Otolith reliability is context-dependent for estimating warming and CO2 acidification impacts on fish growth.

Otoliths are frequently used as proxies to examine the impacts of climate change on fish growth in marine and freshwater ecosystems worldwide. However, the large sensitivity differences in otolith growth responses to typical changing environmental factors (i.e., temperature and CO2 concentration), coupled with unclear drivers and potential inconsistencies with fish body growth, fundamentally challenge the reliability of such otolith applications. Here, we performed a global meta-analysis of experiments investigating the direct effects of warming (297 cases) and CO2 acidification (293 cases) on fish otolith growth and compared them with fish body growth responses. Hierarchical models were used to assess the overall effect and quantify the influence of nine explanatory factors (e.g., fish feeding habit, life history stage, habitat type, and experimental amplitude and duration). The overall effects of warming and acidification on otolith growth were positive and significant, and the effect size of warming (effect size = 0.4003, otolith size of the treatment group increased by 49.23% compared to that of the control group) was larger than that of acidification (0.0724, 7.51%). All factors examined contributed to the heterogeneity of effect sizes, with larger responses commonly observed in carnivorous fish, marine species, and young individuals. Warming amplitudes and durations and acidification amplitudes increased the effect sizes, while acidification durations decreased the effect sizes. Otolith growth responses were consistent with, but greater than, fish body growth responses under warming. In contrast, fish body growth responses were not significant under acidification (effect size = -0.0051, p = .6185) and thus cannot be estimated using otoliths. Therefore, our study highlights that the reliability of applying otoliths to examine climate change impacts is likely varied, as the sensitivity of otolith growth responses and the consistency between the growth responses of otoliths and fish bodies are context-dependent.

Long-term survival outcomes of esophagectomy with off-pump CABG versus esophagectomy alone.

BACKGROUND: This study aimed to evaluate the long-term survival outcomes of esophagectomy with off-pump coronary artery bypass grafting (OPCABG) vs. esophagectomy alone. METHODS: A total of 1798 patients who received esophagectomy between January 2010 and February 2020 were included and divided into the 38 patients who underwent OPCABG followed by esophagectomy (OP + ES group) and 1760 patients had only esophagectomy (ES group). Propensity score matching (PSM) and Cox multivariable analyses were performed to compare postoperative complications, disease-free survival (DFS), and overall survival (OS) between the two groups. RESULTS: There were 37 patients in the OP + ES group matched with 74 in the ES group. The matched OP + ES group had higher total postoperative complications than the ES group, especially more pulmonary infections (P = 0.001) and arrhythmias (P = 0.018), but no other postoperative complications were the difference. The DFS was similar and the OS was a significant difference between the matching 2 groups (log-rank, P = 0.132 and 0.04, respectively). Although pT 3/4 stage, pN (+), and tumor length > 3.0 cm were independently associated with worse OS and DFS in multivariable analysis, CAD and EF < 55% were also found to be a predictive factor for OS and DFS in univariate analysis. CONCLUSION: OPCABG followed by esophagectomy for esophageal cancer associated with coronary artery disease has equivalent DFS and recurrence pattern to esophagectomy for esophageal cancer alone, but with a disadvantage in OS.

Photoelectrochemical sensing of isoniazid and streptomycin based on metal Bi-doped BiOI microspheres grown on book-shape layers of Ti3C2 heterostructures.

Isoniazid and streptomycin are vital drugs for treating tuberculosis, which are utilized as efficient anti-tuberculosis agents. This paper presents a novel visible-light-driven composite photocatalyst Ti3C2/Bi/BiOI, which was built from Ti3C2 nanosheets and Bi/BiOI microspheres. Photoelectrochemical (PEC) sensors based on Ti3C2/Bi/BiOI were synthesized for isoniazid identification, which showed a linear concentration range of 0.1-125 µM with a detection limit of 0.05 µM (S/N = 3). Moreover, we designed a PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI to detect streptomycin in 0.1 M PBS covering the electron donor isoniazid, because the isoniazid consumes photogenerated holes thus increasing the photocurrent effectively and preventing photogenerated electron-hole pairs from being recombined. Furthermore, PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI were synthesized for streptomycin identification, which exhibited a linear concentration range of 0.01-1000 nM with a detection limit of 2.3 × 10-3 nM (S/N = 3), and are well stable in streptomycin sensing.

