The ordered lattice host framework induced guest Li+ disordering in high performance cobalt-free Ni-rich cathode materials.

Recently, due to high price, resource shortage and unstable supply of cobalt, the development of low-cost cobalt-free Ni-rich cathodes has attracted extensive attention with the ever-increasing lithium-ion batteries (LIBs) industry. Selecting cost-effective elements to replace cobalt in Ni-rich cathodes is urgent. However, the principle of structural design of Ni-rich cathode remains unclear, hampering the selection of alternative elements. Herein, the cobalt-free cathodes of LiNi0.95Mg0.05O2 (NiMg) and LiNi0.95Mn0.05O2 (NiMn) are designed as alternatives to LiNi0.96Co0.04O2 (NiCo). NiMg has comparable cycle stability with NiCo, while NiMn has inferior cycle performance. Reverse Monte Carlo modelling was used to generate structural model and uncover local structure by fitting pair distribution function. It reveals Mn causes more severe Jahn-Teller distortions and disordered lattice host framework (Ni0.95M0.05O2, M = Co/Mn/Mg) than Co and Mg due to the strong size effect and coulomb interactions of Mn in Ni0.95Mn0.05O2 layer. The outstanding cycle stability of NiMg and NiCo originates from the ordered lattice host frameworks, which relieve stress and inhibit particle breakage during cycle. Meanwhile, the ordered lattice host framework induced guest Li+ disordering reduces Li+ diffusion energy barrier, improving the rate capability. This study provides a new perspective for the structural design of cobalt-free Ni-rich cathodes.

A large-scale comparison of the meat quality characteristics of different chicken breeds in South China.

Meat quality traits are essential for producing high-quality broilers, but the genetic improvement has been limited by the complexity of measurement methods and the numerous traits involved. To systematically understand the meat quality characteristics of different broiler breeds, this study collected data on slaughter performance, skin color, fat deposition, and meat quality traits of 434 broilers from 12 different breeds in South China. The results showed that there was no significant difference in the live weight and slaughter weight of various broiler breeds at their respective market ages. Commercial broiler breeds such as Xiaobai and Huangma chickens had higher breast muscle and leg muscle rates. The skin and abdominal fat of Huangma chickens cultivated in the consumer market in South China exhibited significantly higher levels of yellowness compared to other varieties. Concerning fat traits, we observed that Wenchang chickens exhibited a strong ability to fat deposition, while the younger breeds showed lower fat deposition. Additionally, there were significant positive correlations found among different traits, including traits related to weight, traits related to fat, and skin color of different parts. Hierarchical clustering analysis revealed that fast-growing and large broiler Xiaobai chickens formed a distinct cluster based on carcass characteristics, skin color, and meat quality traits. Principal component analysis (PCA) was used to extract multiple principal components as substitutes for complex meat quality indicators, establishing a chicken meat quality evaluation model to differentiate between different breeds of chickens. At the same time, we identified 46, 22, and 20 SNP loci and their adjacent genes that were significantly associated with muscle mass traits, fat deposition, and skin color through genome-wide association studies (GWAS). The above results are helpful for systematically understanding the differences and characteristics of meat quality traits among different breeds.

A study on construction of a prognosis model for liver cancer based on analgesic targets and screening therapeutic drugs.

BACKGROUND: Liver cancer is one of the most malignant liver diseases in the world, and the 5-year survival rate of such patients is low. Analgesics are often used to cure pain prevalent in liver cancer. The expression changes and clinical significance of the analgesic targets (ATs) in liver cancer have not been deeply understood. OBJECTIVE: The purpose of this study is to clarify the expression pattern of ATs gene in liver cancer and its clinical significance. Through the comprehensive analysis of transcriptome data and clinical parameters, the prognosis model related to ATs gene is established, and the drug information sensitive to ATs is mined. METHODS: The study primarily utilized transcriptomic data and clinical information from liver cancer patients sourced from The Cancer Genome Atlas (TCGA) database. These data were employed to analyze the expression of ATs, conduct survival analysis, gene set variation analysis (GSVA), immune cell infiltration analysis, establish a prognostic model, and perform other bioinformatic analyses. Additionally, data from liver cancer patients in the International Cancer Genome Consortium (ICGC) were utilized to validate the accuracy of the model. Furthermore, the impact of analgesics on key genes in the prognostic model was assessed using data from the Comparative Toxicogenomics Database (CTD). RESULTS: The study investigated the differential expression of 58 ATs genes in liver cancer compared to normal tissues. Patients were stratified based on ATs expression, revealing varied survival outcomes. Functional enrichment analysis highlighted distinctions in spindle organization, centrosome, and spindle microtubule functions. Prognostic modeling identified low TP53 expression as protective, while elevated CCNA2, NEU1, and HTR2C levels posed risks. Commonly used analgesics, including acetaminophen and others, were found to influence the expression of these genes. These findings provide insights into potential therapeutic strategies for liver cancer and shed light on the molecular mechanisms underlying its progression. CONCLUSIONS: The collective analysis of gene signatures associated with ATs suggests their potential as prognostic predictors in hepatocellular carcinoma patients. These findings not only offer insights into cancer therapy but also provide novel avenues for the development of indications for analgesics.

