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JOURNAL/nrgr/04.03/01300535-202507000-00026/figure1/v/2024-09-09T124005Z/r/image-tiff Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta. Ferroptosis, a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a vital role in the death of dopaminergic neurons. However, the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated. NADPH oxidase 4 is related to oxidative stress, however, whether it regulates dopaminergic neuronal ferroptosis remains unknown. The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis, and if so, by what mechanism. We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model. NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons. Moreover, NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals. Mechanistically, we found that NADPH oxidase 4 interacted with activated protein kinase C α to prevent ferroptosis of dopaminergic neurons. Furthermore, by lowering the astrocytic lipocalin-2 expression, NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation. These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation, which contribute to dopaminergic neuron death, suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

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Nucleotide signalling molecules - mainly cyclic 3',5'-adenosine phosphate (cAMP), bis-(3',5')-cyclic diguanosine monophosphate (c-di-GMP), and bis-(3',5')-cyclic diadenosine monophosphate (c-di-AMP) - contribute to the regulation of cellular pathways. Numerous recent works have focused on the involvement of these cyclic nucleotide phosphates (cNPs) in bacterial resistance and tolerance to antimicrobial treatment. Indeed, the rise of antimicrobial resistance (AMR) is a rising global threat to human health, while the rise of antimicrobial tolerance underlies the development of AMR and long-term infections, placing an additional burden on this problem. Here, we summarise the current understanding of cNP signalling in bacterial physiology with a focus on our understanding of how cNP signalling affects AMR and antimicrobial tolerance in different bacterial species. We also discuss additional cNP-related drug targets in bacterial pathogens that may have therapeutic potential.

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Photodynamic therapy (PDT) has attracted widespread attention from researchers as an emerging cancer treatment method. There have been many reports on various types of NIR-II photosensitizers for imaging and treatment of tumor sites. However, there are few reports on the development of NIR-II organic small molecule photosensitizers that have intelligent response to the tumor microenvironment, precise imaging, real-time treatment, and high biocompatibility. In this work, we developed a series of NIR-II photosensitizers (RBTs) with near-infrared excitation, good photostability, and large Stokes shift. Among them, RBT-Br exhibited higher reactive oxygen species (ROS) generation efficiency due to the introduction of halogen heavy atoms to enhance intersystem crossing (ISC). It is noteworthy that RBT-Br can generate singlet oxygen (1O2) and superoxide anion radicals (•O2-) simultaneously under 730 nm laser. Subsequently, we used molecular engineering technology to construct three pH-responsive NIR-II photosensitizers (RBT-pHs) by utilizing the closure of the lactam ring, among which RBT-pH-1 (pKa = 6.78) is able to be directionally activated under the stimulation of tumor micro-acid environment, with its fluorescence emission window reaching 933 nm. Subsequently, RBT-pH-1 NPs encapsulated in DSPE-mPEG5k were applied for PDT treatment of mouse tumors. The results showed that RBT-pH-1 NPs were activated by the acidic tumor microenvironment and generated ROS under laser excitation, exhibiting precise tumor imaging and significant tumor growth inhibition. We look forward to these multifunctional NIR-II organic small molecule photosensitizers providing a more efficient approach for clinical treatment of tumors. STATEMENT OF SIGNIFICANCE: : A reversible pH-switchable NIR-II nano-photosensitizer RBT-pH-1 NPs (pKa = 6.76) is developed for precise imaging and PDT therapy of mouse tumors, which can be effectively used for targeted enrichment and activation of tumor micro-acid environments. The results show that this NIR-II photosensitizer generates ROS through tumor micro-acid environment stimulation and laser triggering, showing precise tumor imaging guidance and significant tumor growth inhibition.

