Deletion of BACH1 alleviates ferroptosis and protects against LPS-triggered acute lung injury by activating Nrf2/HO-1 signaling pathway.

Multiple lines of evidences have unraveled the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI). In this study, we aimed to decipher the role of BACH1 in the onset and progression of ALI with a focus on ferroptosis and elucidated potential molecular mechanism. We observed that BACH1 expression was drastically elevated in BEAS-2B cells upon exposure to LPS. In the functional aspect, BACH1 deletion exerted an anti-inflammatory property, featured by decreased the secretion of several cytokines including TNF-α, IL-1ß and IL-6 in the face of LPS challenge. What's more important, BACH1 knockout evidently repressed LPS-triggered oxidative stress damage, as evidenced by reduced reactive oxygen species (ROS) production and malondialdehyde (MDA) generation, accompanied with the elevated the activities of superoxide dismutase (SOD), GSH-Px and CAT. Meanwhile, ablation of BACH1 restrained LPS-elicited ferroptosis, as characterized by decreased iron content and PTGS2 expression, accompanied with increased expression of SLC7A11 and GPX4. In terms of mechanism, Nrf2/HO-1 signaling inhibitor effectively abrogated the beneficial effects of BACH1 inhibition on LPS-stimulated inflammation, oxidative damage and ferroptosis. Taken together, these preceding outcomes strongly illuminated that BACH1 was a novel regulator of LPS-evoked injury through regulation of inflammation response, oxidative stress and ferroptosis via activation Nrf2/HO-1 signaling, indicating that BACH1 may represent as a promising novel therapeutic candidate for ALI treatment.

Adding liver R2* quantification to proton density fat fraction MRI of vertebral bone marrow improves the prediction of osteoporosis.

OBJECTIVES: To assess the predictive value of the combination of bone marrow (BM) proton density fat fraction (PDFF) and liver R2* for osteopenia and osteoporosis and the additional role of liver R2*. METHODS: A total of 107 healthy women were included between June 2019 and January 2021. Each participant underwent dual-energy X-ray absorptiometry (DXA) and chemical shift-encoded 3.0-T MRI. PDFF measurements were performed for each lumbar vertebral body, and R2* measurements were performed in liver segments. Agreement among measurements was assessed by Bland-Altman analysis. Receiver operating characteristic (ROC) curves were generated to select optimised cut-offs for BM PDFF and liver R2*. Univariable and multivariable logistic regressions were performed. The C statistic and continuous net reclassification improvement (NRI) were adopted to explore the incremental predictive ability of liver R2*. RESULTS: Bone mass decreased in 42 cases (39.3%) and nonbone mass decreased in 65 cases (60.7%). There were significant differences among the age groups, menopausal status groups, PDFF > 45.0% groups, and R2* > 67.7 groups. Each measurement had good reproducibility. The odds ratios (95% CIs) were 4.05 (1.22-13.43) for PDFF and 4.34 (1.41-13.35) for R2*. The C statistic (95% CI) without R2* was 0.888 (0.827-0.950), and with R2* was 0.900 (0.841-0.960). The NRI resulting from the combination of PDFF and R2* was 75.6% (p < 0.01). CONCLUSION: The predictive improvement over the use of BM PDFF and other traditional risk factors demonstrates the potential of liver R2* as a biomarker for osteopenia and osteoporosis in healthy women. KEY POINTS: • Liver R2* is a biomarker for the assessment of osteopenia and osteoporosis. • Liver R2* improved the ability to predict osteopenia and osteoporosis. • The intra- and interobserver measurements showed high agreement.

Treatment of Preschool Children With Autism Spectrum Disorder: A Trial to Evaluate a Learning Style Profile Intervention Program in China.