Self-evolutionary recycling of flame-retardant polyurethane foam enabled by controllable catalytic cleavage.

Polyurethane (PU) foams, pivotal in modern life, face challenges suh as fire hazards and environmental waste burdens. The current reliance of PU on potentially ecotoxic halogen-/phosphorus-based flame retardants impedes large-scale material recycling. Here, our demonstrated controllable catalytic cracking strategy, using cesium salts, enables self-evolving recycling of flame-retardant PU. The incorporation of cesium citrates facilitates efficient urethane bond cleavage at low temperatures (160 °C), promoting effective recycling, while encouraging pyrolytic rearrangement of isocyanates into char at high temperatures (300 °C) for enhanced PU fire safety. Even in the absence of halogen/phosphorus components, this foam exhibits a substantial increase in ignition time (+258.8%) and a significant reduction in total smoke release (-79%). This flame-retardant foam can be easily recycled into high-quality polyol under mild conditions, 60 °C lower than that for the pure foam. Notably, the trace amounts of cesium gathered in recycled polyols stimulate the regenerated PU to undergo self-evolution, improving both flame-retardancy and mechanical properties. Our controllable catalytic cracking strategy paves the way for the self-evolutionary recycling of high-performance firefighting materials.

Health-related quality of life and influencing factors of patients with paroxysmal nocturnal hemoglobinuria in China.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients' health-related quality of life (HRQOL). Limited research has been conducted to evaluate the HRQOL of Chinese patients with PNH. Understanding the HRQOL in this specific population is crucial for providing effective healthcare interventions and improving patient' health outcomes. This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants. METHODS: A cross-sectional study was conducted during 2022 to recruit patients with PNH in China. The study population was recruited from PNH China, one of the largest public welfare PNH patient mutual aid organization in China. Data were collected via an online questionnaire including the EQ-5D-5L (5L), and social-demographic and clinical characteristics. Descriptive statistics were employed to summarize the characteristics of the participants and their HRQOL. Multiple linear and logistic regression analyses were adopted to explore key factors affecting HRQOL. RESULTS: A total of 329 valid questionnaires were collected. The mean (SD) age of the patients was 35.3 (10.0) years, with 52.3% of them being male. The patients reported more problems in Anxiety/Depression (81.5%) and Pain/Discomfort (69.9%) dimensions compared to the other three 5L dimensions. The mean (SD) of 5L health utility score (HUS) and EQ-VAS score were 0.76 (0.21) and 62.61 (19.20), respectively. According to multiple linear regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) and complication of thrombosis were significant influencing factors affecting 5L HUS. Total personal income of the past year, initial symptom of hemoglobinuria and complication of thrombosis were significantly influencing factors of VAS score. Social-demographic and clinical characteristics, such as gender, income, and thrombosis, were also found to be significantly related to certain 5L health problems as well. CONCLUSION: Our study manifested the HRQOL of PNH patients in China was markedly compromised, especially in two mental-health related dimensions, and revealed several socio-demographic and clinical factors of their HRQOL. These findings could be used as empirical evidence for enhancing the HRQOL of PNH patients in China.

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis.

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.

Genetic characteristics and selection signatures between Southern Chinese local and commercial chickens.

