the occurrence of additional ICEA copies that can trans-complement conjugation-deficient ICEAs. However, this cooperative behavior was limited to the CDS14 surface lipoprotein, which is constitutively expressed by coresident ICEAs, and did not extend to other ICEA proteins, including the cis-acting DDE recombinase and components of the mating channel whose expression was detected only sporadically. Remarkably, conjugation-deficient mutants containing a single ICEA copy knocked out in cds14 can be complemented by neighboring cells expressing CDS14. This result, together with those revealing the conservation of CDS14 functions in closely related species, may suggest a way for mycoplasma ICEs to extend their interaction outside their chromosomal environment. Overall, this report provides a first model of conjugative transfer in mycoplasmas and offers valuable insights into understanding horizontal gene transfer in this highly adaptive and diverse group of minimal bacteria.IMPORTANCE Integrative conjugative elements (ICEs) are self-transmissible mobile genetic elements that are key mediators of horizontal gene flow in bacteria. Recently, a new category of ICEs was identified that confer conjugative properties to mycoplasmas, a highly adaptive and diverse group of wall-less bacteria with reduced genomes. Unlike classical ICEs, these mobile elements have no preferential insertion specificity, and multiple mycoplasma ICE copies can be found randomly integrated into the host chromosome. Here, the prototype ICE of Mycoplasma agalactiae was used to define the minimal conjugative machinery and to propose the first model of ICE transfer in mycoplasmas. This model unveils the complex interactions taking place among coresident ICEs and suggests a way for these elements to extend their influence outside their chromosomal environment. These data pave the way for future studies aiming at deciphering chromosomal transfer, an unconventional mechanism of DNA swapping that has been recently associated with mycoplasma ICEs.

Many strains of Escherichia coli carry a 29,250-bp ETT2 pathogenicity island (PAI), which includes genes predicted to encode type III secretion system (T3SS) components. Because it is similar to the Salmonella pathogenicity island 1 (SPI-1) system, encoding a T3SS in Salmonella enterica, it was assumed that ETT2 also encodes a secretion system injecting effectors into host cells. This assumption was checked in E. coli serotype O2-associated with urinary tract infections and septicemia-which has an intact ETT2 gene cluster, in contrast to most strains in which this cluster carries deletions and mutations. A proteomic search did not reveal any putative secreted effector. Instead, the majority of the secreted proteins were identified as flagellar proteins. A deletion of the ETT2 gene cluster significantly reduced the secretion of flagellar proteins, resulting in reduced motility. There was also a significant reduction in the transcriptional level of flagellar genes, indicating that ETT2 affects the synthesis, rather than secretion, of flagellar proteins. The ETT2 deletion also resulted in additional major changes in secretion of fimbrial proteins and cell surface proteins, resulting in relative resistance to detergents and hydrophobic antibiotics (novobiocin), secretion of large amounts of outer membrane vesicles (OMVs), and altered multicellular behavior. Most important, the ETT2 deletion mutants were sensitive to serum. These major changes indicate that the ETT2 gene cluster has a global effect on cell surface and physiology, which is especially important for pathogenicity, as it contributes to the ability of the bacteria to survive serum and cause sepsis.IMPORTANCE Drug-resistant extraintestinal pathogenic E. coli (ExPEC) strains are major pathogens, especially in hospital- and community-acquired infections. They are the major cause of urinary tract infections and are often involved in septicemia with high mortality. ExPEC strains are characterized by broad-spectrum antibiotic resistance, and development of a vaccine is not trivial because the ExPEC strains include a large number of serotypes. It is therefore important to understand the virulence factors that are involved in pathogenicity of ExPEC and identify new targets for development of antibacterial drugs or vaccines. Such a target could be ETT2, a unique type III secretion system present (complete or in parts) in many ExPEC strains. Here, we show that this system has a major effect on the bacterial surface-it affects sensitivity to drugs, motility, and secretion of extracellular proteins and outer membrane vesicles. Most importantly, this system is important for serum resistance, a prerequisite for septicemia.

