Predictive value of pre-operative prognostic nutritional index and systemic immune-inflammation index for efficacy and survival in patients with non-small cell lung cancer undergoing neoadjuvant chemotherapy.

OBJECTIVE: To explore the predictive value of preoperative prognostic nutritional index (PNI) and systemic immune inflammation index (SII) in relation to the efficacy and prognosis in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy (NACT). METHODS: Data of patients with stage IIIA-N2 NSCLC who received NACT in the 910th Hospital of Chinese People's Liberation Army from January 2017 to April 2020 were retrospectively analysed. Patients undergoing NACT were divided into the pCR group (80 cases with complete remission or partial remission) and the non-pCR group (46 cases with stable disease or progressive disease) in accordance with their treatment outcome. The pathologic and clinical data of the patients were collected and analysed to identify the factors affecting efficacy of NACT for stage IIIa-N2 NSCLC, and to evaluate the predictive value of PNI and SII in determining the efficacy of NACT. The patients were followed up for 3 years to observe the overall survival, and Cox regression analysis was employed to identify the risk factors affecting patient survival. Furthermore, the effect of PNI and SII on the survival time was analysed. RESULTS: Multivariate regression analysis showed that tumor diameter, PNI, and SII were influencing factors for poor efficacy of NACT in patients with stage IIIa-N2 NSCLC. The non-pCR group exhibited a higher mortality within 3 years, thus a lower 3-year overall survival rate than the pCR group (P<0.05). Cox regression analysis revealed that both PNI and SII were risk factors for poor prognosis in patients with stage IIIa-N2 NSCLC undergoing NACT. Further analysis found a lower 3-year survival rate in patients with low PNI and high SII than in counterparts (P<0.05). CONCLUSION: Tumor diameter, PNI and SII are risk factors for poor efficacy in patients with stage IIIa-N2 NSCLC undergoing NACT. Low PNI and high SII can indicate a poor prognosis in these patients.

Cinnamaldehyde alleviates aspirin-induced gastric mucosal injury by regulating pi3k/akt pathway-mediated apoptosis, autophagy and ferroptosis.

BACKGROUND: Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown. PURPOSE: The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics. RESULTS: CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3ß, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury. CONCLUSION: This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

Unveiling the role of mtDNA in Liver-Kidney Crosstalk: Insights from trichloroethylene hypersensitivity syndrome.

In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance. This study seeks to elucidate the role of mtDNA in conditions marked by liver-kidney crosstalk. In previous clinical cases, it has been observed that patients with Trichloroethylene Hypersensitivity Syndrome (TCE-HS) who experience severe liver injury often also exhibit renal injury. In this study, patients diagnosed with trichloroethylene hypersensitivity syndrome were recruited from Shenzhen Occupational Disease Control Center. And Balb/c mice were treated with trichloroethylene. The correlation between liver and kidney injuries in patients with TCE-HS was assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Alterations in mtDNA levels were examined in mouse hepatocytes, red blood cells (RBCs), and renal tubular epithelial cells utilizing immunofluorescence and PCR techniques. TCE-sensitized mice exhibited a significant increase in reactive oxygen species (ROS) and the opening of the mitochondrial permeability transition pore in hepatocytes, resulting in the release of mtDNA. Furthermore, heightened levels of mtDNA and Toll-like Receptor 9 (TLR9) expression were observed in RBCs. Additional experiments demonstrated elevated expression of TLR9 and its downstream mediator MyD88 in renal tubule epithelial cells of TCE-sensitized mice. In vitro investigations confirmed that mtDNA activates the TLR9 pathway in TCMK-1 cells. Collectively, these results suggest that mtDNA released from mitochondrial damage in hepatocytes is carried by RBCs to renal tubular epithelial cells and mediates inflammatory injury in renal tubular epithelial cells through activation of the TLR9 receptor.

Trichloroethylene exposure, multi-organ injury, and potential mechanisms: A narrative review.

Trichloroethylene (TCE) is a common environmental pollutant and industrial chemical that has been associated with adverse health effects, especially on organ systems. The purpose of this review is to summarize the current findings on organ system damage caused by TCE exposure and the underlying mechanisms involved. Numerous studies have shown that TCE exposure may cause damage to multiple organ systems, mainly the skin, liver, kidney, and circulatory system. The mechanisms leading to TCE-induced organ system damage are complex and diverse. TCE is metabolized in vivo to reactive intermediates, through which TCE can induce oxidative stress, interfere with cell signaling pathways, and promote inflammatory responses. In addition, studies have shown that TCE interferes with DNA repair mechanisms, leading to genotoxicity and potentially carcinogenic effects. This review highlights the importance of understanding the deleterious effects of TCE exposure on organ systems and provides insights into the underlying mechanisms involved. Further research is needed to elucidate the full range of organ system damage caused by TCE and to develop effective prevention and treatment strategies.

