Identification and validation of oxidative stress-related genes in sepsis-induced myopathy.

BACKGROUND: Sepsis-induced myopathy (SIM) a complication of sepsis that results in prolonged mechanical ventilation, long-term functional disability, and increased patient mortality. This study was performed to identify potential key oxidative stress-related genes (OS-genes) as biomarkers for the diagnosis of SIM using bioinformatics. METHODS: The GSE13205 was obtained from the Gene Expression Omnibus (GEO) database, including 13 SIM samples and 8 healthy samples, and the differentially expressed genes (DEGs) were identified by limma package in R language. Simultaneously, we searched for the genes related to oxidative stress in the Gene Ontology (GO) database. The intersection of the genes selected from the GO database and the genes from the GSE13205 was considered as OS-genes of SIM, where the differential genes were regarded as OS-DEGs. OS-DEGs were analyzed using GO enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. Hub genes in OS-DEGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed. RESULTS: A total of 1089 DEGs were screened from the GSE13205, and 453 OS-genes were identified from the GO database. The overlapping DEGs and OS-genes constituted 25 OS-DEGs, including 15 significantly upregulated and 10 significantly downregulated genes. The top 10 hub genes, including CD36, GPX3, NQO1, GSR, TP53, IDH1, BCL2, HMOX1, JAK2, and FOXO1, were screened. Furthermore, 5 diagnostic genes were identified: CD36, GPX3, NQO1, GSR, and TP53. The ROC analysis showed that the respective area under the curves (AUCs) of CD36, GPX3, NQO1, GSR, and TP53 were 0.990, 0.981, 0.971, 0.971, and 0.971, which meant these genes had very high diagnostic values of SIM. Finally, based on these 5 diagnostic genes, we found that miR-124-3p and miR-16-5p may be potential targets for the treatment of SIM. CONCLUSIONS: The results of this study suggest that OS-genes might play an important role in SIM. CD36, GPX3, NQO1, GSR, and TP53 have potential as specific biomarkers for the diagnosis of SIM.

Rapid determination of starch and alcohol contents in fermented grains by hyperspectral imaging combined with data fusion techniques.

Starch and alcohol serve as pivotal indicators in assessing the quality of lees fermentation. In this paper, two hyperspectral imaging (HSI) techniques (visible-near-infrared (Vis-NIR) and NIR) were utilized to acquire separate HSI data, which were then fused and analyzed toforecast the starch and alcohol contents during the fermentation of lees. Five preprocessing methods were first used to preprocess the Vis-NIR, NIR, and the fused Vis-NIR and NIR data, after which partial least squares regression models were established to determine the best preprocessing method. Following, competitive adaptive reweighted sampling, successive projection algorithm, and principal component analysis algorithms were used to extract the characteristic wavelengths to accurately predict the starch and alcohol levels. Finally, support vector machine (SVM)-AdaBoost and XGBoost models were built based on the low-level fusion (LLF) and intermediate-level fusion (ILF) of single Vis-NIR and NIR as well as the fused data. The results showed that the SVM-AdaBoost model built using the LLF data afterpreprocessing by standard normalized variable was most accurate for predicting the starch content, with an R P 2 $\ R_P^2$ of 0.9976 and a root mean square error of prediction (RMSEP) of 0.0992. The XGBoost model built using ILF data was most accurate for predicting the alcohol content, with an R P 2 $R_P^2$ of 0.9969 and an RMSEP of 0.0605. In conclusion, the analysis of fused data from distinct HSI technologies facilitates rapid and precise determination of the starch and alcohol contents in fermented grains.

Knowledge, attitude, practice and illness perception toward subarachnoid hemorrhage prevention and management among intracranial aneurysm patients.

