Chitosan modified graphene oxide with MnO2 deposition for high energy density flexible supercapacitors.

To obtain a flexible composite electrode material with excellent electrochemical performance, chitosan (CS)/graphene oxide (GO) composite pretreated from microwave hydrothermal is adopted as the carbon substrate, and MnO2 active material is uniformly deposited on their surface through anodic electrodeposition. In this composite system, CS penetrates into graphene sheets as small molecule units, forming NH-C=O groups with GO via dehydration condensation, which effectively inhibits the stacking of GO and improves the specific surface area, conductivity, as well as the wettability of the carbon support. MnO2 bonding with heteroatom N from CS enables high active material loadings and forms stable three-dimensional network structure, facilitating the enhanced electrochemical performance. Results indicate that increasing depositing MnO2 amount leads to more defective structures of the composite, which promotes their electrochemical performance when used as electrode material. The area specific capacitance of the optimal composite reaches 3553.74 mF/cm2 at 5 mA/cm2 in 1 M Na2SO4 electrolyte. Kinetic analysis shows the energy storage process is capacitance-dominated, with the redox reactions of MnO2 being the main contributor. The prepared asymmetric solid supercapacitor delivers an energy density high up to 0.585 mWh/cm2 at power density of 3000 mW/cm2, and their excellent flexibility makes them promising candidates as flexible sensor.

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma.

BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

Disseminated disease caused by Mycobacterium marseillense: A case report and literature review.

RATIONALE: Among numerous types of nontuberculous mycobacterial infections, Mycobacterium avium complex is a related group of species, which can cause various diseases in humans. Mycobacterium marseillense is a member of the Mycobacterium avium complex, which accounts for only a small proportion of species, but causes rare diseases affecting the lungs, lymph nodes, skin, and tendon sheath. So far, very few cases have been reported. PATIENT CONCERNS: A 76-year-old male of peculiar skin infection. Metagenomic Next Generation Sequencing and bacterial culture of skin secretions revealed M marseillense. To the best of our knowledge, we report the first patient diagnosed with disseminated M marseillense infection. Here, we identified only 8 other reports of patients with M marseillense infection. DIAGNOSES: Disseminated M marseillense infection. INTERVENTIONS: The patient was treated with clarithromycin, rifampicin, moxifloxacin, and ethambutol. OUTCOMES: The skin lesions of the patient showed significant improvement, and his pruritus and limb pain were notably reduced after 7 months of follow-up. LESSONS: Metagenomic Next Generation Sequencing may be a useful tool to diagnose M marseillense infection, but the results should be confirmed by culture and mycobacterial identification.

Lactate and Lactylation: Clinical Applications of Routine Carbon Source and Novel Modification in Human Diseases.

Cell metabolism generates numerous intermediate metabolites that could serve as feedback and feed-forward regulation substances for posttranslational modification. Lactate, a metabolic product of glycolysis, has recently been conceptualized to play a pleiotropic role in shaping cell identities through metabolic rewiring and epigenetic modifications. Lactate-derived carbons, sourced from glucose, mediate the crosstalk among glycolysis, lactate, and lactylation. Furthermore, the multiple metabolic fates of lactate make it an ideal substrate for metabolic imaging in clinical application. Several studies have identified the crucial role of protein lactylation in human diseases associated with cell fate determination, embryonic development, inflammation, neoplasm, and neuropsychiatric disorders. Herein, this review will focus on the metabolic fate of lactate-derived carbon to provide useful information for further research and therapeutic approaches in human diseases. We comprehensively discuss its role in reprogramming and modification during the regulation of glycolysis, the clinical translation prospects of the hyperpolarized lactate signal, lactyl modification in human diseases, and its application with other techniques and omics.

Relative adrenal insufficiency is a risk factor for pediatric sepsis - a proof-of-concept study.