The role of mitochondrial dysfunction in kidney injury and disease.

Mitochondria are the main sites of aerobic respiration in the cell and mainly provide energy for the organism, and play key roles in adenosine triphosphate (ATP) synthesis, metabolic regulation, and cell differentiation and death. Mitochondrial dysfunction has been identified as a contributing factor to a variety of diseases. The kidney is rich in mitochondria to meet energy needs, and stable mitochondrial structure and function are essential for normal kidney function. Recently, many studies have shown a link between mitochondrial dysfunction and kidney disease, maintaining mitochondrial homeostasis has become an important target for kidney therapy. In this review, we integrate the role of mitochondrial dysfunction in different kidney diseases, and specifically elaborate the mechanism of mitochondrial reactive oxygen species (mtROS), autophagy and ferroptosis involved in the occurrence and development of kidney diseases, providing insights for improved treatment of kidney diseases.

Histone demethylase KDM4A mediating macrophage polarization: A potential mechanism of trichloroethylene induced liver injury.

Trichloroethylene (TCE) is a commonly used organic solvent in industry. Our previous studies have found that TCE can cause liver injury accompanied by macrophage polarization, but the specific mechanism is unclear. The epigenetic regulation of macrophage polarization is mainly focused on histone modification. Histone lysine demethylase 4A (KDM4A) is involved in the activation of macrophages. In this study, we used a mouse model we investigated the role of KDM4A in the livers of TCE-drinking mice and found that the expression of KDM4A, M1-type polarization indicators, and related inflammatory factors in the livers of TCE-drinking mice. In the study, BALB/c mice were randomly divided into four groups: 2.5 mg/mL TCE dose group and 5.0 mg/mL TCE dose group, the vehicle control group, and the blank control group. We found that TCE triggered M1 polarization of mouse macrophages, characterized by the expression of CD11c and robust production of inflammatory cytokines. Notably, exposure to TCE resulted in markedly increased expression of KDM4A in macrophages. Functionally, the increased expression of KDM4A significantly impaired the expression of H3K9me3 and H3K9me2 and increased the expression of H3K9me1. In addition, KDM4A potentially represents a novel epigenetic modulator, with its upregulation connected to ß-catenin activation, a signal critical for the pro-inflammatory activation of macrophages. Furthermore, KDM4A inhibitor JIB-04 treatment resulted in a decrease in ß-catenin expression and prevented TCE-induced M1 polarization and the expression of the pro-inflammatory cytokines TNF-α and IL-1ß. These results suggest that the association of KDM4A and Wnt/ß-catenin cooperatively establishes the activation and polarization of macrophages and global changes in H3K9me3/me2/me1. Our findings identify KDM4A as an essential regulator of the polarization of macrophages and the expression of inflammatory cytokines, which might serve as a potential target for preventing and treating liver injury caused by TCE.

The role of PANoptosis in renal vascular endothelial cells: Implications for trichloroethylene-induced kidney injury.

Trichloroethylene (TCE), a widely distributed environmental chemical contaminant, is extensively dispersed throughout the environment. Individuals who are exposed to TCE may manifest occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Renal impairment typically manifests in the initial phase of OMDT and is intricately linked to the disease progression and patient outcomes. Although recombinant human tumor necrosis factor-α receptor II fusion protein (rh TNFR:Fc) has been employed in the clinical management of OMDT, there was no substantial improvement in renal function observed in patients following one week of treatment. This study primarily examined the mechanism of TNFα- and IFNγ-induced endothelial cells (ECs) PANoptosis in TCE-induced kidney injury and hypothesized that the synergistic effect of TNFα and IFNγ could be the key factor affecting the efficacy of rh TNFR:Fc therapy in OMDT patients. A TCE-sensitized mouse model was utilized in this study to investigate the effects of TNFα and IFNγ neutralizing antibodies on renal vascular endothelial cell PANoptosis. The gene of interferon regulatory factor 1 (IRF1) in human umbilical vein endothelial cells (HUVEC) was silenced by using small interfering RNA (siRNA), and the cells were then treated with TNFα and IFNγ recombinant protein to investigate the mechanism of TNFα combined with IFNγ-induced PANoptosis in HUVEC. The findings indicated that mice sensitized to TCE exhibited increased levels of PANoptosis-related markers in renal endothelial cells, and treatment with TNFα and IFNγ neutralizing antibodies resulted in a significant reduction in PANoptosis and improvement in renal function. In vitro experiments demonstrated that silencing IRF1 could reverse TNFα and IFNγ-induced PANoptosis in endothelial cells. These results suggest that the efficacy of rh TNFR:Fc may be influenced by TNFα and IFNγ-mediated PANoptosis in kidney vascular endothelial cells. The joint application of TNFα and IFNγ neutralizing antibody represented a solid alternative to existing therapeutics.