Objective: To investigate whether the provision of learning style profile (LSP) training improves development in preschool children with autism spectrum disorder (ASD) in China and to describe the characteristics of children who benefit from the intervention. Methods: Eighty-one children aged 36 to 72 months who were diagnosed with ASD for the first time were recruited for the intervention group. All of them received 24 weeks of LSP training, consisting of hospital- and home-based training. Twenty-one children with ASD of the same age in the control group had never received any intervention after diagnosis but underwent an assessment. Assessments were conducted at baseline and 24 weeks later. Differences in the developmental level and severity of ASD symptoms over time and between groups were analyzed by repeated standardized measures. Secondary analyses examined age effects among the 36- 48-, 48- 60-, and 60-72-month age groups. Results: Within-group comparison of the intervention group revealed significant treatment effects after the intervention, according to: language, social and adaptive developmental quotients (DQs) of the China Developmental Scale; total Childhood Autism Rating Scale (CARS) score; and hyperactivity, peer problems, total difficulties, and prosocial behavior scores of the Strengths and Difficulties Questionnaire (SDQ). Similar gains were observed in gross and fine motor DQs of the China Developmental Scale and emotional symptoms and conduct problems scores of the SDQ; however, the differences between these pre- and postintervention scores did not reach statistical significance. Comparisons among the three age groups in the intervention groups demonstrated a significant age effect on adaptive DQs of the China Developmental Scale; total CARS score; hyperactivity, peer problems and total difficulties scores of the SDQ. Comparison between the intervention and control groups revealed significant treatment effects on language, social and adaptive DQs of the China Developmental Scale; total CARS score; and emotional symptoms, conduct problems, hyperactivity, peer problems, total difficulties, and prosocial behavior scores of the SDQ after the intervention. Similar gains were observed in gross and fine motor DQs of the China Developmental Scale, although differences between the two groups did not reach statistical significance. Conclusion: Our findings suggest that LSP training can effectively improve social behavior and reduce the severity of ASD symptoms in children with ASD. Our data also highlight the importance of early intervention.

Association between cesarean section and sensory integration dysfunction in preschool children: a prospective cohort study. / å‰–å®«äº§ä¸Žå­¦é¾„å‰å„¿ç«¥æ„Ÿè§‰ç»Ÿåˆå¤±è°ƒçš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the association between cesarean section and sensory integration dysfunction (SID) in preschool children through a prospective cohort study. METHODS: Based on the multicenter mother-infant cohort established by the Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in 2012, the sensory integration functions (three dimensions: vestibular balance, tactile defensiveness, and proprioception) of 392 preschool children were evaluated by the Chinese Children Sensory Integration Capacity Development Rating Scale in 2017. Births by cesarean section were the exposure factors, and the children born by vaginal delivery were enrolled as controls. A multivariable logistic regression analysis was used to evaluate the association of cesarean section with each dimension of SID. RESULTS: The prevalence rate of SID was 21.9% (86/392) among the preschool children, and the prevalence rates of vestibular balance disorder, tactile over-responsivity, and proprioceptive disorder were 5.9% (23/392), 5.4% (21/392), and 15.1% (59/392) respectively. After adjustment for the confounding factors including maternal age at delivery and maternal educational level and child birth situation, the cesarean section group had a significant increase in the risk of proprioceptive disorder (RR=4.16, 95%CI: 1.41-12.30, P<0.05). The stratified analysis based on sex showed that the boys born by cesarean section had a significantly higher risk of proprioceptive disorder than those born by vaginal delivery (RR=5.75, 95%CI: 1.26-26.40, P<0.05). CONCLUSIONS: Cesarean section can significantly increase the risk of proprioceptive disorder in preschool children, especially in boys.

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis.

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

Lymphocyte blood levels that remain low can predict the death of patients with COVID-19.

ABSTRACT: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spreading on a global scale and poses a great threat to human health. However, efficient indicators for disease severity have not been fully investigated. Here, we aim to investigate whether dynamic changes of lymphocyte counts can predict the deterioration of patients with COVID-19.We collected data from 2923 patients with laboratory-confirmed COVID-19. Patients were then screened, and we focused on 145 severe cases and 60 critical cases (29 recovered cases, 31 deaths). The length of hospitalization was divided into five time points, namely admission, 25%, 50%, 75% and discharge or death, according to the principle of interquartile distance. A series of laboratory findings and clinical data were collected and analyzed during hospitalization. The results showed that there were differences in levels of leukocytes, neutrophils and lymphocytes at almost every time point in the severe cases and 60 critical cases (29 recovered cases, 31 deaths). Further analysis showed that 70.2% of the COVID-19 cases had low circulating lymphocyte count, of which 64.1% were severe cases and 85.0% were critical cases (75.9% recovered cases and 93.5% died). Moreover, the lymphocyte count in dead cases was significantly lower than that of critical cases who recovered, at almost every time point in the critical groups. We also divided critical patients into group A (<1.1 × 109/L) and group B (>1.1 × 109/L) according to number of lymphocytes. Through survival analysis, we found that there was no significant difference in survival between group A and group B at admission (P = .3065). However, the survival rate according to lymphocyte levels in group A was significantly lower than that of group B at 25% hospital stay (on average day 6.5), 50% and 75% time points (P < .001).Lymphocyte counts that remain lower after the first week following symptom onset are highly predictive of in-hospital death of adults with COVID-19. This predictor may help clinicians identify patients with a poor prognosis and may be useful for guiding clinical decision-making at an early stage.

