Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes.

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

[Heme oxygenase-1 (HO-1) gene knockout affects the balance of lung immune cell composition and aggravates inflammatory injury in lung tissues of LPS-induced acute lung injury (ALI) mice].

Objective To evaluate the effects of heme oxygenase-1 (HO-1) gene deletion on immune cell composition and inflammatory injury in lung tissues of mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods C57BL/6 wild-type (WT) mice and HO-1 conditional-knockout (HO-1-/-) mice on the same background were randomly divided into four groups (n=5 in every group): WT control group, LPS-treated WT group, HO-1-/- control group and LPS-treated HO-1-/- group. LPS-treated WT and HO-1-/- groups were injected with LPS (15 mg/kg) through the tail vein to establish ALI model, while WT control group and HO-1-/- control group were injected with an equivalent volume of normal saline through the tail vein, respectively. Twelve hours later, the mice were sacrificed and lung tissues from each group were collected for analysis. Histopathological alterations of lung tissues were assessed by HE staining. The levels of mRNA expression of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-6 were determined by PCR. The percentages of neutrophils (CD45+CD11b+Ly6G+Ly6C-), total monocytes (CD45+CD11b+Ly6Chi), pro-inflammatory monocyte subsets (CD45+CD11b+Ly6ChiCCR2hi) and total macrophages (CD45+CD11b+F4/80+), M1 macrophage (CD45+CD11b+F4/80+CD86+), M2 macrophage (CD45+CD11b+F4/80+CD206+), total T cells (CD45+CD3+), CD3+CD4+ T cells, CD3+CD8+ T cells and myeloid suppressor cells (MDSCs, CD45+CD11b+Gr1+) were detected by flow cytometry. Results Compared with the corresponding control groups, HE staining exhibited increased inflammation in the lung tissues of both LPS-treated WT and HO-1-/- model mice; mRNA expression levels of TNF-α, IL-1ß and IL-6 were up-regulated; the proportions of neutrophils, total monocytes, pro-inflammatory monocyte subsets, MDSCs and total macrophages increased significantly. The percentage of CD3+, CD3+CD4+ and CD3+CD8+ T cells decreased significantly. Under resting-state, compared with WT control mice, the proportion of neutrophils, monocytes and pro-inflammatory monocyte subset increased in lung tissues of HO-1-/- control mice, while the proportion of CD3+ and CD3+CD8+ T cells decreased. Compared with LPS-treated WT mice, the mRNA expression levels of TNF-α and IL-1ß were up-regulated in lung tissues of LPS-treated HO-1-/- mice; the proportion of total monocytes, pro-inflammatory monocyte subsets, M1 macrophages and M1/M2 ratio increased greatly; the percentage of CD3+CD8+ T cells decreased significantly. Conclusion The deletion of HO-1 affects the function of the lung immune system and aggravates the inflammatory injury after LPS stimulation in ALI mice.

Identification of the C1qDC gene family in grass carp (Ctenopharyngodon idellus) and the response of C1qA, C1qB, and C1qC to GCRV infection in vivo and in vitro.

Proteins from the C1q domain-containing (C1qDC) family recognize self-, non-self-, and altered-self ligands and serves as an initiator molecule for the classical complement pathway as well as recognizing immune complexes. In this study, C1qDC gene family members were identified and analyzed in grass carp (Ctenopharyngodon idellus). Members of the C1q subfamily were cloned, and their response to infection with the grass carp virus was investigated. In the grass carp genome, 54 C1qDC genes and 67 isoforms have been identified. Most were located on chromosome 3, with 52 shared zebrafish homologies. Seven substantially differentially expressed C1qDC family genes were identified in the transcriptomes of cytokine-induced killer (CIK) cells infected with grass carp reovirus (GCRV), all of which exhibited sustained upregulation. The opening reading frames of grass carp C1qA, C1qB, and C1qC, belonging to the C1q subfamily, were determined to be 738, 732, and 735 base pairs, encoding 245, 243, and 244 amino acids with molecular weights of 25.81 kDa, 25.63 kDa and 26.16 kDa, respectively. Three genes were detected in the nine collected tissues, and their expression patterns were similar, with the highest expression levels observed in the spleen. In vivo after GCRV infection showed expression trends of C1qA, C1qB, and C1qC in the liver, spleen, and kidney. An N-type pattern in the liver and kidney was characterized by an initial increase followed by a decrease, with the highest expression occurring during the recovering period, and a V-type pattern in the spleen with the lowest expression levels during the death period. In vitro, after GCRV infection showed expression trends of C1qA, C1qB, and C1qC, and this gradually increased within the first 24 h, with a notable increase observed at the 24 h time point. After CIK cells incubation with purified recombinant proteins, rC1qA, rC1qB, and rC1qC for 3 h, followed by GCRV inoculation, the GCRV replication indicated that rC1qC exerted a substantial inhibitory effect on viral replication in CIK cells after 24 h of GCRV inoculation. These findings offer valuable insights into the structure, evolution, and function of the C1qDC family genes and provide a foundational understanding of the immune function of C1q in grass carp.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Prognostic role of urinary ketone body in patients with sepsis-associated encephalopathy without hepatic failure: a retrospective cohort study.