OBJECTIVE: This study aims to explore the knowledge, attitude, practice and illness perception toward prevention and management of subarachnoid hemorrhages (SAH) among intracranial aneurysm (IA) patients. METHODS: A cross-sectional study was conducted between March 2023 and June 2023; demographic characteristics and KAP scores were collected by a self-administered questionnaire and analyzed by linear regression and path analysis. RESULTS: A total of 455 patients with IA were included, of them 26.37% experienced SAH before. Mean knowledge, attitude and practice scores were 16.60 ± 5.86, 16.39 ± 1.84, and 35.07 ± 3.51, respectively. The linear regression showed ethnic minority, married, education, family members in healthcare system, monthly per capita household income, experience ruptured intracranial aneurysms, smoking, hypertension, hyperlipidemia, diabetes, and aortic lesion were associated with knowledge scores. Age, ethnic minority, urban residence, education, family members in healthcare system, monthly per capita household income, duration of IA ≥6 months, experience ruptured intracranial aneurysms, smoking, diabetes, and aortic lesion were associated with attitude scores. Age, urban residence, monthly per capita household income, duration of IA ≥6 months, experience of ruptured intracranial aneurysms, smoking, diabetes, and aortic lesion were associated with practice scores. According to the path analysis, knowledge directly affected illness perception (ß=0.156, P<0.001) and attitude (ß=0.708, P<0.001), while attitude (ß=0.909, P<0.001) and illness perception (ß=0.039, P=0.027) affected practice. CONCLUSIONS: Patients had positive attitudes towards SAH prevention and management, but a substantial knowledge gap was found along with notably delayed medical help-seeking behavior.

LncRNA IRAIN overcomes imatinib resistance in chronic myeloid leukemia via NF-κB/CD44 pathway inhibition.

The development of tyrosine kinase inhibitors (TKIs) has revolutionarily increased the overall survival of patients with chronic myeloid leukemia (CML). However, drug resistance remains a major obstacle. Here, we demonstrated that a BCR-ABL1-independent long non-coding RNA, IRAIN, is constitutively expressed at low levels in CML, resulting in imatinib resistance. IRAIN knockdown decreased the sensitivity of CD34+ CML blasts and cell lines to imatinib, whereas IRAIN overexpression significantly increased sensitivity. Mechanistically, IRAIN downregulates CD44, a membrane receptor favorably affecting TKI resistance, by binding to the nuclear factor kappa B subunit p65 to reduce the expression of p65 and phosphorylated p65. Therefore, the demethylating drug decitabine, which upregulates IRAIN, combined with imatinib, formed a dual therapy strategy which can be applied to CML with resistance to TKIs.

Anti-coronavirus and anti-pulmonary inflammation effects of iridoids, the common component from Chinese herbal medicines for the treatment of COVID-19.

The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 µM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1ß and IL-8 at 10 µM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.

Association between long-term visit-to-visit blood pressure variability and depression among Chinese middle-aged and older adults.

BACKGROUND: Whether there is a longitudinal association between long-term blood pressure variability (BPV) and subsequent depression among Chinese adults remains inconclusive. METHODS: This study utilized data from a nationwide cohort of the China Health and Retirement Longitudinal Study, which included participants aged > 45 years without prevalent psychiatric or memory-related diseases. The intra-individual coefficient of variation (CV) and standard deviation (SD) across 3 visits from 2011 to 2015 were used to examine the long-term variability in systolic BP (SBP) and diastolic BP (DBP). The depressive symptoms were examined using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10), and moderate-to-severe depression was defined as CES-D-10 ≥ 15. RESULTS: A total of 5,249 participants (mean age: 61.4 ± 8.1 years, 46.5% were men) were included in the current analysis. Individuals in the highest quartile of both BP CV and SD were independently correlated with a higher total CES-D-10 score compared to those in the lowest quartile after multivariable adjustment. 1,070 participants (20.4%) had moderate-to-severe depression during the 3-year follow-up period. Participants in the Q4 of SBP and DBP CV had 1.23-fold higher odds (95% CI: 1.01, 1.49) and 1.20-fold higher odds (95% CI: 1.01, 1.41) of moderate-to-severe depression compared to those in Q1. Subgroup analyses revealed that men with higher BP CVs had a greater risk of severe depressive symptoms (p for SBP CV-by-sex interaction = 0.050, p for SBP CV-by-sex interaction = 0.025). CONCLUSIONS: Depression was common among Chinese middle-aged and older adults and long-term visit-to-visit BPV was positively associated with depressive symptoms, highlighting the importance of implementing intensive prevention strategies for depression and enhancing blood pressure monitors in China.

Roles of negative emotions and personality traits in psoriasis vulgaris: A mendelian randomization study.

