CT data analysis of catheter morphology and displacement in peritoneal dialysis: an exploratory study.

PURPOSE: Catheter displacement is a common complication of peritoneal dialysis. The aim of this study was to explore the correlation between catheter morphology and displacement by analyzing CT data, providing a scientific basis for optimizing catheter morphology within abdominal wall layers. METHODS: We retrospectively analyzed the clinical data of 94 patients. The parameters for analyzing catheter morphology were defined based on six key points identified from CT images. The covariates considered in the analysis included demographics, primary disease, body size, peritoneal dialysis method, and total weekly urea clearance index. RESULTS: During a mean follow-up period of 1056 ± 480 days, only the angle of the intramuscular part (IM angle) of the catheter significantly correlated with the time to first catheter displacement according to the multivariate analysis (hazard ratio [HR]: 1.039, 95% confidence interval [CI] 1.02-1.058, p < 0.01). When the cut-off value of IM angle was 39.4 ∘ , the area under receiver-operating characteristic (ROC) curve for predicting catheter displacement was 0.791 (95% CI 0.701-0.881, p < 0.01), with a sensitivity and specificity of 82.9% and 66.0%, respectively. Kaplan-Meier survival curves showed that the catheter survival rate was significantly higher in the group with an IM angle < 39.4 ∘ than in the group with an IM angle > 39.4 ∘ (log-rank χ 2 =19.479, p < 0.01). None of the catheter morphology parameters were significantly correlated with technique survival in the multivariate analysis. CONCLUSION: There is a correlation between catheter morphology and catheter displacement. An IM angle > 39.4 ∘ is an independent risk factor for catheter displacement, while the position and angle of the subcutaneous part are not correlated with catheter displacement.

Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

Generation of rat forebrain tissues in mice.

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.

Epidemiological and etiological characteristics of 1266 patients with severe acute respiratory infection in central China, 2018-2020: a retrospective survey.

BACKGROUND: Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020. METHODS: Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records. RESULTS: The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups. DISCUSSION: In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.

Optimizing dietary rumen-degradable starch to rumen-degradable protein ratio improves lactation performance and nitrogen utilization efficiency in mid-lactating Holstein dairy cows.

The dietary rumen-degradable starch (RDS) to rumen-degradable protein (RDP) ratio, denoted as the RDS-to-RDP ratio (SPR), has been proven to enhance in vitro rumen fermentation. However, the effects of dietary SPR in vivo remain largely unexplored. This study was conducted to investigate the effect of dietary SPR on lactation performance, nutrient digestibility, rumen fermentation patterns, blood indicators, and nitrogen (N) partitioning in mid-lactating Holstein cows. Seventy-two Holstein dairy cows were randomly assigned to three groups (24 head/group), balanced for (mean ± standard deviation) days in milk (116 ± 21.5), parity (2.1 ± 0.8), milk production (42 ± 2.1 kg/d), and body weight (705 ± 52.5 kg). The cows were fed diets with low (2.1, control), medium (2.3), or high (2.5) SPR, formulated to be isoenergetic, isonitrogenous, and iso-starch. The study consisted of a one-week adaptation phase followed by an eight-week experimental period. The results indicated that the high SPR group had a lower dry matter intake compared to the other groups (p < 0.05). A quadratic increase in milk yield and feed efficiency was observed with increasing dietary SPR (p < 0.05), peaking in the medium SPR group. The medium SPR group exhibited a lower milk somatic cell count and a higher blood total antioxidant capacity compared to other groups (p < 0.05). With increasing dietary SPR, there was a quadratic improvement (p < 0.05) in the total tract apparent digestibility of crude protein, ether extract, starch, neutral detergent fiber, and acid detergent fiber. Although no treatment effect was observed in rumen pH, the rumen total volatile fatty acids concentration and microbial crude protein synthesis increased quadratically (p < 0.05) as dietary SPR increased. The molar proportion of propionate linearly increased (p = 0.01), while branched-chain volatile fatty acids linearly decreased (p = 0.01) with increasing dietary SPR. The low SPR group (control) exhibited higher concentration of milk urea N, rumen ammonia N, and blood urea N than other groups (p < 0.05). Despite a linear decrease (p < 0.05) in the proportion of urinary N to N intake, increasing dietary SPR led to a quadratic increase (p = 0.01) in N utilization efficiency and a quadratic decrease (p < 0.05) in the proportion of fecal N to N intake. In conclusion, optimizing dietary SPR has the potential to enhance lactation performance and N utilization efficiency. Based on our findings, a medium dietary SPR (with SPR = 2.3) is recommended for mid-lactating Holstein dairy cows. Nevertheless, further research on rumen microbial composition and metabolites is warranted to elucidate the underlying mechanisms of the observed effects.

