CACNA1H restrains chemotherapy resistance in ovarian clear cell carcinoma cells by repressing autophagy.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer and is highly malignant with high chemoresistance. CACNA1H is pivotal in tumor development. However, the role of CACNA1H in the acquisition process of chemotherapeutic resistance in OCCC cells is rarely reported. Therefore, this study aimed to explore the role of CACNA1H in chemotherapy resistance of OCCC cells and its related mechanism. Based on bioinformatics analysis, we found that CACNA1H was downregulated in chemoresistant OCCC patients compared to chemosensitive OCCC patients. Comparing DDP-resistant and sensitive OCCC cell lines, the resistant strain showed lower CACNA1H mRNA expression. CACNA1H expression was associated with calcium signaling pathways in chemoresistant OCCC patients. CACNA1H mRNA expression was significantly downregulated in OCCC cells compared to normal ovarian epithelial cells. When CACNA1H was overexpressed, intracellular Ca2+ concentration and protein levels of p-CaMKII and p-Akt were significantly upregulated, while protein levels of LC3-II/LC3-I and Beclin1 were downregulated, indicating a repression of autophagy. The rescue experiment revealed that CACNA1H overexpression in drug-resistant OCCC cells reduced autophagy-induced DDP resistance via CaMKII/Akt signaling. Overall, CACNA1H increased intracellular Ca2+ concentration and activated CaMKII/Akt signaling pathway in OCCC, thereby repressing autophagy to maintain the sensitivity of OCCC cells to DDP.

Power law analysis of the human milk microbiome.

The human breast milk microbiome (HMM) has far reached health implications for both mothers and infants, and understanding the structure and dynamics of milk microbial communities is therefore of critical biomedical importance. Community heterogeneity, which has certain commonalities with familiar diversity but also with certain fundamental differences, is an important aspect of community structure and dynamics. Taylor's (1961) power law (TPL) (Nature, 1961) was discovered to govern the mean-variance power function relationship of population abundances and can be used to characterize population spatial aggregation (heterogeneity) and/or temporal stability. TPL was further extended to the community level to measure community spatial heterogeneity and/or temporal stability (Ma 2015, Molecular Ecology). Here, we applied TPL extensions (TPLE) to analyze the heterogeneity of the human milk microbiome by reanalyzing 12 datasets (2115 samples) of the healthy human milk microbiome. Our analysis revealed that the TPLE heterogeneity parameter (b) is rather stable across the 12 datasets, and there were approximately no statistically significant differences among ¾ of the datasets, which is consistent with the hypothesis that the heterogeneity scaling (i.e., change across individuals) of the human microbiome, including HMM, is rather stable or even constant. For this, we built a TPLE model for the pooled 12 datasets (b = 1.906), which can therefore represent the scaling rate of community-level spatial heterogeneity of HMM across individuals. Similarly, we also analyzed mixed-species ("averaged virtual species") level heterogeneity of HMM, and it was found that the mixed-species level heterogeneity was smaller than the heterogeneity at the previously mentioned community level (1.620 vs. 1.906).

Ecological and network analyses identify four microbial species with potential significance for the diagnosis/treatment of ulcerative colitis (UC).

BACKGROUND: Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. RESULTS: In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. CONCLUSIONS: Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

Integrated diversity and shared species analyses of human viromes.

Diversity analysis has been performed routinely on microbiomes, including human viromes. Shared species analysis has been conducted only rarely, but it can be a powerful supplement to diversity analysis. In the present study, we conducted integrated diversity and shared species analyses of human viromes by reanalyzing three published datasets of human viromes with more than 250 samples from healthy vs. diseased individuals and/or rural vs. urban individuals. We found significant differences in the virome diversity measured in the Hill numbers between the healthy and diseased individuals, with diseased individuals exhibiting higher virome diversity than healthy individuals, and rural individual exhibiting higher virome diversity than urban individuals. We applied both "read randomization" and "sample randomization" algorithms to perform shared species analysis. With the more conservative sample randomization algorithm, the observed number of shared species was significantly smaller than the expected shared species in 50% (8 of 16) of the comparisons. These results suggest that integrated diversity and shared species analysis can offer more comprehensive insights in comparing human virome samples than standard diversity analysis alone with potentially powerful applications in differentiating the effects of diseases or other meta-factors.

