[A case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning].

Acute carbon monoxide poisoning can cause hypoxic injury to multiple organs. Neurological impairment and cardiac dysfunction are common manifestations of severe poisoning patients, but hemorrhagic complications are rare in clinic. The clinical diagnosis and treatment of a case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning was reported. The pathophysiological mechanism and treatment strategy of rectus sheath hematoma secondary to acute severe carbon monoxide poisoning was analyzed, in order to improve the understanding of hemorrhagic complications of carbon monoxide poisoning. This case suggests that for patients with a history of cardiovascular disease and taking anticoagulants, clinicians should be alert for the risk of bleeding when making medical decisions.

[Clinical features of anti-neurofascin-155 antibody positive autoimmune nodopathy in 6 children].

Objective: To analyze the clinical features of anti-neurofascin-155 (NF155) antibody positive autoimmune nodopathy in children. Methods: This was a case series study. A total of 6 children who were diagnosed accurately as anti-NF155 antibody positive autoimmune nodopathy by cell immunofluorescence assay at the Children's Hospital of Fudan University from January 2020 to December 2023 were collected. This study retrospectively analyzed 6 pediatric children's clinical manifestations, laboratory and electrophysiological examination results, and treatment outcomes. Results: Among 6 children with anti-NF155 antibody positive autoimmune nodopathy, there were 4 boys and 2 girls. The onset age of 6 children ranged from 3 years and 8 months to 12 years. All 6 children had extremity weakness (more severe in the distal and the lower extremities than in the upper extremities), 5 children had sensory deficits such as numbness or pain in the extremities, 4 children had tremors and ataxia, 3 children had cranial nerve involvement. Among the 6 children, 4 children had protein-cell separation in cerebrospinal fluid examinations. Among the 6 children, 1 child had central nervous system demyelination, the brain magnetic resonance imaging showed multiple abnormal signals in the bilateral cerebral hemispheres. Four children showed motor and sensory nerve damage in electrophysiological examination, and 2 children only showed motor nerve damage. Three children showed myelin and axonal damage, and 3 children only showed axonal damage. Among the 6 children, 5 children were treated with intravenous immunoglobulin and steroids. Among them, 2 children underwent plasma exchange due to poor efficacy, and subsequently, rituximab was added. There was 1 child changed the treatment with olfatomumab since the symptoms did not significantly improve after using rituximab. After treatment for 4-15 months, 2 children had no clinical symptoms, 1 child had improvement in clinical symptoms, 2 children had no significant improvement in clinical symptoms, and 1 child who did not receive the immunotherapy had no significant change in clinical symptoms. Conclusions: Anti-NF155 antibody positive autoimmune nodopathy in children presents with varying degrees of clinical manifestations. It is mainly characterized by extremity weakness, numbness and pain, often accompanied bytremorsand ataxia. Some pediatric patients may also have central nervous system demyelination. Cerebrospinal fluid and electrophysiological examination are important auxiliary examination methods. If steroid therapy is not effective, plasma exchange and rituximab treatment should be used as soon as possible.

Circular E3 ubiquitin-protein ligase improves renal function and alleviates inflammation and renal injury in chronic glomerulonephritis rats via the microRNA-146a-5p / tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma axis.