Glucocorticoid (GC) therapy had been strongly recommended for pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. About 32.8% pediatric septic patients develops relative adrenal insufficiency (RAI). But whether GC therapy should be determined by RAI status is controversial. This study utilized 21-day-old SF1CreSRBIfl/fl mice as the first pediatric RAI mouse model to assess the pathogenesis of RAI and evaluate GC therapy. RAI mice exhibited substantially higher mortality rate in both cecal ligation and puncture (CLP) and cecal slurry induced sepsis. These mice featured persistent inflammatory responses, and were effectively rescued by GC therapy. RNA-seq analysis revealed persistent inflammatory responses in RAI mice, caused by transcriptional dysregulation of AP-1 and NF-κB, and cytokine-induced secondary inflammatory response. Our findings support a precision medicine approach to guide GC therapy for pediatric patients - use of GC based on the status of RAI.

A Propensity Score-Matched Study on the Changes of TB Status and TB-IGRA Values in Patients with Psoriasis with Latent TB Receiving Secukinumab.

INTRODUCTION: The utilization of biologics in patients with psoriasis with latent tuberculosis infection (LTBI) has garnered significant attention. Although the tuberculosis (TB) safety profile of second-generation biologics, including secukinumab, has been partially confirmed in both clinical trials and real-world studies, the necessity for prophylactic therapy in patients with LTBI prior to administering this class of biologics remains a topic of controversy. METHODS: This study enrolled 62 patients with psoriasis with LTBI who underwent secukinumab with routine TB reexamination. Patients were divided into two groups based on whether they received antituberculosis therapy (ATB; n = 48) or not (NTB; n = 16). We performed a propensity score-matched (PSM) analysis between ATB and NTB subgroups and retrospectively reviewed their interferon-gamma release assays (IGRA) and radiographic results. RESULTS: No active TB case was reported on the basis of medical records and chest radiographs in either two group. Before PSM, the mean reexamining IGRA value was significantly elevated in patients who received prophylactic therapy (P = 0.00), but no significant increase was observed in patients who were not. After PSM, there was no significant IGRA value enhancement whether or not patients received prophylactic treatment. CONCLUSION: Our data provide additional information on the safety profile of secukinumab in patients with psoriasis with LTBI. Furthermore, our presentation of the reexamined IGRA results revealed no significant elevation in the ATB or NTB group. As such, we believe further exploration is necessary to determine whether anti-TB medication is required prior to administering secukinumab.

In the past decade, biologics have revolutionized psoriasis treatment. Among patients receiving biologics, tuberculosis infection is a big concern. Secukinumab, an interleukin-17 inhibitor, belongs to the second-generation biologics. Clinical trials and real-life experience have partially reported its tuberculosis safety. In 2020, a systematic review of randomized clinical trials of secukinumab found no reactivate tuberculosis case. However, when participants tested positive for latent tuberculosis infection at screening in the clinical trials, they received antituberculosis treatment. Should patients with latent tuberculosis infection receive antituberculosis medication before receiving secukinumab? The answer is controversial and lacks evidence. This study enrolled patients with psoriasis with latent tuberculosis infection who underwent secukinumab with routine tuberculosis reexamination. Then, the patients were divided into two groups based on whether they received antituberculosis therapy and not. We observed that neither of these two groups presented tuberculosis activation cases. We also matched patients who received antituberculosis therapy and those who did not. The interferon-gamma release assay showed no significant increase after balancing the baseline. Our data indicated that secukinumab is safe among patients with latent tuberculosis infection even when they did not receive antituberculosis treatment.

Prediction of composting maturity and identification of critical parameters for green waste compost using machine learning.

Ensuring the maturity of green waste compost is crucial to composting processes and quality control of compost products. However, accurate prediction of green waste compost maturity remains a challenge, as there are limited computational methods available. This study aimed to address this issue by employing four machine learning models to predict two indicators of green waste compost maturity: seed germination index (GI) and T value. The four models were compared, and the Extra Trees algorithm exhibited the highest prediction accuracy with R2 values of 0.928 for GI and 0.957 for T value. To identify the interactions between critical parameters and compost maturity, The Pearson correlation matrix and Shapley Additive exPlanations (SHAP) analysis were conducted. Furthermore, the accuracy of the models was validated through compost validation experiments. These findings highlight the potential of applying machine learning algorithms to predict green waste compost maturity and optimise process regulation.

Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

MicroRNA sequence variation can impact interactions with target mRNA in cattle.

BACKGROUND: Small non-coding microRNAs (miRNAs) are important modulators at post-transcriptional levels. Single-nucleotide polymorphisms (SNPs) located in miRNA genes can alter the secondary structure of pre-miRNA to either impair or promote the miRNA maturation processes. Furthermore, SNPs located in the miRNA seed regions can stabilize or disturb miRNA-target interactions, thereby, quantitatively influence the expression of target genes. Therefore, the main objective of this study was to detect SNPs in bovine miRNAs using the whole-genome re-sequencing datasets of 1632 cattle of five breeds from the 1000 bull genomes project. RESULTS: In total, our study identified 1109, 334, and 130 SNPs in the miRNA precursor, mature, and seed regions, respectively. The heterozygosity values were generally less than 0.3, and the minor allele frequencies (MAFs) were mainly less than 0.1. Most SNPs were in Hardy-Weinberg equilibrium (HWE) (HWE-P > 0.05). Furthermore, we found that the majority of SNPs (MAF > 0.1 and HWE-P > 0.05) in the miRNA seed regions altered the repertoire of target genes, which in turn were enriched in different KEGG pathways or GO terms. Thus target prediction for bta-miR-2888 revealed loss of 309 target genes and gain of 691 target genes. The 691 gained target genes were significantly enriched in 60 KEGG pathways and 21 GO terms. CONCLUSION: In summary, our study identified candidate SNPs in miRNA precursor, mature, and seed regions that are likely to affect target RNA interactions, thereby potentially influencing cattle phenotypic traits.

The adrenal stress response is an essential host response against therapy-induced lethal immune activation.

Cytokine release syndrome (CRS) is a systemic inflammatory syndrome associated with infection- or drug-induced T cell activation and can cause multiple organ failure and even death. Because current treatments are ineffective in some patients with severe CRS, we set out to identify risk factors and mechanisms behind severe CRS that might lead to preventive therapies and better clinical outcomes in patients. In mice, we found that deficiency in the adrenal stress response-with similarities to such in patients called relative adrenal insufficiency (RAI)-conferred a high risk for lethal CRS. Mice treated with CD3 antibodies were protected against lethal CRS by the production of glucocorticoids (GC) induced by the adrenal stress response in a manner dependent on the scavenger receptor B1 (SR-BI), a receptor for high-density lipoprotein (HDL). Mice with whole-body or adrenal gland-specific SR-BI deficiency exhibited impaired GC production, more severe CRS, and increased mortality in response to CD3 antibodies. Pretreatment with a low dose of GC effectively suppressed the development of CRS and rescued survival in SR-BI-deficient mice without compromising T cell function through apoptosis. Our findings suggest that RAI may be a risk factor for therapy-induced CRS and that pretreating RAI patients with GC may prevent lethal CRS.

A new model predicts hepatocellular carcinoma in patients with HBV-related decompensated liver cirrhosis and long-term antiviral therapy: a prospective study.

