Glycolysis and beyond in glucose metabolism: exploring pulmonary fibrosis at the metabolic crossroads.

At present, pulmonary fibrosis (PF) is a prevalent and irreversible lung disease with limited treatment options, and idiopathic pulmonary fibrosis (IPF) is one of its most common forms. Recent research has highlighted PF as a metabolic-related disease, including dysregulated iron, mitochondria, lipid, and glucose homeostasis. Systematic reports on the regulatory roles of glucose metabolism in PF are rare. This study explores the intricate relationships and signaling pathways between glucose metabolic processes and PF, delving into how key factors involved in glucose metabolism regulate PF progression, and the interplay between them. Specifically, we examined various enzymes, such as hexokinase (HK), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), pyruvate kinase (PK), and lactate dehydrogenase (LDH), illustrating their regulatory roles in PF. It highlights the significance of lactate, alongside the role of pyruvate dehydrogenase kinase (PDK) and glucose transporters (GLUTs) in modulating pulmonary fibrosis and glucose metabolism. Additionally, critical regulatory factors such as transforming growth factor-beta (TGF-ß), interleukin-1 beta (IL-1ß), and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were discussed, demonstrating their impact on both PF and glucose metabolic pathways. It underscores the pivotal role of AMP-activated protein kinase (AMPK) in this interplay, drawing connections between diabetes mellitus, insulin, insulin-like growth factors, and peroxisome proliferator-activated receptor gamma (PPARγ) with PF. This study emphasizes the role of key enzymes, regulators, and glucose transporters in fibrogenesis, suggesting the potential of targeting glucose metabolism for the clinical diagnosis and treatment of PF, and proposing new promising avenues for future research and therapeutic development.

Experimental investigation of the influence of mine water on mechanical properties of resin grout.

Resin grout is widely used in geotechnical and underground engineering, and is often affected by different mine water solutions. This study considered the effects of different mine water solutions and soaking times on resin grout. Soaking tests and uniaxial compression tests were conducted to investigate the changes in the solution pH, relative specimen mass, and uniaxial compressive strength (UCS), and the deterioration of the resin grout's mechanical properties caused by the mine water solution was analyzed. The corrosion mechanism of resin grout under the action of different mine water solutions was investigated through scanning electron microscopy tests. The results reveal that the pH value of the solution and the relative mass of the specimen gradually stabilized as the soaking time was extended, and the final solution was weakly alkaline. The increase in the acidity and alkalinity of the solution and the extension of the soaking time led to a gradual decrease in the UCS and elastic modulus of resin grout under the action of mine water. As the soaking was prolonged, the resin grout properties deteriorated to different degrees and Poisson's ratio increased. Moreover, owing to the different types and degrees of mine water action on resin grout in different mine water environments, the changes in the resin grout microstructure were also different. The defined damage parameters can express the damage process of the resin grout's UCS quantitatively under the action of mine water solution. Finally, beneficial engineering application countermeasures are proposed for different resin grout types used in roadway support applications in coal mines.

Genome-wide identification and analysis of the cotton ALDH gene family.

BACKGROUND: Aldehyde dehydrogenases (ALDHs) are a family of enzymes that catalyze the oxidation of aldehyde molecules into the corresponding carboxylic acid, regulate the balance of aldehydes and protect plants from the poisoning caused by excessive accumulation of aldehydes; however, this gene family has rarely been studied in cotton. RESULTS: In the present study, genome-wide identification was performed, and a total of 114 ALDH family members were found in three cotton species, Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii. The ALDH genes were divided into six subgroups by evolutionary analysis. ALDH genes in the same subgroup showed similar gene structures and conserved motifs, but some genes showed significant differences, which may result in functional differences. Chromosomal location analysis and selective pressure analysis revealed that the ALDH gene family had experienced many fragment duplication events. Cis-acting element analysis revealed that this gene family may be involved in the response to various biotic and abiotic stresses. The RT‒qPCR results showed that the expression levels of some members of this gene family were significantly increased under salt stress conditions. Gohir.A11G040800 and Gohir.D06G046200 were subjected to virus-induced gene silencing (VIGS) experiments, and the sensitivity of the silenced plants to salt stress was significantly greater than that of the negative control plants, suggesting that Gohir.A11G040800 and Gohir.D06G046200 may be involved in the response of cotton to salt stress. CONCLUSIONS: In total, 114 ALDH genes were identified in three Gossypium species by a series of bioinformatics analysis. Gene silencing of the ALDH genes of G. hirsutum revealed that ALDH plays an important role in the response of cotton to salt stress.