LncRNA UCA1 remits LPS-engendered inflammatory damage through deactivation of miR-499b-5p/TLR4 axis.

Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPS-injured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1ß, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPS-stimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.

Scoring system for poor limb perfusion after limb fracture in children.

BACKGROUND: Assessment of the vascular status following limb fracture in children is important to evaluate the risk of compartment syndrome, which is an emergency condition. AIM: To establish a simple and efficient grading scale of limb perfusion in children undergoing surgery for limb fracture. METHODS: This retrospective study included pediatric patients with a limb fracture and postoperative plaster fixation who were admitted at The Department of Pediatric Orthopedics of Xinhua Hospital between February 2017 and August 2017. The outcome was poor limb perfusion, which is defined as the postoperative use of mannitol. The children were divided into two groups: The normal perfusion group and the poor perfusion group. Key risk factors have been selected by univariable analyses to establish the Grading Scale for Vascular Status. RESULTS: A total of 161 patients were included in the study: 85 in the normal perfusion group and 76 in the poor perfusion group. There were no significant differences in age, sex, body mass index, ethnicity, cause of fracture, fixation, or site of fracture between the two groups. After surgery, the skin temperature (P = 0.048) and skin color (P < 0.001) of the affected limb were significantly different between the two groups. The relative risk and 95% confidence interval for skin temperature of the affected limb, skin color, and range of motion of the affected limb are 2.18 (1.84-2.59), 2.89 (2.28-3.66), and 2.16 (1.83-2.56), respectively. The grading scale was established based on those three factors (score range: 0-3 points). Forty-one patients (32.5%) with score 0 had poor limb perfusion; all patients with scores 1 (n = 32) and 2 (n = 3) had poor limb perfusion (both 100%). CONCLUSION: In children undergoing surgery for limb fracture, a higher Grading Scale for Vascular Status score is associated with a higher occurrence of poor limb perfusion. A prospective study is required for validation.

Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation.

Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing. Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients. While unfractionated heparin is the most commonly used agent, unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients, including heparin-induced thrombocytopenia and acquired antithrombin deficiency. These complications can result in thrombotic events and subtherapeutic anticoagulation. Direct thrombin inhibitors (DTIs) are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation. Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparin-induced thrombocytopenia. This review outlines the pharmacology, dosing strategies and available protocols, monitoring parameters, and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients. The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.

Tunable spinful matter wave valve.

We investigate the transport problem that a spinful matter wave is incident on a strong localized spin-orbit-coupled Bose-Einstein condensate in optical lattices, where the localization is admitted by atom interaction only existing at one particular site, and the spin-orbit coupling arouse spatial rotation of the spin texture. We find that tuning the spin orientation of the localized Bose-Einstein condensate can lead to spin-nonreciprocal/spin-reciprocal transport, meaning the transport properties are dependent on/independent of the spin orientation of incident waves. In the former case, we obtain the conditions to achieve transparency, beam-splitting, and blockade of the incident wave with a given spin orientation, and furthermore the ones to perfectly isolate incident waves of different spin orientation, while in the latter, we obtain the condition to maximize the conversion of different spin states. The result may be useful to develop a novel spinful matter wave valve that integrates spin switcher, beam-splitter, isolator, and converter. The method can also be applied to other real systems, e.g., realizing perfect isolation of spin states in magnetism, which is otherwise rather difficult.

Knockdown of aristaless-like homeobox1 inhibits epithelial-mesenchymal transition through Wnt/ß-catenin signaling pathway in melanoma cells.

Aristaless-like homeobox1 (ALX1), a member of the ALX family, is capable of mediating survival and development of mesenchyme-derived elements in vertebrates and its mutation will prevent the fusion of frontonasal and maxillary elements. Recently, ALX1 has been reported to be associated with cancer progression. However, the specific roles of ALX1 in melanoma remain unclear. In this study, we investigated the expression pattern and biological functions of ALX1 in melanoma. We found that ALX1 was highly expressed in melanoma tissues and cell lines. Knockdown of ALX1 suppressed the proliferation and invasion of melanoma cells. Furthermore, we showed that ALX1 knockdown reversed the epithelial-mesenchymal transition (EMT) process in melanoma cells, which might be attributed to inactivation of the Wnt/ß-catenin pathway. Taken together, this study provided a new insight into the role of ALX1 as a therapeutic target for melanoma treatment.

