Efficient RNA interference method by feeding in Brachionus plicatilis (Rotifera).

Rotifers are small, ubiquitous invertebrate animals found throughout the world and have emerged as a promising model system for studying molecular mechanisms in the fields of experimental ecology, aquatic toxicology, and geroscience. However, the lack of efficient gene expression manipulation techniques has hindered the study of rotifers. In this study, we used the L4440 plasmid with two reverse-oriented T7 promoters, along with RNase-deficient E. coli HT115, to efficiently produce dsRNA and thereby present an efficient feeding-based RNAi method in Brachionus plicatilis. We targeted Bp-Ku70 & Ku80, key proteins in the DNA double-strand breaks repair pathway, and then subjected rotifers to UV radiation. We found that the mRNA expression, fecundity, as well as survival rate diminished significantly as a result of RNAi. Overall, our results demonstrate that the feeding-based RNAi method is a simple and efficient tool for gene knockdown in B. plicatilis, advancing their use as a model organism for biological research.

Reproductive toxicity of hexabromocyclododecane in rotifer Brachionus plicatilis: Involvement of reactive oxygen species and calcium signaling pathways.

To assess the toxicity of Hexabromocyclododecane (HBCD), the population, individual, and cellular biochemical parameters of the rotifer Brachionus plicatilis exposed to different concentrations of HBCD were investigated. The results showed that the population growth rate, reproductive period, and offspring number in B. plicatilis significantly decreased under 324 µg/L and 648 µg/L HBCD. Antioxidant enzyme activity and mRNA expression of CAT and Mn-SOD were promoted at low concentrations (32 µg/L and 64 µg/L) and inhibited at high concentrations (324 µg/L and 648 µg/L), while MDA content accumulated continuously with increasing HBCD concentrations, indicating that HBCD induced oxidation imbalance in rotifers. Further evidence was provided by the correlation between DNA fragmentation and physiological changes. The increased intercellular concentration of Ca2+ and the expression of CaM mRNA suggested that HBCD activated pathways related to calcium signaling. In summary, the excessive production of ROS induced by HBCD was considered to be the main cause of reproductive toxicity.

Ecotoxicological assessment, oxidative response, and enzyme activity disorder of the rotifer Brachionus asplanchnoidis exposed to a toxic cocktail of spent lithium-ion battery leachate.

Spent lithium-ion batteries (LIBs) have emerged as a major source of waste due to their low recovery rate. The physical disposal of spent LIBs can lead to the leaching of their contents into the surrounding environment. While it is widely agreed that hazardous substances such as nickel and cobalt in the leachate can pose a threat to the environment and human health, the overall composition and toxicity of LIB leachate remain unclear. In this study, a chemical analysis of leachate from spent LIBs was conducted to identify its primary constituents. The ecotoxicological parameters of the model organism, rotifer Brachionus asplanchnoidis, were assessed to elucidate the toxicity of the LIB leachate. Subsequent experiments elucidated the impacts of the LIB leachate and its representative components on the malondialdehyde (MDA) level, antioxidant capacity, and enzyme activity of B. asplanchnoidis. The results indicate that both the LIB leachate and its components are harmful to individual rotifers due to the adverse effects of stress-induced disturbances in biochemical indicators, posing a threat to population development. The intensified poisoning phenomenon under combined stress suggests the presence of complex synergistic effects among the components of LIB leachate. Due to the likely environmental and biological hazards, LIBs should be strictly managed after disposal. Additionally, more economical and eco-friendly recycling and treatment technologies need to be developed and commercialized.

Unraveling the role of tissue colonized microbiome in ovarian cancer progression.