Sepsis-associated encephalopathy (SAE) is defined as a dysfunction of the central nervous system experienced during sepsis with variable clinical features. The study aims to identify the prognostic role of urinary ketone bodies in relation to clinical outcomes in patients with SAE. The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to conduct a retrospective cohort study. We recruited 427 patients with SAE admitted to the intensive care unit (ICU) from the MIMIC-III database. Patients with SAE were divided into a survival group (380 patients) and a non-survival group (47 patients). We used the Wilcoxon signed-rank test and the multivariate logistic regression analysis to analyze the relationship between the level of urinary ketone bodies and the clinical prognosis in patients with SAE. The primary outcome was the relationship between urinary ketone body levels and 28-day mortality of SAE. The secondary outcomes were the relationship between urinary ketone body levels and length of ICU stays, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment (SOFA), Glasgow Coma Scale, mechanical ventilation, renal replacement therapy, and the use of vasopressors. The 28-day mortality of patients with SAE was 11.0%. Urinary ketone body levels were not significantly associated with the 28-day mortality of patients with SAE. Urinary ketone body levels were associated with SOFA score and the use of vasopressors in patients with SAE. The SOFA score was an independent risk factor for the 28-day mortality in patients with SAE. Urinary ketone body levels were significantly associated with SOFA score and the use of vasopressors in patients with SAE. Furthermore, the SOFA score can predict the prognosis of short-term outcomes of patients with SAE. Therefore, we should closely monitor the changes of urinary ketone bodies and SOFA score and intervene in time.

Chalcogen Atom-Modulated Croconaine for Efficient NIR-II Photothermal Theranostics.

Organic dye-based agents with near-infrared (NIR)-II absorption have great potential for cancer theranostics because of the deeper tissue penetration and good biocompatibility. However, proper design is required to develop NIR-II-absorbing dyes with good optical properties. We proposed to construct chalcogen atom-modulated croconaine for NIR-II light-triggered photothermal theranostics. By introducing different chalcogen atoms (O, S, Se, or Te) into the structure of croconaine, the light absorption of croconaine can be precisely regulated from the NIR-I to the NIR-II range due to the heavy-atom effect. Especially, Te-substituted croconaine (CRTe) and its nanoformulations exhibit superior NIR-II responsiveness, a high photothermal conversion efficiency (70.6%), and good photostability. With their favorable tumor accumulation, CRTe-NPs from tumor regions can be visualized by NIR-II optoacoustic systems with high resolution and high contrast; meanwhile, their superior photothermal performance also contributes to efficient cell killing and tumor elimination upon 1064 nm laser irradiation. Therefore, this work provides an efficient strategy for the molecular design of NIR-II organic photothermal agents.

Enhanced EPR effects by tumour stromal cell mimicking nanoplatform on invasive pituitary adenoma.

Rapid advances in nanomedicine have enabled potential applications in cancer therapy. The enhanced permeability and retention (EPR) effect is the primary rationale for the passive targeting of nanoparticles in oncology. However, growing evidence indicates that the accumulation of nanomaterials via the EPR effect could be more efficient. Inspired by our clinical observation of the Gap Junction connecpion between folliculostellate cells and pituitary adenoma cells, we designed a novel drug delivery system that targets tumours by coating folliculostellate cell (FS) membranes onto PLGA nanoparticles (NPs). The resulting FSNPs, inheriting membrane proteins from the folliculostellate cell membrane, significantly enhanced the EPR effect compared to nanoparticles without cancer cell membranes. We further demonstrated that mitotane encapsulation improved the therapeutic efficacy of mitotane in both heterotopic and orthotopic pituitary adenoma models. Owing to its significant efficacy, our FS cell membrane-coated nanoplatforms has the potential to be translated into clinical applications for the treatment of invasive pituitary adenoma.

