Analysis of PD-1/PD-L1 variations in lung cancer and association with immunotherapeutic efficacy and prognosis: A nonrandomized controlled trial.

INTRODUCTION: This study aims to explore Programmed Death Receptor-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) variations in Lung Cancer (LC) tissues and Peripheral Blood (PPB) and their association with immunotherapy efficacy and prognosis. METHOD: 72 patients with LC were included in the LC group and 39 patients with concurrent benign lung disease were included in the benign group. PD-1/PDL-1 was compared in PPB and lung tissue. All LC patients were treated with immunotherapy. The relationship between PD-1/PDL-1 in LC tissue and PPB and immunotherapy efficacy was analyzed. Patients were divided into death and survival groups, and PD-1/PDL-1 in tumor tissues and PPB were compared. RESULTS: The authors found that PD-1 and PDL-1 positive expression in lung tissue and PPB in LC patients was elevated. Combined detection of PD-1 and PDL-1 was effective in diagnosing LC and evaluating the prognosis of LC patients. PD-1 and PDL-1 positive expression was reduced after disease remission while elevated in dead patients. The 3-year survival rate of patients with PD-1 positive expression was 45.45 % (25/55), which was lower (82.35 %, 14/17) than those with PD-1 negative expression. The 3-year survival rate of patients with positive and negative expression of PDL-1 was 48.78 % (20/41) and 61.29 % (19/31), respectively. DISCUSSION: The present results demonstrated that PD-1 and PDL-1 are abnormal in cancer tissue and PPB of LC patients. The combined detection of PD-1 and PDL-1 has diagnostic value for LC and evaluation value for the efficacy and prognosis of immunotherapy.

Silymarin effectively prevents and treats Eimeria tenella infection in chicks.

Silymarin, a botanical medicine derived from milk thistle seeds and is known to improve chicken growth and gut health when added to the feed. However, its role in the prevention and treatment of chicken coccidiosis remains unclear. This study investigated the efficacy of various doses of silymarin in preventing and treating Eimeria tenella infection in chicks. A total of 180 one-day-old specific pathogen-free chicks were randomized into six groups of 30 chicks each, no treatment (NC group); E. tenella infection (CC group); diclazuril medication during d 14 to 21 and E. tenella infection (DC group); and three groups infected with E. tenella and administered low, medium, or high doses of silymarin during d 12 to 21. All groups except NC were infected with E. tenella on d 14, with indicators observed on d 21. The growth performance was higher in the silymarin treated groups than that in the CC group, and the oocyst count per gram of manure, blood stool, and cecal lesion scores decreased. The medium-dose silymarin group exhibited the best treatment effect. Additionally, the silymarin groups displayed improved histological, morphology, and intestinal barrier integrity. The amounts of proinflammatory factors and harmful bacteria in the cecum were also reduced. Additionally, the activity of serum and cecal antioxidant enzymes, as well as the abundance of beneficial gut microbiota, increased in the cecum. In conclusion, this study demonstrated that silymarin can prevent and treat E. tenella infections. These data provide a scientific and conceptual basis for the development of a botanical dietary supplement from silymarin for the treatment and control of coccidiosis in chicks.

Enhanced antibacterial and corrosion resistance of copper-containing 2205 duplex stainless steel against the corrosive bacterium Shewanella algae.

2205 DSS is an excellent corrosion-resistant engineering metal material, but it is still threatened by microbiological corrosion. The addition of copper elements is a new approach to improving the resistance of 2205 DSS to microbiological corrosion. In this study, 2205-Cu DSS was compared with 2205 DSS to study its antimicrobial properties and resistance to microbiological corrosion in the presence of the electroactive bacterium Shewanella algae. The results showed that compared to 2205 DSS, the biofilm thickness and the number of live bacteria on the surface of 2205-Cu DSS were significantly reduced, demonstrating excellent antimicrobial properties against S. algae. Electrochemical tests and surface morphology characterization results showed that the corrosion rate and pitting of 2205-Cu DSS by S. algae were lower than that of 2205 DSS, indicating better resistance to microbiological corrosion. The good antimicrobial properties and resistance to microbiological corrosion exhibited by 2205-Cu DSS are attributed to the contact antimicrobial properties of copper elements in the 2205-Cu DSS matrix and the release of copper ions for antimicrobial effects. This study provides a new strategy for combating microbiological corrosion.

Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines.

The application of sulfinamides has been witnessed in medicinal and agrochemistry with employment in asymmetric transformations. However, methods for their asymmetric catalytic synthesis have rarely been explored. Herein, the catalytic enantioselective addition of aryl boroxines to sulfinylamines via Cu catalyst and the newly developed Xuphos ligand were reported. A series of chiral aryl sulfinamides can be readily accessed in one step. This protocol enables the stereospecific transformation of sulfinamides to sulfonimidoyl fluorides, sulfonimidamides, and sulfonimidate esters. DFT calculations have revealed the reaction pathway, and the migratory insertion is the enantio-determining step. The noncovalent interaction between the oxygen atom of sulfinylamines and the C-H bonds in the ligand is crucial for enantioselectivity control.

Temperature-Modulated Evolution of Surface Structures Induces Significant Enhancement of Two-Photon Fluorescent Emission from a Dye Molecule.

Fluorescence is an essential property of molecules and materials that plays a pivotal role across various areas such as lighting, sensing, imaging, and other applications. For instance, temperature-sensitive fluorescence emission is widely utilized for chemo-/biosensing but usually decreases the intensity upon the increase in temperature. In this study, we observed a temperature-induced enhancement of up to ∼150 times in two-photon fluorescence (TPF) emission from a dye molecule, 4-(4-diethylaminostyry)-1-methylpyridinium iodide (D289), as it interacted with binary complex vesicles composed of two commonly applied surfactants: sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB). By employing second harmonic generation (SHG) and TPF techniques, we clearly revealed the temperature-dependent kinetic behavior of D289 on the surface of the vesicles and utilized it to interpret the origin of the significant TPF enhancement. Additionally, we also demonstrated a similar heating-induced enhancement of the TPF emission from D289 on the membrane of phospholipid vesicles, indicating the potential application of TPF in temperature sensing in the biology systems. The embedding of D289 in the tightly packed alkane chains was identified as the key factor in enhancing the TPF emission from D289. This finding may provide valuable information for synthesizing fluorescence materials with a high optical yield.

A new anti-CRISPR gene promotes the spread of drug-resistance plasmids in Klebsiella pneumoniae.

The Klebsiella pneumoniae (K. pneumoniae, Kp) populations carrying both resistance-encoding and virulence-encoding mobile genetic elements (MGEs) significantly threaten global health. In this study, we identified a new anti-CRISPR gene (acrIE10) on a conjugative plasmid with self-target sequence in K. pneumoniae with type I-E* CRISPR-Cas system. AcrIE10 interacts with the Cas7* subunit of K. pneumoniae I-E* CRISPR-Cas system. The crystal structure of the AcrIE10-KpCas7* complex suggests that AcrIE10 suppresses the I-E* CRISPR-Cas by binding directly to Cas7 to prevent its hexamerization, thereby preventing the surveillance complex assembly and crRNA loading. Bioinformatic and functional analyses revealed that AcrIE10 is functionally widespread across diverse species. Our study reports a novel anti-CRISPR and highlights its potential role in spreading resistance and virulence among pathogens.

Hierarchically porous MOF@COF structures with ultrafast gas diffusion rate for C2H6/C2H4 separation.

For ethylene purification, C2H6-selective metal-organic frameworks (MOFs) show great potential to directly produce polymer-grade C2H4 from C2H6/C2H4 mixtures. Most C2H6-traping MOFs are ultra-microporous structures so as to strengthen multiple supramolecular interactions with C2H6. However, the narrowed pore channels of C2H6-traping MOFs cause large guest diffusion barriers, greatly hampering their practical applications. Herein, we present a feasible strategy by precisely constructing hierarchically porous MOF@COF core-shell structures to address this issue. Additional mesoporous diffusion channels were incorporated between MOF crystals through the construction of the COF shell, thereby enhancing the gas adsorption kinetics. Notably, designing a core-shell MOF@COF structure with an optimal coating amount of mesoporous COF shell will further improve the gas diffusion rate. Breakthrough experiments reveal that the tailored MOF@COF composites can effectively achieve C2H6/C2H4 separation and maintain its separation performance over five continuous measurement cycles. This investigation opens up a new avenue to solve the diffusion/transfer issues and provides more opportunities and potentials for MOF@COF composites in practical separation applications.