BACKGROUND: Ovarian cancer (OC) is found to be the third most common gynecologic malignancy over the world, having the highest mortality rate among such tumors. Emerging studies underscore the presence of microorganisms within tumor tissues, with certain pathogens intricately linked to disease onset and progression. Disruption of the microbiome frequently precipitates disturbances in host metabolic and immune pathways, thereby fostering the development of cancer. METHODS: In this study, we initiated the investigation by conducting microbial reannotation on the RNA sequencing data derived from ovarian cancer tissues. Subsequently, a comprehensive array of analyses on tissue microbes was executed. These analyses encompassed the assessment of intergroup variations in microbial diversity, differential microbiological analysis, exploration of the association between host gene expression and microbial abundance, as well as an enrichment analysis of functional pathways linked to host genes associated with microbes. RESULTS: The analysis results revealed that Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes were the main components at phylum level in ovarian tissue. Notably, the microbial composition of ovarian cancer tissue significantly diverged from that of normal ovarian tissue e, exhibiting markedly lower alpha diversity and distinct beta diversity. Besides, pathogenic microorganisms Achromobacter xylosoxidans and Enterobacter hormaechei were enriched in cancer tissue. Host genes associated with these pathogens were enriched in key pathways including "JAK-STAT signaling pathway", "Transcriptional misregulation in cancer", and "Th1 and Th2 cell differentiation", suggesting their role in ovarian cancer progression through microbial dysbiosis and immune response interaction. CONCLUSION: Abundance of pathogenic microorganisms in ovarian cancer tissue could modulate the expression of host genes, consequently impacting cancer-related signaling pathways and fostering cancer progression.

Functional roles of circular RNAs in lung injury.

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

Growth and physiological responses of submerged macrophytes to linear alkylbenzene sulfonate (LAS).

The potential toxic effects of linear alkylbenzene sulfonate (LAS), widely used in commercial detergents and cleaners, on submerged macrophytes remain unclear. We conducted a two-week exposure experiment to investigate LAS toxicity on five submerged macrophytes (four native and one exotic), focusing on their growth and physiological responses. The results showed that lower concentrations of LAS (< 5 mg/L) slightly stimulated the growth of submerged macrophytes, while higher doses inhibited it. Increasing LAS concentration resulted in decreased chlorophyll content, increased MDA content and POD activity, and initially increased SOD and CAT activities before declining. Moreover, Elodea nuttallii required a higher effective concentration for growth compared to native macrophytes. These findings suggest that different species of submerged macrophytes exhibited specific responses to LAS, with high doses (exceeding 5 ∼ 10 mg/L) inhibited plant growth and physiology. However, LAS may promote the dominance of surfactant-tolerant exotic submerged macrophytes in polluted aquatic environments.

Variations in life history parameters, population dynamics, and transcriptome regulation of Brachionus plicatilis exposed to triclosan.

Triclosan (TCS) poses an ecological health risk due to its lipophilic nature, long half-life, and bioconcentration. To evaluate the toxicity of TCS on aquatic organisms, the life history parameters, population dynamics, and transcriptome regulation of Brachionus plicatilis exposed to TCS were investigated. In this study, the fecundity of rotifers was promoted by 25 µg/L of TCS and inhibited by higher concentrations (100 µg/L, 200 µg/L). The reproductive period of rotifers was shortened by 46.24 % but the post-reproductive period was prolonged by 176.47 % in 200 µg/L TCS. Both population growth and life table parameters indicated that a high concentration of TCS (200 µg/L) had negative impacts on population growth. Transcriptomic analysis showed that the effects of TCS on the life history parameters and population dynamics of rotifers were determined by regulating the expression of functional genes in cilium organization and cilium assembly and involved in pathways of focal adhesion.

Physiological response and molecular mechanisms against UV-B radiation in Brachionus asplanchnoidis (Rotifera).