A global dataset on species occurrences and functional traits of Schizothoracinae fish.

The Schizothoracinae fish are a natural group of cyprinids widely distributed in rivers and lakes in the Qinghai-Tibetan Plateau (QTP) and adjacent regions. These fish parallelly evolved with the QTP uplift and are thus important for uncovering geological history, the paleoclimatic environment, and the mechanisms of functional adaptation to environmental change. However, a dataset including species occurrences and functional traits, which are essential for resolving the above issues and guiding relevant conservation, remains unavailable. To fill this gap, we systematically compiled a comprehensive dataset on species occurrences and functional traits of Schizothoracinae fish from our long-term field samplings and various sources (e.g., publications and online databases). The dataset includes 7,333 occurrence records and 3,204 records of 32 functional traits covering all the genera and species of Schizothoracinae fish (i.e., 12 genera and 125 species or subspecies). Sampling records spanned over 180 years. This dataset will serve as a valuable resource for future research on the evolution, historical biogeography, responses to environmental change, and conservation of the Schizothoracinae fish.

Spatiotemporal variability and drivers of water microchemistry in the upper Nu-Salween river: With implications for fish habitat conservation.

Microchemical maps, also known as "chemoscapes", hold immense potential for reconstructing fish habitat utilization and guiding conservation efforts. This approach relies on matching the microchemical composition of fish calcified structures (e.g., otoliths) with the surrounding water's microchemistry. However, applying this method faces a major challenge: a clear understanding of the spatiotemporal variability and drivers of water microchemistry, particularly in vast, free-flowing river ecosystems like the Nu-Salween River, Southeast Asia's longest free-flowing river. We analyzed the spatiotemporal variability and influencing factors of water microchemistry (i.e., Na:Ca, Mg:Ca, Mn:Ca, Cu:Ca, Zn:Ca, Se:Ca, Sr:Ca, and Ba:Ca) in the upper Nu-Salween River, based on a two-year sampling. Five elemental ratios (excluding Na:Ca, Mg:Ca, and Zn:Ca) in water demonstrated significant spatiotemporal variability, with Cu:Ca having the largest spatial variation, and Mn:Ca and Sr:Ca showing the greatest temporal variation. More specifically, four elemental ratios (Cu:Ca, Se:Ca, Sr:Ca, and Ba:Ca), exhibited significant variations along the longitudinal gradient, and Mn:Ca, Cu:Ca, Sr:Ca, and Ba:Ca, showed significant differences between mainstreams and tributaries. Temporally, Mn:Ca, Cu:Ca, and Ba:Ca displayed higher values and variations during the wet season, opposing the seasonal patterns of Na:Ca, Mg:Ca, and Sr:Ca. The four-element (Ba:Ca, Sr:Ca, Mg:Ca, and Mn:Ca) forest model showed the highest classification accuracy of 93%. Linear mixed-effects models showed that spatial factors have the largest influence on the variances in water microchemistry (56.36 ± 28.64%). Our study highlights the feasibility and reliability of utilizing microchemistry to reconstruct fish habitat utilization, thereby unveiling promising avenues for a more accurate understanding of fish life history in large rivers characterized by high heterogeneity in water microchemistry. By proportionally accounting for contribution of different factors to water microchemistry variability and relating them to microchemical composition of fish calcified structures, key fish habitats (e.g., spawning grounds) and migratory routes can be more precisely identified and thus protected.

High cervical anastomosis reduces leakage-related complications after a McKeown esophagectomy.