A new insight to characterize immunomodulation based on hepatopancreatic transcriptome and humoral immune factor analysis of the Cherax quadricarinatus infected with Aeromonas veronii.

Cherax quadricarinatus is a type of large freshwater crayfish that is characterized by rapid growth and formidable adaptability. It has also been widely cultured and studied as a model organism. Aeromonas veronii is the dominant pathogen in aquatic environments and the primary threat to aquaculture's economic stability. To better understand the interactions between C. quadricarinatus and A. veronii, high-throughput RNA sequencing of the C. quadricarinatus hepatopancreas was carried out on a control group, susceptible group (6 h after infection), and resistant group (48 h after infection). A total of 65,850,929 genes were obtained. Compared with the control group, 2616 genes were up-regulated and 1551 genes were down-regulated in the susceptible group; while 1488 genes were up-regulated and 1712 genes were down-regulated in the resistant group. GO and KEGG analysis showed that these differentially expressed genes (DEGs) were associated with multiple immune pathways, including Toll-like receptors (TLRs), antigen processing and presentation, NOD-like receptor signaling pathway, phagosome, lysosome, JAK-STAT signaling pathway. qRT-PCR showed that infection by A. veronii changed the expression pattern of the serine proteinase inhibitor (SPI), crustacean hyperglycemic hormone (CHH), anti-lipopolysaccharide factor (ALF), and extracellular copper/zinc superoxide dismutase (SOD1), all of which were significantly higher than in the control group up to 48 h after infection. In addition, detection of superoxide dismutase (SOD), catalase (CAT), lysozyme (LZM), and phenoloxidase (PO) activity, as well as ceruloplasmin (CP) concentration at different times after infection showed diverse trends. Furthermore, pathological sections obtained 24 h after infection show lesions on the hepatopancreas and intestinal tissues caused by A. veronii. The results of this study provide a foundation for analyzing the immune mechanism of C. quadricarinatus infected with A. veronii at the transcriptional level and a theoretical basis for screening disease-resistant individuals to ensure healthy economic development of the aquatic industry.

Hyperbaric oxygen therapy for people with autism spectrum disorder (ASD).

BACKGROUND: The rising prevalence of autism spectrum disorder (ASD) has increased the need for evidence-based treatments to lessen the impact of symptoms. Presently, no therapies are available to effectively treat individuals with all of the symptoms of this disorder. It has been suggested that hyperbaric oxygen therapy may alleviate the biochemical dysfunction and clinical symptoms of ASD. OBJECTIVES: To determine whether treatment with hyperbaric oxygen:1. improves core symptoms of ASD, including social communication problems and stereotypical and repetitive behaviors;2. improves noncore symptoms of ASD, such as challenging behaviors;3. improves comorbid states, such as depression and anxiety; and4. causes adverse effects. SEARCH METHODS: On 10 December 2015, we searched CENTRAL, Ovid MEDLINE, Embase, and 15 other databases, four of which were Chinese language databases. We also searched multiple trial and research registers. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) and quasi-RCTs of any dose, duration, and frequency for hyperbaric oxygen therapy compared with no treatment or sham treatment for children and adults with ASD. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration, in that three review authors independently selected studies, assessed them for risk of bias, and extracted relevant data. We also assessed the quality of the evidence by using the GRADE approach. MAIN RESULTS: We included one trial with a total of 60 children with a diagnosis of ASD who randomly received hyperbaric oxygen therapy or a sham treatment. Using GRADE criteria, we rated the quality of the evidence as low because of the small sample size and wide confidence intervals (CIs). Other problems included selection bias and short duration or follow-up.Overall, study authors reported no improvement in social interaction and communication, behavioral problems, communication and linguistic abilities, or cognitive function. With regard to the safety of hyperbaric oxygen therapy (adverse events), they reported minor-grade ear barotrauma events. Investigators found significant differences between groups in total number of side effect events (Peto odds ratio (OR) 3.87, 95% CI 1.53 to 9.82) and in the number of children who experienced side effects (Peto OR 4.40, 95% CI 1.33 to 14.48). AUTHORS' CONCLUSIONS: To date, there is no evidence that hyperbaric oxygen therapy improves core symptoms and associated symptoms of ASD. It is important to note that adverse effects (minor-grade ear barotrauma events) can occur. Given the absence of evidence of effectiveness and the limited biological plausibility and possible adverse effects, the need for future RCTs of hyperbaric oxygen therapy must be carefully considered.