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Vascular endothelial injury is closely related to the progression of various cardio-cerebrovascular diseases. Whether Human Urinary Kallidinogenase (HUK) has a protective effect on endothelial injury remains unclear. This study established an in vivo model of rat common carotid artery intima injury and an in vitro model of human umbilical vein endothelial cell (HUVECs) injury induced by hydrogen peroxide (H2O2). To explore the protective effect and mechanism of HUK on endothelial injury. In vivo, HUK can reduce the hyperplasia and lumen stenosis of rat common carotid artery after intimal injury, and promote the fluorescence expression of vWF in the common carotid artery. HUK also activated the Nrf2/HO-1 signaling pathway in rat common carotid artery tissue to reduce endothelial damage. In vitro, HUK can inhibit the H2O2-induced decline in HUVECs activity, improve the migration ability of HUVECs induced by H2O2, inhibit the apoptosis and necrosis of HUVECs and the generation of ROS, and regulate the expression of VEGFA, ET-1 and eNOS proteins related to endothelial function in cells. The Nrf2/HO-1 signaling pathway is activated, and the HO-1 specific inhibitor zinc porphyrin (ZnPP) can partially reverse the protective effect of HUK on H2O2-induced HUVECs injury in terms of cell migration, necrosis and oxidative stress. The Nrf2/HO-1 signaling pathway plays an important role in the regulation of migration, necrosis and oxidative stress of HUVECs cells. HUK has a protective effect on vascular endothelial injury. HUK can inhibit oxidative stress and apoptotic necrosis by activating Nrf2/HO-1 signaling pathway.

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Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

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Birefringent crystal, which has the capacity to manipulate polarization light, holds an indispensable position in optics and optoelectronics, while it remains challenging to fulfill the modulation of birefringence. Here, we present wide spectral photo-pyroelectric effect in a silver-based hybrid pyroelectric, (N-CHM)Ag2I3 (N-CHM = N-cyclohexylmethylamine), serving as a feasible strategy to regulate birefringence through light stimuli. As the first silver-based hybrid pyroelectric, (N-CHM)Ag2I3 exhibits strong room-temperature photo-pyroelectricity with a large polarization of ~3.23 µC/cm2 and high voltage responsivity of ~0.96 m2/C across the UV-NIR spectral region. Strikingly, the photomodulation of its in-plane birefringence is established through pyroelectric effect, giving a saturation value of ~1.68×10-2 that is among the highest level achieved to date. This study on the birefringence photomodulation of lead-free hybrid pyroelectric is anticipated to boost future development of new smart optical and optoelectronic devices.

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The objective of this study was to evaluate the incidence, clinical features, and risk factors of generic tigecycline-associated hypofibrinogenemia. A single-center retrospective study was conducted in adult patients treated with generic tigecycline. Clinical data were extracted from the electronic medical records. The endpoint was tigecycline-related hypofibrinogenemia, defined as a condition with no abnormality in fibrinogen before tigecycline application, but developing hypofibrinogenemia upon prescription. The risk factors were determined by logistic regression analysis, and the ROC curve was subsequently established. A total of 240 adults prescribed generic tigecycline from May 1st to November 30th 2023 were included. It was shown that hypofibrinogenemia is a frequent side effect of generic tigecycline, with an adverse reaction rate of 42.9% (103/240). However, the incidence of adverse reactions to generic drugs was lower than in previous studies. The cumulative dose of tigecycline (OR:1.002, 95%CI 1.001-1.002, P < 0.001), baseline FIB (OR:0.995, 95%CI 0.992-0.997, P < 0.001), baseline PT (OR:1.247, 95%CI 1.071-1.452, P = 0.004) and baseline ALB (OR:0.931, 95%CI 0.879-0.986, P = 0.025) were identified as independent prognostic factors of tigecycline-related hypofibrinogenemia. We recommend intensive monitoring of coagulation function in patients exhibiting the aforementioned risk factors for generic tigecycline-associated hypofibrinogenemia to ensure patients safety.

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Concerns about food safety and environmental impact from chemical surfactants have prompted interest in natural lignocellulosic materials as alternatives. In this study, we combined hydrated deep eutectic solvent (DES) pretreatment with ultrasound treatment to prepare lignocellulosic nanofibrils (LCNF) from bamboo shoot shells with appropriate surface properties for stabilizing Pickering emulsions. The pretreatment intensity effectively modulated the surface characteristics of LCNF, achieving desirable wettability through lignin retention and in-situ esterification. The resulting LCNF/curcumin Pickering emulsion (CPE) demonstrated curcumin protection and pH-responsive color changes, while the ensuing CPE/PVA composite film exhibited ultraviolet shielding, mechanical strength, oxygen barrier, and antioxidant properties. Furthermore, the CPE/PVA film showed promise as a real-time indicator for monitoring shrimp freshness, maintaining sensitivity to spoilage even after six months of storage. These findings advance the advancement of green LCNF technologies, providing eco-friendly solutions for valorizing bamboo shoot shells and enhancing the application of LCNF in Pickering emulsions.