Resin screening and process optimization for erythritol mother liquor chromatographic separation.

In order to improve the utilization value of the erythritol mother liquor, the separation and purification of the erythritol mother liquor was selected in this study. The selected chromatographic separation programme for erythritol crystallizing mother liquor is as follows: Firstly, erythritol is resolved from mannitol and arabitol with DTF-01Ca (Suqing Group) resin and then mannitol is resolved from arabitol with 99Ca/320 (Dowex) resin. At the same time, the chromatographic conditions of the DTF-01Ca (Suqing Group) and 99Ca/320 (Dowex) resins were optimized, resulting in an optimal separation temperature and mobile phase flow rate of 70 °C, 10 ml/min. On this basis, a single-column chromatographic model was used to calculate the TD model parameter (N) and the mass transfer coefficient (km ) of the separation of erythritol mother liquor by DTF-01Ca (Suqing Group) and 99Ca/320 (Dowex) resins. The adsorption isotherms, TD model parameter (N) and the mass transfer coefficient (km ) provides data references for the design and operation of the simulated moving beds (SMB) separation system for the industrial-scale separation of erythritol crystallizing mother liquor.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

Rare-earth-based chalcogenides and their derivatives: an encouraging IR nonlinear optical material candidate.

With the continuous development of laser technology and the increasing demand for lasers of different frequencies in the infrared (IR) spectrum, research on infrared nonlinear optical (NLO) crystals has garnered growing attention. Currently, the three main commercially available types of borate materials each have their drawbacks, which limit their applications in various areas. Rare-earth (RE)-based chalcogenide compounds, characterized by the unique f-electron configuration, strong positive charges, and high coordination numbers of RE cations, often exhibit distinctive optical responses. In the field of IR-NLO crystals, they have a research history spanning several decades, with increasing interest. However, there is currently no comprehensive review summarizing and analyzing these promising compounds. In this review, we categorize 85 representative examples out of more than 400 non-centrosymmetric (NCS) compounds into four classes based on the connection of different asymmetric building motifs: (1) RE-based chalcogenides containing tetrahedral motifs; (2) RE-based chalcogenides containing lone-pair-electron motifs; (3) RE-based chalcogenides containing [BS3] and [P2Q6] motifs; and (4) RE-based chalcohalides and oxychalcogenides. We provide detailed discussions on their synthesis methods, structures, optical properties, and structure-performance relationships. Finally, we present several favorable suggestions to further explore RE-based chalcogenide compounds. These suggestions aim to approach these compounds from a new perspective in the field of structural chemistry and potentially uncover hidden treasures within the extensive accumulation of previous research.

Parkinson's disease impairs cortical sensori-motor decision-making cascades.

The transformation from perception to action requires a set of neuronal decisions about the nature of the percept, identification and selection of response options and execution of the appropriate motor response. The unfolding of such decisions is mediated by distributed representations of the decision variables-evidence and intentions-that are represented through oscillatory activity across the cortex. Here we combine magneto-electroencephalography and linear ballistic accumulator models of decision-making to reveal the impact of Parkinson's disease during the selection and execution of action. We used a visuomotor task in which we independently manipulated uncertainty in sensory and action domains. A generative accumulator model was optimized to single-trial neurophysiological correlates of human behaviour, mapping the cortical oscillatory signatures of decision-making, and relating these to separate processes accumulating sensory evidence and selecting a motor action. We confirmed the role of widespread beta oscillatory activity in shaping the feed-forward cascade of evidence accumulation from resolution of sensory inputs to selection of appropriate responses. By contrasting the spatiotemporal dynamics of evidence accumulation in age-matched healthy controls and people with Parkinson's disease, we identified disruption of the beta-mediated cascade of evidence accumulation as the hallmark of atypical decision-making in Parkinson's disease. In frontal cortical regions, there was inefficient processing and transfer of perceptual information. Our findings emphasize the intimate connection between abnormal visuomotor function and pathological oscillatory activity in neurodegenerative disease. We propose that disruption of the oscillatory mechanisms governing fast and precise information exchanges between the sensory and motor systems contributes to behavioural changes in people with Parkinson's disease.