Neighborhood psychosocial stressors like crime and physical disorder may influence obesity-related outcomes through chronic stress or through adverse effects on health behaviors. Google Street View imagery provides a low-cost, reliable method for auditing neighborhood physical disorder, but few studies have examined associations of Street View-derived physical disorder scores with health outcomes. We used Google Street View to audit measures of physical disorder for residential census blocks from 225 women aged 18⁻44 enrolled from 4 Chicago neighborhoods. Latent neighborhood physical disorder scores were estimated using an item response theory model and aggregated to the block group level. Block-group level physical disorder scores and rates of police-recorded crime and 311 calls for service requests were linked to participants based on home addresses. Associations were estimated for 6 obesity-related outcomes: body mass index, obesity, total moderate-to-vigorous physical activity, and weekly consumption of sugar-sweetened beverages, fast food, and snacks. Hierarchical regression models estimated cross-sectional associations adjusting for individual sociodemographics and neighborhood poverty. Higher neighborhood physical disorder was associated with greater odds of obesity (OR: 1.43, 95% CI: 1.01, 2.02). Living in a neighborhood with a higher crime rate was associated with an increase in weekly snack consumption of 3.06 (95% CI: 1.59, 4.54).

Blast disease is one of the major rice diseases, and causes nearly 30% annual yield loss worldwide. Resistance genes that have been cloned, however, are effective only against specific strains. In cultivation practice, broad-spectrum resistance to various strains is highly valuable, and requires researchers to investigate the basal defense responses that are effective for diverse types of pathogens. In this study, we took a quantitative proteomic approach and identified 634 rice proteins responsive to infections by both Magnaporthe oryzae strains Guy11 and JS153. These two strains have distinct pathogenesis mechanisms. Therefore, the common responding proteins represent conserved basal defense to a broad spectrum of blast pathogens. Gene ontology analysis indicates that the “responding to stimulus” biological process is explicitly enriched, among which the proteins responding to oxidative stress and biotic stress are the most prominent. These analyses led to the discoveries of OsPRX59 and OsPRX62 that are robust callose inducers, and OsHSP81 that is capable of inducing both ROS production and callose deposition. The identified rice proteins and biological processes may represent a conserved rice innate immune machinery that is of great value for breeding broad-spectrum resistant rice in the future.

The human health risks posed by exposure to cyanobacterial toxins such as microcystin (MC) through water and fish consumption remain poorly described. During the last two decades, coastal regions of Lake Victoria such as Nyanza Gulf (Kisumu Bay) have shown severe signs of eutrophication with blooms formed by Microcystis producing MC. In this study, the spatial variability in MC concentration in Kisumu Bay was investigated which was mostly caused by Microcystis buoyancy and wind drifting. Small fish (<6 cm) mainly composed of Rastrineobola argentea were examined for MC content by means of biological methods such as ELISA and protein phosphatase inhibition assay (PPIA) and partly by chemical-analytical methods such as LC-MS/MS. Overall, the MC content in small fish was related to the MC content observed in the seston. When comparing the MC content in the seston in relation to dry weight with the MC content in small fish the latter was found three orders of magnitude decreased. On average, the ELISA-determined MC contents exceeded the PPIA-determined MC contents by a factor of 8.2 ± 0.5 (SE) while the MC contents as determined by LC-MS/MS were close to the detection limit. Using PPIA, the MC content varied from 25⁻109 (mean 62 ± 7) ng/g fish dry weight in Kisumu Bay vs. 14 ± 0.8 ng MC/g in the more open water of L. Victoria at Rusinga channel. Drying the fish under the sun showed little effect on MC content, although increased humidity might indirectly favor photocatalyzed MC degradation.

Long noncoding RNAs (lncRNAs) have been emerging as master regulators of tumor growth and metastasis, but the functions and underlying mechanisms of lncRNAs in colorectal cancer (CRC) still need to be clarified. Here, we found a novel lncRNA u50535, which was greatly overexpressed in CRC tissues and was associated with poor prognosis in CRC patients. Function studies showed that u50535 was an oncogene in CRC both in vitro and in vivo. In mechanism, through RNA sequencing and rescue assay, we found that u50535 activates CCL20 signaling to promote cell proliferation and migration in CRC. Taken together, these findings suggest that u50535 can promote CRC growth and metastasis and may serve as a potential biomarker in CRC.