Nicotinamide mononucleotide alleviates endotoxin-induced acute lung injury by modulating macrophage polarization via the SIRT1/NF-κB pathway.

CONTEXT: Sepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities. OBJECTIVE: This study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro. MATERIALS AND METHODS: Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI. MH-S cells were stimulated with LPS (1 µg/mL) and NMN (500 µM) for 12 h grouping as control, LPS, and LPS + NMN. Cell viability, apoptotic status, and M1/2 macrophage-related markers were detected. The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527. After 12 h, lung histopathology, W/D ratio, MPO activity, NAD+ and ATP levels, M1/2 macrophage-related markers, and expression of the SIRT1/NF-κB pathway were detected. RESULTS: In MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%. In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD+ and ATP levels. Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation. Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization. CONCLUSIONS: NMN protects against sepsis-induced ALI by promoting M2 macrophage polarization via the SIRT1/NF-κB pathway, it might be an effective strategy for preventing or treating sepsis-induced ALI.

VNS-mediated α7nAChR signaling promotes SPM synthesis via regulation of netrin-1 expression during LPS-induced ALI.

The α7 nicotinic acetylcholine receptor (α7nAChR) plays a crucial role in the cholinergic anti-inflammatory pathway (CAP) during sepsis-associated acute lung injury (ALI). Increasing evidence suggests that specialized pro-resolving mediators (SPMs) are important in resolving α7nAChR-mediated ALI resolution. Our study aims to elucidate the pivotal role of α7nAChR in the CAP during LPS-associated acute lung injury (ALI). By employing vagus nerve stimulation (VNS), we identified α7nAChR as the key CAP subunit in ALI mice, effectively reducing lung permeability and the release of inflammatory cytokines. We further investigated the alterations in SPMs regulated by α7nAChR, revealing a predominant synthesis of lipoxin A4 (LXA4). The significance of α7nAChR-netrin-1 pathway in governing SPM synthesis was confirmed through the use of netrin-1 knockout mice and siRNA-transfected macrophages. Additionally, our evaluation identified a synchronous alteration of LXA4 synthesis in the α7nAChR-netrin-1 pathway accompanied by 5-lipoxygenase (5-LOX), thereby confirming an ameliorative effect of LXA4 on lung injury and macrophage inflammatory response. Concurrently, inhibiting the function of LXA4 annulled the lung-protective effect of VNS. As a result, our findings reveal a novel anti-inflammatory pathway wherein VNS modulates netrin-1 expression via α7nAChR, ultimately leading to LXA4 synthesis and subsequent lung protection.

4-Octyl itaconate alleviates renal ischemia reperfusion injury by ameliorating endoplasmic reticulum stress via Nrf2 pathway.

Renal ischemia-reperfusion injury (IRI) is a common clinical complication of multiple severe diseases. Owing to its high mortality and the lack of effective treatment, renal IRI is still an intractable problem for clinicians. Itaconate, which is a metabolite of cis-aconitate, can exert anti-inflammatory and antioxidant roles in many diseases. As a derivative of itaconate with high cell membrane permeability, 4-octyl itaconate (4-OI) could provide a protective effect for various diseases. However, the role of 4-OI in renal IRI is still unclear. Herein, we examined whether 4-OI afforded kidney protection through attenuating endoplasmic reticulum stress (ERS) via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. To observe the effects of 4-OI on alleviating renal pathologic injury, improving renal dysfunction, decreasing inflammatory cytokines, and reducing oxidative stress, we utilized C57BL/6J mice with bilateral renal pedicle clamped and HK-2 cells with hypoxia/reoxygenation (H/R) exposure in our study. In addition, through western blot assay, we found 4-OI ameliorated renal IRI-induced ERS, and activated Nrf2 pathway. Moreover, Nrf2-knockout (KO) mice and Nrf2 knockdown HK-2 cells were used to validate the role of Nrf2 signaling pathway in 4-OI-mediated alleviation of ERS caused by renal IRI. We demonstrated that 4-OI relieved renal injury and suppressed ERS in wild-type mice, while the therapeutic role was not shown in Nrf2-KO mice. Similarly, 4-OI could exert cytoprotective effect and inhibit ERS in HK-2 cells after H/R, but not in Nrf2 knockdown cells. Our in vivo and in vitro studies revealed that 4-OI protected renal IRI through attenuating ERS via Nrf2 pathway.

