Detoxification effect of sodium thiosulfate on cadmium poisoning in Litopenaeus vannamei and the mechanisms of intestinal flora regulation.

Cadmium (Cd) is currently one of the heavy metals with the highest environmental toxicity impact. Sodium thiosulfate (Na2S2O3) is a commonly used heavy metal detoxification drug in clinical practice, however, it has not been used for Cd detoxification of Litopenaeus vannamei. The present study used exposure of L. vannamei to 150 µg/L of Cd while mitigating in the addition of 75 µg/L of Na2S2O3 for 28 days. The goal was to study the detoxifying effect of Na2S2O3 on L. vannamei poisoning and its role in intestinal flora. The results showed that the growth of Cd group was inhibited, and the growth rate and weight gain of Cd + ST group were greater than that of Cd group. The function and structure of L. vannamei intestinal microorganisms were significantly changed under Cd stress. This work reveals that Na2S2O3 can mitigate the damage caused by this concentration to L. vannamei to a certain extent.

Vitamin B12 protects necrosis of acinar cells in pancreatic tissues with acute pancreatitis.

Pharmacological agents regarding the most optimal treatments of acute pancreatitis remain. One-carbon metabolism nutrients as therapeutic agents in many diseases might be involved in acute pancreatitis. The roles are acquired exploration in acute pancreatitis. We utilized Mendelian randomization to assess the causal impact of folate, homocysteine, and vitamin B12 (VB12) on acute pancreatitis. Wild-type and corresponding genetically modified mouse models were used to verify the genetic correlating findings. A negative association between genetically predicted serum VB12 levels and risks of acute pancreatitis was identified in human population. The transcobalamin receptor (TCblR)/CD320 gene ablation that decreased cellular VB12 uptake and ATP production in pancreatic tissues promoted necrosis, resulting in much severe pathological changes of induced acute pancreatitis in mice. VB12 pretreatment and posttreatment dramatically increased ATP levels in pancreatic tissues and reduced the necrosis, then the elevated levels of amylase in serum, the levels of CK-19, the activity of trypsin, and T lymphocyte infiltration in pancreatic tissues, prevented the pancreatic gross loss and ameliorated histopathological changes of mouse pancreases with induced acute pancreatitis. The results reveal that VB12 is potential as a therapeutic agent to inhibit tissue injuries and adaptive inflammatory responses in the pancreas in patients with acute pancreatitis.

Network Pharmacology Analysis and Retrospective Cohort Study Revealing the Effect of Qingyi Decoction on Intestinal Paralysis in Patients with Severe Acute Pancreatitis.

BACKGROUND: Intestinal dysfunction plays an important role in the clinical progress and prognosis of severe acute pancreatitis (SAP). Qingyi decoction (QYD) has shown beneficial effects on intestinal function recovery, but the prevention actions of the QYD on intestinal paralysis and its mechanism have not been fully explored. METHODS: The possible molecular mechanism was unraveled by network pharmacology, including active ingredients and potential target prediction, as well as GO, KEGG, and REATCOME pathway enrichment analyses. The potential interactions between the main active ingredients of the QYD and core genes were explored by molecular docking. A retrospective cohort study on 137 patients with SAP from Tianjin Nankai Hospital was conducted to evaluate the preventive effect of QYD on intestinal paralysis. RESULTS: A total of 110 active ingredients in QYD were screened out, and 37 key targets were predicted by network pharmacology. GO, KEGG, and REATCOME enrichment analyses showed that bioinformatics annotation of the hub genes was mainly involved in intestinal epithelial functions and inflammatory response pathways. The main components of QYD possessed good affinity with IL-6, TNF, CASP3, CXCL8, and CRP by molecular docking. Patients who used QYD plus usual care seemed to have fewer intestinal paralysis rates, lower risk of renal insufficiency, ARDS and blood purification therapy, and shorter hospital and ICU stays. The multivariable regression analyses indicated that the mode of nasogastric and enemas administration of QYD (P = 0.010) and timely intervention with QYD (P = 0.045) were the independent protective factors for intestinal paralysis prevention in patients with SAP. CONCLUSION: In conclusion, QYD can be used as an effective adjuvant procedure to prevent the occurrence and development of intestinal paralysis in patients with SAP. The mechanisms may be involved in the anti-inflammatory response and maintenance of intestinal epithelial function.

Myxobolus dabryi n. sp. (Myxozoa: Myxobolidae) Infecting the Gills of Chanodichthys dabryi, Bleeker, 1871 (Cypriniformes: Cyprinidae) in Hunan Province, China.

Culters are a popular and economically important carnivorous freshwater fish, widely distributed in rivers, lakes, and reservoirs in China. An investigation of Myxozoa was conducted to enhance the understanding of Myxozoan diversity in Culters in China, as only 15 Myxosporean species have been previously reported in 6 Culters species. A new species with typical Myxobolus characteristics was discovered exclusively in the gills of Chanodichthys dabryi, Bleeker, 1871, and no other species were found in other Culters fish or organs. The new species elicited whitish plasmodia in the serosa layer of the gill arch, with no distinct inflammatory reaction observed. This species is morphologically different from all reported Myxobolus spp. from Culters, differing in plasmodium and spore size, as well as the coils of polar filaments. Molecular analysis further supports that it does not match any sequences available in GenBank. Therefore, we identified it as a new species and named it Myxobolus dabryi n. sp.