The rapid increase in carbapenem resistance among gram-negative bacteria has renewed focus on the importance of polymyxin antibiotics (colistin or polymyxin E). However, the recent emergence of plasmid-mediated colistin resistance determinants (mcr-1, -2, -3, -4, -5, -6, and -7), especially mcr-1, in carbapenem-resistant Enterobacteriaceae is a serious threat to global health. Here, we characterized a novel mobile colistin resistance gene, mcr-8, located on a transferrable 95,983-bp IncFII-type plasmid in Klebsiella pneumoniae. The deduced amino-acid sequence of MCR-8 showed 31.08%, 30.26%, 39.96%, 37.85%, 33.51%, 30.43%, and 37.46% identity to MCR-1, MCR-2, MCR-3, MCR-4, MCR-5, MCR-6, and MCR-7, respectively. Functional cloning indicated that the acquisition of the single mcr-8 gene significantly increased resistance to colistin in both Escherichia coli and K. pneumoniae. Notably, the coexistence of mcr-8 and the carbapenemase-encoding gene blaNDM was confirmed in K. pneumoniae isolates of livestock origin. Moreover, BLASTn analysis of mcr-8 revealed that this gene was present in a colistin- and carbapenem-resistant K. pneumoniae strain isolated from the sputum of a patient with pneumonia syndrome in the respiratory intensive care unit of a Chinese hospital in 2016. These findings indicated that mcr-8 has existed for some time and has disseminated among K. pneumoniae of both animal and human origin, further increasing the public health burden of antimicrobial resistance.

Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.

Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer angiogenesis remain unclear. Here we found that the clinical expression of nuclear FOXP3 was inversely correlated with breast cancer angiogenesis. Moreover, the animal study demonstrated that FOXP3 significantly reduced the microvascular density of MDA-MB-231 tumors transplanted in mice. The cytological experiments showed that the supernatant from FOXP3-overexpressing cells exhibited a diminished ability to stimulate tube formation and sprouting in HUVECs in vitro. In addition, expression of vascular endothelial growth factor (VEGF) was downregulated by FOXP3 in breast cancer cell lines. Luciferase reporter assays and chromatin immunoprecipitation assays demonstrated that FOXP3 can directly interact with the VEGF promoter via specific forkhead-binding motifs to suppress its transcription. Importantly, the inhibitory effects of FOXP3 in the supernatant on tube formation and sprouting in HUVECs could be reversed by adding VEGF in vitro. Nuclear FOXP3 expression was inversely correlated with VEGF expression in clinical breast cancer tissues, and FOXP3 downregulation and VEGF upregulation were both correlated with reduced survival in breast cancer data sets in the Kaplan-Meier plotter. Taken together, our data demonstrate that FOXP3 suppresses breast cancer angiogenesis by downregulating VEGF expression.

Numerous findings have demonstrated that long noncoding RNA (lncRNA) dysregulation plays a key role in many human neoplasms, including tongue squamous cell carcinoma (TSCC), yet the potential mechanisms of lncRNAs in chemo-resistance remain elusive. Our research showed that the lncRNA KCNQ1OT1 was upregulated in chemo-insensitive TSCC tissues compared with chemo-sensitive TSCC specimens. Meanwhile, high KCNQ1OT1 expression was closely correlated with poor prognosis. Furthermore, KCNQ1OT1 promoted TSCC proliferation and conferred TSCC resistance to cisplatin-induced apoptosis in vitro and in vivo. Using online database analysis, we predicted that the lncRNA KCNQ1OT1 facilitates tumor growth and chemo-resistance by acting as a competing endogenous RNA (ceRNA) to modulate the expression of miR-211-5p. And miR-211-5p upregulation significantly impaired TSCC proliferation and resumed TSCC chemo-sensitivity, which is contrary to the function of lncRNA KCNQ1OT1. Luciferase experiments confirmed that miR-211-5p harbor binding sites for the 3'-UTRof Ezrin mRNA, and Ezrin/Fak/Src signaling was activated in cisplatin-resistant TSCC cells. Finally, miR-211-5p inhibition in sh-KCNQ1OT1-expressing TSCC cells rescued the suppressed cell proliferation and cisplatin resistance induced by KCNQ1OT1 knockdown. In summary, our study has elucidated the role of the oncogenic lncRNA KCNQ1OT1 in TSCC growth and chemo-resistance, which may serve as a new target for TSCC therapy.

