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Ferroptosis is a form of programmed cell death that was only recognized in 2012. Until recently, numerous researchers have turned their attention to the mechanism and function of ferroptosis. A large number of studies have shown potential links between cell ferroptosis and infection, inflammation, and tumor. At the same time, immune cells are vital players in these above-mentioned processes. To date, there is no comprehensive literature review to summarize the relationship between ferroptosis and immune cells. Therefore, it is of great significance to explore the functional relationship between the two. This review will attempt to explain the link between ferroptosis and various immune cells, as well as determine the role ferroptosis plays in infection, inflammation, and malignancies. From this, we may find the potential therapeutic targets of these diseases.

We study the propagation and injection models of cosmic rays using the latest measurements of the boron-to-carbon ratio and fluxes of protons, helium, carbon, and oxygen nuclei by the Alpha Magnetic Spectrometer and the Advanced Composition Ex- plorer at top of the Earth, and the Voyager spacecraft outside the heliosphere. The Advanced Composition Explorer (ACE) data during the same time interval of the AMS-02 data are extracted to minimize the complexity of the solar modulation effect. We find that the cosmic ray nucleus data favor a modified version of the diffusion-reacceleration scenario of the propagation. The diffusion coefficient is, however, required to increase moderately with decreasing rigidity at low energies, which has interesting implications on the particle and plasma interaction in the Milky Way. We further find that the low rigidity (< a few GV) injection spectra are different for different compositions. The injection spectra are softer for lighter nuclei. These results are expected to be helpful in understanding the acceleration process of cosmic rays.

High-mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) molecule, participates in multiple processes of various inflammatory diseases through binding to its corresponding receptors. In the early phase, sepsis is mainly characterized as a multi-bacterial-induced complex, excessive inflammatory response accompanied by the release of pro-inflammatory mediators, which subsequently develops into immune paralysis. A growing number of in vivo and in vitro investigations reveal that HMGB1 plays a pivotal role in the processes of inflammatory response and immunosuppression of sepsis. Therefore, HMGB1 exerts an indispensable role in the immune disorder and life-threatening inflammatory syndrome of sepsis. HMGB1 mainly mediate the release of inflammatory factors via acting on immune cells, pyroptosis pathways and phosphorylating nuclear factor-κB. Moreover HMGB1 is also associated with the process of sepsis-related immunosuppression. Neutrophil dysfunction mediated by HMGB1 is also an aspect of the immunosuppressive mechanism of sepsis. Myeloid-derived suppressor cells (MDSCs), which are also one of the important cells that play an immunosuppressive effect in sepsis, may connect with HMGB1. Thence, further understanding of HMGB1-associated pathogenesis of sepsis may assist in development of promising treatment strategies. This review mainly discusses current perspectives on the roles of HMGB1 in sepsis-related inflammation and immunosuppressive process and its related internal regulatory mechanisms.

Although the prognostic value of blood creatinine levels in patients with paraquat (PQ) poisoning has been studied for a long time, the results are still controversial. Therefore, we performed the first meta-analysis to comprehensively assess the value of blood creatinine in predicting the prognosis of patients with PQ poisoning. We searched PubMed, EMBase, Web of Science, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and China Online Journals to identify all relevant papers published up to June 2022. Data were extracted for pooled analysis, heterogeneity testing, sensitivity analysis, publication bias analysis, and subgroup analysis. Ultimately, 10 studies involving 862 patients were included. The I2 of diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of this study were all greater than 50%, which showed the existence of heterogeneity in this study, and a random effects model was used for the combination of the above five effect sizes. Pooled analysis showed a high predictive value of blood creatinine for prognosis of PQ poisoning [pooled DOR:22.92, 95% confidence interval (CI):15.62–33.65, P < 0.001]. The combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 86% (95% CI: 0.79–0.91), 78% (95% CI: 0.69–0.86), 4.01 (95% CI: 2.81–5.71), and 0.17 (95% CI: 0.12–0.25), respectively. Deeks publication bias test revealed there was publication bias. Sensitivity analysis showed no significant differences in the estimates of impact. Serum creatinine is an effective predictor of mortality in patients with PQ poisoning.

Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.