[Effects of PINK1 gene on cell apoptosis and cell autophagy in neonatal mice with hypoxic-ischemic brain damage].

OBJECTIVE: To study the effect of PINK1 (phosphatase and tensin homolog deleted on chromosome ten induced putative kinase 1) gene on cell apoptosis and cell autophagy in neonatal mice with hypoxic-ischemic brain damage (HIBD). METHODS: Seventy-two wild-type C57BL/6 mice and 72 PINK1 gene knockout neonatal C57BL/6 mice were randomly divided into four groups: sham-operated wild-type (SWT), HIBD model wild-type (MWT), sham-operated knockout (SKO) and HIBD model knockout (MKO). HIBD model was prepared by low oxygen exposure for 2.5 hours after right carotid artery ligation. After 24 hours of hypoxia-ischemia treatment, TTC (2,3,5-triphenyl four azole nitrogen chloride) staining was used to measure brain infarct volume. The immunohistochemical staining was used to measure the expression of cell apoptosis protein cleaved-caspase-3 (CC3) in brain tissues. The TUNEL method was used to measure cell apoptosis. The immunofluorescence staining and Western blot were used to measure the expression of cell autophagy protein LC3. RESULTS: Compared with the MWT group, the infarct volume of brain tissues was markedly reduced in the MKO group (P<0.05), the number of apoptotic cells and the cell apoptosis index were markedly decreased in the MKO group (P<0.05), the expression of apoptosis protein CC3 was significantly reduced in the MKO group (P<0.05), the expression of cell autophagy protein LC3 was significantly decreased in the MKO group, and the autophagy indicator LC3II/LC3I was also markedly reduced in the MKO group (P<0.05). CONCLUSIONS: PINK1 gene knockout can protect neonatal mice from HIBD.

[Instrumentation and Application of a Portable Pretreating System for a Speedy Plasmon-Enhanced Raman Spectroscopy Detection Towards Food Safety].

The present paper developed a portable and fast sample pretreatment apparatus. It has many virtues like being portable, low power consumption and convenient operation, short extraction time and sound repeatability. Therefore, it can meet the requirements of on-site rapid detection pretreatment. The apparatus consists of four functional modules: ultrasonic extraction unit, heating unit, exhaust gas evaporation and absorption unit and control system. In addition, LED control panel and alarm device were designed. The whole treatment process needs three steps: ultrasonic extraction, liquid-liquid extraction and solvent evaporation by heating and pumping. For test of this apparatus performance, three real samples (pepper powder, pepper oil, bean sauce) containing banned additive Rhodamine B were taken as experiment objects. Compared with conventional laboratory pretreatment method, the PERS spectra achieved by two methods were little changed, but the experiment time was halved. In addition, the test results showed relative standard deviation less than ±5%.

[The Involvement of CRMP-2 on Axonal and Dendrictic Injury after Hypoxic-Ischemic Brain Injury in Neonatal Rat].

OBJECTIVE: To investigate the activity of collapsin response mediator protein 2 (CRMP-2) and its possible regulation for axonal and dendrictic injury under hypoxia-ischemia (HI). METHODS: Postnatal day 10 SD rats were suffered the right common carotid artery ligation and 8% mixture of oxygen and nitrogen hypoxia 2.5 h to produce HI model. The expression of total and phosphorylated CRMP-2 and amyloid precursor protein (APP) were detected by Western blot after HI. After pretreatment of protein kinase B (Akt) inhibitor, wortmannin or LY294002, western blot and immunohistochemistry were applied to detect the expression of total and phosphorylated of CRMP-2 at 4 h and 24 h after HI. At 72 h after HI, APP was detected by Western blot and immunohistochemistry, axonal and dendrictic injury was determined by electron microscope. RESULTS: Total CRMP-2 was not obviously changed after HI, compared with that of sham controls. However, the phosphorylated CRMP-2 (p-CRMP-2) protein transiently increased at 0.5 h, started to decrease at 2 h, remained at a low level at the rest of the time points, compared with that of sham controls. APP protein started to increase at 2 h, remained at a high level at 4, 8, 24 h, and then progressively increased at 48 and 72 h. In wortmannin and LY294002 group, CRMP-2 protein was not obviously changed at 4 h and 24 h after HI. However, p-CRMP-2 increased at 4 h and 24 h. At 72 h, wortmannin pretreatment increased APP expression, leading to more severe ultrastructure failure of axon and dendrite. CONCLUSION: As a downstream effector of Akt pathway, CRMP-2 is involved in axonal and dendritic injury regulation after HI in neonatal rat.