OBJECTIVES: Anastomotic leak (AL) is one of the most serious complications after oesophageal cancer surgery. A high cervical anastomosis using a narrow gastric tube based on optimized procedures has the potential to reduce the AL after a McKeown oesophagectomy. METHODS: A narrow gastric tube was defined as 2-2.5 cm in diameter. Meanwhile, we defined a high anastomosis (HA) and a normal anastomosis (NA) based on the position of the intraoperative cervical anastomosis above or below the level of the inferior thyroid artery, respectively. A total of 533 patients who had a McKeown oesophagectomy from March 2018 to March 2023 were included in this study, including 281 patients in the NA group and 252 patients in the HA group. Potential confounding factors in baseline characteristics were balanced by propensity score matching. RESULTS: After matching, 190 patients remained in both groups. When comparing the pathological and surgical results, we found that more lymph nodes, both in total number (21.1 ± 10.0 vs 15.8 ± 7.7, P = 0.001) and thoracic part (13.5 ± 7.8 vs10.8 ± 6.1, P = 0.005), were harvested from the HA group . The pathological T and TNM stages of patients in the HA group were earlier than those in the NA group (P = 0.001). Overall postoperative complications (P = 0.001), including pulmonary infection (P = 0.001), AL (P < 0.001), leakage-related pyothorax (P < 0.001), recurrent laryngeal nerve palsy (P = 0.031) and pleural effusion (P < 0.001), were all significantly lower in the HA group. Finally, multivariable logistic regression analysis indicated that HA was an independent protective factor for AL (odds ratio = 0.331, 95% confidence interval: 0.166-0.658; P = 0.002). CONCLUSIONS: For patients undergoing a McKeown oesophagectomy, a high cervical anastomosis using a narrow gastric tube can effectively reduce leakage-related complications.

MFishBT: A global database of biogeochemical tags in migratory fish.

Humans have long been fascinated by the mysteries surrounding fish migrations and addressing these complex behaviors often requires large data sets. Biogeochemical tags, including trace elements and stable isotopes, are the most accessible biomarkers for tracking fish migrations. However, access to standardized biogeochemical tag data is rarely available for migratory fish, which limits our understanding of the evolutionary origins, drivers, timing, and corridors of migration. This precludes the development of conservation strategies and the implementation of management actions. Here, we present MFishBT, a global, open-access database of Migratory Fish's Biogeochemical Tags. As of April 2023, the MFishBT contains biogeochemical records from 1,305 studies, of which 53% used element-to-calcium (E/Ca) ratios, 34% used isotopic ratios, and 13% used both. The database covers 17,413 field sampling locations (inland 47% vs. marine 53%) around the globe, comprising 490 migratory fish species of four classes, 44 orders/suborders, and 137 families. In total, 77 trace elements and 11 isotope systems were measured across various fish biological archives, including otoliths, scales, eye lenses, and vertebrae. E/Ca ratios were examined more frequently than isotopic ratios, led by Sr/Ca, Mg/Ca, Ba/Ca, and 87 Sr/86 Sr, δ13 C, and δ18 O. The MFishBT compiles 27,030, 16,222, and 2,481,714 records with biogeochemical data detected in the core, edge, and core-to-edge transects for biological archives of migratory fish. This is the most globally comprehensive open-access database on biogeochemical tags in migratory fish to date, and can serve a variety of needs in scientific research, conservation, and management. We encourage researchers to add more data sets to this database in the future. This database is released for noncommercial use only. There are no copyright restrictions, and please cite this paper when using these data, or a subset of these data, for publication.

Perioperative tislelizumab plus chemotherapy for locally advanced resectable thoracic esophageal squamous cell carcinoma trial: a prospective single-arm, phase II study (PILOT trial).