The introduction of exotic breeds and the cultivation of new lines by breeding companies have posed challenges to native chickens in South China, including loss of breed characteristics, decreased genetic diversity, and declining purity. Understanding the population genetic structure and genetic diversity of native chickens in South China is crucial for further advancements in breeding efforts. In this study, we analyzed the population genetic structure and genetic diversity of 321 individuals from 10 different breeds in South China. By comparing commercial chickens with native ones, we identified selection signatures occurring between local chickens and commercial breeds. The analysis of population genetic structure revealed that the native chicken populations in South China exhibited a considerable level of genetic diversity. Moreover, the commercial lines of Xiaobai chicken and Huangma chicken displayed even higher levels of genetic diversity, which distinguished them from other native varieties at the clustering level. However, certain individuals within these commercial varieties showed a discernible genetic relationship with the native populations. Notably, both commercial varieties also retained a significant degree of genetic similarity to their respective native counterparts. In order to investigate the genomic changes occurring during the commercialization of native chickens, we employed 4 methods (Fst, ROD, XPCLR, and XPEHH) to identify potential candidate regions displaying selective signatures in Southern Chinese native chicken population. A total of 168 (identified by Fst and ROD) and 86 (identified by XPCLR and XPEHH) overlapping genes were discovered. Functional annotation analysis revealed that these genes may be associated with reproduction and growth (SAMSN1, HYLS1, ROBO3, FGF14, PRSS23), musculoskeletal development (DNER, MYBPC1, DGKB, ORC1, KLF10), disease resistance and environmental adaptability (PUS3, CRB2, CALD1, USP15, SGCD, LTBP1), as well as egg production (ADGRB3, ACSF3). Overall, native chickens in South China harbor numerous selective sweep regions compared to commercial chickens, enriching valuable genomic resources for future genetic research and breeding conservation.

Gas chromatography-ion mobility spectrometry (GC-IMS) technique and its recent applications in grain research.

Grains are the primary source of food for most people worldwide and constitute a major source of carbohydrates. Many novel technologies are being employed to ensure the safety and reliability of grain supply and production. Gas chromatography-ion mobility spectrometry (GC-IMS) can effectively separate and sensitively detect volatile organic compounds. It possesses advantages such as speed, convenience, high sensitivity, no pretreatment, and wide applicability. In recent years, many studies have shown that the application of GC-IMS technology for grain flavor analysis can play a crucial role in grains. This article elucidates the working principle of GC-IMS technology, reviews the application of GC-IMS in grains in the past 5 years. GC-IMS technology is mainly applied in four aspects in grains. In grain classification, it distinguishes varieties, quality, origin, production year, and processing methods based on the trace differences in volatile organic compounds, thereby fulfilling various grain classification requirements such as origin tracing, geographical indication product recognition, variety identification, production year identification, and detection of counterfeit and inferior grain samples. In optimizing the processing technology of grains and their products, it can improve food flavor, reduce undesirable flavors, and identify better processing parameters. In grain storage, it can determine the storage time, detect spoilage phenomena such as mold and discoloration during storage, eliminate pests affecting storage, and predict the vitality of seeds after storage. In aroma evaluation of grains and their processed products, it can assess the impact of new raw materials, new technologies, fermentation processes, and even oral processing on the quality of grain products. This article also summarizes the characteristics of GC-IMS technology, compiles typical grain flavor compounds, and provides prospects for the future application of GC-IMS. © 2024 Society of Chemical Industry.

Cannabinoid receptor 2 selective agonist alleviates systemic sclerosis by inhibiting Th2 differentiation through JAK/SOCS3 signaling.

Systemic sclerosis (SSc) poses a significant challenge in autoimmunology, characterized by the development of debilitating fibrosis of skin and internal organs. The pivotal role of dysregulated T cells, notably the skewed polarization toward Th2 cells, has been implicated in the vascular damage and progressive fibrosis observed in SSc. In this study, we explored the underlying mechanisms by which cannabinoid receptor 2 (CB2) highly selective agonist HU-308 restores the imbalance of T cells to alleviate SSc. Using a bleomycin-induced SSc (BLM-SSc) mouse model, we demonstrated that HU-308 effectively attenuates skin and lung fibrosis by specifically activating CB2 on CD4+ T cells to inhibit the polarization of Th2 cells in BLM-SSc mice, which was validated by Cnr2-specific-deficient mice. Different from classical signaling downstream of G protein-coupled receptors (GPCRs), HU-308 facilitates the expression of SOCS3 protein and subsequently impedes the IL2/STAT5 signaling pathway during Th2 differentiation. The deficiency of SOCS3 partially mitigated the impact of HU-308. Analysis of a cohort comprising 80 SSc patients and 82 healthy controls revealed an abnormal elevation in the Th2/Th1 ratio in SSc patients. The proportion of Th2 cells showed a significant positive correlation with mRSS score and positivity of anti-Scl-70. Administration of HU-308 to PBMCs and peripheral CD4+ T cells from SSc patients led to the upregulation of SOCS3, which effectively suppressed the aberrantly activated STAT5 signaling pathway and the proportion of CD4+IL4+ T cells. In conclusion, our findings unveil a novel mechanism by which the CB2 agonist HU-308 ameliorates fibrosis in SSc by targeting and reducing Th2 responses. These insights provide a foundation for future therapeutic approaches in SSc by modulating Th2 responses.