Construction and in vivo evaluation of a mammary gland-specific expression vector for human lysozyme.

A mammary gland-specific expression vector p205C3 was constructed with the 5'- and 3'-flanking regions of ß-lactoglobulin gene and the first intron of ß-casein gene of Chinese dairy goat as regulatory sequences. Human lysozyme (hLYZ) cDNA from mammary gland was cloned into p205C3 and the recombinant vector was used to generate transgenic mice by microinjection. Based on the lysoplate assay, four female offspring of one male founder were detected expressing recombinant hLYZ in their milk at the levels of 5-200 mg/l, and the expressed protein had the same molecular weight as that of normal hLYZ. Besides mammary glands, ectopic expressions were also found in the spleens and the small intestines of the transgenic mice. Among the offspring, the female transgenic mice maintained and expressed the transgene stably with a highest expression level of 750 mg/l. Therefore, p205C3 could be used to develop animal mammary gland bioreactors expressing hLYZ.

[SERS spectrum recognition for Malachite Green real-time detection in aquaculture used seawater].

Surface enhanced Raman spectroscopy (SERS) is a useful chemical analysis technique for its high sensitivity, which was used for Malachite Green qualitative analysis in real cases in the present article. Automatic recognition algorithms were put forward, which is a combination of three modules, including a robust Fourier transform for background rejection, a principal component analysis based character extraction method and artificial neural networks for classifying. Low-frequency background was rejected by iterative Fourier transform in order to eliminate the effect of variable background. The best principal component combination was obtained according to the Euclidean distances between-class and within-class in the sample space. And a three-layer back-propagating neural network was constructed for classifying. As it was shown, it would both minimize the network and reduce the classifying mistakes from variable baseline and Raman characters of other substances in seawater with best principal component combination. Malachite Green real-time detection in aquaculture used seawater was realized with a lower density limit of 0. 1 microg L-1. Moreover, the method proposed in this article could be extended for other sol analysis based on SERS technique.

Vasodilators for persistent pulmonary hypertension of the newborn: A network meta-analysis.

OBJECTIVES: To compare the efficacy and safety of different vasodilators in the treatment of persistent pulmonary hypertension of the newborn (PPHN) by a Bayesian network meta-analysis. METHODS: We searched databases (Cochrane, PubMed, Embase, and Web of Science) from January, 1990 up to December, 2023. Randomized controlled trials on the use of vasodilators in the treatment of PPHN. We extracted details of population, intervention, and outcome indicators. R and STATA software were used for data analysis. Sixteen articles were included, encompassing 776 neonates with PPHN. Among them, 12 articles were included in the quantitative analysis. The vasodilators included Sildenafil, Bosentan, Milrinone, Magnesium, Adenosine, and Tadalafil. RESULTS: The Bayesian network meta-analysis results suggested that compared to placebo, Milrinone [OR = 0.125, 95% CI (0.0261, 0.562)], Sildenafil [OR = 0.144, 95% CI (0.0428, 0.420)], and Sildenafil_Milrinone [OR = 0.0575, 95% CI (0.00736, 0.364)] reduced the mortality, but the difference among the three was not significant. There was also no significant difference in the incidence of hypotension, the duration of mechanical ventilation, and the use of extracorporeal membrane oxygenation among the vasodilators. Compared to Bosentan, Adenosine was more effective in reducing the oxygenation index [MD = -12.78, 95% CI (-25.56, -0.03)], and Magnesium was less effective in reducing the oxygenation index than Sildenafil [MD = 5.19, 95% CI (1.23, 9.2)]. CONCLUSIONS: Milrinone, Sildenafil, and Sildenafil_Milrinone reduced the mortality of neonates with PPHN. More clinical trials are needed to verify the efficacy and safety of vasodilators in the treatment of PPHN.