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Unmanned aerial vehicles (UAVs) equipped with a miniaturized sensor package were developed for aerial observations, which realizes aerial observations affordable to scientists in atmospheric science and achieves aerial measurements in high spatial resolution. UAVs are deployed to a variety of aerial detecting tasks in different scientific scenarios including chemical industry parks (CIPs) with hazardous gases emissions, and some places difficult for humans to reach. In this study, UAV sensing technology was deployed to detect air pollutants in a suburb, a CIP and a natural gas plant, respectively. The effects of atmospheric conditions such as the atmospheric boundary layer height, long-distance transport and atmospheric stability on the spatiotemporal variations of the air pollutants vertical profiles were investigated by the UAV. The UAV with the sensor package was deployed to capture the methane (CH4) leakages in a natural gas plant. The spatiotemporal variations of CH4 in both vertical and horizontal directions studied by UAV were employed to calculate accurate CH4 emissions, which is crucial to reducing the emissions of greenhouse gases. The low-cost UAV sensing technology for air pollutants was developed by Dr. Xiaobing Pang, who was funded by the Newton Fellowship in 2009 and worked in the University of York. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'.

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 The use of propensity score methods has become ubiquitous in causal inference. At the heart of these methods is the positivity assumption. Violation of the positivity assumption leads to the presence of extreme propensity scoreweights when estimating average causal effects, which affects statistical inference. To circumvent this issue, trimming or truncating methods have been widely used. Unfortunately, these methods require that we pre-specify a threshold. There are anumber of alternative methods to deal with the lack of positivity when we estimate the average treatment effect (ATE). However, no other methods exist beyond trimming and truncation to deal with the same issue when the goal is to estimate theaverage treatment effect on the treated (ATT). In this article, we propose a propensity score weight-based alternative for the ATT, called overlap weighted average treatment effect on the treated. The appeal of our proposed method lies in its abilityto obtain similar or even better results than trimming and truncation while relaxing the constraint to choose an a priori threshold (or related measures). The performance of the proposed method is illustrated via a series of Monte Carlo simulationsand a data analysis on racial disparities in health care expenditures.

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Herein, we presented a bifunctional photocatalytic system for 5-hydroxymethylfurfural (HMF) valorization over Ni(OH)2-modified ZnIn2S4. Instead of forming 2,5-diformylfuran C6 products from conventional HMF aerobic oxidation, C-C coupling C12 products and H2 were produced in anaerobic water, which can be an important liquid fuel intermediate and gaseous energy carrier, respectively. This work could spark more insight for biomass utilization.

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Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. Methods: In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. Results: The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; p =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.

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BACKGROUND: Although healthy sleep patterns have been linked to a lower risk of cardiovascular disease in earlier research, it is unclear how beneficial they are for venous thromboembolism (VTE). AIM: This research aimed to examine the correlation between sleep patterns, genetic susceptibility, and VTE. METHODS: In the UK Biobank cohort, healthy sleep behaviors were defined as early chronotype, 7-8 hours of sleep each day, no snoring, infrequent insomnia, and infrequent daytime sleepiness. Each of the five criteria was given 1 point, creating a healthy sleep score ranging from 0 to 5. Cox proportional hazards regression models were utilized to examine the associations between genetic susceptibility, healthy sleep score and VTE. RESULTS: The UK Biobank study included 384,758 participants aged 56.6 ± 8.0 years. After a median of 11.9 years of follow-up, 8,885 (2.3%) participants were diagnosed with VTE. A healthy sleep score inversely affected VTE risk. For participants with a score of 5, the hazard ratio of VTE was 0.813 (95% confidence interval: 0.758-0.873, P<0.001) compared to those with a score ≤2. Early chronotype, sleeping 7-8 hours each day, infrequent insomnia, and infrequent daytime sleepiness were significantly associated with a 7.9%, 8.3%, 5.1%, and 20.7% lower risk of VTE, respectively. In addition, the correlation between sleep pattern and the incidence of VTE was consistent, regardless of genetic susceptibility (P for interaction = 0.366). CONCLUSIONS: Our secondary analysis of a large-scale prospectively gathered registry revealed that individuals with a healthy sleep pattern are significantly correlated with lower risk of developing VTE, irrespective of genetic susceptibility.