Advances in research on renal injury in paroxysmal nocturnal.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease. Clinical manifestations include intravascular hemolysis, renal dysfunction, fatigue, jaundice, pulmonary hypertension, and so on. Renal injury, as a clinical feature of PNH, is difficult to diagnose and is one of the causes of death in patients with PNH. This article reviews the progress in research on PNH combined with renal injury,to improve clinicians' understanding of renal injury in PNH patients, define and judge staging in a timely and accurate manner, enable patients to receive timely and appropriate treatment, and reduce mortality.

SOX9 promotes stemness in the CAL27 cell line of tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is a prevalent form of oral malignancy, with increasing incidence. Unfortunately, the 5-year survival rate for patients has not exceeded 50%. Studies have shown that sex-determining region Y box 9 (SOX9) correlates with malignancy and tumor stemness in a variety of tumors. To investigate the role of SOX9 in TSCC stemness, we analyzed its influence on various aspects of tumor biology, including cell proliferation, migration, invasion, sphere and clone formation, and drug resistance in TSCC. Our data suggest a close association between SOX9 expression and both the stemness phenotype and drug resistance in TSCC. Immunohistochemical experiments revealed a progressive increase of SOX9 expression in normal oral mucosa, paracancerous tissues, and tongue squamous carcinoma tissues. Furthermore, the expression of SOX9 was closely linked to the TNM stage, but not to lymph node metastasis or tumor diameter. SOX9 is a crucial gene in TSCC responsible for promoting the stemness function of cancer stem cells. Developing drugs that target SOX9 is extremely important in clinical settings.

Flash healing of laser-induced graphene.

The advancement of laser-induced graphene (LIG) technology has streamlined the fabrications of flexible graphene devices. However, the ultrafast kinetics triggered by laser irradiation generates intrinsic amorphous characteristics, leading to high resistivity and compromised performance in electronic devices. Healing graphene defects in specific patterns is technologically challenging by conventional methods. Herein, we report the rapid rectification of LIG's topological defects by flash Joule heating in milliseconds (referred to as F-LIG), whilst preserving its overall structure and porosity. The F-LIG exhibits a decreased ID/IG ratio from 0.84 - 0.33 and increased crystalline domain from Raman analysis, coupled with a 5-fold surge in conductivity. Pair distribution function and atomic-resolution imaging delineate a broader-range order of F-LIG with a shorter C-C bond of 1.425 Å. The improved crystallinity and conductivity of F-LIG with excellent flexibility enables its utilization in high-performance soft electronics and low-voltage disinfections. Notably, our F-LIG/polydimethylsiloxane strain sensor exhibits a gauge factor of 129.3 within 10% strain, which outperforms pristine LIG by 800%, showcasing significant potential for human-machine interfaces.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Improved empirical mode decomposition method based on amplitude-frequency characteristic of vortex signals.

The vortex flowmeter occupies a vital position in flow measurement with its unique advantages. It is essentially a fluid vibration instrument, and its measurement process is susceptible to interference, which seriously affects measurement accuracy. In particular, at low flow rates, it is an urgent problem to extract vortex signals from the complex noise. Among many signal processing methods, Empirical Mode Decomposition (EMD) is a time-frequency analysis method suitable for nonlinear, non-stationary signals. EMD can adaptively decompose noisy signals into noise and useful signal components arranged from high frequency to low frequency. For the above problems, an innovative, improved EMD method is proposed in this paper. The digital filter is designed according to the amplitude-frequency characteristic of vortex signals. After filtering, the vortex signal is adjusted to a fixed value, and high-frequency noise is filtered. According to the consistency of the filtered signal's amplitude, we design a decomposition stop criterion for EMD to process the output signal of the vortex sensor. This method not only maintains the characteristic of adaptive decomposition in EMD but also completes the automatic extraction of the vortex signal under complex noise. It provides a new comprehensive method for realizing high-precision and anti-interference vortex flowmeters.

Quercetin attenuates lipopolysaccharide-induced hepatic inflammation by modulating autophagy and necroptosis.