BACKGROUND: The promising therapeutic outcomes of neoadjuvant immunotherapy combined with chemotherapy in the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) have been confirmed by several phase II clinical trials and have been widely demonstrated in clinical work. Theoretically, postoperative adjuvant immunotherapy may further improve the therapeutic effect, but there is still lack of evidence. The aim of this study was to analyse the safety and efficacy of perioperative immunotherapy (tislelizumab) in locally advanced resectable thoracic ESCC (PILOT trial). METHODS: Seventy-three eligible patients with pathologically confirmed thoracic ESCC of clinical T1b-3N1-3M0 or T3N0M0 stage were allocated to receive neoadjuvant immunotherapy (tislelizumab 200 mg d1, q3w × 2 cycles) plus chemotherapy (nad-paclitaxel 260 mg/m2 d1 + carboplatin AUC = 5 d1, q3w × 2 cycles) treatment. Patients with pathologic complete response (pCR) after esophagectomy received adjuvant tislelizumab (200 mg every 3 weeks for up to one year), and patients with non-pCR were assigned adjuvant tislelizumab plus chemotherapy for two cycles and then maintenance tislelizumab (200 mg every 3 weeks for up to 15 cycles). The primary endpoint of this study is 2-year disease-free survival (DFS) in non-pCR patients. The secondary endpoints include pCR rate, major pathological response rate, 2-year DFS in pCR patients, R0 resection rate, adverse events, and overall survival. DISCUSSION: This protocol was reviewed and approved by the Ethics Committee of Shanghai Chest Hospital (IS23059). This is the first prospective clinical trial to investigate the safety and efficacy of perioperative immunotherapy for locally advanced resectable thoracic ESCC. We hypothesize that perioperative immunotherapy could be a promising therapeutic strategy that can provide better 2-year DFS in non-pCR patients. TRIAL REGISTRATION: ClinicalTrial.gov: NCT0605633.

Short-term responses of macroinvertebrate assemblages to the "ten-year fishing ban" in the largest highland lake of the Yangtze basin.

The rapid decline of freshwater biodiversity caused by overfishing has led to the implementation of a series of conservation measures, including fishing bans. However, existing studies have mostly focused on the effects of fishing bans on economically important species, while impacts on freshwater macroinvertebrates in lake ecosystems have been rarely studied. This study used a before-and-after methodology to determine the short-term effects of the "ten-year fishing ban" on the macroinvertebrates of the Dianchi Lake, the largest highland freshwater lake in the upper Yangtze basin, between 2015 and 2022. Following the fishing ban, the overall macroinvertebrate species richness (median [interquartile]) across sites increased from 4 [2-6] to 5 [4-7]. The total density increased from 128 [80-272] to 212 [140-325] n/m2. The median biomass increased from 0.18 [0.08-0.41] to 0.51 [0.26-2.36] g/m2. In particular, the Chironomidae density in the offshore sites increased from 16.00 [0.00-32.00] to 33.30 [16.00-48.00] n/m2, and the biomass increased from 0.03 [0.00-0.09] to 0.16 [0.07-0.22] g/m2. Within the inshore sites, the aquatic insect density increased from 4 [1.33-15.33] to 56 [22.00-86.67] n/m2. The Malacostraca density increased from 34.67 [11.67-95.33] to 110 [53.33-223.33] n/m2, and the biomass increased from 0.43 [0.11-1.00] to 1.48 [0.50-2.00] g/m2. Two endangered Margarya species were rediscovered at multiple sites compared to the pre-fishing ban period. A significant change in macroinvertebrate community structure across the lake was observed, which can be largely attributed to the fishing ban. The immediate increase in species richness, density, and biomass of most macroinvertebrate species suggests a combination of effects from both reduced exploitation pressure and lessened disturbances on lake habitats. The findings indicate that the fishing ban is beneficial for the recovery of most macroinvertebrate species in freshwater lakes.

Development and application of an indirect ELISA for the serological detection of bovine viral diarrhea virus infection based on the protein E2 antigen.

BACKGROUND: Bovine viral diarrhea virus (BVDV) causes continuous economic losses to the livestock industry. Monitoring antibodies with enzyme-linked immunosorbent assay (ELISA) is a valuable tool to ensure the purification of BVDV in cattle. However, currently available ELISA kits based on the whole BVDV virion are both costly and time-consuming. The E2 protein has good immunogenicity, induces the secretion of neutralizing antibodies and is an essential immunogen for serological detection. METHODS AND RESULTS: We developed a novel recombinant E2 protein-based indirect ELISA (rE2-iELISA) and conducted a serological survey for BVDV antibodies in 2021-2022 in Beijing, China. The results showed that E2 protein was successfully expressed with high immunogenicity and the optimal rE2-iELISA displayed high sensitivity, reproducibility and specificity. Clinical testing of 566 serum specimens indicated that 318 BVDV positive samples and 194 BVDV negative samples were tested by rE2-iELISA and the IDEXX BVDV ELISA-Ab kit, with a positive coincidence rate of 93.3%, a negative coincidence rate of 86.3%, and an overall coincidence rate of 90.5%. CONCLUSION: This study established an rE2-iELISA method, which is a highly sensitive, specific and robust ELISA-test validated to detect anti-BVDV antibodies. These findings indicate that the newly developed rE2-iELISA method has the potential to be used as a rapid, reliable and cost-effective screening tool for BVDV infection and provides technical support for the evaluation of vaccine efficacy in cattle herds in the future.