Widespread occurrence of two typical N, N'-substituted p-phenylenediamines and their quinones in humans: Association with oxidative stress and liver damage.

While N, N'-substituted p-phenylenediamines (PPDs) and their quinone derivatives (PPDQs) have been widely detected in the environment, there is currently limited data on their occurrence in humans. In this study, we conducted the first serum analysis of two PPDs and PPDQs in the healthy and secondary nonalcoholic fatty liver disease (S-NAFLD) cohorts in South China. The concentrations of four oxidative stress biomarkers (OSBs), namely, 8-iso-prostaglandin F2α (8-PGF2α), 11ß-prostaglandin F2α (11-PGF2α), 15(R)-prostaglandin F2α (15-PGF2α), and 8-hydroxy-2'-deoxyguanosine in serum samples were also measured. Results showed that N-(1,3-dimethybutyl)-N'-phenyl-p-phenylenediamine (6PPD) quinone was the predominant target analytes both in the healthy and S-NAFLD cohorts, with the median concentrations of 0.13 and 0.20 ng/mL, respectively. Significant (p < 0.05) and positive correlations were found between 6PPD concentration and 8-PGF2α, 11-PGF2α, and 15-PGF2α in both the healthy and S-NAFLD cohorts, indicating that 6PPD may be associated with lipid oxidative damage. In addition, concentrations of 6PPD in serum were associated significantly linked with total bilirubin (ß = 0.180 µmol/L, 95%CI: 0.036-0.396) and direct bilirubin (DBIL, ß = 0.321 µmol/L, 95%CI: 0.035-0.677) related to hepatotoxicity. Furthermore, 8-PGF2α, 11-PGF2α, and 15-PGF2α mediated 17.1%, 24.5%, and 16.6% of 6PPD-associated DBIL elevations, respectively. Conclusively, this study provides novel insights into human exposure to and hepatotoxicity assessment of PPDs and PPDQs.

Early microbial intervention reshapes phenotypes of newborn Bos taurus through metabolic regulations.

BACKGROUND: The rumen of neonatal calves has limited functionality, and establishing intestinal microbiota may play a crucial role in their health and performance. Thus, we aim to explore the temporal colonization of the gut microbiome and the benefits of early microbial transplantation (MT) in newborn calves. RESULTS: We followed 36 newborn calves for 2 months and found that the composition and ecological interactions of their gut microbiomes likely reached maturity 1 month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion and antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. CONCLUSIONS: Our study provides a metagenomic and metabolomic atlas of the temporal development of the gut microbiome in newborn calves. MT can alter the gut microbiome of newborns, leading to improved physiological status and later milk production. The data may help develop strategies to manipulate the gut microbiota during early life, which may be relevant to the health and production of newborn calves.

Effects of dietary palmitic acid and oleic acid ratio on milk production, nutrient digestibility, blood metabolites and milk fatty acids profile of lactating dairy cows.