Circular RNA MKLN1 promotes epithelial-mesenchymal transition in pulmonary fibrosis by regulating the miR-26a/b-5p/CDK8 axis in human alveolar epithelial cells and mice models.

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.

IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells.

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.

C5b-9 promotes ferritinophagy leading to ferroptosis in renal tubular epithelial cells of trichloroethylene-sensitized mice.

Trichloroethylene (TCE) is a common environmental contaminant that can cause a severe allergic reaction called TCE hypersensitivity syndrome, which often implicates the patient's kidneys. Our previous study revealed that C5b-9-induced tubular ferroptosis is involved in TCE-caused kidney damage. However, the study did not explain how tubule-specific C5b-9 causes free iron overload, a key event in ferroptosis. Here, we aimed to explore the role of NCOA4-mediated ferritinophagy in C5b-9-induced iron overload and ferroptosis in TCE-sensitized mice. Our results showed that TCE sensitization does not affect iron import or export, but does affect iron storage, causing ferritin degradation and free iron overload. In addition, mitochondrial ROS was upregulated, and these changes were blocked by C5b-9 inhibition. Interestingly, TCE-induced ferritin degradation and ferroptosis were significantly antagonized by the application of the mitochondrial ROS inhibitor, Mito-TEMPO. Moreover, all of these modes of action were further verified in C5b-9-attack signalling HK-2 cells. Further investigation demonstrated that C5b-9-upregulated mitochondrial ROS induced a marked increase in nuclear receptor coactivator 4 (NCOA4), a master regulator of ferritinophagy. In addition, the application of NCOA4 small interfering RNA not only significantly reversed ferritinophagy caused by C5b-9 but also reduced C5b-9-induced ferroptosis in HK-2 cells. Taken together, these results suggest that tubule-specific C5b-9 deposition activates NCOA4 through the upregulation of mitochondrial ROS, causing ferritin degradation and elevated free iron, which ultimately leads to tubular epithelial cell ferroptosis and kidney injury in TCE-sensitized mice.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR.

Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

The correlation between lung ultrasound scores and outcomes of high-flow nasal cannula therapy in infants with severe pneumonia.

OBJECTIVE: The study aimed to explore the effectiveness of bedside lung ultrasound (LUS) combined with the PaO2/FiO2 (P/F) ratio in evaluating the outcomes of high-flow nasal cannula (HFNC) therapy in infants with severe pneumonia. METHODS: This retrospective study analyzed the clinical data of 150 infants diagnosed with severe pneumonia and treated with HFNC therapy at our hospital from January 2021 to December 2021. These patients were divided into two groups based on their treatment outcomes: the HFNC success group (n = 112) and the HFNC failure group (n = 38). LUS was utilized to evaluate the patients' lung conditions, and blood gas results were recorded for both groups upon admission and after 12 h of HFNC therapy. RESULTS: At admission, no significant differences were observed between the two groups in terms of age, gender, respiratory rate, partial pressure of oxygen, and partial pressure of carbon dioxide. However, the P/F ratios at admission and after 12 h of HFNC therapy were significantly lower in the HFNC failure group (193.08 ± 49.14, 228.63 ± 80.17, respectively) compared to the HFNC success group (248.51 ± 64.44, 288.93 ± 57.17, respectively) (p < 0.05). Likewise, LUS scores at admission and after 12 h were significantly higher in the failure group (18.42 ± 5.3, 18.03 ± 5.36, respectively) than in the success group (15.09 ± 4.66, 10.71 ± 3.78, respectively) (p < 0.05). Notably, in the success group, both P/F ratios and LUS scores showed significant improvement after 12 h of HFNC therapy, a trend not observed in the failure group. Multivariate regression analysis indicated that lower P/F ratios and higher LUS scores at admission and after 12 h were predictive of a greater risk of HFNC failure. ROC analysis demonstrated that an LUS score > 20.5 at admission predicted HFNC therapy failure with an AUC of 0.695, a sensitivity of 44.7%, and a specificity of 91.1%. A LUS score > 15.5 after 12 h of HFNC therapy had an AUC of 0.874, with 65.8% sensitivity and 89.3% specificity. An admission P/F ratio < 225.5 predicted HFNC therapy failure with an AUC of 0.739, 60.7% sensitivity, and 71.1% specificity, while a P/F ratio < 256.5 after 12 h of HFNC therapy had an AUC of 0.811, 74.1% sensitivity, and 73.7% specificity. CONCLUSION: Decreased LUS scores and increased P/F ratio demonstrate a strong correlation with successful HFNC treatment outcomes in infants with severe pneumonia. These findings may provide valuable support for clinicians in managing such cases.