Polydopamine-modified konjac glucomannan scaffold with sustained release of vascular endothelial growth factor to promote angiogenesis.

The fabrication of scaffolds capable of the sustained release of the vascular endothelial growth factor (VEGF) to promote angiogenesis for a long time remains a challenge in tissue engineering. Here, we report a facile approach for effectively fabricating a bioactive scaffold that gradually releases VEGF to promote angiogenesis. The scaffold was fabricated by coating polydopamine (PDA) on a konjac glucomannan (KGM) scaffold, followed by the surface immobilization of VEGF with PDA. The resulting VEGF-PDA/KGM scaffold, with a porous and interconnected microstructure (392 µm pore size with 84.80 porosity), combined the features of long-term biodegradability (10 weeks with 51 % degradation rate), excellent biocompatibility, and sustained VEGF release for up to 21 days. The bioactive VEGF-PDA/KGM scaffold exhibited multiple angiogenic activities over time, as confirmed by in vivo and in vitro experiments. For example, the scaffold significantly promoted the attachment and proliferation of human umbilical vein endothelial cells and the formation of vascular tubes in vitro. Moreover, the in vivo results demonstrated the formation and maturation of blood vessels after subcutaneous implantation in rats for four weeks. This promising strategy is a feasible approach for producing bioactive materials that can induce angiogenesis in vivo. These findings provide a new avenue for designing and fabricating biocompatible and long-term biodegradable scaffolds for sustained VEGF release to facilitate angiogenesis.

Multicenter Investigation of Drug-Resistance in Burkholderia Cepacia Bloodstream Infections in Hebei Province, China, from 2016 to 2021.

Objective: To compare the epidemiological characteristics and drug resistance of Burkholderia cepacia isolated from blood cultures, and to provide data support and a scientific basis for the clinical treatment and detection of hospital infections. Methods: The Hebei Province Antimicrobial Surveillance Network received 349 B. cepacia strains isolated from blood cultures reported by 83 hospitals, from 2016 to 2021. These strains were identified by MALDI-TOF MS and, the antibiotic sensitivity tests were carried out using the VITEK 2 COMPACT system. The 2023 Institute of Clinical and Laboratory Standardization drug-susceptibility breakpoints were used for drug susceptibility testing and the data were analyzed using WHONET5.6 software. Results: A total of 349 B. cepacia strains were isolated from 2016 to 2021, including 68 strains from secondary hospitals and 281 strains from tertiary hospitals. The ratios of male: female patients with B. cepacia bloodstream infections in all hospitals, secondary hospitals, and tertiary hospitals were 1.49:1 (209/140), 2.09:1 (46/22), and 1.38:1 (163/118), respectively. Most B. cepacia strains were isolated in intensive care units (ICUs), followed by internal medicine departments, accounting for 49.57% (173/349) and 22.92% (80/349), respectively. Regarding the age distribution, most patients were elderly (>65 years, 57.59%, 201/349), with numbers of patients gradually declining with decreasing of age. The resistance rates for levofloxacin, ceftazidime, and sulfamethoxazole decreased over the 6-year period (P<0.05), while there were no significant changes in the resistance rates for meropenem, chloramphenicol, and minocycline (P>0.05). There was no significant difference in drug-resistance rates between secondary and tertiary hospitals (P>0.05). Conclusion: Attention should be paid to bloodstream infections caused by B. cepacia, especially elderly patients and patients admitted to the ICU. The difficult treatment characteristics of B. cepacia bloodstream infections mean that laboratories and clinicians should pay careful attention to drug resistance to provide a basis for their prevention and empirical treatment.

Less interference fluorescence analytical strategy: Bridging substance-triggered ratiometric sensor with convenient preparation and application.