Adequate energy supply is a crucial factor for maintaining the production performance in early lactating cows. Adding fatty acids to diets can improve energy supply, while the effect could be related to the chain length and degree of saturation of fatty acids. This study was conducted to evaluate the effect of different ratios of palmitic acid (C16:0) to oleic acid (cis-9 C18:1) on the production performance, nutrient digestibility, blood metabolites and milk fatty acids profile in early lactating dairy cows. Seventy-two multiparous Holstein cows (63.5 ± 2.61 d in milk) blocked by parity (2.39 ± 0.20), body weight (668.3 ± 20.1 kg), body condition score (3.29 ± 0.06), and milk yield (47.9 ± 1.63 kg) were used in a completely randomized design. Cows were divided into 3 groups with 24 cows in every group. Cows in 3 treatments were provided iso-energy and iso-nitrogen diets, whereas the C16:0 to cis-9 C18:1 ratio was different: (1) 90.9% C16:0 + 9.1% cis-9 C18:1 (90.9:9.1); (2) 79.5% C16:0 + 20.5% cis-9 C18:1 (79.5:20.5); (3) 72.7% C16:0 + 27.3% cis-9 C18:1 (72.7:27.3). Fatty acids were added at 1.3% in dry matter basis. Although the dry matter intake fat-corrected milk yield and energy-corrected milk yield were not affected, the milk yield, milk protein yield and feed efficiency increased linearly with the increasing of cis-9 C18:1 ratio. The milk protein percentage and milk fat yield did not differ among treatments, whereas the milk fat percentage tended to decrease linearly with the increasing of cis-9 C18:1 ratio. The lactose yield increased linearly and lactose percentage tended to increase linearly with increasing cis-9 C18:1 ratio, whereas the percentage of milk total solids and somatic cell count decreased linearly. Though the changes of body condition score were not affected by treatments, the body weight loss decreased linearly with the increasing of cis-9 C18:1 ratio. The effect of treatment on nutrient digestibility was limited, except a linear increase in ether extract and neutral detergent fiber digestibility with the increasing of cis-9 C18:1 ratio. There was a linear increase in the concentrations of plasma glucose, whereas the triglyceride and nonesterified fatty acid concentration decreased linearly with the increasing of cis-9 C18:1 ratio. As the cis-9 C18:1 ratio increased, the concentration of de novo fatty acids decreased quadratically, while the mixed and preformed fatty acids increased linearly. In conclusion, increasing cis-9 C18:1 ratio could increase production performance and decrease body weight loss by increasing nutrient digestibility, and the ratio had the most powerful beneficial effect on early lactating cows suggested by 72.7:27.3.

A review of sources, pathways, and toxic effects of human exposure to benzophenone ultraviolet light filters.

Benzophenone ultraviolet light filters (BPs) are high-production-volume chemicals extensively used in personal care products, leading to widespread human exposure. Given their estrogenic properties, the potential health risks associated with exposure to BPs have become a public health concern. This review aims to summarize sources and pathways of exposure to BPs and associated health risks. Dermal exposure, primarily through the use of sunscreens, constitutes a major pathway for BP exposure. At a recommended application rate, dermal exposure of BP-3 via the application of sunscreens may reach or exceed the suggested reference dose. Other exposure pathways to BPs, such as drinking water, seafood, and packaged foods, contribute minimal to the overall dose. Inhalation is a minor pathway of exposure; however, its contribution cannot be ignored. Human exposure to BPs is an order of magnitude higher in North America than in Asia and Europe. Studies conducted on laboratory animals and cells have consistently demonstrated the toxic effects of BP exposure. BPs are estrogenic and elicit reproductive and developmental toxicities. Furthermore, neurotoxicity, hepatotoxicity, nephrotoxicity, and carcinogenicity have been reported from chronic BP exposure. In addition to animal and cell studies, epidemiological investigations have identified associations between BPs and couples' fecundity and other reproductive disorders, as well as adverse birth outcomes. Further studies are urgently needed to understand the risks posed by BPs on human health.

Quantitative identification of the co-exposure effects of e-waste pollutants on human oxidative stress by explainable machine learning.