Identification and characterization of ACR gene family in maize for salt stress tolerance.

Background: Members of the ACR gene family are commonly involved in various physiological processes, including amino acid metabolism and stress responses. In recent decades, significant progress has been made in the study of ACR genes in plants. However, little is known about their characteristics and function in maize. Methods: In this study, ACR genes were identified from the maize genome, and their molecular characteristics, gene structure, gene evolution, gene collinearity analysis, cis-acting elements were analyzed. qRT-PCR technology was used to verify the expression patterns of the ZmACR gene family in different tissues under salt stress. In addition, Ectopic expression technique of ZmACR5 in Arabidopsis thaliana was utilized to identify its role in response to salt stress. Results: A total of 28 ZmACR genes were identified, and their molecular characteristics were extensively described. Two gene pairs arising from segmented replication events were detected in maize, and 18 collinear gene pairs were detected between maize and 3 other species. Through phylogenetic analysis, three subgroups were revealed, demonstrating distinct divergence between monocotyledonous and dicotyledonous plants. Analysis of ZmACR cis-acting elements revealed the optional involvement of ZmACR genes in light response, hormone response and stress resistance. Expression analysis of 8 ZmACR genes under salt treatment clearly revealed their role in the response to salt stress. Ectopic overexpression of ZmACR5 in Arabidopsis notably reduced salt tolerance compared to that of the wild type under salt treatment, suggesting that ZmACR5 has a negative role in the response to salt stress. Conclusion: Taken together, these findings confirmed the involvement of ZmACR genes in regulating salt stress and contributed significantly to our understanding of the molecular function of ACR genes in maize, facilitating further research in this field.

Hepatitis B virus X protein promotes tumor glycolysis by downregulating lncRNA OIP5-AS1/HKDC1 in HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with Hepatitis B virus (HBV) infection being the leading cause. This study aims to investigate the role of HBV in HCC pathogenesis involving glucose metabolism. Long non-coding RNA (lncRNA) OIP5-AS1 was significantly downregulated in HBV-positive HCC patients, and its low expression indicated a poor prognosis. This lncRNA was primarily localized in the cytoplasm, acting as a tumor suppressor. HBV protein X (HBx) repressed OIP5-AS1 expression by inhibiting a ligand-activated transcriptional factor peroxisome proliferator-activated receptor α (PPARα). Furthermore, mechanistic studies revealed that OIP5-AS1 inhibited tumor growth by suppressing Hexokinase domain component 1 (HKDC1)-mediated glycolysis. The expression of HKDC1 could be enhanced by transcriptional factor sterol regulatory element-binding protein 1 (SREBP1). OIP5-AS1 facilitated the ubiquitination and degradation of SREBP1 to suppress HKDC1 transcription, which inhibited glycolysis. The results suggest that lncRNA OIP5-AS1 plays an anti-oncogenic role in HBV-positive HCC via the HBx/OIP5-AS1/HKDC1 axis, providing a promising diagnostic marker and therapeutic target for HBV-positive HCC patients.

Chemical Reaction of FA Cations Enables Efficient and Stable Perovskite Solar Cells.

Organometal halide perovskite solar cells (PSCs) have received great attention owing to a rapid increase in power conversion efficiency (PCE) over the last decade. However, the deficit of long-term stability is a major obstacle to the implementation of PSCs in commercialization. The defects in perovskite films are considered as one of the primary causes. To address this issue, isocyanic acid (HNCO) is introduced as an additive into the perovskite film, in which the added molecules form covalent bonds with FA cations via a chemical reaction. This chemical reaction gives rise to an efficient passivation on the perovskite film, resulting in an improved film quality, a suppressed non-radiation recombination, a facilitated carrier transport, and optimization of energy band levels. As a result, the HNCO-based PSCs achieve a high PCE of 24.41% with excellent storage stability both in an inert atmosphere and in air. Different from conventional passivation methods based on coordination effects, this work presents an alternative chemical reaction for defect passivation, which opens an avenue toward defect-mitigated PSCs showing enhanced performance and stability.