High interference and narrow application range are key of bottleneck of recent fluorescence analysis methods, which limit their wide application in the sensing field. Therefore, to overcome these disadvantages, a ratiometric fluorescence sensing system utilizing berberine (BER) and silver nanoclusters protected by dihydrolipoic acid (DHLA-AgNCs) was constructed for the first time in this work, to achieve determination of BER and daunorubicin (Dau). BER aqueous solution (non-planar conformation) has no fluorescence emission. When it was mixed with DHLA-AgNCs, the conformation of BER became planar, producing fluorescence emission at 515 nm besides the fluorescence emission peak of DHLA-AgNCs at 653 nm. With the increase of BER concentration added in system, the fluorescence intensity of BER (planar conformation) at 515 nm increased obviously and the fluorescence intensity of DHLA-AgNCs decreased slightly. Therefore, the dual emission fluorescence sensing system was constructed based on a fluorescence substance and non fluorescence substance, to achieve determination of BER. Meanwhile, based on the bridging effect of BER and fluorescence resonance energy transfer effect from Dau, the altering of two peaks intensity was utilized to achieve determination of Dau. Thus, this dual emission sensing system can not only be used for fluorescence analysis of BER and its analogues, but also based on the bridging effect of BER, allowing the determination of Dau and its analogues that could not be directly measured with silver nanoclusters, expanding the application range of traditional dual emission detection systems. Meanwhile, this system has strong anti-interference ability and low toxicity to the human body and less pollution to the sample and environment. This provides a new direction and universal research strategy for the construction of new fluorescence sensing systems in the future for the analysis of target substances that cannot be directly detected with conventional fluorescence analysis methods.

Lactobacillus acidophilus and Bacillus subtilis significantly change the growth performance, serum immunity and cecal microbiota of Cherry Valley ducks during the fattening period.

This study explored the effects of a Bacillus subtilis and Lactobacillus acidophilus mixture containing the co-fermented products of the two probiotics on growth performance, serum immunity and cecal microbiota of Cherry Valley ducks. This study included 480 one-day-old Cherry Valley ducks divided into four feeding groups: basal diet (control group) and basal diet supplemented with 300, 500, or 700 mg/kg of the probiotic powder; the ducks were raised for 42 days. Compared with the control group, body weight on day 42 and the average daily gain on days 15-42 significantly increased (p < 0.05), and the feed conversion rate significantly decreased (p < 0.05) in the experimental groups. Furthermore, the serum immunoglobulin (Ig) A, IgG, IgM, and interleukin (IL)-4 levels increased significantly (p < 0.05), and IL-1ß, IL-2, and tumor necrosis factor-α decreased significantly (p < 0.05) in the experimental groups. Finally, Sellimonas, Prevotellaceae NK3B31 group, Lachnospiraceae NK4A136 group and Butyricoccus played an important role in the cecal microbiota of the experimental group. Thus, the probiotic powder has impacts on the growth performance, serum immunity and cecal microbiota of Cherry Valley Ducks.

Establishment of an in vitro model of monocyte-like THP-1 cells for trained immunity induced by bacillus Calmette-Guérin.

BACKGROUND: Mycobacteria bloodstream infections are common in immunocompromised people and usually have disastrous consequences. As the primary phagocytes in the bloodstream, monocytes and neutrophils play critical roles in the fight against bloodstream mycobacteria infections. In contrast to macrophages, the responses of monocytes infected with the mycobacteria have been less investigated. RESULTS: In this study, we first established a protocol for infection of non-adherent monocyte-like THP-1 cells (i.e. without the differentiation induced by phorbol 12-myristate 13-acetate (PMA) by bacillus Calmette-Guérin (BCG). Via the protocol, we were then capable of exploring the global transcriptomic profiles of non-adherent THP-1 cells infected with BCG, and found that NF-κB, MAPK and PI3K-Akt signaling pathways were enhanced, as well as some inflammatory chemokine/cytokine genes (e.g. CCL4, CXCL10, TNF and IL-1ß) were up-regulated. Surprisingly, the Akt-HIF-mTOR signaling pathway was also activated, which induces trained immunity. In this in vitro infection model, increased cytokine responses to lipopolysaccharides (LPS) restimulation, higher cell viability, and decreased Candida albicans loads were observed. CONCLUSIONS: We have first characterized the transcriptomic profiles of BCG-infected non-adherent THP-1 cells, and first developed a trained immunity in vitro model of the cells.