Prone position thoracoscopic-assisted total mesoesophageal excision: initial experiences and benefits of lymph node dissection.

OBJECTIVE: Total mesoesophageal excision (TME) is a promising procedure. Prone position thoracoscopic-assisted TME might be a good choice, even without robust evidence yet. Therefore, it is necessary to explore the safety and efficacy of this procedure. METHODS: We retrospectively analyzed the short-term outcomes regarding intraoperative unplanned events, postoperative complications, and lymphadenectomy in 61 patients who underwent prone position thoracoscopic-assisted TME from June, 2020 to August, 2021. The learning curve was also defined. RESULTS: Of these sixty-one patients, there were 10, 24 and 27 cases of tumor in the upper, middle, and lower thoracic, respectively. Although there were five cases of unplanned events during surgery, no conversion to thoracotomy occurred. The median thoracic operation time was 113(43-161) minutes, R0 resection rate was 93.4% (57/61), and negative circumferential resection margin rate was 96.7% (59/61). Median overall lymph node dissection was 21(9-47), with 13(5-41) thoracic lymph node dissection. Incidence of postoperative pulmonary complications, cardiovascular complications, and leakage were 9.8%, 3.3%, and 9.8%, respectively, with no death within 30 days after operation. The positive rate of middle and lower mediastinal lymph nodes was 1.1%, 3.5%, and 2.4% for upper, middle, and lower tumors, and 5.5%, 1.8%, and 1.3% for pT3-4, pT2, and pT1 patients. Learning curve showed that 36 cases are the best cut-off value for proficiency of prone position thoracoscopic-assisted TME. CONCLUSIONS: The prone position thoracoscopic-assisted TME is a safe procedure that is more conducive to thoracic lymph node dissection, especially for middle and lower mediastinum.

Boosting freshwater fish conservation with high-resolution distribution mapping across a large territory.

The lack of high-resolution distribution maps for freshwater species across large extents fundamentally challenges biodiversity conservation worldwide. We devised a simple framework to delineate the distributions of freshwater fishes in a high-resolution drainage map based on stacked species distribution models and expert information. We applied this framework to the entire Chinese freshwater fish fauna (>1600 species) to examine high-resolution biodiversity patterns and reveal potential conflicts between freshwater biodiversity and anthropogenic disturbances. The correlations between spatial patterns of biodiversity facets (species richness, endemicity, and phylogenetic diversity) were all significant (r = 0.43-0.98, p < 0.001). Areas with high values of different biodiversity facets overlapped with anthropogenic disturbances. Existing protected areas (PAs), covering 22% of China's territory, protected 25-29% of fish habitats, 16-23% of species, and 30-31% of priority conservation areas. Moreover, 6-21% of the species were completely unprotected. These results suggest the need for extending the network of PAs to ensure the conservation of China's freshwater fishes and the goods and services they provide. Specifically, middle to low reaches of large rivers and their associated lakes from northeast to southwest China hosted the most diverse species assemblages and thus should be the target of future expansions of the network of PAs. More generally, our framework, which can be used to draw high-resolution freshwater biodiversity maps combining species occurrence data and expert knowledge on species distribution, provides an efficient way to design PAs regardless of the ecosystem, taxonomic group, or region considered.