Hepatitis B Virus-Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape.

Hepatitis B viral (HBV) persistent infection plays a significant role in hepatocellular carcinoma (HCC) tumorigenesis. Many studies have revealed the pivotal roles of N6-methyladenosine (m6A) in multiple cancers, while the regulatory mechanism in stemness maintenance of HBV persistent infection-related HCC remains elusive. Here, we demonstrated that the level of m6A modification was downregulated by HBV in HBV-positive HCC, through enhanced stability of ALKBH5 mRNA. More specifically, we also identified that ALKBH5 mRNA was functionally required for the stemness maintenance and self-renewal in the HBV-positive HCC, but dispensable in HBV-negative HCC. Mechanistically, ALKBH5 demethylated the m6A modification in the 3' untranslated region of the oncogenic gene SNAI2 to prevent the recognition of YTHDF2 therewith stabilize SNAI2 transcripts, contributing to cancer stem cell traits in HBV-positive HCC. Moreover, the expression of SNAI2 reversed the suppression of stemness properties by knocking down ALKBH5. In addition, ALKBH5/SNAI2 axis accelerates tumor immune evasion through activated ligand of immune checkpoint CD155. Our study unveiled that the ALKBH5 induces m6A demethylation of the SNAI2 as a key regulator in HBV-related HCC, and identifies the function of ALKBH5/SNAI2/YTHDF2 axis in promoting the stem-like cells phenotype and immune escape during HBV infection. IMPLICATIONS: HBV promotes HCC stemness maintenance through elevate m6A modification of SNAI2 in an ALKBH5-YTHDF2-dependent manner and increases the expression of the ligand of immune checkpoint CD155.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

An analysis of lncRNAs related to fiber quality and the discovery of their target genes in a Gossypium hirsutum line with Gossypium mustelinum introgression.

KEY MESSAGE: Analysis of fiber quality lncRNAs and their target genes from a pair of Gossypium mustelinum near-isogenic lines provide new prospects for improving the fiber quality of Upland cotton. Long noncoding RNAs (lncRNAs) are an important part of genome transcription and play roles in a wide range of biological processes in plants. In this research, a pair of near-isogenic cotton lines, namely, a Gossypium mustelinum introgression line (IL9) with outstanding fiber quality and its recurrent Upland cotton parent (PD94042), were used as the experimental materials. Cotton fibers were selected for lncRNA sequencing at 17 and 21 days post-anthesis. A total of 2693 differentially expressed genes were identified. In total, 5841 lncRNAs were ultimately screened, from which 163 differentially expressed lncRNAs were identified. Target genes of the lncRNAs were predicted by two different methods: cis and trans. Some of the target genes were related to cell components, membrane components, plant hormone signal transduction and catalytic metabolism, and the results indicated that there might also be important effects on the development of fiber. Four differentially expressed target genes related to fiber quality (Gomus.D05G015100, Gomus.A05G281300, Gomus.A12G023400 and Gomus.A10G226800) were screened through gene function annotation, and the functions of these four genes were verified through virus-induced gene silencing (VIGS). Compared to the negative controls, plants in which any of these four genes were silenced showed significant reductions in fiber strength. In addition, the plants in which the Gomus.A12G023400 gene was silenced showed a significant reduction in fiber uniformity, whereas the plants in which Gomus.A05G281300 was silenced showed a significant increase in fiber fineness as measured via micronaire. Our results showed that these genes play different roles during fiber development, impacting fiber quality.

Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment.

BACKGROUND: Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment. METHODS: From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC. RESULTS: In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC. CONCLUSIONS: The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.

In Situ Surface Reconstruction toward Planar Heterojunction for Efficient and Stable FAPbI3 Quantum Dot Solar Cells.

Pure-phase α-FAPbI3 quantum dots (QDs) are the focus of an increasing interest in photovoltaics due to their superior ambient stability, large absorption coefficient, and long charge-carrier lifetime. However, the trap states induced by the ligand-exchange process limit the photovoltaic performances. Here, a simple post treatment using methylamine thiocyanate is developed to reconstruct the FAPbI3 -QD film surface, in which a MAPbI3 capping layer with a thickness of 6.2 nm is formed on the film top. This planar perovskite heterojunction leads to a reduced density of trap-states, a decreased band gap, and a facilitated charge carrier transport. As a result, a record high power conversion efficiency (PCE) of 16.23% with negligible hysteresis is achieved for the FAPbI3 QD solar cell, and it retains over 90% of the initial PCE after being stored in ambient environment for 1000 h.