The interest of researchers in UHPC has increased over the past decade. It is crucial to understand the structural behavior of reinforced UHPC (R/UHPC) components under various loading conditions before they can be used as a replacement for conventional concrete. Although several studies on ultra-high-performance concrete (UHPC) have been conducted, the knowledge is scattered, and no one can easily judge the performance and methodology of UPHC. Therefore, the purpose of this study was to review the research studies already carried out on UHPC. The review focuses on the materials’ physical and chemical composition, mechanical and durability characteristics, fire resistance, and environmental benefits of UHPC. Design considerations for effectively utilizing UHPC in structural elements are also presented. The best UHPFRC mixture is obtainable with a steel fiber content of 2–3% and a water-to-cement ratio of 0.2–0.3. The review also discusses the essentials recommendation for future research on UHPC.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n  = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n  = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%–58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%–33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%–39.6%; P  = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%–35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%–17.9%); P  = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3–4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 . In the phase 2 trial NEOSUMMIT-01, perioperative treatment of patients with locally advanced gastric or gastro-esophageal junction adenocarcinoma with anti-PD-1 and SOX/XELOX versus SOX/XELOX alone improved pathological complete response or near-complete response rate.

The coronavirus disease 2019 (COVID-19) has been spreading worldwide. Severe cases quickly progressed with unfavorable outcomes. We aim to investigate the clinical features of COVID-19 and identify the risk factors associated with its progression. Data of confirmed SARS-CoV-2-infected patients and healthy participants were collected. Thirty-seven healthy people and 79 confirmed patients, which include 48 severe patients and 31 mild patients, were recruited. COVID-19 patients presented with dysregulated immune response (decreased T, B, and NK cells and increased inflammatory cytokines). Also, they were found to have increased levels of white blood cell, neutrophil count, and D-dimer in severe cases. Moreover, lymphocyte, CD4 + T cell, CD8 + T cell, NK cell, and B cell counts were lower in the severe group. Multivariate logistic regression analysis showed that CD4 + cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Both CT score and clinical pulmonary infection score (CPIS) were associated with disease severity. The receiver operating characteristic (ROC) curve analysis has shown that all these parameters and scores had quite a high predictive value. Immune dysfunction plays critical roles in disease progression. Early and constant surveillance of complete blood cell count, T lymphocyte subsets, coagulation function, CT scan and CPIS was recommended for early screening of severe cases.

Temporal lobe epilepsy (TLE) is characterized as an impaired ability of learning and memory with periodic and unpredictable seizures. Status epilepticus (SE) is one of the main causes of TLE. Neuroinflammation and oxidative stress are directly involved in epileptogenesis and neurodegeneration, promoting chronic epilepsy and cognitive deficit. Previous studies have shown that ursolic acid (UA) represses inflammation and oxidative stress, contributing to neuroprotection. Herein, we demonstrated that UA treatment alleviated seizure behavior and cognitive impairment induced by epilepsy. Moreover, UA treatment rescued hippocampal neuronal damage, aberrant neurogenesis, and ectopic migration, which are commonly accompanied by epilepsy occurrence. Our study also demonstrated that UA treatment remarkably suppressed the SE-induced neuroinflammation, evidenced by activated microglial cells and decreased inflammation factors, including TNF-α and IL-1β. Likewise, the expression levels of oxidative stress damage markers and oxidative phosphorylation (OXPHOS) enzyme complexes of mitochondria were also remarkably downregulated following the UA treatment, suggesting that UA suppressed the damage caused by the high oxidative stress and the defect mitochondrial function induced by SE. Furthermore, UA treatment attenuated GABAergic interneuron loss. In summary, our study clarified the notable anti-seizure and neuroprotective properties of UA in pilocarpine-induced epileptic rats, which is mainly achieved by abilities of anti-inflammation and anti-oxidation. Our study indicates the potential advantage of UA application in ameliorating epileptic sequelae.

Diffuse γ-ray emission between 10 and 1000 TeV from the Galactic plane was recently measured by the Large High Altitude Air Shower Observatory (LHAASO). These observations will help tremendously in constraining the propagation and interaction of cosmic rays in the Milky Way. Additionally, new measurements of cosmic-ray spectra reach a very high precision of up to 100 TeV energies, revealing multiple spectral structures of various species. In this work, based on up-to-date measurements of local cosmic-ray spectra and a simplified propagation setup, we confront a model prediction of diffuse γ-ray emission with measurements of diffuse γ-rays. To better constrain the low-energy part of the model, we analyze the 14.6 yr of Fermi Large Area Telescope (Fermi-LAT) data to extract the Galactic diffuse emission between 1 and 500 GeV from the same sky regions of LHAASO, after subtracting the contribution from known sources and the isotropic diffuse γ-ray background. The joint Fermi-LAT and LHAASO spectra thus cover a very wide energy range from 1 GeV to 1 PeV with small gaps from 0.5 to 10 TeV. Compared with the prediction, we find that clear excesses between several GeV and ∼60 TeV of the diffuse emission exist. Possible reasons to explain the excesses may include unresolved sources or more complicated propagation models. We illustrate that an exponential cutoff power-law component with an index of −2.40 and a cutoff energy of ∼30 TeV is able to account for such excesses.