Acute kidney injury associated with thrombotic microangiopathy: Characterization, prevalence, and prognosis.

Acute kidney injury (AKI) is an important feature of thrombotic microangiopathy (TMA). This present study aimed to describe and analyze the characterization, prevalence, and prognosis in TMA patients with AKI. This study was an observational, retrospective patient cohort study in which patients were classified as AKI and non-AKI groups. An analysis of the relationship between the risk factors and AKI and in-hospital mortality was conducted using logistic regression. Kaplan-Meier curves were adopted to obtain the link between AKI and in-hospital mortality. There were 27 and 51 patients in the AKI and non-AKI groups, respectively, and the morbidity and mortality of AKI were 34.62% and 40.74%, respectively. AKI was associated with an older age (P = .033) and higher infection rates (P < .001). In comparison with the non-AKI group, the AKI group had tremendously intrarenal manifestations: hematuria (P < .001), proteinuria (P < .001). The AKI group received all continuous renal replacement therapy treatment (P < .001), but fewer glucocorticoids were used (P = .045). In-hospital mortality (P = .045) were higher in the AKI group. The risk factors for AKI (P = .037) were age. In addition, higher total bilirubin (P = .011) and age (P = .022) were significantly correlated with increasing risk of in-hospital mortality. Survival analysis by Kaplan-Meier revealed a significantly poor prognosis predicted by the AKI group (P = .045). Acute kidney injury could be commonly seen in TMA pneumonia and was related to a higher mortality rate.

The mitigating effects and mechanisms of Bacillus cereus on chronic cadmium poisoning in Litopenaeus vannamei based on histopathological, transcriptomic, and metabolomic analyses.

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.

Electroacupuncture pretreatment maintains mitochondrial quality control via HO-1/MIC60 signaling pathway to alleviate endotoxin-induced acute lung injury.

Electroacupuncture has been demonstrated to mitigate endotoxin-induced acute lung injury by enhancing mitochondrial function. This study investigates whether electroacupuncture confers lung protection through the regulation of mitochondrial quality control mediated by heme oxygenase-1 (HO-1) and the mitochondrial inner membrane protein MIC60. HO-1, an inducible stress protein, is crucial for maintaining mitochondrial homeostasis and protecting against lung injury. MIC60, a key component of the mitochondrial contact site and cristae organizing system, supports mitochondrial integrity. We employed genetic knockout/silencing and cell transfection techniques to model lipopolysaccharide (LPS)-induced lung injury, assessing changes in mitochondrial structure, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and the expression of proteins essential for mitochondrial quality control. Our findings reveal that electroacupuncture alleviates endotoxin-induced acute lung injury and associated mitochondrial dysfunction, as evidenced by reductions in lung injury scores, decreased ROS production, and suppressed expression of proteins involved in mitochondrial fission and mitophagy. Additionally, electroacupuncture enhanced MMP and upregulated proteins that facilitate mitochondrial fusion and biogenesis. Importantly, the protective effects of electroacupuncture were reduced in models with Hmox1 knockout or Mic60 silencing, and in macrophages transfected with Hmox1-siRNA or Mic60-siRNA. Moreover, HO-1 was found to influence MIC60 expression during electroacupuncture preconditioning and LPS challenge, demonstrating that these proteins not only co-localize but also interact directly. In conclusion, electroacupuncture effectively modulates mitochondrial quality control through the HO-1/MIC60 signaling pathway, offering an adjunctive therapeutic strategy to ameliorate endotoxin-induced acute lung injury in both in vivo and in vitro settings.

Toxic effects and mechanisms of chronic cadmium exposure on Litopenaeus vannamei growth performance based on combined microbiome and metabolome analysis.