Circular E3 ubiquitin-protein ligase (circ-ITCH), a novel circRNA, is generated from several exons of itchy E3 ubiquitin protein ligase. Reports on circ-ITCH have discussed its pathogenic performance in human diseases. Based on this, this study determines whether and how circ-ITCH is involved in the pathogenesis of chronic glomerulonephritis (CGN). First, a rat model of CGN induced by cationic bovine serum albumin was established. Then, CGN rats were injected with lentiviruses interfering with the expression of circ-ITCH, miR-146a-5p or tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG). Then, blood urea nitrogen and serum creatinine levels were measured to evaluate renal function; inflammatory factor content and fibrosis marker expression in kidney tissue were detected; renal pathological damage was analyzed by hematoxylin-eosin staining and periodic acid-Schiff staining. Finally, the binding relationship between miR-146a-5p and circ-ITCH or YWHAG was verified. Elevating circ-ITCH or depleting miR-146a-5p improved renal function (both P<0.05), reduced inflammatory factor content and fibrosis marker expression (all P<0.05) and alleviated renal pathological damage in CGN rats. Circ-ITCH negatively regulated miR-146a-5p expression by adsorbing miR-146a-5p (P<0.05), and miR-146a-5p inhibited YWHAG expression by binding to the 3'-UTR of YWHAG (P<0.05). Loss of YWHAG reversed the protective effect of upregulated circ-ITCH in CGN rats (all P<0.05). We conclude that circ-ITCH improves renal function and attenuates inflammation and renal injury in rats with CGN via the miR-146a-5p/YWHAG axis.

Dietary sodium sulphate supplementation during mid-to-late gestation improves placental angiogenesis, bile acid metabolism, and serum amino acid concentrations of sows.

Sulphate plays a vital role in the growth and development of the foetus. Sodium sulphate (Na2SO4) is utilised as a dietary protein nutrient factor and helps replenish sulphur elements in livestock and poultry. Therefore, this study aimed to investigate the effects of Na2SO4 supplementation in mid to late pregnancy on bile acid metabolism, amino acid metabolism, placental vascular development and antioxidant capacity of sows. At day 1 of gestation (G1), a total of twenty-six primiparous sows were carefully chosen and randomised into two groups: (1) control group, (2) Na2SO4 group (1.40 g/kg). Blood samples and placentas from sows were collected to measure biochemistry parameters, antioxidant indexes, placental vascular density, and indicators related to bile acid metabolism and amino acid concentrations, respectively. We found that dietary supplementation with Na2SO4 had a tendency for a reduction of incidence of stillborn at farrowing. Further observation showed that sows supplemented with Na2SO4 had decreased total bile acid level in cord blood, and increased placental gene expression of sulphotransferase and organic anion transport peptide. Na2SO4 supplementation increased catalase and total superoxide dismutase activity in cord blood, decreased placental malondialdehyde content, and enhanced placental protein expression of Sirtuin 1. Moreover, Na2SO4 consumption resulted in increased vascular density of placental stroma and elevated amino acid levels in sows and cord blood. Furthermore, maternal Na2SO4 consumption reduced serum urea concentrations of sows and umbilical cord blood at G114. In addition, dietary supplementation with Na2SO4 activated the protein expression of the placental mechanistic target of rapamycin complex 1. Collectively, these findings indicated that maternal supplementation with Na2SO4 during mid-to-late gestation elevated foetal survival via improving placental angiogenesis, bile acid metabolism and amino acid utilisation.

[Application of Bi's intestinal loop binding in treating patients with critical esophagojejunal anastomosis leakage].

Objective: To assess the safety and feasibility of Bi's intestinal loop binding treatment of esophageal jejunal anastomotic leak after total gastrectomy. Methods: Bi's Intestinal loop binding are suitable for patients who underwent radical total gastrectomy+Roux-en-Y anastomosis and were confirmed by upper gastrointestinal angiography to have esophageal jejunal anastomotic leakage and whose conservative or endoscopic treatment was ineffective. The operation procedure is as follows: take the original central incision of the upper abdomen, remove the abscess around the anastomoses after ventral incision, and place drainage tube inside the abscess, which is convenient to rinse and drain after operation. A double 1-0 VICRYL is applied to the loop of gastrointestinal surrogate 10-15 cm proximal to the jejuno-jejunal anastomosis. The knot tension is tight to prevent regurgitation of digestive juices, but too much force should be avoided to cut the intestinal tract. Nutritional jejunostomy fistula was performed at 10‒15 cm distal to the jejuno-jejunal anastomosis and gastric tube was retained during the operation. The preoperative and postoperative data from 12 patients with jejunal esophageal anastomotic leak after total radical gastrectomy and Roux-en-Y anastomosis were retrospectively analyzed from October 2016 to January 2023 in gastrointestinal surgery and pancreas surgery at Shanxi People's Hospital, and observed the curative effect. Results: 12 patients were managed with Bi's Intestinal loop binding, operative time (60.0±20.8) minutes, median bleeding (50±10.8) ml, median hospital stay 20(12~28) days, and median reviewing upper and mid Gastrointestinal Contrast time postoperatively 61(52~74) days. The results showed that the anastomoses healed well, all the small intestine showed good imaging, the binding wire fell off by itself, and two patients had incision infection. Conclusions: It is safe and feasible for patients with esophageal jejunostomy fistulae after total gastrectomy to use the method of Bi's Intestinal loop binding.