Ultraviolet B (UV-B, 280-320 nm) radiation is a major environmental stressor for aquatic organisms on Earth's surface. Its effects on biological systems are well known, but the mechanisms by which organisms respond and adapt to UV-B radiation are still being explored. In this study, we investigated the effects of UV-B radiation on the monogonont rotifer Brachionus asplanchnoidis, focusing on physiological parameters, antioxidant systems, DNA damage, and DNA repair-related molecular mechanism. Our results showed that the LD50 was at 28.53 kJ/m2, indicating strong tolerance to UV-B. However, UV-B radiation caused adverse effects on growth and reproduction, with shortened reproductive period and longevity, decreased fecundity and hatchability, and inhibition of population growth. Biochemical analyses revealed severe oxidative damage and lipid peroxidation, with increased ROS and MDA levels. Activities of antioxidant enzymes were highly induced at low doses but decreased at high doses. DNA damage also occurred in UV-B-exposed rotifers. Furthermore, selected DNA repair-related genes were up-regulated in a dose-dependent manner. These findings provide a comprehensive understanding of the effects of UV-B radiation on rotifers and highlight the importance of considering both ecological and molecular responses in assessing the impact of UV-B radiation on aquatic organisms.

A potential link between fibroblast growth factor-23 and the progression of AKI to CKD.

BACKGROUND: Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear. METHOD: Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFß/Smad and Wnt/ß-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis. RESULTS: The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of ß-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of ß-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells. CONCLUSION: The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-ß and Wnt/ß-catenin activation.

m6A-mediated nonhomologous end joining (NHEJ) pathway regulates senescence in Brachionus plicatilis (Rotifera).

Epigenetic modifications play an important role in the regulation of senescence. N6-methyladenosine (m6A) is the most abundant modification of mRNA. However, the impact of m6A on senescence remains largely unknown at the animal individual level. Standard model organisms Caenorhabditis elegans and Drosophila melanogaster lack many gene homologs of vertebrate m6A system that are present in other invertebrates. In this study, we employed a small aquatic invertebrate Brachionus plicatilis which has been used in aging studies for nearly 100 years to study how m6A affects aging. Phylogenetic analysis confirmed that rotifers' m6A pathway has a conserved methyltransferase complex but no demethylases and the m6A reading system was more akin to that of vertebrates than that of D. melanogaster. m6A methyltransferases are highly expressed during development but reduces dramatically during aging. Knockdown of METTL3 results in decreased fecundity and premature senescence of rotifers. Furthermore, RT-qPCR analysis indicates a role for m6A in the nonhomologous end joining (NHEJ) pathway of DNA double-strand breaks (DSBs) repair. Altogether, our work reveals a senescence regulatory model for the rotifer METTL3-m6A-NHEJ pathway.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

Gut Microbiota Characteristics Are Associated With Severity of Acute Radiation-Induced Esophagitis.

Background: Acute radiation-induced esophagitis (ARIE) is one of the most debilitating complications in patients who receive thoracic radiotherapy, especially those with esophageal cancer (EC). There is little known about the impact of the characteristics of gut microbiota on the initiation and severity of ARIE. Materials and Methods: Gut microbiota samples of EC patients undergoing radiotherapy (n = 7) or concurrent chemoradiotherapy (n = 42) were collected at the start, middle, and end of the radiotherapy regimen. Assessment of patient-reported ARIE was also performed. Based on 16S rRNA gene sequencing, changes of the gut microbial community during the treatment regimen and correlations of the gut microbiota characteristics with the severity of ARIE were investigated. Results: There were significant associations of several properties of the gut microbiota with the severity of ARIE. The relative abundance of several genera in the phylum Proteobacteria increased significantly as mucositis severity increased. The predominant genera had characteristic changes during the treatment regimen, such as an increase of opportunistic pathogenic bacteria including Streptococcus. Patients with severe ARIE had significantly lower alpha diversity and a higher abundance of Fusobacterium before radiotherapy, but patients with mild ARIE were enriched in Klebsiella, Roseburia, Veillonella, Prevotella_9, Megasphaera, and Ruminococcus_2. A model combining these genera had the best performance in prediction of severe ARIE (area under the curve: 0.907). Conclusion: The characteristics of gut microbiota before radiotherapy were associated with subsequent ARIE severity. Microbiota-based strategies have potential use for the early prediction of subsequent ARIE and for the selection of interventions that may prevent severe ARIE.