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Development and Validation of a Nomogram for Prognosis Prediction in Patients with Synchronous Primary Thyroid and Breast Cancer Based on SEER Database.

This study aimed to develop prognostic prediction models for patients diagnosed with synchronous thyroid and breast cancer (TBC). Utilizing the SEER database, key predictive factors were identified, including T stage of thyroid cancer, T stage of breast cancer, M stage of breast cancer, patient age, thyroid cancer surgery type, and isotope therapy. A nomogram predicting 5-year and 10-year survival rates was constructed and validated, exhibiting strong performance (C-statistic: 0.79 in the development cohort (95% CI: 0.74-0.84), and 0.82 in the validation cohort (95% CI: 0.77-0.89)). The area under the Receiver Operator Characteristic (ROC) curve ranged from 0.798 to 0.883 for both cohorts. Calibration and decision curve analyses further affirmed the model's clinical utility. Stratifying patients into high-risk and low-risk groups using the nomogram revealed significant differences in survival rates (P < 0.0001). The successful development and validation of this nomogram for predicting 5-year and 10-year survival rates in patients with synchronous TBC hold promise for similar patient populations, contributing significantly to cancer research.

TGF-α/EGFR signaling promotes lipopolysaccharide-induced abnormal elastin deposition and alveolar simplification.

Bronchopulmonary dysplasia (BPD) is characterized by shortened secondary septa and fewer, larger alveoli. Elastin deposition to the distal tips of the secondary septa is critical for elongation of the secondary septa. Alveolar myofibroblasts, which are thought to migrate to the septal tips during alveolarization, are mainly responsible for elastin production and deposition. Antenatal exposure to inflammation induces abnormal elastin deposition, thereby increasing the risk of developing BPD. Here, we found that lipopolysaccharide (LPS) significantly increased the expression of transforming growth factor-α (TGF-α) in an LPS-induced rat model of BPD and in LPS-treated human pulmonary epithelial cells (BEAS-2B). In addition, in vitro experiments suggested that LPS upregulated TGF-α expression via toll-like receptor 4 (TLR4)/tumor necrosis factor α-converting enzyme (TACE) signaling. Increased TGF-α levels via its receptor epidermal growth factor receptor (EGFR)-induced lysyl oxidase (LOX) overactivation and cell division cycle 42 (Cdc42) activity inhibition of myofibroblasts. Similarly, in vivo LOX overactivation and inhibition of Cdc42 activity were observed in the lungs of LPS-exposed pups. LOX overactivation led to abnormal elastin deposition, and inhibition of Cdc42 activity disturbed the directional migration of myofibroblasts and disrupted elastin localization. Most importantly, the EGFR inhibitor erlotinib partially rescued LOX overactivation and Cdc42 activity inhibition, and improved elastin deposition and alveolar development in antenatal LPS-treated rats. Taken together, our data suggest that TGF-α/EGFR signaling is critically involved in the regulation of elastin deposition and represents a novel therapeutic target.

REGγ Mitigates Radiation-Induced Enteritis by Preserving Mucin Secretion and Sustaining Microbiome Homeostasis.

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.

NOTCH1 as a Negative Regulator of Avian Adipocyte Differentiation: Implications for Fat Deposition.

The NOTCH signaling pathway plays a pivotal role in diverse developmental processes, including cell proliferation and differentiation. In this study, we investigated whether this signaling molecules also contribute to avian adipogenesis. Using previous mRNA-seq datasets, we examined the expression of 11 signaling members during avian adipocyte differentiation. We found most members are down-regulated throughout differentiation (p < 0.05). As a representative, NOTCH1 was decreased in cultured chicken abdominal adipocytes during adipogenesis at mRNA and protein levels (p < 0.05). Moreover, using an overexpression plasmid for NOTCH1's intracellular domain (NICD1), as well as siRNA and DAPT to activate or deplete NOTCH1 in cells, we investigated the role of NOTCH1 in avian adipogenesis. Our findings illuminate that NOTCH1 activates the expression of HES1 and SOCS3 while it decreases NR2F2 and NUMB (p < 0.05), as well as inhibits oleic acid-induced adipocyte differentiation (p < 0.01). We further demonstrate that HES1, a downstream transcription factor activated by NOTCH1, also significantly inhibits adipogenesis by suppressing PPARγ and C/EBPα (p < 0.01). Collectively, these findings establish NOTCH1 as a negative regulator of avian adipocyte differentiation, unveiling NOTCH signaling as a potential target for regulating avian fat deposition.