Background: We aimed to evaluate the prediction values of non-invasive models for hepatocellular carcinoma (HCC) development in patients with HBV-related liver cirrhosis (LC) and long-term NA treatment. Methods: Patients with compensated or decompensated cirrhosis (DC), who achieved long-term virological response, were enrolled. DC and its stages were defined by the complications including ascites, encephalopathy, variceal bleeding, or renal failure. Prediction accuracy of several risk scores, including ALBI, CAMD, PAGE-B, mPAGE-B and aMAP, was compared. Results: The median follow-up duration was 37 (28-66) months. Among the 229 patients, 9 (9.57%) patients in the compensated LC group and 39 (28.89%) patients in the DC group developed HCC. The incidence of HCC was higher in the DC group ( X 2 = 12.478, P < 0.01). The AUROC of ALBI, aMAP, CAMD, PAGE-B and mPAGE-B scores were 0.512, 0.667, 0.638, 0.663, 0.679, respectively. There was no significant difference in AUROC between CAMD, aMAP, PAGE-B and mPAGE-B (all P > 0.05). Univariable analysis showed that age, DC status and platelet were associated with HCC development, and multivariable analysis showed that age and DC status (both P < 0.01) were independent risk factors for HCC development, then Model (Age_DC) was developed and its AUROC was 0.718. Another model, Model (Age_DC_PLT_TBil) consisting of age, DC stage, PLT, TBil was also developed, and its AUROC was larger than that of Model (Age_DC) (0.760 vs. 0.718). Moreover, AUROC of Model (Age_DC_PLT_TBil) was larger than the other five models (all P < 0.05). With an optimal cut-off value of 0.236, Model (Age_DC_PLT_TBil) achieved 70.83% sensitivity, 76.24% specificity. Conclusion: There is a lack of non-invasive risk scores for HCC development in HBV-related DC, and a new model consisting of age, DC stage, PLT, TBil may be an alternative.

[Preparation of Iron-modified Biochar and Its Application in Arsenic Contaminated Soil Remediation].

Biochar has a range of advantages including large porosity, high specific surface area, and strong adsorption capacity. It has been widely used in environmental pollution remediation, soil improvement, and carbon sequestration and emission reduction. Arsenic (As) is a highly toxic pollutant widely distributed throughout the soil. In typical surface soils, the most common forms of As are arsenite (AsO33-) and arsenate (AsO43-). Since most biochar surfaces are negatively charged, the adsorption efficiency of biochar to arsenic is usually low, and the biochar material needs to be modified to enhance its As adsorption performance. Iron-based materials, such as zero valent iron and iron oxide, are excellent As adsorption materials with wide environmental sources. They can be loaded to biochar to form iron-modified biochar via precipitation, pyrolysis, ball-milling, and micro-biological methods. The combined advantages of the iron-modified biochar will expand the application of biochar materials in environmental remediation. Based on a systematic analysis of the literature on iron-modified biochar in recent years, this study reviewed the common preparation methods of iron-modified biochars; analyzed biochar substrates, iron-modified biochar, and their synergistic mechanisms on As adsorption; and briefly expounded the application status of iron-modified biochar in soil pollution remediation. The prospects of the future research direction of iron-modified biochar were put forward as a reference for the large-scale application of biochar materials in the future.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer: A critical review.

Gastric cancer (GC) is a common gastrointestinal tumor. Gastric precancerous lesions (GPL) are the last pathological stage before normal gastric mucosa transforms into GC. However, preventing the transformation from GPL to GC remains a challenge. Traditional Chinese medicine (TCM) has been used to treat gastric disease for millennia. A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL. This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC, especially focusing on anti-inflammatory, anti-angiogenesis, proliferation, and apoptosis. This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

The role of traditional herbal medicine for ischemic stroke: from bench to clinic-A critical review.

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.

Photoprotective Effects of Cannabidiol against Ultraviolet-B-Induced DNA Damage and Autophagy in Human Keratinocyte Cells and Mouse Skin Tissue.

Cannabidiol (CBD) has emerged as a phytocannabinoid with various beneficial effects for the skin, including anti-photoaging effects, but its mechanisms of action are not fully elucidated. The study assessed CBD's photoprotective effects against acute ultraviolet B (UVB)-induced damage in HaCaT human keratinocyte cells and murine skin tissue. CBD (8 µM) alleviated UVB-induced cytotoxicity, apoptosis, and G2/M cell cycle arrest in HaCaT cells. The contents of γH2AX and cyclobutane pyrimidine dimers were decreased after CBD treatment. CBD reduced the production of reactive oxygen species and modulated the expression of antioxidant-related proteins such as nuclear factor erythroid 2-related factor 2 in UVB-stimulated HaCaT cells. Furthermore, CBD mitigated the UVB-induced cytotoxicity by activating autophagy. In addition, a cream containing 5% CBD showed effectiveness against UVB-induced photodamage in a murine model. The CBD cream improved the skin's condition by lowering the photodamage scores, reducing abnormal skin proliferation, and decreasing expression of the inflammation-related protein cyclooxygenase-2 in UVB-irradiated skin tissue. These findings indicate that CBD might be beneficial in alleviating UVB-induced skin damage in humans. The photoprotective effects of CBD might be attributed to its modulatory effects on redox homeostasis and autophagy.