Potenciación de la conservación de peces de agua dulce con mapeos de distribución de alta resolución a lo largo de un territorio extenso Resumen La falta de mapas de distribución en alta resolución para las especies de agua dulce en grandes extensiones es un reto importante para la conservación mundial de la biodiversidad. Diseñamos un marco simple para delinear la distribución de los peces de agua dulce en un mapa de drenaje en alta resolución basado en los modelos apilados de la distribución de las especies y la información de expertos. Aplicamos este marco a toda la ictiofauna de agua dulce en China (>1600 especies) para analizar los patrones en alta resolución de la biodiversidad y revelar los conflictos potenciales entre la biodiversidad de agua dulce y las perturbaciones antropogénicas. Todas las correlaciones entre los patrones espaciales de las facetas de la biodiversidad (riqueza de especies, endemismo y diversidad filogenética) fueron importantes (r = 0.43-0.98, p < 0.001). Las áreas con valores altos de diferentes facetas de la biodiversidad se traslaparon con las perturbaciones antropogénicas. Las áreas protegidas existentes que actualmente cubren el 22% del territorio de China, protegen 25-2% del hábitat de los peces, 16-23% de las especies y 30-31% de las áreas de conservación prioritarias. Además, 6-21% de las especies se encontraban totalmente desprotegidas. Estos resultados sugieren que se necesita extender la red de áreas protegidas para asegurar la conservación de los peces de agua dulce de China y los bienes y servicios que proporcionan. En concreto, los niveles medio a bajo de los grandes ríos y sus lagos asociados del noreste al suroeste de China albergaron los ensambles de especies más diversos y por lo tanto deberían ser el objetivo de las futuras expansiones de la red de áreas protegidas. De forma más generalizada, nuestro marco, el cual puede usarse para trazar mapas en alta resolución de la biodiversidad de agua dulce al combinar los datos de presencia de las especies y el conocimiento de los expertos sobre su distribución, proporciona un método eficiente para diseñar las áreas protegidas sin importar el ecosistema, región o grupo taxonómico considerado.

River fragmentation and barrier impacts on fishes have been greatly underestimated in the upper Mekong River.

River barriers reduce river connectivity and lead to fragmentation of fish habitats, which can result in decline or even extinction of aquatic biota, including fish populations. In the Mekong basin, previous studies have mainly focused on the impacts of large dams but ignored the impacts of small-scale barriers, or drew conclusions from incomplete barrier databases, potentially leading to research biases. To test the completeness of existing databases and to evaluate the catchment-scale fragmentation level, a detailed investigation of river barriers for the whole Upper Mekong (Lancang catchment) was performed, by conducting visual interpretation of high-resolution remotely sensed images. Then, a complete catchment-scale barrier database was created for the first time. By comparing our barrier database with existing databases, this study indicates that 93.7% of river barriers were absent from the existing database, including 75% of dams and 99.5% of small barriers. Barrier density and dendritic connectivity index (DCID and DCIP) were used to measure channel fragmentation within the catchment. Overall, 50.5% of sub-catchments contained river barriers. The Middle region is the most fragmented area within the Lancang catchment, with a median [quartiles] barrier density of 5.34 [0.70-9.67] per 100 km, DCIP value of 49.50 [21.50-90.00] and DCID value of 38.50 [9.00-92.25]. Furthermore, since 2010, distribution ranges of two representative fish species Schizothorax lissolabiatus (a rheophilic cyprinid) and Bagarius yarrelli (a large catfish) have reduced by 19.2% and 32.8% respectively, probably due in part to the construction of river barriers. Our findings indicate that small-scale barriers, in particular weirs and also small dams are the main reason for habitat fragmentation in the Lancang and must be considered alongside large dams in water management and biodiversity conservation within the Mekong.

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells.

Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the present work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p's promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase, which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p's promoter. In addition of inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. These data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Furthermore, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.

Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury.