Global electronic waste (e-waste) generation continues to grow. The various pollutants released during precarious e-waste disposal activities can contribute to human oxidative stress. This study encompassed 129 individuals residing near e-waste dismantling sites in China, with elevated urinary concentrations of e-waste-related pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs), organophosphorus flame retardants (OPFRs), bisphenols (BPs), and phthalate esters (PAEs). Utilizing an explainable machine learning framework, the study quantified the co-exposure effects of these pollutants, finding that approximately 23% and 18% of the variance in oxidative DNA damage and lipid peroxidation, respectively, was attributable to these substances. Heavy metals emerged as the most critical factor in inducing oxidative stress, followed by PAHs and PAEs for oxidative DNA damage, and BPs, OPFRs, and PAEs for lipid peroxidation. The interactions between different pollutant classes were found to be weak, attributable to their disparate biological pathways. In contrast, the interactions among congeneric pollutants were strong, stemming from their shared pathways and resultant synergistic or additive effects on oxidative stress. An intelligent analysis system for e-waste pollutants was also developed, which enables more efficient processing of large-scale and dynamic datasets in evolving environments. This study offered an enticing peek into the intricacies of co-exposure effect of e-waste pollutants.

The association between levosimendan and mortality in patients with sepsis or septic shock: a systematic review and meta-analysis.

BACKGROUND: Levosimendan is increasingly being used in patients with sepsis or septic shock because of its potential to improve organ function and reduce mortality. We aimed to determine if levosimendan can reduce mortality in patients with sepsis or septic shock via meta-analysis. EVIDENCE SOURCES AND STUDY SELECTION: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane Library databases from inception through 1 October 2022. Literature evaluating the efficacy of levosimendan in patients with sepsis or septic shock was included. DATA EXTRACTION AND OUTCOME MEASUREMENTS: Two reviewers extracted data and assessed study quality. A meta-analysis was performed to calculate an odds ratio (OR), 95% confidence intervals (CI), and P -values for 28-day mortality (primary outcome). Secondary outcomes included changes in indexes reflecting cardiac function before and after treatment, changes in serum lactate levels in the first 24 h of treatment, and the mean SOFA score during the study period. Safety outcomes included rates of tachyarrhythmias and total adverse reactions encountered with levosimendan. RESULTS: Eleven randomized controlled trials were identified, encompassing a total of 1044 patients. After using levosimendan, there was no statistical difference between groups for 28-day mortality (34.9% and 36.2%; OR: 0.93; 95% CI [0.72-1.2]; P  = 0.57; I 2  = 0%; trial sequential analysis-adjusted CI [0.6-1.42]) and sequential organ failure assessment (SOFA) score, and more adverse reactions seemed to occur in the levosimendan group, although the septic shock patient's heart function and serum lactate level improved. CONCLUSION: There was no association between the use of levosimendan and 28-day mortality and SOFA scores in patients with septic shock, though there was statistically significant improvement in cardiac function and serum lactate.

2-Methoxyestradiol ameliorates paraquat-induced pulmonary fibrosis by inhibiting the TGF-ß1/Smad2/3 signaling pathway.

Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial-mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-ß1/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-ß1/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.

Dispersive wave manipulation by the spectral Heaviside step phase modulation.

We investigate the dispersive waves (DWs) emitted from shaped pulses with spectral Heaviside step phases (HSPs). The spectrally HSP-modulated pulse exhibits a unique double-peak structure, where the intensity and separation of the twin peaks are determined by the modulation depth and frequency detuning. By tailoring the parameters of the HSP suitably, we can control the DW emission with regard to resonant frequency and conversion efficiency. As the intensity ratio or relative separation of neighboring peaks is elaborately chosen, the DW emission can be effectively boosted, or a solitonic cage can be constructed for realizing temporal reflections and refractions associated with spectral broadening and multi-peak spectra of the output DWs. These findings offer a straightforward and efficient approach for controlling the DW emission, which is highly relevant to the advancement of supercontinuum generation and wavelength conversion technology.