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OBJECTIVE: Acetaminophen (APAP), an antipyretic and analgesic commonly used during pregnancy, has been recognized as a novel environmental contaminant. Preliminary evidence suggests that prenatal acetaminophen exposure (PAcE) could adversely affect offspring's gonadal and neurologic development, but there is no systematic investigation on the characteristics of APAP's fetal developmental toxicity. METHODS: Pregnant mice were treated with 100 or 400 mg/kg∙d APAP in the second-trimester, or 400 mg/kg∙d APAP in the second- or third-trimester, or different courses (single or multiple) of APAP, based on clinical regimen. The effects of PAcE on pregnancy outcomes, maternal/fetal blood phenotypes, and multi-organ morphological and functional development of fetal mice were analyzed. RESULTS: PAcE increased the incidence of adverse pregnancy outcomes and altered blood phenotypes including aminotransferases, lipids, and sex hormones in dams and fetuses. The expression of key functional genes in fetal organs indicated that PAcE inhibited hippocampal synaptic development, sex hormone synthesis, and osteogenic and chondrogenic development, but enhanced hepatic lipid synthesis and uptake, renal inflammatory hyperplasia, and adrenal steroid hormone synthesis. PAcE also induced marked pathological alterations in the fetal hippocampus, bone, kidney, and cartilage. The sensitivity rankings of fetal organs to PAcE might be hippocampus/bone > kidney > cartilage > liver > gonad > adrenal gland. Notably, PAcE-induced multi-organ developmental toxicity was more considerable under high-dose, second-trimester, and multi-course exposure and in male fetuses. CONCLUSION: This study confirmed PAcE-induced alterations in multi-organ development and function in fetal mice and elucidated its characteristics, which deepens the comprehensive understanding of APAP's developmental toxicity.

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Cardiac biological pacing (BP) is one of the future directions for bradyarrhythmias intervention. Currently, cardiac pacemaker cells (PCs) used for cardiac BP are mainly derived from pluripotent stem cells (PSCs). However, the production of high-quality cardiac PCs from PSCs remains a challenge. Here, we developed a cardiac PC differentiation strategy by adopting dual PC markers and simulating the developmental route of PCs. First, two PC markers, Shox2 and Hcn4, were selected to establish Shox2:EGFP; Hcn4:mCherry mouse PSC reporter line. Then, by stepwise guiding naïve PSCs to cardiac PCs following naïve to formative pluripotency transition and manipulating signaling pathways during cardiac PCs differentiation, we designed the FSK method that increased the yield of SHOX2+; HCN4+ cells with typical PC characteristics, which was 12 and 42 folds higher than that of the embryoid body (EB) and the monolayer M10 methods respectively. In addition, the in vitro cardiac PCs differentiation trajectory was mapped by single-cell RNA sequencing (scRNA-seq), which resembled in vivo PCs development, and ZFP503 was verified as a key regulator of cardiac PCs differentiation. These PSC-derived cardiac PCs have the potential to drive advances in cardiac BP technology, help with the understanding of PCs (patho)physiology, and benefit drug discovery for PC-related diseases as well.

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AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.