Exercise training and vascular heterogeneity in db/db mice: evidence for regional- and duration-dependent effects.

Exercise training (ET) has several health benefits; however, our understanding of regional adaptations to ET is limited. We examined the functional and molecular adaptations to short- and long-term ET in elastic and muscular conduit arteries of db/db mice in relation to changes in cardiovascular risk factors. Diabetic mice and their controls were exercised at moderate intensity for 4 or 8 weeks. The vasodilatory and contractile responses of thoracic aortae and femoral arteries isolated from the same animals were examined. Blood and aortic samples were used to measure hyperglycemia, oxidative stress, inflammation, dyslipidemia, protein expression of SOD isoforms, COX, eNOS, and Akt. Short-term ET improved nitric oxide (NO) mediated vasorelaxation in the aortae and femoral arteries of db/db mice in parallel with increased SOD2 and SOD3 expression, reduced oxidative stress and triglycerides, and independent of weight loss, glycemia, or inflammation. Long-term ET reduced body weight in parallel with reduced systemic inflammation and improved insulin sensitivity along with increased SOD1, Akt, and eNOS expression and improved NO vasorelaxation. Exercise did not restore NOS- and COX-independent vasodilatation in femoral arteries, nor did it mitigate the hypercontractility in the aortae of db/db mice; rather ET transiently increased contractility in association with upregulated COX-2. Long-term ET differentially affected the aortae and femoral arteries contractile responses. ET improved NO-mediated vasodilation in both arteries likely due to collective systemic effects. ET did not mitigate all diabetes-induced vasculopathies. Optimization of the ET regimen can help develop comprehensive management of type 2 diabetes.

Dynamic physiological and transcriptomic changes reveal memory effects of salt stress in maize.

BACKGROUND: Pre-exposing plants to abiotic stresses can induce stress memory, which is crucial for adapting to subsequent stress exposure. Although numerous genes involved in salt stress response have been identified, the understanding of memory responses to salt stress remains limited. RESULTS: In this study, we conducted physiological and transcriptional assays on maize plants subjected to recurrent salt stress to characterize salt stress memory. During the second exposure to salt stress, the plants exhibited enhanced salt resistance, as evidenced by increased proline content and higher POD and SOD activity, along with decreased MDA content, indicative of physiological memory behavior. Transcriptional analysis revealed fewer differentially expressed genes and variations in response processes during the second exposure compared to the first, indicative of transcriptional memory behavior. A total of 2,213 salt stress memory genes (SMGs) were identified and categorized into four response patterns. The most prominent group of SMGs consisted of genes with elevated expression during the first exposure to salt stress but reduced expression after recurrent exposure to salt stress, or vice versa ([+ / -] or [- / +]), indicating that a revised response is a crucial process in plant stress memory. Furthermore, nine transcription factors (TFs) (WRKY40, WRKY46, WRKY53, WRKY18, WRKY33, WRKY70, MYB15, KNAT7, and WRKY54) were identified as crucial factors related to salt stress memory. These TFs regulate over 53% of SMGs, underscoring their potential significance in salt stress memory. CONCLUSIONS: Our study demonstrates that maize can develop salt stress memory, and the genes identified here will aid in the genetic improvement of maize and other crops.

Optimal Look-Back Period to Identify True Incident Cases of Diabetes in Medical Insurance Data in the Chinese Population: Retrospective Analysis Study.