[Recent advance in neurological complications following wasp stings].

Wasp sting refers to a series of clinical syndromes caused by the venom in the tail poison sac of the poisonous bee when attacking the attacked body, mainly manifested as local skin damage, systemic allergic reaction and multi-organ dysfunction syndrome (MODS) . Wasp venom can also act on the nervous system, and cause rare complications such as cerebral hemorrhage, subarachnoid hemorrhage, cerebral infarction, epilepsy, encephalitis, and Parkinson's disease, which can seriously affect the prognosis. This review will elaborate the above complications for clinical reference.

[Pulmonary artery stenosis after single lung transplantation: a case report and literature review].

Objective: To summarize and analyze the clinical features, treatment, and prognosis of pulmonary artery stenosis post-lung transplantation. Methods: A 62-year-old male patient was admitted to the hospital with a cough and chest tightness of over a year's duration, which had worsened in the last two months, leading to the diagnosis of idiopathic pulmonary fibrosis. The clinical data were observed and reviewed post-left allograft single lung transplantation. Literature searches were conducted using the keywords "lung transplantation" "stenosis, pulmonary artery" and "postoperative complications" in CNKI, Wanfang Medical Network, and PubMed databases up to December 2022. Results: On January 26, 2022, a left allograft single lung transplantation was performed under general anesthesia. Postoperatively, extracorporeal membrane oxygenation and mechanical ventilation were successfully weaned off at 22 hours and 2 days, respectively, with transfer from the intensive care unit 12 days after surgery. PaO2 and PaCO2 were 50 mmHg and 40 mmHg after deoxygenation. Both pulmonary CT angiography and ventilatory-perfusion imaging indicated stenosis of the left pulmonary anastomosis. Balloon dilation and pulmonary artery stenting were performed, with PaO2 and PaCO2 improving to 87 mmHg and 42 mmHg, respectively. The patient was discharged 102 days post-surgery, and was followed up for 1 year, with a good prognosis. Additionally, 36 related articles were retrieved, encompassing 69 cases with a median age of 53 years (38.5-59.0 years). Of these, 27.54% (19/69) were diagnosed with idiopathic pulmonary fibrosis, 46.38% (32/69) underwent single lung transplantation, with the primary clinical symptom being hypoxemia in 71.01% (49/69) cases. Left pulmonary artery anastomotic stenosis was observed in 43.48% (30/69), with 65.22% (45/69) being diagnosed in the late postoperative period. Interventional therapy was performed to 44.93% (31/69), with a mortality rate of 21.74% (15/69). Conclusions: The primary clinical manifestation of post-lung transplantation pulmonary artery stenosis is hypoxemia and can be diagnosed by pulmonary artery CT angiography, transesophageal echocardiography, and pulmonary angiography. Early diagnosis can significantly reduce mortality, and interventional therapy is an effective treatment for severe pulmonary artery stenosis post-lung transplantation.

[A case of acute poisoning of typhonium giganteum engler].