BACKGROUND: Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence. METHODS: Our analysis utilized 15 genome-wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two-sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p-values using the Benjamini-Hochberg method. RESULTS: Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed-up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris. CONCLUSION: Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed-up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.

Peptostreptococcus anaerobius mediates anti-PD1 therapy resistance and exacerbates colorectal cancer via myeloid-derived suppressor cells in mice.

Bacteria such as the oral microbiome member Peptostreptococcus anaerobius can exacerbate colorectal cancer (CRC) development. Little is known regarding whether these immunomodulatory bacteria also affect antitumour immune checkpoint blockade therapy. Here we show that administration of P. anaerobius abolished the efficacy of anti-PD1 therapy in mouse models of CRC. P. anaerobius both induced intratumoral myeloid-derived suppressor cells (MDSCs) and stimulated their immunosuppressive activities to impair effective T cell responses. Mechanistically, P. anaerobius administration activated integrin α2ß1-NF-κB signalling in CRC cells to induce secretion of CXCL1 and recruit CXCR2+ MDSCs into tumours. The bacterium also directly activated immunosuppressive activity of intratumoral MDSCs by secreting lytC_22, a protein that bound to the Slamf4 receptor on MDSCs and promoted ARG1 and iNOS expression. Finally, therapeutic targeting of either integrin α2ß1 or the Slamf4 receptor were revealed as promising strategies to overcome P. anaerobius-mediated resistance to anti-PD1 therapy in CRC.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Nanoscale zero-valent iron reverses resistance of Pseudomonas aeruginosa to chloramphenicol.

Zero-valent iron (ZVI) has been extensively studied for its capacity to remove various contaminants in the environments. However, whether ZVI affects bacterial resistance to antibiotics has not been fully explored. Herein, it was unexpected that, compared with microscale ZVI (mZVI), nanoscale ZVI (nZVI) facilitated the susceptibility of Pseudomonas aeruginosa (P. aeruginosa) to chloramphenicol (CAP), with a decrease in the minimal inhibitory concentration (MIC) of about 60 %, demonstrating a nanosize-specific effect. nZVI enhanced CAP accumulation in P. aeruginosa via inhibitory effect on efflux pumps activated by MexT, thus conferring the susceptibility of P. aeruginosa to CAP. Circular dichroism spectroscopy revealed that the structure of MexT was changed during the evolution. More importantly, molecular dynamic simulations uncovered that, once the structure of MexT changed, it would be more likely to interact with nZVI, resulting in more serious changes in its secondary structure, which was consistent with the increasing susceptibility of P. aeruginosa to CAP. Collectively, this study elucidated the size-specific effect and the underlying mechanism of ZVI on the bacterial evolution of susceptibility toward antibiotics, highlighting the potentials of nZVI-based technologies on the prevention of bacterial resistance to antibiotics, one of the most important issue for globally public health.

Explorative Study on Volatile Organic Compounds of Cinnamon Based on GC-IMS.

Cinnamon is one of the most popular spices worldwide, and volatile organic compounds (VOCs) are its main metabolic products. The misuse or mixing of cinnamon on the market is quite serious. This study used gas chromatography-ion migration spectroscopy (GC-IMS) technology to analyze the VOCs of cinnamon samples. The measurement results showed that 66 VOCs were detected in cinnamon, with terpenes being the main component accounting for 45.45%, followed by aldehydes accounting for 21.21%. The content of esters and aldehydes was higher in RG-01, RG-02, and RG-04; the content of alcohols was higher in RG-01; and the content of ketones was higher in RG-02. Principal component analysis, cluster analysis, and partial least squares regression analysis can be performed on the obtained data to clearly distinguish cinnamon. According to the VIP results of PLS-DA, 1-Hexanol, 2-heptanone, ethanol, and other substances are the main volatile substances that distinguish cinnamon. This study combined GC-IMS technology with chemometrics to accurately identify cinnamon samples, providing scientific guidance for the efficient utilization of cinnamon. At the same time, this study is of great significance for improving the relevant quality standards of spices and guiding the safe use of spices.

Advancing Automatic Gastritis Diagnosis: An Interpretable Multilabel Deep Learning Framework for the Simultaneous Assessment of Multiple Indicators.