BACKGROUND: Accurate estimation of incidence and prevalence is vital for preventing and controlling diabetes. Administrative data (including insurance data) could be a good source to estimate the incidence of diabetes. However, how to determine the look-back period (LP) to remove cases with preceding records remains a problem for administrative data. A short LP will cause overestimation of incidence, whereas a long LP will limit the usefulness of a database. Therefore, it is necessary to determine the optimal LP length for identifying incident cases in administrative data. OBJECTIVE: This study aims to offer different methods to identify the optimal LP for diabetes by using medical insurance data from the Chinese population with reference to other diseases in the administrative data. METHODS: Data from the insurance database of the city of Weifang, China from between January 2016 and December 2020 were used. To identify the incident cases in 2020, we removed prevalent patients with preceding records of diabetes between 2016 and 2019 (ie, a 4-year LP). Using this 4-year LP as a reference, consistency examination indexes (CEIs), including positive predictive values, the κ coefficient, and overestimation rate, were calculated to determine the level of agreement between different LPs and an LP of 4 years (the longest LP). Moreover, we constructed a retrograde survival function, in which survival (ie, incident cases) means not having a preceding record at the given time and the survival time is the difference between the date of the last record in 2020 and the most recent previous record in the LP. Based on the survival outcome and survival time, we established the survival function and survival hazard function. When the survival probability, S(t), remains stable, and survival hazard converges to zero, we obtain the optimal LP. Combined with the results of these two methods, we determined the optimal LP for Chinese diabetes patients. RESULTS: The κ agreement was excellent (0.950), with a high positive predictive value (92.2%) and a low overestimation rate (8.4%) after a 2-year LP. As for the retrograde survival function, S(t) dropped rapidly during the first 1-year LP (from 1.00 to 0.11). At a 417-day LP, the hazard function reached approximately zero (ht=0.000459), S(t) remained at 0.10, and at 480 days, the frequency of S(t) did not increase. Combining the two methods, we found that the optimal LP is 2 years for Chinese diabetes patients. CONCLUSIONS: The retrograde survival method and CEIs both showed effectiveness. A 2-year LP should be considered when identifying incident cases of diabetes using insurance data in the Chinese population.

Resuscitation of out-of-hospital cardiac arrest in China: A systematic review and Utstein-style data analysis based on the Chain of Survival.

AIM: Out-of-hospital cardiac arrest (OHCA) contributes to substantial mortality, but its resuscitation status in China is unknown. We aimed to describe and analyze out-of-hospital cardiac arrest in terms of Chain of Survival. METHODS: We systematically collected Utstein-style publications. Scenarios were prespecified, including either emergency medical service (EMS) assessing and attending cardiac arrest, resuscitation attempted by a bystander, resuscitation attempted by EMS, or in-hospital treatment. Random-effect models were used in a meta-analysis to pool rate ratios (RRs) with 95% confidence intervals (CIs) from multiple cohorts. RESULTS: We analyzed 59 Chains involving 233,376 Chinese patients. The median rate of survival to discharge (interquartile range) was 0.35 % (0.06 %-0.61 %), 3.66 % (3.06 %-3.85 %), 1.23 % (0.57%-1.36%), and 2.73% (2.04%-3.42%) for four scenarios. The rate was significantly higher for bystander resuscitation than for EMS (P = 0.025) or in-hospital treatment (P = 0.301). However, only 4.8 % (1.6 %-8.2 %) of patients received bystander resuscitation, with no bystander defibrillation and a median response time of 9-15 minutes for EMS. Compared with controls without witnesses, arrest being witnessed and with bystander resuscitation increased rates of survival to discharge by 1.97 (I2 = 0, P for I2 = 0.583; pooled RR 2.97; 95% CI 1.47-6.02) and 6.79 (I2 = 0, P for I2 = 0.593; pooled RR 7.79; 95 % CI 3.40-17.84) times, following a markedly increasing trend. CONCLUSIONS: A low probability of first aid at multiple points is linked to poor survival following OHCA. It is essential to strengthen front links in the Chain of Survival in China, including among witnesses, bystanders, and emergency response.

Genome-wide analysis of the LAZ1 gene family in Gossypium hirsutum.