Unicorn lotus is a plant tuber in the araceae family, which has therapeutic effects such as dispelling cold and dampness, dispelling wind and phlegm, and treating stroke. However, acute poisoning of fresh Unicorn lotus has been rarely reported domestically and internationally. This article reports a case of poisoning caused by chewing unicorn lotus. The patient experienced numbness in the lips, swelling and rupture of the oral cavity, continuous salivation, difficulty swallowing and obvious burning sensation in the throat, accompanied by shortness of breath and mild hypoxemia. After receiving comprehensive treatments such as oxygen therapy, electrocardiographic monitoring, cleaning of necrotic oral mucosa, anti infection, inhibition of oral salivary secretion, and nutritional support, the patient finally recovered and was discharged.

Development of a clinical prediction model for diabetic kidney disease with glucose and lipid metabolism disorders based on machine learning and bioinformatics technology.

OBJECTIVE: In this study, we investigated the internal relationship between the pathogenesis of diabetic kidney disease (DKD) and abnormal glucose and lipid metabolism to identify potential biomarkers for diagnosis and treatment and investigated the role of the immune microenvironment of glucose and lipid metabolism disorders in the occurrence and progression of DKD. MATERIALS AND METHODS: The chip datasets GSE104948 and GSE96804 from the Gene Expression Common Database (GEO) were merged using the "lima" and "sva" software packages in R Software (4.2.3), and the merged dataset was used as the validation set. The intersection between the differential genes of DKD and the glucose and lipid metabolism genes in the MSigDB database was identified, and a nomogram of the incidence risk of DKD was built using three machine learning methods, namely LASSO regression, support vector machine (SVM), and random forest (RF), to validate the accuracy of the prediction model. Immune scores were conducted using the unsupervised clustering method, and patients were divided into two subgroups. The two subgroups were screened for differential genes for enrichment analysis. The differential genes of patients diagnosed with DKD were clustered into two gene subgroups for co-expression analysis. In this study, we utilized the Cytoscape software to construct a network of interactions among key genes. RESULTS: Using machine learning, a diagnostic model was developed with G6PC and HSD17B14 as key factors. Enrichment analysis and immune scoring demonstrated that the development of DKD was related to the imbalance in the microenvironment brought about by glucose lipid metabolism disorders. CONCLUSIONS: G6PC and HSD17B14 may be potential biomarkers for DKD, and the established predictive model is more helpful in predicting the incidence of DKD.

Dietary supplementation of proteases on growth performance, nutrient digestibility, blood characteristics and gut microbiota of growing pigs fed sorghum-based diets.

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.

Gold(I) ion and the phosphine ligand are necessary for the anti-Toxoplasma gondii activity of auranofin.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondii's invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.

Size- and concentration-dependent effects of microplastics on soil aggregate formation and properties.

Plastics fragment and threaten soil ecosystems. Degradation of soil structure is one of the risks. Despite this, data on impacts of different sized microplastics (MPs) on soil aggregates is lacking. This study systematically investigated the effects of pristine polyethylene powders of different sizes (< 35, < 125, < 500 µm) and concentrations (0, 0.1, 1.0, 10 wt%) on aggregate formation and their properties for two contrasting soils (woodland soil, WS; agricultural soil, AS). 75 day wet-dry cycles produced newly-formed aggregates in all treatments. MP size and concentration impacted the incorporation of MPs in aggregates and this varied with aggregate size; the size distribution of aggregates also varied with MP size and concentration. Aggregates produced in soil containing 10 wt% < 35 µm MPs had significantly lower MWDs (mean weight diameters) than controls. The wettability of aggregates (> 4 mm) reduced with increasing MP exposure concentration and decreasing MP exposure size. MP incorporation decreased the water stability of aggregates (1-2 mm) in WS but increased it in AS. The particle density of aggregates (> 4 mm) significantly decreased with increasing MP concentration, whereas MP size had no effect. As MPs breakdown, fragment and become smaller over time, their potential risk to the aggregated structure of soil increases.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

[Clinical value of arterial stiffness assessment on risk prediction of vascular stiffness in the octogenarian elderly].

Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.

Effects of dietary methionine supplementation from different sources on growth performance and meat quality of barrows and gilts.