The evaluation of morphologic features, such as inflammation, gastric atrophy, and intestinal metaplasia, is crucial for diagnosing gastritis. However, artificial intelligence analysis for nontumor diseases like gastritis is limited. Previous deep learning models have omitted important morphologic indicators and cannot simultaneously diagnose gastritis indicators or provide interpretable labels. To address this, an attention-based multi-instance multilabel learning network (AMMNet) was developed to simultaneously achieve the multilabel diagnosis of activity, atrophy, and intestinal metaplasia with only slide-level weak labels. To evaluate AMMNet's real-world performance, a diagnostic test was designed to observe improvements in junior pathologists' diagnostic accuracy and efficiency with and without AMMNet assistance. In this study of 1096 patients from seven independent medical centers, AMMNet performed well in assessing activity [area under the curve (AUC), 0.93], atrophy (AUC, 0.97), and intestinal metaplasia (AUC, 0.93). The false-negative rates of these indicators were only 0.04, 0.08, and 0.18, respectively, and junior pathologists had lower false-negative rates with model assistance (0.15 versus 0.10). Furthermore, AMMNet reduced the time required per whole slide image from 5.46 to only 2.85 minutes, enhancing diagnostic efficiency. In block-level clustering analysis, AMMNet effectively visualized task-related patches within whole slide images, improving interpretability. These findings highlight AMMNet's effectiveness in accurately evaluating gastritis morphologic indicators on multicenter data sets. Using multi-instance multilabel learning strategies to support routine diagnostic pathology deserves further evaluation.

Biomass-derived polymer as a flexible "zincophilic-hydrophobic" solid electrolyte interphase layer to enable practical Zn metal anodes.

Aqueous zinc ion batteries (AZIBs) face significant challenges stemming from Zn dendrite growth and water-contact attack, primarily due to the lack of a well-designed solid electrolyte interphase (SEI) to safeguard the Zn anode. Herein, we report a bio-mass derived polymer of chitin on Zn anode (Zn@chitin) as a novel and robust artificial SEI layer to boost the Zn anode rechargeability. The polymeric chitin SEI layer features both zincophilic and hydrophobic characteristics to target the suppressed dendritic Zn formation as well as the water-induced side reactions, thus harvesting a dendrite-free and corrosion-resistant Zn anode. More importantly, this polymeric interphase layer is strong and flexible accommodating the volume changes during repeated cycling. Based on these benefits, the Zn@chitin anode demonstrates prolonged cycling performance surpassing 1300 h under an ultra-large current density of 20 mA cm-2, and a long cycle life of 680 h with a record-high zinc utilization rate of 80 %. Besides, the assembled Zn@chitin/V2O5 full batteries reveal excellent capacity retention and rate performance under practical conditions, proving the reliability of our proposed strategy for industrial AZIBs. Our research offers valuable insights for constructing high-performance AZIBs, and simultaneously realizes the high-efficient use of cheap biomass from a "waste-to-wealth" concept.

Ppb-level unsymmetrical dimethylhydrazine detection based on In2O3 hollow microspheres with Nd doping.

As one of main high-energy fuels for rocket launching, unsymmetrical dimethylhydrazine (UDMH) and its decomposition products do harm to environment and human health. It is significant to develop a device to monitor its leakage. In this work, a UDMH gas sensor based on In2O3 hollow microspheres with Nd dopant was fabricated. The pure, 1.0 mol%, 3.0 mol% and 5.0 mol% Nd doped In2O3 were synthesized via one-step solvothermal method. Among them, 3.0% Nd-In2O3 based sensor exhibits the highest response toward UDMH vapor. Its response value to 100 ppm UDMH is 183.3 at optimal working temperature of 250 °C, 6.8 times higher than that of pure In2O3 (26.8). Besides high response to UDMH, the 3% Nd-In2O3 based sensor represents excellent selectivity, rapid response speed (2 s) and ultra-low theoretical LOD to UDMH (0.28 ppb). The improved gas sensing performance via Nd doping could be attributed to the enhanced specific surface area, increased concentration of adsorbed oxygen and improved adsorption capacity for UDMH molecular on the surface. The excellent sensing performance of Nd doped In2O3 hollow microspheres makes it a promising candidate for real-time UDMH detection.