Continuous cereal-based cropping has led to a rapid decline in soil fertility in the Guinea savanna agro-ecological zone of northern Ghana with corresponding low crop yields. We evaluated the effects of cropping system and soil fertility status on grain yields and N2-fixation by grain legumes and net N contribution to soil fertility improvement in contrasting sites in this agro-ecological zone. Maize was intercropped with cowpea, soybean and groundnut within a row, with a maize stand alternated with two equally spaced cowpea or groundnut stands and in the maize-soybean system, four equally spaced soybean stands. These intercrops were compared with sole crops of maize, cowpea, soybean and groundnut in fertile and poorly fertile fields at sites in the southern (SGS) and the northern (NGS) Guinea savanna. The proportion of N derived from N2-fixation (%Ndfa) was comparable between intercrops and sole crops. However, the amount of N2-fixed was significantly larger in sole crops due to a greater biomass accumulation. Legumes in poorly fertile fields had significantly smaller shoot δ15N enrichment (-2.8 to +0.7‰) and a larger %Ndfa (55-94%) than those in fertile fields (-0.8 to +2.2‰; 23-85%). The N2-fixed however was larger in fertile fields (16-145 kg N ha-1) than in poorly fertile fields (15-123 kg N ha-1) due to greater shoot dry matter and N yields. The legumes grown in the NGS obtained more of their N requirements from atmospheric N2-fixation (73-88%) than legumes grown in the SGS (41-69%). The partial soil N balance (in kg ha-1) was comparable between intercrops (-14 to 21) and sole legumes (-8 to 23) but smaller than that of sole maize receiving N fertiliser (+7 to +34). With other N inputs (aerial deposition) and outputs (leaching and gaseous losses) unaccounted for, there is uncertainty surrounding the actual amount of soil N balances of the cropping systems, indicating that partial N balances are not reliable indicators of the sustainability of cropping systems. Nevertheless, the systems with legumes seem more attractive due to several non-N benefits. Our results suggest that soybean could be targeted in the SGS and cowpea in the NGS for greater productivity while groundnut is suited to both environments. Grain legumes grown in poorly fertile fields contributed more net N to the soil but growing legumes in fertile fields seems more lucrative due to greater grain and stover yields and non-N benefits.

Skeletal muscle wasting is an independent predictor of health-related quality of life and survival in patients with COPD, but the complexity of molecular mechanisms associated with this process has not been fully elucidated. We aimed to determine whether an impaired ability to repair DNA damage contributes to muscle wasting and the accelerated aging phenotype in patients with COPD.

Using the Surveillance, Epidemiology, and End Results database (SEER) to assess the incidence and risk factors of morbidity and prognosis for bone metastases in initial metastatic prostate cancer.

The purpose of this research was to determine whether neck dissection is necessary for the adenoid cystic carcinoma (ACC) of head and neck.

Autism spectrum disorder (ASD) refers to a large set of neurodevelopmental disorders, which have in common both repetitive behavior and abnormalities in social interactions and communication. Interestingly, most forms of ASD have a strong genetic contribution. However, the molecular underpinnings of this disorder remain elusive. The SHANK3 gene (and to a lesser degree SHANK2) which encode for the postsynaptic density (PSD) proteins SHANK3/SHANK2 and the CONTACTIN 4 gene which encodes for the neuronal glycoprotein CONTACTIN4 (CNTN4) exhibit mutated variants which are associated with ASD. Like many of the other genes associated with ASD, both SHANKs and CNTN4 affect synapse formation and function and are therefore related to the proper development and signaling capability of excitatory and inhibitory neuronal networks in the adult mammal brain. In this study, we used mutant/knock-out mice of Shank2 (Shank2-/-), Shank3 (Shank3αβ-/-), and Cntn4 (Cntn4-/-) as ASD-models to explore whether these mice share a molecular signature in glutamatergic and GABAergic synaptic transmission in ASD-related brain regions. Using a biotinylation assay and subsequent western blotting we focused our analysis on cell surface expression of several ionotropic glutamate and GABA receptor subunits: GluA1, GluA2, and GluN1 were analyzed for excitatory synaptic transmission, and the α1 subunit of the GABAA receptor was analyzed for inhibitory synaptic transmission. We found that both Shank2-/- and Shank3αβ-/- mice exhibit reduced levels of several cell surface glutamate receptors in the analyzed brain regions-especially in the striatum and thalamus-when compared to wildtype controls. Interestingly, even though Cntn4-/- mice also show reduced levels of some cell surface glutamate receptors in the cortex and hippocampus, increased levels of cell surface glutamate receptors were found in the striatum. Moreover, Cntn4-/- mice do not only show brain region-specific alterations in cell surface glutamate receptors but also a downregulation of cell surface GABA receptors in several of the analyzed brain regions. The results of this study suggest that even though mutations in defined genes can be associated with ASD this does not necessarily result in a common molecular phenotype in surface expression of glutamatergic and GABAergic receptor subunits in defined brain regions.