Enhanced polarization via Joule heating in wood-derived carbon materials for absorption-dominated EMI shielding.

To cope with sophisticated application scenarios, carbon materials can provide opportunities for integrating multi-functionalities into superior electromagnetic interference (EMI) shielding properties. Nevertheless, carbon materials usually possess high electrical conductivity, which allows them to counteract electromagnetic waves by reflection. Moreover, the identification of factors that dominate the shielding mechanisms has typically been result-oriented, leading to a reliance on a trial-and-error approach for the development of shielding materials. Thus, it is crucial to identify the dominant factors for EMI shielding and elucidate the mechanism underlying the coordination of the balance between reflection and absorption in carbon materials. In this study, we developed a promising and viable approach to create Co@CNTs embedded in carbonized wood (CW) via chemical vapor deposition, producing Co@CNTs/CW foams. The CNTs, densely grown on the CW surface, tightly encapsulated the Co nanoparticles within them. By manipulating the Co content, the defect density and CNT length varied within the Co@CNTs. Through first-principles calculations, these variations substantially influenced the work function, charge density, and dipole moment of the Co@CNTs. Thus, defect-induced and interfacial polarizations were improved, inducing a transformation of the shielding mechanism from reflection to absorption. Regarding the Co@CNTs/CW foams, while high conductivity was essential for achieving satisfactory shielding performance, the enhanced polarization loss dominated the contribution of absorption to the overall shielding effectiveness. Taking advantage of the enhanced polarizations, the Co@CNTs/CW foams exhibited an impressive shielding effectiveness of 42.0 dB, along with an absorptivity of 0.64, which were instrumental in effectively minimizing secondary reflections. Remarkably, these as-prepared foams possessed outstanding hydrophobicity and Joule heating features with a water contact angle of 138° and a saturation temperature of 85.5 °C (2.5 V). Through the stimulation of voltage-driven Joule heating, the absorptivity of Co@CNTs/CW foams can be significantly enhanced to a range of 0.61 to 0.73, irrespective of the Co content. This research would provide a new avenue for designing carbon materials with an absorption-dominated mechanism integrated into EMI shielding performance.

HIF-1α promotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming.

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm. However, the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated. Here, we identified hypoxia inducible factor-1α (HIF-1α) as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells. Specifically, HIF-1α protein expression is upregulated after H1N1 infection. Deficiency of HIF-1α attenuates pulmonary injury, viral replication and cytokine storm in vivo. In addition, viral replication and cytokine storm were inhibited after HIF-1α knockdown in vitro. Mechanistically, the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis, with rapid production of ATP and lactate. Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses. Further analysis revealed that H1N1-induced HIF-1α can promote the expression of hexokinase 2 (HK2), the key enzyme of glycolysis, and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate, which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/ß production. In conclusion, this study demonstrated that the upregulation of HIF-1α by H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2, providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T.

Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category selectivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside posteromedial (including retrosplenial) and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus.

The regulation of RGLG2-VWA by Ca2+ ions.

RGLG2, an E3 ubiquitin ligase in Arabidopsis thaliana, affects hormone signaling and participates in drought regulation. Here, we determined two crystal structures of RGLG2 VWA domain, representing two conformations, open and closed, respectively. The two structures reveal that Ca2+ ions are allosteric regulators of RGLG2-VWA, which adopts open state when NCBS1(Novel Calcium ions Binding Site 1) binds Ca2+ ions and switches to closed state after Ca2+ ions are removed. This mechanism of allosteric regulation is identical to RGLG1-VWA, but distinct from integrin α and ß VWA domains. Therefore, our data provide a backdrop for understanding the role of the Ca2+ ions in conformational change of VWA domain. In addition, we found that RGLG2closed, corresponding to low affinity, can bind pseudo-ligand, which has never been observed in other VWA domains.