Variations in the life-cycle parameters and population growth of rotifer Brachionus plicatilis under the stress of microplastics and 17ß-estradiol.

The toxic effects of microplastics (MPs) on biota are related to their particle size. In addition, MPs could adsorb ambient pollutants in water, which increase the threat of MPs to organisms. In this study, the effects of different particle sizes and concentrations of MPs on the life-cycle parameters and population growth of rotifer Brachionus plicatilis were investigated, and the combined effects of MPs and 17ß-estradiol (E2) on rotifers were studied. Results showed small particle size (50 nm) MPs had negative effects on the lifespan, time to first batch of eggs, fecundity, and population growth rate of rotifers, which were dose-dependent, but large (100 nm and 500 nm) MPs were not. In addition, both life-cycle parameters and the population growth of rotifers were not affected by E2. However, the combination effects of different particle sizes of MPs and E2 on the lifespan, reproductive period, offspring per female, and population growth of rotifers were significant. Therefore, rotifers were more vulnerable to smaller particle MPs, and the coexistence of MPs and other environmental pollutants posed a serious threat to rotifers.

Quality Control of DNA Extracted from All-Cell Pellets After Cryopreservation for More Than 10 Years.

Background: Cryopreserved whole blood, all-cell pellets (ACPs), and buffy coats in biobanks are widely used to obtain DNA for genetic testing. However, there are few studies concerning the quality control of DNA extracted from them. Our research aimed to perform quality control of DNA extracted from ACPs after cryopreservation for >10 years. Materials and Methods: A total of 1377 ACP samples (separated from 3 mL of whole blood) were retrieved from our biobank, where they had been cryopreserved for 10-15 years. Chemagic STAR was used to extract the DNA. Absorbance at A260, A280, and A230 were measured by spectrophotometry, and integrity was analyzed by agarose gel electrophoresis. The quality thresholds for an Illumina Asian Screening Array (ASA) were yields greater than 0.5 µg, concentration of 25-150 ng/µL, A260/280 ratio of 1.6-2.1, and no degradation fragments in the electrophoresis gel. Results: The median yield of genomic DNA was 54.30 µg (interquartile range [IQR] 35.55-74.64). The median A260/280 and A260/230 ratios were 1.90 (IQR 1.87-1.94) and 1.98 (IQR 1.64-2.41), respectively. In total, 1377 samples (100%) had qualified yields, and 1366 samples (99.20%) had qualified integrity results. Finally, 1328 (96.44%) samples were used for ASA. Of the remaining samples, 34 needed to be repurified, 4 were obtained at an insufficient concentration, and 11 were unqualified for integrity. In addition, we analyzed the influence of hemolysis (90 samples) and clots (102 samples) on the quality of DNA samples. Hemolysis and clotting did not influence yield or integrity, but a significant difference was found in A260/230 compared to normal samples (p < 0.05). Furthermore, the samples (14 samples) with both hemolysis and clots had higher A260/280 (p < 0.05). Conclusion: ACP samples stored for >10 years at -80°C produced DNA with high quality for use in genetic analysis. Hemolysis and clots in the ACPs led to lower purity, but did not significantly affect yield or integrity.

Efficacy of using stable isotopes coupled with chemometrics to differentiate the production method and geographical origin of farmed salmonids.

The δ2H and δ18O of 105 salmonids cultured in freshwater and seawater and from different regions were combined with linear discriminant analysis (LDA), k-nearest neighbor (KNN), and random forest (RF) to create discrimination models. To assess the stability of the discrimination models, seasonal variation in δ2H and δ18O in salmonids cultured in different systems was studied. δ2H and δ18O were significantly different between salmonids cultured in freshwater and seawater and from different geographical origins. δ2H and δ18O of salmonids cultured in an open system were vulnerable to seasonal effects. The KNN model had 100% accuracy for identifying the production methods of salmonids and was less affected by seasonal variation. The RF model had the highest accuracy for identifying the geographical origins of salmonids with an accuracy of over 80%. Thus, δ2H and δ18O were more effective for identifying the production methods of salmonids than their geographical origins.