Cadmium (Cd) pollution seriously affects marine organisms' health and poses a threat to food safety. Although Cd pollution has attracted widespread attention in aquaculture, little is known about the toxic mechanisms of chronic Cd exposure on shrimp growth performance. The study investigated the combined effects of chronic exposure to Cd of different concentrations including 0, 75, 150, and 300 µg/L for 30 days on the growth performance, tissue bioaccumulation, intestinal microbiology, and metabolic responses of Litopenaeus vannamei. The results revealed that the growth was significantly inhibited under exposure to 150 and 300 µg/L Cd2+. The bioaccumulation in gills and intestines respectively showed an increasing and inverted "U" shaped trend with increasing Cd2+ concentration. Chronic Cd altered the intestinal microflora with a significant decrease in microbial richness and increasing trends in the abundances of the potentially pathogenic bacteria Vibrio and Maribacter at exposure to 75 and 150 µg/L Cd2+, and Maribacter at 300 µg/L. In addition, chronic Cd interfered with intestinal metabolic processes. The expressions of certain metabolites associated with growth promotion and enhanced antioxidant power, including N-methyl-D-aspartic acid, L-malic acid, guanidoacetic acid, betaine, and gluconic acid were significantly down-regulated, especially at exposure to 150 and 300 µg/L Cd2+, and were negatively correlated with Vibrio and Maribacter abundance levels. In summary, chronic Cd exposure resulted in severe growth inhibition and increased Cd accumulation in shrimp tissues. Increased levels of intestinal pathogenic bacteria and decreased levels of growth-promoting metabolites may be the key causes of growth inhibition. Harmful bacteria Vibrio and Maribacter may be associated with the inhibition of growth-promoting metabolite expression and may be involved in disrupting intestinal metabolic functions, ultimately impairing shrimp growth potential. This study sheds light on the potential toxicological mechanisms of chronic Cd inhibition on shrimp growth performance, offering new insights into Cd toxicity studies in aquaculture.

Solar Energy-Driven Reverse Water Gas Shift Reaction: Photothermal Effect, Photoelectric Activation and Selectivity Regulation.

Excessive carbon dioxide (CO2) emissions are one of the main causes of the greenhouse effect. Thermal catalytic reverse water gas shift (RWGS) reaction, which is a pre reaction for Fischer-Tropsch synthesis, is considered an effective way to convert CO2 and synthesize high value-added chemicals in industry. However, traditional thermal catalysis requires a large amount of fossil fuels to drive reactions, which cannot achieve the true goal of carbon neutrality. Photothermal catalysis, as a novel conversion pathway, can achieve efficient CO2 conversion while significantly improving solar energy utilization. This review provides a detailed introduction of CO2 and H2 adsorption/activation and reaction pathways in thermal catalysis, as well as the catalytic mechanisms of thermal and chemical effects in photothermal catalytic RWGS to supply readers valuable insights on the mechanism of photothermal catalytic RWGS reaction and provide a reference for better catalyst design.

[Nuclear factor E2-related factor 2 attenuates endotoxin-induced acute lung injury by up-regulating cellular tight junction protein Claudin-18 expression].

OBJECTIVE: To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) on the cellular tight junction protein Claudin-18 in endotoxin-induced acute lung injury (ALI). METHODS: Eighteen healthy male C57BL/6 mice were divided into control group, endotoxin-induced ALI model group (ALI group) and Nrf2 activator tert-butylhydroquinone (tBHQ) pretreatment group (tBHQ+ALI group) according to random number table method, with 6 mice in each group. Mice endotoxin-induced ALI model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS, 15 mg/kg), and the mice in the control group was injected with an equal amount of phosphate buffer solution (PBS). The mice in the tBHQ+ALI group received three intraperitoneal injections of tBHQ (a total of 50 mg/kg) at an interval of 1 hour before molding. The last injection of tBHQ was accompanied by LPS of 15 mg/kg. The mice in the control group and model group were given equal amounts of PBS, and PBS or LPS was given at the last injection. The mice were sacrificed at 12 hours after LPS injection to take lung tissues. After the lung tissue was stained with hematoxylin-eosin (HE) staining, the pathological changes were observed under light microscopy, and the lung injury score was calculated. The lung wet/dry ratio (W/D) was determined. Nrf2 protein expression in the lung tissue was detected by Western blotting. Positive expression of Claudin-18 in the lung tissue was determined by immunohistochemistry. RESULTS: The lung tissue showed normal structure, without significant pathological change in the control group. Compared with the control group, the alveolar septum widened accompanied by inflammatory cell infiltration, capillary hyperemia and tissue edema in the ALI group, the lung injury score and lung W/D ratio were significantly increased (lung injury score: 6.50±1.05 vs. 1.83±0.75, lung W/D ratio: 3.79±0.22 vs. 3.20±0.14, both P < 0.01), and the Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly lowered [Nrf2 protein (Nrf2/ß-actin): 0.41±0.33 vs. 1.22±0.33, Claudin-18 (A value): 0.28±0.07 vs. 0.44±0.10, both P < 0.05]. After tBHQ pretreatment, the degree of lung histopathological injury was significantly reduced compared with the ALI group, the alveolar space slightly abnormal, inflammatory cell infiltration and tissue edema reduced, the lung injury score and lung W/D ratio were significantly decreased (lung injury score: 3.00±0.89 vs. 6.50±1.05, lung W/D ratio: 3.28±0.19 vs. 3.79±0.22, both P < 0.01), and Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly increased [Nrf2 protein (Nrf2/ß-actin): 1.26±0.09 vs. 0.41±0.33, Claudin-18 (A valure): 0.45±0.04 vs. 0.28±0.07, both P < 0.05]. CONCLUSIONS: Nrf2 alleviated pulmonary edema and improved endotoxin-induced ALI by up-regulating Claudin-18 expression.

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.

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.

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.

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.

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.

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.