Establishment and evaluation of animal models of sepsis-associated encephalopathy.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is a critical disease caused by sepsis. In addition to high mortality, SAE can also adversely affect life quality and lead to significant socioeconomic costs. This review aims to explore the development of evaluation animal models of SAE, giving insight into the direction of future research in terms of its pathophysiology and therapy. METHODS: We performed a literature search from January 1, 2000, to December 31, 2022, in MEDLINE, PubMed, EMBASE, and Web of Science using related keywords. Two independent researchers screened all the accessible articles based on the inclusion and exclusion criteria and collected the relevant data of the studies. RESULTS: The animal models for sepsis are commonly induced through cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) injection. SAE can be evaluated using nervous reflex scores and sepsis evaluation during the acute phase, or through Morris water maze (MWM), open-field test, fear condition (FC) test, inhibitory avoidance, and other tests during the late phase. CONCLUSION: CLP and LPS injection are the most common methods for establishing SAE animal models. Nervous reflexs cores, MWM, FC test, and inhibitory avoidance are widely used in SAE model analysis. Future research should focus on establishing a standardized system for SAE development and analysis.

Bakuchiol regulates TLR4/MyD88/NF-κB and Keap1/Nrf2/HO-1 pathways to protect against LPS-induced acute lung injury in vitro and in vivo.

Bakuchiol (Bak) possesses a protective effect in acute lung injury (ALI). Nonetheless, the molecular processes that regulate the protective activity of Bak in ALI remain elusive. Lipopolysaccharide (LPS)-treated rats and RLE-6TN cells were used as the ALI models in vivo and in vitro to investigate the function and mechanism of Bak. Rats were divided into four groups: control, LPS, LPS + Bak (30 mg/kg), and LPS + Bak (60 mg/kg). RLE-6TN cells were assigned into four groups: control, LPS, LPS + Bak (10 µM), and LPS + Bak (20 µM). Myeloperoxidase (MPO) and 4-hydroxy-2-nonenal (4-HNE) levels were detected by immunohistochemistry (IHC). The levels of TNF-α, IL-6, and IL-1ß were quantified by ELISA. Apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were assayed to evaluate oxidative stress. In LPS-induced rats, Bak attenuated pathological injury, lung wet/dry weight ratio, MPO expression, and protein concentration and cell number in bronchial alveolar lavage fluid (BALF). Bak decreased the secretion of TNF-α, IL-6, and IL-1ß in BALF. Bak reduced MDA content and 4-HNE expression, and increased SOD and GSH-Px activities in lung tissues. Bak also repressed pulmonary apoptosis by decreasing Bax expression and enhancing Bcl-2 expression. In LPS-treated RLE-6TN cells, Bak downregulated the mRNA levels of TNF-α, IL-6, and IL-1ß and inhibited the protein expression of iNOS and COX2. Bak decreased MDA level and ROS production and increased SOD and GSH-Px activities. Bak also suppressed cell apoptosis, reduced Bax expression, and increased Bcl-2 expression. Moreover, Bak decreased the expression of TLR4, MyD88, p-IκBα, and p-p65. Additionally, Bak inhibited Keap1 expression and increased Nrf2 and HO-1 levels. Bak protects against LPS-induced inflammation, oxidative stress, and apoptosis in ALI by regulating TLR4/MyD88/NF-κB and Keap1/Nrf2/HO-1 pathways.

Case report: A case of new mutation in SERPINC1 leading to thrombotic microangiopathy.