Effects of different temperatures on seawater acclimation in rainbow trout Oncorhynchus mykiss: osmoregulation and branchial phospholipid fatty acid composition.

This study aimed to investigate the effects of different temperatures on seawater acclimation in rainbow trout (Oncorhynchus mykiss), in terms of growth performance, osmoregulatory capacity, and branchial phospholipid fatty acid (PLFA) composition. The fish (initial weight, 94.73 g) were reared at 9, 12.5, and 16 °C for 28 days, then acclimated to seawater, and subsequently reared for 14 days. Sampling points were on the last day in freshwater, and the 1st, 4th, 7th, and 14th days after the salinity reached 30. The results showed the final weight, percent weight gain, and specific growth rate of rainbow trout at 12.5 °C were significantly higher than those at 9 °C, while the thermal growth coefficient at 16 °C was significantly lower than that in other treatments. The branchial PLFA composition in rainbow trout changed more rapidly at 9 and 12.5 °C than at 16 °C. The branchial PLFA composition was significantly affected by temperature and salinity and their interaction. The polyunsaturated fatty acid content of phospholipids in the gill at 9 and 12.5 °C was significantly higher than those at 16 °C. Low temperature (9 °C) and seawater acclimation significantly increased the degree of unsaturation of membrane, enhancing membrane fluidity, which is related to Na+-K+ ATPase activity. Responses of plasma ion, Na+-K+ ATPase activity, and plasma glucose followed a similar pattern at different temperatures. Overall, the study suggests that 12.5 °C is the ideal temperature for seawater acclimation in rainbow trout.

Visual outcomes and complications following one-way air-fluid exchange technique for vitreous hemorrhage post vitrectomy in proliferative diabetic retinopathy patients.

BACKGROUND: To evaluate the efficacy and outcomes of one-way surgical technique for the treatment of vitreous hemorrhage post vitrectomy on proliferative diabetic retinopathy (PDR) patients. METHODS: This retrospective case series include 47 PDR patients who had vitrectomy with balanced saline solution tamponade and have developed vitreous hemorrhage without significant absorption. The one-way air-fluid exchange procedure which involves the application of a 0.22-µm pore size filter to exchange about 4.5-5.5 ml of fluid with a 10 ml syringe was performed on 47 patients (47 eyes). Post procedure, additional treatments were administered when needed. Best corrected visual acuity (BCVA), occurrence of intra-procedural and post-procedural complications were recorded and analyzed. RESULTS: A total of 47 eyes of 47 PDR patients with a mean age of 50.8 ± 12.0 years were reviewed. Because of vitreous hemorrhage or tractional retinal detachment of PDR, all 47 eyes underwent vitrectomy with balanced saline solution tamponade prior to the exchange procedure. Four patients (8.51%) and 43 patients (91.5%) were diagnosed with type 1 diabetes mellitus (T1DM), or type 2 diabetes mellitus (T2DM), respectively. All 47 eyes were given the one-way air-fluid exchange procedure in the treatment room. Forty-two cases (89.4%) needed the air-fluid exchange procedure only once, 4 cases (8.51%) underwent the procedure twice, and 1 case (2.13%) was given the procedure three times, followed by additional retinal photocoagulation and one intravitreal injection of Conbercept. In addition to the procedure, no further treatment was needed for 5 eyes (10.6%) while additional retinal laser treatment was provided for 41 eyes (87.2%). The BCVA at the final follow-up was significantly improved from the initial acuity baseline in all cases. No complications were observed during the follow-ups. CONCLUSION: This one-way air-fluid exchange procedure can effectively exchange the vitreous hemorrhage and improve visual acuity of PDR patients who develop vitreous rehemorrhage post vitrectomy without obvious complications.

Preliminary report on screening IGSF3 gene mutation in families with congenital absence of lacrimal puncta and canaliculi.