Paleoclimatic information recorded in fluid inclusions in halites from Lop Nur, Western China.

The homogenization temperature (Th) of primary fluid inclusions in halite can be used for paleoclimate interpretations. Lop Nur, in Central Asia, is an extremely arid zone where large amounts of glauberite were deposited from the late Middle to Late Pleistocene. This deposition was accompanied by formation of large-scale potash-bearing brines. However, quantitative paleotemperature data are still lacking, hindering reconstruction of Quaternary climate conditions and their control over potash formation. We measured the Th of inclusions in halite from the salt field and the top of Upper Pleistocene strata in Lop Nur. The maximum homogenization temperature (Th MAX) of inclusions in halite from the salt field was 41.1 °C, consistent with the maximum ambient temperature (43.4 °C) in the same period. The Th MAX of inclusions in halite from the Upper Pleistocene strata ranged from 35.6 °C to 43 °C, where maximum air temperatures may have reached 37.9 °C to 45.3 °C. The results show that a hot and arid climate prevailed in Lop Nur at the end of the Late Pleistocene. Furthermore, changes of the brine chemical composition due to supply variations instead of climate change, may have caused glauberite deposition to cease at the end of the Late Pleistocene.

Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury: a characteristic analysis using magnetic resonance imaging.

Some in vitro experiments have shown that erythropoietin (EPO) increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg) 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL) were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.

Protective effects of oridonin on the sepsis in mice.

This study aimed to investigate the protective effects of oridonin (ORI) on cecal ligation and puncture (CLP)-induced sepsis in mice. Male C57BL/6 mice weighing 22-30 g and aged 8-10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 µg/kg) was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin-eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05). Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05). The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05). Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

Engineering entangled microwave photon states through multiphoton interactions between two cavity fields and a superconducting qubit.

It has been shown that there are not only transverse but also longitudinal couplings between microwave fields and a superconducting qubit with broken inversion symmetry of the potential energy. Using multiphoton processes induced by longitudinal coupling fields and frequency matching conditions, we design a universal algorithm to produce arbitrary superpositions of two-mode photon states of microwave fields in two separated transmission line resonators, which are coupled to a superconducting qubit. Based on our algorithm, we analyze the generation of evenly-populated states and NOON states. Compared to other proposals with only single-photon process, we provide an efficient way to produce entangled microwave photon states when the interactions between superconducting qubits and microwave fields are in the strong and ultrastrong regime.

[Effect of repeated hypoxic preconditioning on renal ischemia-reperfusion-induced hepatic dysfunction in rats].

OBJECTIVE: To explore the effect of repeated hypoxic preconditioning (RHP) on renal ischemia-reperfusion-induced hepatic dysfunction in rats and the underlying mechanism. METHODS: A total of 120 normal SD rats were randomly divided into 4 groups (n=40), namely RHP surgical group, RHP sham-operated (RHPS) group, nonhypoxic surgical group (IRI group), and nonhypoxic sham-operated group (S group). The rats in the hypoxic groups were exposed to hypoxia in a hypoxic chamber for 5 days prior to establishment of renal ischemia-reperfusion model by resection of the right kidney and clamping the left renal hilum. Serum alanine aminotransferase (ALT), IL-17 A, TNF-a, liver superoxide dismutase (SOD) and nitric oxide (NO) were detected at 2, 8 and 24h after reperfusion, and Western blotting was used to determine the expression of p-PI3K and p-AKT;HE staining was used to observe the structural changes in the liver. RESULTS: Compared with IRI group, RHP group showed significantly milder hepatic damage, lower ALT levels and higher NO levels at 2, 8, and 24 after reperfusion (P<0.05); TNF-a levels were lowered at 24 h (P<0.05) and SOD increased at 8 h after the reperfusion (P<0.05). Compared with S group, IRI group and RHP group showed significantly higher IL-17A levels (P<0.05) but without significant difference between the latter two groups (P>0.05). The expressions of p-PI3K and P-Al

Dual role of leukotriene B4 receptor type 1 in experimental sepsis.

BACKGROUND: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis. METHODS: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate. RESULTS: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice. CONCLUSIONS: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.

Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study.