Methionine is indispensable for growth and meat formation in pigs. However, it is still unclear that increasing dietary sulphur-containing amino acid (SAA) levels using different methionine sources affects the growth performance and meat quality of barrows and gilts. To investigate this, 144 pigs (half barrows and half gilts) were fed the control (100% SAA, CON), DL-Methionine (125% SAA, DL-Met)-supplemented, or OH-Methionine (125% SAA, OH-Met)-supplemented diets during the 11-110 kg period. The results showed that plasma methionine levels varied among treatments during the experimental phase, with increased plasma methionine levels observed following increased SAA consumption during the 25-45 kg period. In contrast, pigs fed the DL-Met diet had lower plasma methionine levels than those fed the CON diet (95-110 kg). Additionally, gilts fed the DL-Met or OH-Met diets showed decreased drip loss in longissimus lumborum muscle (LM) compared to CON-fed gilts. OH-Met-fed gilts had higher pH45min values than those fed the CON or DL-Met diets, whereas OH-Met-fed barrows had higher L45min values than those fed the CON or DL-Met diets. Moreover, increased consumption of SAA, regardless of the methionine source, tended to decrease the shear force of the LM in pigs. In conclusion, this study indicates that increasing dietary levels of SAA (+25%) appeared to improve the meat quality of gilts by decreasing drip loss and increasing meat tenderness.

[Notch1 inhibits the mechanistic role of STING signaling to regulate hepatocyte lipophagy in nonalcoholic steatohepatitis].

Objective: To study the mechanistic role of myeloid-specific Notch1 knockout inhibiting STING signaling to regulate hepatocyte lipophagy. Methods: A mouse model of nonalcoholic steatohepatitis (NASH) was established using a high-fat diet (HFD) and mouse bone marrow-derived macrophages (BMMs). Primary hepatocytes were isolated to construct a co-culture system. Twelve Notch1(FL/FL) mice were randomly divided into two groups: the Notch1(FL/FL) + normal diet (NCD) and the Notch1(FL/FL) + HFD group. Further, 12 Notch1(M-KO) mice were randomly divided into two groups: Notch1(M-KO) + NCD, and Notch1(M-KO) + HFD group.Serum alanine aminotransferase (sALT), total cholesterol (TC) and triglyceride (TG) were collected from mice serum samples. Liver tissue samples were collected for H&E staining, immunofluorescence (IF), Western blot and qRT-PCR. Tumor necrosis factor (TNF)-α was detected in the supernatant by enzyme-linked immunosorbent assay (ELISA). The comparison of inter group data was conducted using a t-test. Results: The mouse NASH model, mouse BMMs co-culture system, and primary hepatocytes were successfully constructed. Compared with the Notch1(FL/FL) + HFD group, the Notch1(M-KO) + HFD group showed a significant increase in serum ALT [(250.02 ± 58.21) U/L vs (370.70 ± 54.57) U/L, t = 3.705, P = 0.004], TG [(29.90 ± 3.54) mg/g vs (43.83 ± 8.56) mg/g, t = 3.685, P = 0.004], and TC [(33.70 ± 8.43) mg/g vs (90.53 ± 12.53) mg/g, t = 9.917, P < 0.001]. HE staining of liver tissue showed remarkable balloon-like alterations in liver cells, while IF staining demonstrated increased macrophage infiltration (t = 7.346, P < 0.001). Compared with the hepatocyte group co-cultured with Notch1(FL/FL) BMMs, the BODIPY probe showed a significant increase in lipid droplet (LDs) deposition in liver cells in the Notch1(M-KO) group (t = 3.835, P < 0.001). The co-localization of lysosomal associated membrane protein 1 (LAMP1), LDs (t = 7.103, P < 0.001), microtubule-associated protein light chain 3 (LC3) -II/LC3-I (t = 5.0, P = 0.007), and autophagy associated gene 12 (Atg12) (t = 28.36, P < 0.001) had decreased expression, while P-62 had increased expression (t = 3.253, P = 0.03), indicating a decrease in autophagic flow. Additionally, LC3 and LDs colocalization decreased (t = 5.24, P = 0.0003), indicating reduced lipophagy. Compared with the Notch1(FL/FL) group, the Notch1(M-KO) BMMS mouse group showed an increase in the expression of p-STING (t = 5.318, P = 0.006), p-TANK1 binding kinase 1 (TKB1) (t = 6.467, P = 0.002), p-interferon regulatory factor 3 (IRF3) (t = 14.61, P < 0.001), and p-P65 (t = 12.7, P = 0.002) protein, accompanied by mRNA expression of the inflammatory mediators interferon (IFN)-ß (t = 7.978, P < 0.001), TNFα (t = 8.496, P = 0.001), interleukin-1 ß (IL-1 ß) (t = 4.7, P < 0.001), and CXCL-10 (t = 4.428, P = 0.001). The STING gene was knocked out in the BMMs Notch1(M-KO) mice using CRISPR/Cas9. Compared with the CRISPR-Control group, the expression of P-TKB1 (t = 2.909, P = 0.044), p-IRF3 (t = 10.96, P < 0.001), p-IRF3 (t = 10.96, P < 0.001), and p-P65 (t = 7.091, P = 0.002) proteins was lower in the STING-KO BMMs group. The release of TNF-α in the supernatant was decreased (732.3 ± 129.35 pg/ml vs. 398.17 ± 47.15 pg/ml, t = 4.204, P = 0.014). However, in hepatocytes co-cultured with STING-KO BMMs, LC3-II/LC3-I (t = 7.546, P = 0.001) increased, p-62 (t = 10.96, P < 0.001) expression decreased, autophagic flow increased, and the colocalization of LC3 and LDs increased, lipophagy increased, and LDs deposition decreased. Conclusion: Myeloid-specific Notch1 knockout can activate macrophages STING signaling, increase the expression of inflammatory mediator genes, inhibit the occurrence of autophagy flow and lipophagy in hepatocyte cells, and aggravate LDs deposition and NASH progression.