AIM: To investigate the variation of IGSF3 gene in three families with congenital absence of lacrimal puncta and canaliculi, and to lay a foundation for further research on the pathogenic gene of congenital lacrimal duct agenesis. METHODS: The members of the three families were recruited. The ophthalmologic examinations in details, including slit-lamp biomicroscope, intraocular pressure and fundus examination, etc. were carried out. All patients were checked with paracentesis of puncta membrane and lacrimal duct probing, as well as the computed tomography-dacryocystography (CT-DCG). Peripheral blood of 14 participants (3 normal) from three families were collected, 4 mL each, for genomic DNA extraction, and 11 exon fragments of IGSF3 gene were amplified and sequenced by polymerase chain reaction (PCR) to determine whether there were IGSF3 genetic variation. RESULTS: A total of 14 members from three families were screened for 4 synonymous variants: c.930C>T (p.Pro366=), c.1359T>C (p.Ser709=), c.1797G>A (p.Ser855=), c.1539G>A (p.Ser769=), and 6 missense variants: c.1507G>A (p.Gly759Ser), c.1783T>C (p.Trp851Arg), c.1952G>T (p.Ser 907Ile), c.3120C>G (p.Asp1040Glu), c.3123C>G (p.Asp1041Glu), c.3139_3140insGAC (p.Asp1046_Pro1047insAsp), and the latter three were only found in two patients with absence of lacrimal puncta and canaliculi combined with congenital osseous nasolacrimal canal obstruction from the first family. CONCLUSION: The same IGSF3 gene mutation c.3139_3140insGAC is found in the patients with congenital absence of lacrimal puncta and canaliculi combine with osseous nasolacrimal canal obstruction.

Roflumilast, a phosphodiesterase-4 inhibitor, improves hyperoxia-induced lung injury via anti-inflammation.

Roflumilast is an inhibitor of phosphodiesterase-4 (PDE4) and can suppress the hydrolysis of cAMP in inflammatory cells, conferring anti-inflammatory effects. This study aimed to investigate the protective effects of roflumilast on hyperoxia-induced acute lung injury (HALI) in a rat model. Male Sprague-Dawley rats were randomly assigned into: control group; HALI group; 2.5 mg/kg roflumilast group; and 5 mg/kg roflumilast group. Rats were pressurized to 250 kPa with pure oxygen to induce lung injury. In the roflumilast groups, rats were orally administered with roflumilast at 2.5 or 5 mg/kg once before hyperoxia exposure and once daily for two days after exposure. Rats were sacrificed 72 hours after hyperoxia exposure. The lung tissues were collected for the detection of lung water content, inflammatory cytokines and NF-κB/p-NF-κB protein expression, and the bronchoalveolar lavage fluid was harvested for the measurement of protein concentration and lactate dehydrogenase activity. Results showed roflumilast at different doses could significantly reduce lung edema, improve lung pathology and reduce the expression of inflammatory cytokines in the lung. The protective effects seemed to be related to the dose of roflumilast. Our study indicates roflumilast has the potential as a medication for the treatment of HALI.

Neurocognitive sequelae after carbon monoxide poisoning and hyperbaric oxygen therapy.

Carbon monoxide (CO) has been the leading cause of poisoning mortality in many countries and hyperbaric oxygen (HBO) is a widely accepted treatment for CO poisoning. However, some patients with CO poisoning will still develop neurocognitive sequelae regardless of HBO therapy, which can persist since CO poisoning or be present days to weeks after a recovery from CO poisoning. HBO has been used in the prevention and treatment of neurocognitive sequelae after CO poisoning, and some mechanisms are also proposed for the potential neuroprotective effects of HBO on the neurocognitive impairment after CO poisoning, but there is still controversy on the effectiveness of HBO on neurocognitive sequelae after CO poisoning. In this paper, we briefly introduce the neurocognitive sequelae after CO poisoning, summarize the potential predictive factors of neurocognitive sequelae, and discuss the use of HBO in the treatment and prevention of neurocognitive sequelae after CO poisoning.