Lipopolysaccharide (LPS) from Gram-negative bacteria initially induces liver inflammation with proinflammatory cytokines expressions. However, the underlying hepatoprotective mechanism of quercetin on LPS-induced hepatic inflammation remains unclear. Specific pathogen-free chicken embryos (n = 120) were allocated control vehicle, PBS with or without ethanol vehicle, LPS (125 ng/egg) with or without quercetin treatment (10, 20, or 40 nmol/egg, respectively), quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated abovementioned solutions via the allantoic cavity. At embryonic d 19, the livers of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, and immunohistochemistry investigation. We found that the liver presented inflammatory response (heterophils infiltration) after LPS induction. The LPS-induced mRNA expressions of inflammation-related factors (TLR4, TNFα, IL-1ß, IL-10, IL-6, MYD88, NF-κB1, p38, and MMP3) were upregulated after LPS induction when compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. Quercetin significantly decreased the immunopositivity to TLR4 and MMP3 in the treatment group when compared with the LPS group. Quercetin could significantly downregulate the mRNA expressions of autophagy-related genes (ATG5, ATG7, Beclin-1, LC3A, and LC3B) and necroptosis-related genes (Fas, Bcl-2, Drp1, and RIPK1) after LPS induction. Quercetin significantly decreased the immunopositivity to LC3 in the treatment group when compared with the LPS group; meanwhile, quercetin significantly decreased the protein expressions of LC3-I, LC3-II, and the rate of LC3-II/LC3-I. In conclusions, quercetin can alleviate hepatic inflammation induced by LPS through modulating autophagy and necroptosis.

'Surviving and thriving': intersectional stigma and resilience of dual minority identities among Chinese gay and bisexual men living with HIV.

Intersectionality has facilitated an understanding of the complexities of the adversities and challenges faced by individuals with multiple disadvantaged identities, including gay and bisexual men living with HIV. This study used deficiency- and empowerment-based perspectives together with an intersectionality lens to examine the intersections between sexuality minority and HIV-related stigma and resilience, as well as their compound effects on Chinese gay and bisexual men living with HIV. We conducted in-depth interviews with 21 gay and bisexual men living with HIV in Shenzhen, identifying two overarching themes and six subthemes in the provided accounts via thematic analysis. The theme of 'Interplay between Minority Identities' comprised aggravating effects and alleviating effects at the intrapersonal, interpersonal, community and structural levels. The theme of 'Compound Impact of Intersecting Identities' was contributed to by the subthemes 'the pressure to continue family lineage', 'persistent health concerns', 'financial concerns', and 'heightened psychological distress and resilience'. Integrating deficiency and empowerment perspectives, our findings highlight the importance of addressing intersectional stigma and identifying resilience resources to empower Chinese gay and bisexual men living with HIV to thrive amidst compounded adversities. Findings have implications for future intersectional research and intervention practice, especially in fostering resilience within the context of intersectional stigma.

OMA1 competitively binds to HSPA9 to promote mitophagy and activate the cGAS-STING pathway to mediate GBM immune escape.

BACKGROUND: Immunotherapy with checkpoint inhibitors, especially those targeting programmed death receptor 1 (PD-1)/PD-1 ligand (PD-L1), is increasingly recognized as a highly promising therapeutic modality for malignancies. Nevertheless, the efficiency of immune checkpoint blockade therapy in treating glioblastoma (GBM) is constrained. Hence, it is imperative to expand our comprehension of the molecular mechanisms behind GBM immune escape (IE). METHODS: Protein chip analysis was performed to screen aberrantly expressed OMA1 protein in PD-1 inhibitor sensitive or resistant GBM. Herein, public databases and bioinformatics analysis were employed to investigate the OMA1 and PD-L1 relation. Then, this predicted relation was verified in primary GBM cell lines through distinct experimental methods. To investigate the molecular mechanism behind OMA1 in immunosuppression, a series of experimental methods were employed, including Western blotting, co-immunoprecipitation (Co-IP), mass spectrometry (MS), immunofluorescence, immunohistochemistry, and qRT-PCR. RESULTS: Our findings revealed that OMA1 competitively binds to HSPA9 to induce mitophagy and mediates the IE of GBM. Data from TCGA indicated a significant correlation between OMA1 and immunosuppression. OMA1 promoted PD-L1 levels in primary cells from patients with GBM. Next, the results of Co-IP and MS conducted on GBM primary cells revealed that OMA1 interacts with HSPA9 and induces mitophagy. OMA1 promoted not only cGAS-STING activity by increasing mitochondrial DNA release but also PD-L1 transcription by activating cGAS-STING. Eventually, OMA1 has been found to induce immune evasion in GBM through its regulation of PD-1 binding and PD-L1 mediated T cell cytotoxicity. CONCLUSIONS: The OMA1/HSPA9/cGAS/PD-L1 axis is elucidated in our study as a newly identified immune therapeutic target in GBM.