Ethanol, not water, should be used as the dispersant when measuring microplastic particle size distribution by laser diffraction.

Size distribution is a crucial characteristic of microplastics (MPs). A typical method for measuring this property is wet laser diffraction. However, when measuring size distributions of MPs, despite it being a poor dispersant for many MPs, water is commonly selected, potentially limiting the reliability of reported measurements. To evaluate dispersant suitability, different aqueous concentrations of ethanol (0, 10, 20, 30, 40, 50, 75, 100 wt%) and aqueous solutions of 0.001 wt% Triton X-100 and a mixture comprising 10 wt% sodium pyrophosphate and 10 wt% methanol were used as dispersants in a laser granulometer (Mastersizer 2000) to determine particle size distributions (PSDs) of granular polyethylene MP35, MP125 and MP500 particles (nominally <35, <125 and, < 500 µm in size). The reliability of the PSDs depended on the dispersant used and size of primary MPs. With increasing ethanol concentrations, PSD curves of MP35 particles shifted from multi-modal to mono-modal distributions. The measured size distribution reduced from 1588.7 to 4.5 µm in water to 39.9 to 0.1 µm in 100 wt% ethanol. Generally, as ethanol concentration increased, uncertainty associated with the PSD parameters decreased. Although Triton X-100 and the mixed solution also showed better dispersion than water, measured particle sizes and coefficient of variation (COV, %) were notably larger than those for 100 wt% ethanol. Similar trends were observed for larger-sized MP125 and MP500 particles, but differences in PSD curves, PSD parameters, and COV (%) among dispersants were less pronounced. In all dispersants, the volume weighted mean diameters (VWMD) in 100 wt% ethanol (MP35: 14.1 µm, MP125: 102.5 µm, MP500: 300.0 µm) were smallest and close to diameters determined from microscope observations (MP35: 14.6 µm, MP125: 109.0 µm, MP500: 310.6 µm). Therefore, for accurate determinations of the PSDs of MP by wet laser diffraction, ethanol rather than water should be used as the dispersant.