IP3R-1 aggravates endotoxin-induced acute lung injury in mice by regulating MAM formation and mitochondrial function.

Acute lung injury (ALI) caused by endotoxin represents one of the common clinical emergencies. Mitochondria-associated endoplasmic reticulum membranes (MAM) serve as a critical link between mitochondria and endoplasmic reticulum (ER), which has an essential effect on maintaining intracellular homeostasis. As an important component of MAM, type-1 inositol-1,4,5-trisphosphate receptor (IP3R-1) mediates the ER-to-mitochondrial transport of Ca2+. This study explored the role of IP3R-1 and MAM in ALI. Besides the levels of inflammasome-associated components interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malonyldialdehyde (MDA) were increased in both bronchoalveolar lavage fluid (BALF) and serum, increased cross-sectional area of mitochondria, elevated MAM formation, and decreased respiratory control ratio (RCR) were observed within lung tissues collected in lipopolysaccharide (LPS)-treated mice, accompanied by upregulation of IP3R-1 in total lung lysates and MAM. Ca2+ uptake level in the mitochondria, production of reactive oxygen species (ROS) in the mitochondria, and the formation of MAM were elevated within LPS-treated MLE-12 cells, and all those changes in response to LPS were partly inhibited by knocking down of IP3R-1 expression in MLE-12 cells. Collectively, IP3R-1 has a critical effect on MAM formation and mitochondrial dysfunction, which could be innovative therapeutic targets for ALI caused by endotoxin.

Myxobolus dumerilii sp. n. (Myxozoa: Myxobolidae) infecting the brain of Chinese longsnout catfish Tachysurus dumerili (Bleeker) in China.

During an investigation of Myxobolus diversity in the Chinese longsnout catfish Tachysurus dumerili (Bleeker), a new species infecting the intracranial epidermis of the host was discovered. Upon opening the cranial cavity, several round whitish plasmodia measuring 0.55-0.80 mm in diameter were observed. Fresh spores (n= 50) were pyriform in the frontal view and fusiform in the sutural view, with a length of 15.4±0.6 (13.9-16.5) µm, width of 9.1±0.4 (8.3-9.8) µm, and thickness of 7.0±0.4 (6.3-7.9) µm. The spores had smooth shell surfaces and transparent membrane sheaths in the posterior. No folds, intercapsular appendix, and caudal appendages were observed. Two equal polar capsules were pyriform and measured 7.5±0.5 (6.7-8.7) µm in length and 3.2±0.3 (2.5-3.6) µm in width. The polar filaments were coiled with five to six turns and perpendicular to the polar capsule length. A BLAST search indicated M. dumerilii sp. n. was closely related to five Myxobolus species (with sequences similarities ranging from 90.54% to 96.52%) found in different organs of yellow catfish Tachysurus fulvidraco (Richardson), rather than the T. dumerili-infecting species M. branchiola Dong and Zhao, 2014 (with 90.5% sequence similarity). Phylogenetic analysis showed that M. dumerilii sp. n. didn't form sister clade with brain-infecting Myxobolus spp, but clustered with M. jianlinensis Gao et Zhao, 2020 and M. voremkhai Akhmerov, 1960 within the Siluriformes-clade with highly supported values, indicating that the host specificity may play a stronger signal than site infections during the evolution of Myxobolus species. Based on the morphological, ecological, and molecular differences observed between the newly discovered species and other available Myxobolus species, M. dumerilii sp. n., is proposed and described in this study.

Structural comparison and expression function analysis of BF/C2 in Ctenopharyngodon idella and Squaliobarbus curriculus.