A new therapeutic perspective: Erastin inhibits tumor progression by driving ferroptosis in myelodysplastic syndromes.

Ferroptosis is a recently identified and evolutionarily conserved form of programmed cell death. This process is initiated by an imbalance in iron metabolism, leading to an overload of ferrous ions. These ions promote lipid peroxidation in the cell membrane through the Fenton reaction. As the cell's antioxidant defenses become overwhelmed, a fatal buildup of reactive oxygen species (ROS) occurs, resulting in the rupture of the plasma membrane. Ferroptosis is implicated in conditions such as ischemia-reperfusion injuries and a range of cancers. In our research, we explored ferroptosis in myelodysplastic syndromes (MDS) by measuring iron levels, transferrin receptor expression, and glutathione peroxidase 4 (GPX4) mRNA. Our findings revealed that MDS patients had significantly higher Fe2+ levels in CD33+ cells and increased transferrin receptor mRNA compared to healthy individuals. GPX4 expression was also higher in MDS but not statistically significant. To investigate potential treatments for myeloid hematological diseases through ferroptosis induction, we treated the myelodysplastic syndrome cell line (SKM-1) and two myeloid leukemia cell lines (KG-1 and K562) with erastin, an iron transfer inducer. We observed that erastin treatment led to glutathione depletion, reduced GPX4 activity, and increased ROS, culminating in cell death by ferroptosis. Furthermore, combining erastin with azacitidine demonstrated a synergistic effect on MDS and leukemia cell lines, suggesting a promising approach for treating these hematological conditions with this drug combination. Our experiments confirm erastin's ability to induce ferroptosis in MDS and highlight its potential synergistic use with azacitidine for treatment.

Stress responses and Physiological Changes of Salmonella enterica Serovar Enteritidis on Short-Term and Long-Term Benzalkonium Bromide Adaptation.

Salmonella enterica is a common foodborne pathogen that poses significant safety risks across the world. And benzalkonium bromide (BK) is widely used as a disinfectant to sterilize the food processing equipment. It has been reported that sub-lethal concentration of disinfectants induced not only the homologous resistance but also cross-resistances. This work analyzed the induced resistances of Salmonella Enteritidis by short-term adaptation (STA) and long-term adaptation (LTA) to BK. We have demonstrated that inefficient sterilization exposes Salmonella Enteritidis to sub-lethal concentrations of BK, and adapts bacteria to a higher minimum inhibitory concentration and minimum bactericidal concentration. In addition, STA, but not LTA, to BK induced heterogeneous resistance to sodium hypochlorite, and cross-resistance to freezing, desiccation, and heating, which may be caused by the membrane composition change of Salmonella Enteritidis. This work could be useful to the optimization of cleaning protocol.

Lactic acid bacteria modulate the CncC pathway to enhance resistance to ß-cypermethrin in the oriental fruit fly.

The gut microbiota of insects has been shown to regulate host detoxification enzymes. However, the potential regulatory mechanisms involved remain unknown. Here, we report that gut bacteria increase insecticide resistance by activating the cap "n" collar isoform-C (CncC) pathway through enzymatically generated reactive oxygen species (ROS) in Bactrocera dorsalis. We demonstrated that Enterococcus casseliflavus and Lactococcus lactis, two lactic acid-producing bacteria, increase the resistance of B. dorsalis to ß-cypermethrin by regulating cytochrome P450 (P450) enzymes and α-glutathione S-transferase (GST) activities. These gut symbionts also induced the expression of CncC and muscle aponeurosis fibromatosis. BdCncC knockdown led to a decrease in resistance caused by gut bacteria. Ingestion of the ROS scavenger vitamin C in resistant strain affected the expression of BdCncC/BdKeap1/BdMafK, resulting in reduced P450 and GST activity. Furthermore, feeding with E. casseliflavus or L. lactis showed that BdNOX5 increased ROS production, and BdNOX5 knockdown affected the expression of the BdCncC/BdMafK pathway and detoxification genes. Moreover, lactic acid feeding activated the ROS-associated regulation of P450 and GST activity. Collectively, our findings indicate that symbiotic gut bacteria modulate intestinal detoxification pathways by affecting physiological biochemistry, thus providing new insights into the involvement of insect gut microbes in the development of insecticide resistance.