BACKGROUND: Recent studies have shown that neutrophils may display an antigen-presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 (PD-L1). The current study was performed to investigate the effect of neutrophils and their pathophysiological significance during sepsis. METHODS: Neutrophil PD-L1 expression was determined in both septic mice (n = 6) and patients (n = 41). Neutrophils from septic mice were subtyped into PD-L1 and PD-L1 populations to determine their phenotypes and functions. Septic neutrophils were cocultured with lymphocytes to observe the effect of septic neutrophils on lymphocyte apoptosis. RESULTS: The PD-L1 level on neutrophils from septic mice was significantly up-regulated (21.41 ± 4.76%). This level increased with the progression of sepsis and the migration of neutrophils from the bone marrow to the blood and peritoneal cavity. The percentages of CD11a, CD62L, and C-C chemokine receptor type 2 were lower, whereas the percentages of CD16 and CD64 were higher on PD-L1 neutrophils than on PD-L1 neutrophils. The migratory capacity of PD-L1 neutrophils was compromised. Septic neutrophils induced lymphocyte apoptosis via a contact mechanism, and this process could be reversed by anti-PD-L1 antibody. PD-L1 was also up-regulated on neutrophils from patients with severe sepsis (14.6% [3.75%, 42.1%]). The levels were negatively correlated with the monocyte human leukocyte antigen-DR level and positively correlated with the severity of septic patients. Neutrophil PD-L1 was a predictor for the prognosis of severe sepsis, with an area of 0.74 under the receiver operating curve. CONCLUSIONS: PD-L1 is up-regulated on neutrophils during sepsis, which may be related to sepsis-induced immunosuppression.

Late Eocene to early Oligocene quantitative paleotemperature record: evidence from continental halite fluid inclusions.

Climate changes within Cenozoic extreme climate events such as the Paleocene-Eocene Thermal Maximum and the First Oligocene Glacial provide good opportunities to estimate the global climate trends in our present and future life. However, quantitative paleotemperatures data for Cenozoic climatic reconstruction are still lacking, hindering a better understanding of the past and future climate conditions. In this contribution, quantitative paleotemperatures were determined by fluid inclusion homogenization temperature (Th) data from continental halite of the first member of the Shahejie Formation (SF1; probably late Eocene to early Oligocene) in Bohai Bay Basin, North China. The primary textures of the SF1 halite typified by cumulate and chevron halite suggest halite deposited in a shallow saline water and halite Th can serve as an temperature proxy. In total, one-hundred-twenty-one Th data from primary and single-phase aqueous fluid inclusions with different depths were acquired by the cooling nucleation method. The results show that all Th range from 17.7°C to 50.7°C,with the maximum homogenization temperatures (ThMAX) of 50.5°C at the depth of 3028.04 m and 50.7°C at 3188.61 m, respectively. Both the ThMAX presented here are significantly higher than the highest temperature recorded in this region since 1954 and agree with global temperature models for the year 2100 predicted by the Intergovernmental Panel on Climate Change.

Blockade of ICAM-1 improves the outcome of polymicrobial sepsis via modulating neutrophil migration and reversing immunosuppression.

Intercellular adhesion molecule-1 (ICAM-1) is a key adhesion molecule mediating neutrophil migration and infiltration during sepsis. But its role in the outcome of sepsis remains contradictory. The current study was performed to investigate the role of anti-ICAM-1 antibody in the outcome of polymicrobial sepsis and sepsis-induced immune disturbance. Effect of anti-ICAM-1 antibody on outcome of sepsis induced by cecal ligation and puncture (CLP) was evaluated by the survival analysis, bacterial clearance, and lung injury. Its influence on neutrophil migration and infiltration, as well as lymphocyte status, in thymus and spleen was also investigated. The results demonstrated that ICAM-1 mRNA was upregulated in lung, thymus, and spleen of CLP mice. Anti-ICAM-1 antibody improved survival and bacterial clearance in CLP mice and attenuated lung injury. Migration of neutrophils to peritoneal cavity was enhanced while their infiltration into lung, thymus, and spleen was hampered by ICAM-1 blockade. Anti-ICAM-1 antibody also prevented sepsis-induced apoptosis in thymus and spleen. Positive costimulatory molecules including CD28, CD80, and CD86 were upregulated, while negative costimulatory molecules including PD-1 and PD-L1 were downregulated following anti-ICAM-1 antibody administration. In conclusion, ICAM-1 blockade may improve outcome of sepsis. The rationale may include the modulated neutrophil migration and the reversed immunosuppression.