Ctenopharyngodon idella and Squaliobarbus curriculus, members of the Cyprinidae family and Yaroideae subfamily, have shown different levels of resistance to grass carp reo virus (GCRV), with S. curriculus exhibiting higher resilience. In the pursuit to explore the distinctions in the structural and expression traits of BF/C2 (A,B) between the two species, we conducted an analysis involving the cloning and examination of various coding sequences (CDS). We successfully cloned the CDS of ci-BF/C2A and ci-BF/C2B from C. idella, which spanned 2259 bp and 2514 bp respectively, encoding 752 and 837 amino acids. Similarly, the CDS of sc-BF/C2A and sc-BF/C2B from S. curriculus were cloned, featuring lengths of 1353 bp and 2517 bp and encoding 450 and 838 amino acids, respectively. A chromosome collinearity assessment revealed that ci-BF/C2A demonstrated collinearity with sc-BF/C2A, a finding not replicated with ci-BF/C2B and sc-BF/C2B. Delving into gene structure, we discerned that ci-BF/C2A harbored a greater number of Tryp_SPc domains compared to sc-BF/C2A. Following this, we engineered and purified six prokaryotic recombinant proteins: CI-BF/C2A, CI-BF/C2A1 (a variant resulting from the deletion of the Tryp_SPc domain of CI-BF/C2A), CI-BF/C2A2 (representing the Tryp_SPc domain of CI-BF/C2A), CI-BF/C2B, SC-BF/C2A, and SC-BF/C2B. Through serum co-incubation tests with these recombinant proteins, we established the activation of the complement marker C3 in each case. Utilizing fluorescence quantitative expression analysis, we observed ubiquitous expression of ci-BF/C2A and ci-BF/C2B across all grass carp tissues, predominantly in the liver. This pattern mirrored in S. curriculus, where sc-BF/C2A was highly expressed in the gills, and sc-BF/C2B manifested notably in the liver. Kidney cell infection experiments on both species revealed enhanced resistance to GCRV post-incubation with the recombinant proteins. Notably, cells treated with SC-BF/C2 (A, B) exhibited pronounced resilience compared to those treated with CI-BF/C2 (A, B, A1, A2). However, cells incubated with CI-BF/C2A1 and CI-BF/C2A2 showed strengthen resistance relative to cells treated with CI-BF/C2A and CI-BF/C2B. In GCRV infection trials on grass carp, ci-BF/C2A and ci-BF/C2B expressions reached a zenith on the seventh day post-infection, highlighting a distinctive functional mode in immune defense against GCRV infection orchestrated by BF/C2. The empirical data underscores the pivotal role of the Tryp_SPc domain in immune responses to GCRV infection, pinpointing its influence on ci-BF/C2A expression. Conclusively, this investigation provides a foundational understanding of the unique immune function characteristics of BF/C2 in grass carp, paving the way for further scholarly exploration in this realm.

Interleukin-17D produced by alveolar epithelial type II cells alleviates LPS-induced acute lung injury via the Nrf2 pathway.

BACKGROUND: Sepsis engenders an imbalance in the body's inflammatory response, with cytokines assuming a pivotal role in its progression. A relatively recent addition to the interleukin-17 family, denominated interleukin-17D (IL-17D), is notably abundant within pulmonary confines. Nevertheless, its implication in sepsis remains somewhat enigmatic. The present study endeavors to scrutinize the participation of IL-17D in sepsis-induced acute lung injury (ALI). METHODS: The levels of IL-17D in the serum and bronchoalveolar lavage fluid (BALF) of both healthy cohorts and septic patients were ascertained through an ELISA protocol. For the creation of a sepsis-induced ALI model, intraperitoneal lipopolysaccharide (LPS) injections were administered to male C57/BL6 mice. Subsequently, we examined the fluctuations and repercussions associated with IL-17D in sepsis-induced ALI, probing its interrelation with nuclear factor erythroid 2-related factor 2 (Nrf2), alveolar epithelial permeability, and heme oxygenase-1. RESULTS: IL-17D levels exhibited significant reduction both in the serum and BALF of septic patients (P<0.001). Similar observations manifested in mice subjected to LPS-induced acute lung injury (ALI) (P=0.002). Intraperitoneal administration of recombinant interleukin 17D protein (rIL-17D) prompted increased expression of claudin 18 and concomitant enhancement of alveolar epithelial permeability, thus, culminating in improved lung injury (P<0.001). Alveolar epithelial type II (ATII) cells were identified as the source of IL-17D, regulated by Nrf2. Furthermore, a deficiency in HO-1 yielded elevated IL-17D levels (P=0.004), albeit administration of rIL-17D ameliorated the exacerbated pulmonary damage resulting from HO-1 deficiency. CONCLUSION: Nrf2 fosters IL-17D production within AT II cells, thereby conferring a protective role in sepsis-induced ALI.

Tetramethylpyrazine ameliorates endotoxin-induced acute lung injury by relieving Golgi stress via the Nrf2/HO-1 signaling pathway.