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Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

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Background: Sepsis-induced acute lung injury (ALI) leads to severe hypoxemia and respiratory failure, contributing to poor prognosis in septic patients. Endotoxin dissemination triggers oxidative stress and the release of inflammatory cytokines in macrophages, initiating diffuse alveolar damage. The role of epigenetic histone modifications in organ injury is increasingly recognized. The present study aimed to investigate the use of a histone modification inhibitor to alleviate sepsis-induced ALI, revealing a new strategy for improving sepsis patient survival. Methods: In vivo models of ALI were established through the intraperitoneal injection of lipopolysaccharide and cecal ligation and puncture surgery. Furthermore, the disease process was simulated in vitro by stimulating Tamm-Horsfall protein-1 (THP-1) cells with lipopolysaccharide. Hematoxylin and eosin staining, blood gas analysis and pulmonary function tests were utilized to assess the extent of lung tissue damage. Western blot analysis, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunofluorescence were used to measure the levels and distribution of the indicated indicators within cells and tissues. Reactive oxygen species and autophagic flux alterations were detected using specific probes. Results: BRD3308, which is a inhibitor of histone deacetylase 3, improved lung tissue damage, inflammatory infiltration and edema in ALI by inhibiting Nod-like receptor protein3-mediated pyroptosis in macrophages. By upregulating autophagy, BRD3308 improved the disruption of redox balance in macrophages and reduced the accumulation of reactive oxygen species. Mechanistically, BRD3308 inhibited histone deacetylase 3 activity by binding to it and altering its conformation. Following histone deacetylase 3 inhibition, acetylation of H3K27 was significantly increased. Moreover, the increase in H3K27Ac led to the upregulation of autophagy-related gene 5, a key component of autophagosomes, thereby activating autophagy. Conclusions: BRD3308 inhibits oxidative stress and pyroptosis in macrophages by modulating histone acetylation, thereby preventing sepsis-induced ALI. The present study provides a potential strategy and theoretical basis for the clinical treatment of sepsis-induced ALI.

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BACKGROUND: Pulmonary hypertension is a serious disease. Emerging studies have shown that M2 macrophages play an essential role in pulmonary hypertension; however, their mechanism of action is uncertain. METHODS: Four GEO datasets were downloaded. The differentially expressed genes (DEGs) were obtained using the limma package. Simultaneously, the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and weighted gene co-expression network analysis (WGCNA) were used to get the information about M2 macrophage-related modules. Potential key genes were obtained by intersecting DEGs with M2 macrophage-related module genes (M2MRGs), and finally the area under the curve (AUC) was calculated. Rats were exposed to hypoxia condition (10 % O2) for 4 weeks to induce PH. Subsequently, potential key genes with AUC>0.7 were analyzed by quantitative real-time polymerase chain reaction and Western blot using normoxia and hypoxia rat lungs. We knocked down EPHA3 in Raw264.7 cells and detected the protein expression of M2 macrophage markers including arginase 1 (ARG1) and interleukin 10 (IL-10), phospho-protein kinase B (P-Akt), and protein kinase B (Akt) to explore the downstream pathways of EPHA3. RESULTS: Seven potential hub genes were detected by intersecting M2MRGs and DEGs. Six genes with AUC values above 0.7 were used for further exploration. The expression of EPHA3 mRNA and protein was significantly more upregulated in rats with hypoxia than in rats with normoxia. The expression levels of IL10, ARG1, and P-Akt/Akt decreased after knocking down EPHA3. CONCLUSIONS: This study suggested that the activation of the P-Akt/Akt signaling pathway promoted by EPHA3 played an essential role in the progression of pulmonary hypertension.

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Neuromorphic computing, marked by its parallel computational abilities and low power usage, has become pivotal in advancing artificial intelligence. However, the advancement of neuromorphic computing has faced significant obstacles due to the performance limitations of traditional memory devices struggling with high power consumption and limited reliability. Two-dimensional (2D) materials have been extensively investigated as high-performance memristive materials, but they are often restricted by fixed memristive properties, which complicate circuit design and limit flexibility. Here, we report that multilayer borophene nanosheets represent a breakthrough material, displaying anisotropic variable memristive properties. The nanosheets, comprising semiconductor α'-4H-borophene sheets and metal ß12-borophene sheets, have been synthesized on aluminum foil surface through chemical vapor deposition (CVD) method. The multilayer borophene nanosheets exhibit volatile memory behavior in the vertical direction and non-volatile memory behavior in the planar direction. This innovative class of 2D nanosheets not only overcomes the limitations of conventional memory devices but also expands the potential applications of borophene-based memories in information storage and in-memory computing.