Introduction: Uveitis is an eye disease characterized by inflammation of the uvea and an early and exhaustive diagnosis is essential for its treatment. The aim of our study is to assess the potential toxicity and anti-inflammatory efficacy of Bevacizumab in an experimental uveitis model by subcutaneously injecting lipopolysaccharide into Lewis rats and to clarify its mechanism. Material and Methods: Blood-aqueous barrier integrity was assessed 24 h after endotoxin-induced uveitis (EIU) by analyzing two parameters: cell count and protein concentration in aqueous humors. Histopathology of all eye structures was also studied. Enzyme-linked immunosorbent analyses of the aqueous humor samples were performed in order to calculate the diverse chemokine and cytokine protein levels and oxidative stress-related markers were also evaluated. Results: The aqueous humor's cellular content significantly increased in the group treated with only Bevacizumab, but it had no effect on retina histopathological grading. Nevertheless, the inflammation noted in ocular structures when administering Bevacizumab with endotoxin was mostly prevented since aqueous humor cell content considerably lowered, and concomitantly with a sharp drop in uveal, vitreous, and retina histopathological grading. The values of the multi-faceted cytokine IL-2 also significantly decreased (p < 0.05 vs. endotoxin group), and the protective IL-6 and IL-10 cytokines values rose with related anti-oxidant system recovery (p < 0.05 vs. endotoxin group). Concurrently, some related M1 macrophage chemokines substantially increased, e.g., GRO/KC, a chemokine that also displays any kind of protective role. Conclusion: All these results revealed that 24 h after being administered, Bevacizumab treatment in EIU significantly prevented inflammation in various eye structures and correct results in efficacy vs. toxicity balance were obtained.

Background: Li-Ru-Kang (LRK) has been used in the treatment of hyperplasia of mammary glands (HMG) for several decades and can effectively improve clinical symptoms. This study aims to investigate the mechanism by which LRK intervenes in HMG based on an integrated approach that combines metabolomics and network pharmacology analyses. Methods: The effects of LRK on HMG induced by estrogen-progesterone in rats were evaluated by analyzing the morphological and pathological characteristics of breast tissues. Moreover, UPLC-QTOF/MS was performed to explore specific metabolites potentially affecting the pathological process of HMG and the effects of LRK. Pathway analysis was conducted with a combination of metabolomics and network pharmacology analyses to illustrate the pathways and network of LRK-treated HMG. Results: Li-Ru-Kang significantly improved the morphological and pathological characteristics of breast tissues. Metabolomics analyses showed that the therapeutic effect of LRK was mainly associated with the regulation of 10 metabolites, including prostaglandin E2, phosphatidylcholine, leukotriene B4, and phosphatidylserine. Pathway analysis indicated that the metabolites were related to arachidonic acid metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Moreover, principal component analysis showed that the metabolites in the model group were clearly classified, whereas the metabolites in the LRK group were between those in the normal and model groups but closer to those in the normal group. This finding indicated that these metabolites may be responsible for the effects of LRK. The therapeutic effect of LRK on HMG was possibly related to the regulation of 10 specific metabolites. In addition, we further verified the expression of protein kinase C alpha (PKCα), a key target predicted by network pharmacology analysis, and showed that LRK could significantly improve the expression of PKCα. Conclusion: Our study successfully explained the modulatory properties of LRK treatment on HMG using metabolomics and network pharmacology analyses. This systematic method can provide methodological support for further understanding the complex mechanism underlying HMG and possible traditional Chinese medicine (TCM) active ingredients for the treatment of HMG.