Introduction: Hereditary antithrombin-III deficiency can significantly increase the risk for thrombosis, which is common in limb deep vein and pulmonary cases. However, thrombotic microangiopathy (TMA) caused by hereditary antithrombin deficiency is rare. Case Presentation: We reported the case of a 32-year-old Chinese female patient with TMA with renal injury caused by decreased antithrombin-III activity due to a new mutation (chr1-173884049 c.50A>G) in SERPINC1, which encodes antithrombin-III. In this case, the patient had no history of relevant drug use, diabetes, or monoclonal plasma cells in the bone marrow puncture. Consequently, TMA of the kidney was considered secondary to hereditary antithrombin-III deficiency. Gene detection was the only clue that led us to suspect that TMA was caused by hereditary antithrombin deficiency. Conclusion: Our findings indicated that for patients with repeated findings of antithrombin-III activity less than 50%, the possibility of antithrombin-III deficiency and complete gene detection must be considered immediately after excluding the use of anticoagulants and lack of availability to facilitate early detection, diagnosis, and intervention.

Could extracellular vesicles derived from mesenchymal stem cells be a potential therapy for acute pancreatitis-induced cardiac injury?

Acute pancreatitis (AP) often leads to a high incidence of cardiac injury, posing significant challenges in the treatment of severe AP and contributing to increased mortality rates. Mesenchymal stem cells (MSCs) release bioactive molecules that participate in various inflammatory diseases. Similarly, extracellular vesicles (EVs) secreted by MSCs have garnered extensive attention due to their comparable anti-inflammatory effects to MSCs and their potential to avoid risks associated with cell transplantation. Recently, the therapeutic potential of MSCs-EVs in various inflammatory diseases, including sepsis and AP, has gained increasing recognition. Although preclinical research on the utilization of MSCs-EVs in AP-induced cardiac injury is limited, several studies have demonstrated the positive effects of MSCs-EVs in regulating inflammation and immunity in sepsis-induced cardiac injury and cardiovascular diseases. Furthermore, clinical studies have been conducted on the therapeutic application of MSCs-EVs for some other diseases, wherein the contents of these EVs could be deliberately modified through prior modulation of MSCs. Consequently, we hypothesize that MSCs-EVs hold promise as a potential therapy for AP-induced cardiac injury. This paper aims to discuss this topic. However, additional research is essential to comprehensively elucidate the underlying mechanisms of MSCs-EVs in treating AP-induced cardiac injury, as well as to ascertain their safety and efficacy.

Correction to: Evaluation of salinity resistance and combining ability analysis in the seedlings of mulberry hybrids (Morus alba L.).

[This corrects the article DOI: 10.1007/s12298-023-01304-w.].

Within-person variability of urinary neonicotinoids and their metabolites and recommendation for sampling strategy.

Humans are exposed to neonicotinoid insecticides (NEOs) from various routes. Urine has been widely used to characterize the internal exposure levels of NEOs in humans. However, variable sampling methods can result in highly variable measurements of NEOs, potentially leading to misunderstanding of human exposure. In this study, we collected the first morning voids urine (FMVU), spot urine (SU), and 24 h urine (24hU) samples from 8 healthy adults during 7 consecutive days. The concentration, variability, and reproducibility of six parent NEOs (p-NEOs) and three NEOs metabolites (m-NEOs) were measured. Over 79 % of the urine samples had detectable levels of NEOs. Dinotefuran (DIN) and olefin-imidacloprid (of-IMI) were excreted in the highest concentration of p-NEO and m-NEO, respectively. All of the p-NEOs except thiacloprid (THD) and of-IMI were recommended as biomarkers for biomonitoring studies. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were used to evaluate the temporal variability and reproducibility of urinary NEOs in SU, FMVU and 24hU, respectively. We observed low ICCs ranging from 0.016 to 0.39 for NEOs regardless of the sample types. However, the higher CV and lower ICC values observed in SU samples suggested lower reproducibility compared to FMVU and 24hU samples. Significant correlations of several NEOs between FMVU and 24hU were also observed in the current study. Considering the comparable concentrations and similarity between FMVU and 24hU, our study proposed possible biomarkers and indicated that the potential for FMVU samples to estimate adequately an individual's exposure to NEOs. Therefore, we suggested FMVU as a sampling strategy in future human biomonitoring studies, while multiple samples were recommended to detect exposure over time intervals of weeks or months.