Acute lung injury (ALI) is a common lung pathology that is accompanied by alveolar macrophage (AM) activation and inflammatory response. This study investigated the role of the long non-coding RNA NONRATT004344 (hereafter named lncRNA NLRP3) in regulating the Nod-like receptor protein 3 (NLRP3)-triggered inflammatory response in early ALI and the underlying mechanism as well. We established LPS-induced ALI models to explore their interactive mechanisms in vitro and in vivo. Luciferase reporter assays were performed to determine that miR-138-5p could bind to lncRNA NLRP3 and NLRP3. We observed increased lncRNA NLRP3 expression, decreased miR-138-5p expression, NLRP3 inflammasome activation, and upregulated caspase-1, IL-1ß, and IL-18 expression in the LPS-induced ALI model. Furthermore, lncRNA NLRP3 overexpression activated the NLRP3 inflammasome and promoted IL-1ß and IL-18 secretion; the miR-138-5p mimic abolished these effects in vivo and in vitro. Consistently, miR-138-5p inhibition reversed the effects of lncRNA NLRP3 silencing on the expression of NLRP3-related molecules and inhibition of the NLRP3/caspase-1/IL-1ß signalling pathway. Mechanistically, lncRNA NLRP3 sponging miR-138-5p facilitated NLRP3 activation through a competitive endogenous RNA (ceRNA) mechanism. In summary, our results suggested that lncRNA NLRP3 binding miR-138-5p promotes NLRP3-triggered inflammatory response via lncRNA NLRP3/miR-138-5p/NLRP3 ceRNA network (ceRNET) and provides insights into the treatment of early ALI.

Berberine activates the ß-catenin/TCF4 signaling pathway by down-regulating miR-106b to promote GLP-1 production by intestinal L cells.

Berberine facilitates the production of glucagon-like peptide-1 (GLP-1) by intestinal L cells. Here, we aimed to reveal the mechanism of berberine facilitating the production of GLP-1 by intestinal L cells. In this study, we confirmed that the 100 mg/kg berberine daily through diet decreased the miR-106b expression and elevated the expressions of ß-catenin and T-cell factor 4 (TCF4) in colon tissues of high-fat diet mice; berberine decreased the concentrations of triglycerides, total cholesterol and the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in mouse serum samples; berberine decreased the blood glucose in the mouse tail vein blood and promoted GLP-1 production by intestinal L cells in mouse serum samples and elevated the GLP-1 expression in mouse colon tissues. Meanwhile, the mechanism analysis demonstrated that a dose of 100 µM berberine down-regulated the miR-106b expression by elevating the methylation levels of miR-106b in STC-1 cells and miR-106b bound to TCF4 in 293T cells. Moreover, the 100 mg/kg berberine daily through diet activated the ß-catenin/TCF4 signaling pathway by decreasing miR-106b, thereby facilitating GLP-1 production in intestinal L cells through the in vivo assays. Conclusively, our experimental data illustrated that berberine decreased miR-106b expression by increasing its methylation levels and then activated the ß-catenin/TCF4 signaling pathway, thereby facilitating GLP-1 production by intestinal L cells.

Metabolic profiling of nanosilver toxicity in the gills of common carp.

Studies have shown silver nanoparticles (AgNPs) exposure can result in a series of toxic effects in fish gills. However, it is still unclear how AgNPs affect metabolite expression and their related molecular metabolic pathways in fish gills. In this study, we employed untargeted metabolomics to study the effects of AgNPs and silver supernatant ions on fish gill metabolites. The results showed that AgNPs can induce significant changes in 96 differentially expressed metabolites, which mainly affect amino acid metabolism and energy metabolism in fish gills. Among these metabolites, AgNPs specifically induce significant changes in 72 differentially expressed metabolites, including L-histidine, L-isoleucine, L-phenylalanine, and citric acid. These metabolites were significantly enriched in the pathways of aminoacyl-tRNA biosynthesis, ABC transporters, and the citrate cycle. In contrast, Ag+ supernatant exposure can specifically induce significant changes in 14 differentially expressed metabolites that mainly interfere with sphingolipid metabolism in fish gills. These specifically regulated fish gill metabolites include sphinganine, sphingosine, and phytosphingosine, which were significantly enriched in the sphingolipid metabolism pathway. Our results clearly reveal the effects and potential toxicity mechanisms of AgNPs on fish gill metabolites. Furthermore, our study further determined the unique functions of released silver ions in AgNPs toxicity in fish gills.