A real-world pharmacovigilance analysis of the FDA adverse event reporting system events for polatuzumab vedotin.

BACKGROUND: Polatuzumab vedotin is the first antibody-drug conjugate approved by the US Food and Drug Administration (FDA) for patients with diffuse large B-cell lymphoma. This study evaluated adverse events (AEs) associated with polatuzumab vedotin by data mining of the FDA Adverse Event Reporting System (FAERS). METHODS: This study included AEs registered in FAERS between 2019 Q2 and 2023 Q2. Four algorithms were used to quantify the signals of polatuzumab vedotin-associated AEs, including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. RESULTS: A total of 7,609,450 reports were collected from the FAERS database, and 1,388 reports of polatuzumab vedotin were identified as primary suspected AEs. Polatuzumab vedotin-associated AEs involved 26 organ systems. According to the four algorithms, 108 significant disproportionality AEs were retained simultaneously. Unexpected significant AEs included gastrointestinal hemorrhage, ileus, gastrointestinal perforation, cholecystitis, hypogammaglobulinemia, hepatitis B reactivation, hypercalcemia, hydronephrosis, cystitis hemorrhagic, interstitial lung disease, and thrombophlebitis. The median time to onset of polatuzumab vedotin-associated AEs was 20 (interquartile range 4-56) days. CONCLUSIONS: Our study identified significant new AE signals for polatuzumab vedotin through real-world disproportionality analysis data and may provide additional evidence for risk identification of polatuzumab vedotin.

Comparing the efficacy of 308-nm light-emitting diode and 308-nm excimer lamp for treating vitiligo: A randomized controlled trial.

BACKGROUND: In previous studies, the 308-nm light-emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308-nm LED and 308-nm excimer lamp (308-nm MEL) for the treatment of vitiligo are lacking. OBJECTIVE: To compare the efficacy of the 308-nm LED and 308-nm MEL for treating nonsegmental stable vitiligo. PATIENTS AND METHODS: This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308-nm LED or the 308-nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented. RESULTS: In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308-nm LED group, and 138 lesions were included in the 308-nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308-nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308-nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p = .968). The incidence of adverse effects with the two phototherapy devices was comparable (p = .522). CONCLUSIONS: Treatment of vitiligo with the 308-nm LED had a similar efficacy rate to the 308-nm MEL, and the incidence of adverse effects was comparable between the two devices.

E93 is indispensable for reproduction in ametabolous and hemimetabolous insects.

Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.

EZH2 Promotes Multiple Myeloma Progression via STAT3 Pathway Activation.

BACKGROUND: Multiple myeloma (MM) is a malignant disorder of plasma cells in the bone marrow. MM causes the clonal proliferation of terminally differentiated plasma cells and the accumulation of monoclonal plasma cells. The enhancer of zeste homolog 2 (EZH2) has been proven to play a significant role in disease development and could act on the signal transducers and activators of the transcription 3 (STAT3) signaling pathway. This pathway contributes to the pathogenesis and maintenance of malignancies. This study aimed to explore the effect of EZH2 on MM progression and the role of the STAT3 pathway in this process. The goal was to increase knowledge and provide further insights about the pathogenesis of MM and identify novel targets for potential therapies. METHODS: The abnormal expression of EZH2 in MM cell lines was tested through real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot analysis. Based on the MM cell line H929, transfection was used to modify EZH2 expression, followed by the subsequent evaluation of induced alteration in STAT3 activation. The STAT3 phosphorylation activator colivelin and inhibitor stattic were used for promoting and inhibiting the STAT3 activation, respectively. Colony-forming assay, transwell migration assay, and flow cytometry were used to explore cell proliferation, cell migration, and cell apoptosis, respectively. RESULTS: Both the EZH2 mRNA and protein were over-expressed in multiple MM cell lines including H929 (p < 0.001), U266 (p < 0.01), RPMI-8226 (p < 0.01) and MM.1S (p < 0.001). Increased EZH2 promoted cell proliferation (p < 0.001) and migration (p < 0.001) and simultaneously inhibited cell apoptosis (p < 0.001), which could be reversed by inhibited STAT3 activation (p < 0.001). In contrast, promoted STAT3 activation increased cell proliferation (p < 0.001) and migration (p < 0.001), while simultaneously inhibiting cell apoptosis (p < 0.001), despite decreased EZH2 expression. CONCLUSIONS: The effect of EZH2 and STAT3 pathways on MM regulation was revealed and verified. EZH2 promoted the progression of MM cells by activating the STAT3 pathway. The EZH2 and STAT3 pathways could be potential targets for effective MM treatment.