BACKGROUND: As the world's leading fiber crop and a major oil-producing crop, cotton fiber yield and fiber quality are affected by environmental stresses, especially heat, drought and salinity. The LAZ1 (Lazarus 1) family genes are responsive to abscisic acid, drought, and salt treatments. Currently, mining and functional analyses of LAZ1 family genes in cotton have not been reported. METHODS AND RESULTS: In this study, 20 GhLAZ1 genes, designated GhLAZ1-1 - GhLAZ1-20, were identified in the genome of Gossypium hirsutum through the construction of an HMM model, and their molecular properties, chromosomal localization, phylogeny, gene structure, evolutionary selection pressure, promoter cis elements and gene expression under salt stress were analyzed. With the exception of GhLAZ1-17 and GhLAZ1-20, the remaining 18 GhLAZ1 genes were unevenly localized on 13 chromosomes in G. hirsutum; evolutionary analysis showed that these genes could be divided into three subfamilies; and evolutionary selection pressure analysis demonstrated that the GhLAZ1 genes were all under purifying selection. Many elements related to light responses, hormone responses, and abiotic stresses were predicted on the GhLAZ1 family gene promoters, and real-time quantitative PCR results showed that GhLAZ1-2, GhLAZ1-8, and GhLAZ1-18 were upregulated significantly in salt-treated cotton leaves. CONCLUSIONS: Our results suggested that GhLAZ1 genes were involved in the salt tolerance mechanism in G. hirsutum and provided a reference for further exploring the function and molecular mechanism of LAZ1 genes.

Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3+CD8+ and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.

Biological functions and molecular subtypes regulated by miR-142-3p in colon cancer.

MicroRNA-142-3p (miR-142-3p) has been reported to be implicated in colon cancer; however, the possible regulatory mechanisms and molecular subtypes regulated by miR-142-3p have not been fully elucidated. This study aimed to investigate the biological functions and regulatory mechanism of miR-142-3p in colon cancer. The expression level of miR-142-3p in colon cancer was analyzed based on the mRNA and miRNA expression datasets of colon cancer retrieved from The Cancer Genome Atlas. Target genes of miR-142-3p were also predicted. Based on these target genes, the functions and subtypes of miR-142-3p were investigated. The metabolic and tumor-related pathways, immune microenvironment, and target gene expression between the 2 subtypes were analyzed. MiR-142-3p was upregulated in tumor tissues, and its high expression indicated a poor prognosis. A total of 39 target genes were predicted, which were significantly involved in autophagy- and metabolism-related functions and pathways. Based on these target genes, the colon cancer samples were clustered into 2 subtypes. There were 35 metabolism-related pathways that were significantly different between the 2 clusters. The immune and stromal scores in cluster 2 were higher than those in cluster 1, whereas the tumor purity of cluster 2 was significantly lower than that of cluster 1. TP53INP2 expression in cluster 2 was higher than that in cluster 1. MiR-142-3p may promote colon cancer progression via autophagy- and metabolism-related pathways. MiR-142-3p may be served as a candidate target for the treatment of colon cancer.

Rhein alleviates advanced glycation end products (AGEs)-induced inflammatory injury of diabetic cardiomyopathy in vitro and in vivo models.

In diabetic patients, diabetic cardiomyopathy (DCM) is one of the most common causes of death. The inflammatory response is essential in the pathogenesis of DCM. Rhein, an anthraquinone compound, is extracted from the herb rhubarb, demonstrating various biological activities. However, it is unclear whether rhein has an anti-inflammatory effect in treating DCM. In our research, we investigated the anti-inflammatory properties as well as its possible mechanism. According to the findings in vitro, rhein could to exert an anti-inflammatory effect by reducing the production of NO, TNF-α, PGE2, iNOS, and COX-2 in RAW264.7 cells that had been stimulated with advanced glycosylation end products (AGEs). In addition, rhein alleviated H9C2 cells inflammation injury stimulated by AGEs/macrophage conditioned medium (CM). In vivo have depicted that continuous gavage of rhein could improve cardiac function and pathological changes. Moreover, it could inhibit the accumulation of AGEs and infiltration of inflammatory factors inside the heart of rats having DCM. Mechanism study showed rhein could suppress IKKß and IκB phosphorylation via down-regulating TRAF6 expression to inhibit NF-κB pathway in AGEs/CM-induced H9C2 cells. Moreover, the anti-inflammation effect of rhein was realized through down-regulation phosphorylation of JNK MAPK. Furthermore, we found JNK MAPK could crosstalk with NF-κB pathway by regulating IκB phosphorylation without affecting IKKß activity. And hence, the protective mechanism of rhein may involve the inhibiting of the TRAF6-NF/κB pathway, the JNK MAPK pathway, and the crosstalk between the two pathways. These results suggested that rhein may be a promising drug candidate in anti-inflammation and inflammation-related DCM therapy.

Special Issue "Genomics of Fungal Plant Pathogens".

Plant diseases can be classified according to pathogenic organisms, and 70-80% of them are fungal diseases [...].