Effects of Circ_0109046 Regulating Mir-338-3p on the Malignant Behavior of A2780 Cells.

Objective: The objective is to explore the action and mechanism of circ_0109046 on the malignant phenotypes of ovarian cancer cells. Methods: Circ_0109046 and miR-338-3p expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). In vitro assays were conducted to investigate the action of circ_0109046 and miR-338-3p on ovarian cancer cell growth and metastasis. Western blotting was utilized to investigate the contents of apoptosis-related markers. The binding between circ_0109046 and miR-338-3p was validated using dual-luciferase reporter assay. Results: Circ_0109046 was increased, while miR-338-3p content was decreased in ovarian cancer tissues. Deficiency of circ_0109046 or the upregulation of miR-338-3p was observed to weaken cell proliferative, migratory, and invasive abilities and elevated cell apoptosis rate in ovarian cancer. Circ_0109046 targetedly suppressed miR-338-3p. Down-regulation of miR-338-3p was able to reverse the repressing impacts of circ_0109046 silencing on ovarian cancer growth and mobility. Conclusion: Circ_0109046 silencing impaired the proliferation, migration, and invasion of ovarian cancer cells through negatively regulating miR-338-3p in vitro, indicating the potential implication of circ_0109046 in ovarian cancer progression.

Transcriptomic signatures responding to PKM2 activator TEPP-46 in the hyperglycemic human renal proximal epithelial tubular cells.

Pyruvate kinase M2 (PKM2), as the terminal and last rate-limiting enzyme of the glycolytic pathway, is an ideal enzyme for regulating metabolic phenotype. PKM2 tetramer activation has shown a protective role against diabetic kidney disease (DKD). However, the molecular mechanisms involved in diabetic tubular have not been investigated so far. In this study, we performed transcriptome gene expression profiling in human renal proximal tubular epithelial cell line (HK-2 cells) treated with 25 mM high D-glucose (HG) for 7 days before the addition of 10 µM TEPP-46, an activator of PKM2 tetramerization, for a further 1 day in the presence of HG. Afterwards, we analyzed the differentially expressed (DE) genes and investigated gene relationships based on weighted gene co-expression network analysis. The results showed that 2,902 DE genes were identified (adjusted P-value ≤ 0.05), where 2,509 DE genes (86.46%) were co-expressed in the key module. Four extremely downregulated DE genes (HSPA8, HSPA2, HSPA1B, and ARRB1) and three extremely upregulated DE genes (GADD45A, IGFBP3, and SIAH1) enriched in the downregulated endocytosis (hsa04144) and upregulated p53 signaling pathway (hsa04115), respectively, were validated by qRT-PCR experiments. The qRT-PCR results showed that the relative expression levels of HSPA8 [adjusted P-value = 4.45 × 10-34 and log2(FC) = -1.12], HSPA2 [adjusted P-value = 6.09 × 10-14 and log2(FC) = -1.27], HSPA1B [adjusted P-value = 1.14 × 10-11 and log2(FC) = -1.02], and ARRB1 [adjusted P-value = 2.60 × 10-5 and log2(FC) = -1.13] were significantly different (P-value < 0.05) from the case group to the control group. Furthermore, the interactions and predicted microRNAs of the key genes (HSPA8, HSPA2, HSPA1B, and ARRB1) were visualized in networks. This study identified the key candidate transcriptomic biomarkers and biological pathways in hyperglycemic HK-2 cells responding to the PKM2 activator TEPP-46 that can highlight a possibility of PKM2 tetramerization reshaping the interplay among endocytic trafficking through the versatile networks of Hsp70s and rewiring the crosstalk between EGFR signal transduction circuits and metabolic stress to promote resilience, which will be valuable for further research on PKM2 in DKD.