Comprehensive Analysis of LncRNA-mRNA Expression Profiles and the ceRNA Network Associated with Pyroptosis in LPS-Induced Acute Lung Injury.

PURPOSE: To explore the molecular mechanism and search for candidate lncRNA and mRNA associated with pyroptosis in the gene expression profile of LPS-induced acute lung injury (ALI). METHODS: We investigated lncRNA and mRNA expression in lipopolysaccharide (LPS)-induced ALI at an early stage. RNA sequencing (RNA-Seq) was carried out to analyze lncRNA and mRNA expression profiles between the LPS-induced and control groups. We used bioinformatics analysis to predict target genes of early differential lncRNAs among obtained the differential mRNAs. RESULTS: A total of 78 lncRNAs and 248 mRNAs were upregulated at 2 hours and downregulated at 9 hours, and 21 lncRNAs and 107 mRNAs were downregulated at 2 and upregulated at 9 hours in early ALI models. We predicted 7 cis-and trans-regulated target genes of the top 20 lncRNAs. Gene Ontology (GO) analysis indicated that the target genes for the screened lncRNAs were most enriched in three-terms: regulation of protein serine/threonine kinase activity, pertussis, and cellular response to LPS. Additionally, target genes of lncRNAs were the top three enriched in pertussis, osteoclast differentiation, and cAMP signaling pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also identified vital mRNAs and lncRNAs. Protein-protein interaction (PPI) network analysis suggested that Tnf, Jun, and Atf3 were the top three key genes. Hub lncRNA4344 (NONRATT004344.2) and cis-regulated target mRNA (NLRP3) were validated in vitro. Finally, luciferase assay results confirmed that lncRNA4344 sponged miR-138-5p to promote pyroptosis in inflammatory responses to LPS-induced acute lung injury by targeting NLRP3. CONCLUSION: Based on analysis of lncRNA and mRNA expression profiles by RNA-Seq and experimental verification, this study is the first to reveal that lncRNA4344 sponged miR-138-5p to promote pyroptosis in inflammatory responses of LPS-induced acute lung injury by targeting NLRP3. These newly identified lncRNA, miRNA, and mRNA might be novel potential targets for early treatment and prevention in early ALI.

Propofol suppresses lung cancer tumorigenesis by modulating the circ-ERBB2/miR-7-5p/FOXM1 axis.

BACKGROUND: Propofol is a commonly used anesthetic for cancer surgery. Previous studies have shown that propofol has an anticancer role in various cancers, including lung cancer. This study aimed to investigate the role of propofol in lung cancer and its underlying mechanism. METHODS: Cell proliferation was determined by cell counting kit-8 (CCK-8) and colony formation assays. Flow cytometry and transwell assays were used to detect cell apoptosis and invasion, respectively. Glycolysis was evaluated by detecting glucose consumption, lactate production and ATP/ADP ratios. The levels of circular RNA erb-b2 receptor tyrosine kinase 2 (circ-ERBB2), microRNA-7-5p (miR-7-5p) and forkhead box M1 (FOXM1) were tested by quantitative real-time PCR and Western blot. The binding relationship between miR-7-5p and circ-ERBB2/FOXM1 was verified by dual-luciferase reporter assay. Moreover, in vivo experiments were performed by establishing a mouse xenograft model. RESULTS: Propofol suppressed cell proliferation, invasion and glycolysis and expedited apoptosis in lung cancer cells. Circ-ERBB2 and FOXM1 were upregulated, while miR-7-5p was decreased in lung cancer tissues and cells. Propofol suppressed lung cancer cell progression by regulating circ-ERBB2. Additionally, miR-7-5p directly interacted with circ-ERBB2 and FOXM1. Also, propofol played an antitumor role in lung cancer via modulating miR-7-5p or FOXM1. Moreover, circ-ERBB2 knockdown enhanced the suppressive effect of propofol on tumor growth in vivo. CONCLUSIONS: Propofol inhibited lung cancer progression via mediating circ-ERBB2/miR-7-5p/FOXM1 axis, which might provide an effective therapeutic target for lung cancer therapy.