Ben-JNK signaling is required for host mortality during Periplaneta fuliginosa densovirus infection.

BACKGROUND: Cockroaches are widely acknowledged as significant vectors of pathogenic microorganisms. The Periplaneta fuliginosa densovirus (PfDNV) infects the smoky-brown cockroach P. fuliginosa and causes host mortality, which identifies the PfDNV as a species-specific and environmentally friendly biopesticide. However, although the biochemical characterization of PfDNV has been extensively studied, the immune response against PfDNV remains largely unclear. RESULTS: Here, we investigated the replication of PfDNV and its associated pathological phenotype in the foregut and hindgut. Consequently, we dissected and performed transcriptome sequencing on the foregut, midgut, and hindgut separately. We revealed the up-regulation of immune response signaling pathway c-Jun N-terminal kinase (JNK) and apoptosis in response to viral infection. Furthermore, knockdown of the JNK upstream gene Ben resulted in a decrease in virus titer and delayed host mortality. CONCLUSION: Taken together, our findings provide evidence that the Ben-JNK signaling plays a crucial role in PfDNV infection, leading to excessive apoptosis in intestinal tissues and ultimately resulting in the death of the host. Our results indicated that the host response to PfDNV fosters viral infection, thereby increasing host lethality. This underscores the potential of PfDNV as a viable, environmentally friendly biopesticide. © 2024 Society of Chemical Industry.

Dorsal dentate gyrus mediated enriched environment-induced anxiolytic and antidepressant effects in cortical infarcted mice.

Anxiety and depression are the most common mental health disorders worldwide, each affecting around 30% stroke survivors. These complications not only affect the functional recovery and quality of life in stroke patients, but also are distressing for caregivers. However, effective treatments are still lacking. Enriched environment (EE), characterized with novel and multi-dimensional stimulation, has been reported to exert therapeutic effects on physical and cognitive function. In addition, EE also had potential positive effects on emotional disorders after ischemic stroke; however, the underling mechanisms have not been well elucidated. This study aimed to explore the effectiveness of EE on emotional disorders after cerebral ischemia and its underling mechanism. Sensorimotor cortical infarction was induced by photothrombosis with stable infarct location and volume, resulting in motor dysfunction, anxiety and depression-like behaviors in mice, with decreased ALFF and ReHo values and decreased c-fos expression in the infarction area and adjacent regions. Seven days' EE treatment significantly improved motor function of contralateral forelimb and exhibited anxiolytic and antidepressant effects in infarcted mice. Compared to the mice housing in a standard environment, those subjected to acute EE stimulation had significantly increased ALFF and ReHo values in the bilateral somatosensory cortex (S1, S2), dorsal dentate gyrus (dDG), dorsal CA1 of hippocampus (dCA1), lateral habenular nucleus (LHb), periaqueductal gray (PAG), ipsilateral primary motor cortex (M1), retrosplenial cortex (RSC), parietal association cortex (PtA), dorsal CA3 of hippocampus (dCA3), claustrum (Cl), ventral pallidum (VP), amygdala (Amy), and contralateral auditory cortex (Au). Some of, but not all, the ipsilateral brain regions mentioned above showed accompanying increases in c-fos expression with the most significant changes in the dDG. The number of FosB positive cells in the dDG, decreased in infarcted mice, was significantly increased after chronic EE treatment. Chemogenetic activation of dDG neurons reduced anxiety and depressive-like behaviors in infarcted mice, while neuronal inhibition resulted in void of the anxiolytic and antidepressant effects of EE. Altogether, these findings indicated that dDG neurons may mediate EE-triggered anxiolytic and antidepressant effects in cortical infarcted mice.