Monitoring the response of a model protocell to dye and surfactant molecules through second harmonic generation and fluorescence imaging.

Probing the interaction between molecules and protocells is crucial for understanding the passive transport of functional molecules in and out of artificial and real cells. Second-harmonic generation (SHG) has been proven to be a powerful method for analyzing the adsorption and cross-membrane transport of molecules on lipid bilayers. In this study, we used SHG and two-photon fluorescence (TPF) imaging to study the interaction of charged dye molecules (D289) with a lipid vesicle. Unexpectedly, it was observed that the transport of D289 at a relatively high concentration is not as efficient as that at a lower dye concentration. Periodic shrinking of the model protocell and discharging of D289 out from the vesicle were revealed by combined analyses of SHG and TPF images. The response of the vesicle to a surfactant was also analyzed with D289 as a probe. This work demonstrates that the combined SHG and TPF imaging method is a unique approach that can provide detailed information on the interaction of molecules and lipids (both morphology and molecular kinetics). Determining these subtle interfacial kinetics in molecules is important for understanding the mechanism of many biophysical processes occurring on lipids.

Enhanced corrosion of 2205 duplex stainless steel by Acetobacter aceti through synergistic electron transfer and organic acids acceleration.

Acetobacter aceti is a microbe that produces corrosive organic acids, causing severe corrosion of industrial equipment. Previous studies have focused on the organic acid corrosion of A. aceti, but neglected the possibility that it has electron transfer corrosion. This study found that electron transfer and organic acids can synergistically promote the corrosion of 2205 duplex stainless steel (DSS). Electrochemical measurement results showed that corrosion of 2205 DSS was more severe in the presence of A. aceti. Surface analysis indicated a thick biofilm formed on the steel surface, with low pH and dissolved oxygen concentrations under the biofilm. Corrosion intensified when A. aceti lacked a carbon source, suggesting that A. aceti can corrode metals by using metallic substrates as electron donors, in addition to its acidic by-products.

m6A/HOXA10-AS/ITGA6 axis aggravates oxidative resistance and malignant progression of laryngeal squamous cell carcinoma through regulating Notch and Keap1/Nrf2 pathways.

As the second most prevalent malignant tumor of head and neck, laryngeal squamous cell carcinoma (LSCC) imposes a substantial health burden on patients worldwide. Within recent years, resistance to oxidative stress and N6-methyladenosine (m6A) of RNA have been proved to be significantly involved in tumorigenesis. In current study, we investigated the oncogenic role of m6A modified long non coding RNAs (lncRNAs), specifically HOXA10-AS, and its downstream signaling pathway in the regulation of oxidative resistance in LSCC. Bioinformatics analysis revealed that heightened expression of HOXA10-AS was associated with the poor prognosis in LSCC patients, and N (6)-Methyladenosine (m6A) methyltransferase-like 3 (METTL3) was identified as a factor in promoting m6A modification of HOXA10-AS and further intensify its RNA stability. Mechanistically, HOXA10-AS was found to play as a competitive endogenous RNA (ceRNA) by sequestering miR-29 b-3p and preventing its downregulation of Integrin subunit alpha 6 (ITGA6), ultimately enhancing the oxidative resistance of tumor cells and promoting the malignant progression of LSCC. Furthermore, our research elucidated the mechanism by which ITGA6 accelerates Keap1 proteasomal degradation via enhancing TRIM25 expression, leading to increased Nrf2 stability and exacerbating its aberrant activation. Additionally, we demonstrated that ITGA6 enhances γ-secretase-mediated Notch signaling activation, ultimately promoting RBPJ-induced TRIM25 transcription. The current study provides the evidence supporting the effect of m6A modified HOXA10-AS and its downstream miR-29 b-3p/ITGA6 axis on regulating oxidative resistance and malignant progression in LSCC through the Notch and Keap1/Nrf2 pathways, and proposed that targeting this axis holds promise as a potential therapeutic approach for treating LSCC.