PURPOSE: Endotoxin-induced acute lung injury (ALI) is a severe disease caused by an imbalanced host response to infection. It is necessary to explore novel mechanisms for the treatment of endotoxin-induced ALI. In endotoxin-induced ALI, tetramethylpyrazine (TMP) provides protection through anti-inflammatory, anti-apoptosis, and anti-pyroptosis effects. However, the mechanism of action of TMP in endotoxin-induced ALI remains unclear. Here, we aimed to determine whether TMP can protect the lungs by inhibiting Golgi stress via the Nrf2/HO-1 pathway. METHODS AND RESULTS: Using lipopolysaccharide (LPS)-stimulated C57BL/6J mice and MLE12 alveolar epithelial cells, we observed that TMP pretreatment attenuated endotoxin-induced ALI. LPS + TMP group showed lesser lung pathological damage and a lower rate of apoptotic lung cells than LPS group. Moreover, LPS + TMP group also showed decreased levels of inflammatory factors and oxidative stress damage than LPS group (P < 0.05). Additionally, LPS + TMP group presented reduced Golgi stress by increasing the Golgi matrix protein 130 (GM130), Golgi apparatus Ca2+/Mn2+ ATPases (ATP2C1), and Golgin97 expression while decreasing the Golgi phosphoprotein 3 (GOLPH3) expression than LPS group (P < 0.05). Furthermore, TMP pretreatment promoted Nrf2 and HO-1 expression (P < 0.05). Nrf2-knockout mice or Nrf2 siRNA-transfected MLE12 cells were pretreated with TMP to explore how the Nrf2/HO-1 pathway affected TMP-mediated Golgi stress in endotoxin-induced ALI models. We observed that Nrf2 gene silencing partially reversed the alleviating effect of Golgi stress and the pulmonary protective effect of TMP. CONCLUSION: Our findings showed that TMP therapy reduced endotoxin-induced ALI by suppressing Golgi stress via the Nrf2/HO-1 signaling pathway in vivo and in vitro.

5-Methoxytryptophan ameliorates endotoxin-induced acute lung injury in vivo and in vitro by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway.

BACKGROUND AND AIM: Endotoxin-induced acute lung injury (ALI) is a complicated and fatal condition with no specific or efficient clinical treatments. 5-Methoxytryptophan (5-MTP), an endogenous metabolite of tryptophan, was revealed to block systemic inflammation. However, the specific mechanism by which 5-MTP affects ALI still needs to be clarified. The purpose of this study was to determine whether 5-MTP protected the lung by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway. METHODS AND RESULTS: We used lipopolysaccharide (LPS)-stimulated C57BL/6 J mice and MH-S alveolar macrophages to create models of ALI, and 5-MTP (100 mg/kg) administration attenuated pathological lung damage in LPS-exposed mice, which was associated with decreased inflammatory cytokines and oxidative stress levels, upregulated protein expression of Nrf2 and HO-1, and suppressed Caspase-1 activation and NLRP3-mediated pyroptosis protein levels. Moreover, Nrf2-deficient mice or MH-S cells were treated with 5-MTP to further confirm the protective effect of the Nrf2/HO-1 pathway on lung damage. We found that Nrf2 deficiency partially eliminated the beneficial effect of 5-MTP on reducing oxidative stress levels and inflammatory responses and abrogating the inhibition of NLRP3-mediated pyroptosis induced by LPS. CONCLUSION: These findings suggested that 5-MTP could effectively ameliorate ALI by inhibiting NLRP3-mediated pyroptosis via the Nrf2/HO-1 signaling pathway.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Asymmetric Directional Control of Thermal Emission.

Control over the directionality of thermal emission plays a fundamental role in efficient heat transport. Although nanophotonic technologies have demonstrated the capability for angular-selective thermal emission, achieving asymmetric directional thermal emission in reciprocal systems with energy directed to a single output angle remains challenging due to symmetric band dispersion. In this work, a general strategy for achieving asymmetric directional thermal emission in reciprocal systems is presented. With periodic perturbation and broken mirror symmetry, metasurfaces behave as resonant metagratings whose resonances can be diffracted to symmetric output angles with distinct efficiency, allowing for high emissivity toward a single direction. An asymmetric directional thermal emitter is experimentally demonstrated at mid-infrared wavelengths with high emissivity (ɛ = 0.61) at the observation angle of +30°, and low emissivity (ɛ < 0.3) at other angles. This work highlights the potential for manipulating the directionality of thermal emission, which holds promise for developing ultrathin customized thermal sources and impacts on various thermal-engineering applications.