The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to explore the potential impact of the route of administration on the efficacy of therapies and occurrence of adverse events when administering medications to premature infants with patent ductus arteriosus (PDA). Method: The protocol for this review has been registered with PROSPERO (CRD 42022324598). We searched relevant studies in PubMed, Embase, Cochrane, and the Web of Science databases from March 26, 1996, to January 31, 2022. Results: A total of six randomized controlled trials (RCTs) and five observational studies were included for analysis, involving 630 premature neonates in total. Among these infants, 480 were in the ibuprofen group (oral vs. intravenous routes), 78 in the paracetamol group (oral vs. intravenous routes), and 72 in the ibuprofen group (rectal vs. oral routes). Our meta-analysis revealed a significant difference in the rate of PDA closure between the the initial course of oral ibuprofen and intravenous ibuprofen groups (relative risk (RR) = 1.27, 95% confidence interval (CI) [1.13-1.44]; P < 0.0001, I2 = 0%). In contrast, the meta-analysis of paracetamol administration via oral versus intravenous routes showed no significant difference in PDA closure rates (RR = 0.86, 95% CI [0.38-1.91]; P = 0.71, I2 = 76%). However, there was no statistically significant difference in the risk of adverse events or the need for surgical intervention among various drug administration methods after the complete course of drug therapy. Conclusion: This meta-analysis evaluated the safety and effectiveness of different medication routes for treating PDA in premature infants. Our analysis results revealed that compared with intravenous administration, oral ibuprofen may offer certain advantages in closing PDA without increasing the risk of adverse events. Conversely, the use of paracetamol demonstrated no significant difference in PDA closure and the risk of adverse events between oral and intravenous administration.

A comprehensive diversity analysis on the gut microbiomes of ASD patients: from alpha, beta to gamma diversities.

Autism spectrum disorder (ASD) is estimated to influence as many as 1% children worldwide, but its etiology is still unclear. It has been suggested that gut microbiomes play an important role in regulating abnormal behaviors associated with ASD. A de facto standard analysis on the microbiome-associated diseases has been diversity analysis, and nevertheless, existing studies on ASD-microbiome relationship have not produced a consensus. Here, we perform a comprehensive analysis of the diversity changes associated with ASD involving alpha-, beta-, and gamma-diversity metrics, based on 8 published data sets consisting of 898 ASD samples and 467 healthy controls (HC) from 16S-rRNA sequencing. Our findings include: (i) In terms of alpha-diversity, in approximately 1/3 of the studies cases, ASD patients exhibited significantly higher alpha-diversity than the HC, which seems to be consistent with the "1/3 conjecture" of diversity-disease relationship (DDR). (ii) In terms of beta-diversity, the AKP (Anna Karenina principle) that predict all healthy microbiomes should be similar, and every diseased microbiome should be dissimilar in its own way seems to be true in approximately 1/2 to 3/4 studies cases. (iii) In terms of gamma-diversity, the DAR (diversity-area relationship) modeling suggests that ASD patients seem to have large diversity-area scaling parameter than the HC, which is consistent with the AKP results. However, the MAD (maximum accrual diversity) and RIP (ratio of individual to population diversity) parameters did not suggest significant differences between ASD patients and HC. Throughout the study, we adopted Hill numbers to measure diversity, which stratified the diversity measures in terms of the rarity-commonness-dominance spectrum. It appears that the differences between ASD patients and HC are more propounding on rare-species side than on dominant-species side. Finally, we discuss the apparent inconsistent diversity-ASD relationships among different case studies and postulate that the relationships are not monotonic.

Effects of Yellow Sea Warm Current on zooplankton community composition and functional groups in winter.

The Yellow Sea Warm Current (YSWC) constitutes a significant hydrological feature in the Yellow Sea, particularly prominent during winter, facilitating the transport of warm, saline waters and warm-water species from the open sea to the Bohai and Yellow Seas. The YSWC induces alterations in the community structure and function of zooplankton. However, the effects of the YSWC on the functional trait compositions and functional groups of zooplankton remain unclear. This study aimed to elucidate the influence of the YSWC on the community structure, functional trait composition, and functional groups of zooplankton during winter of 2016. The YSWC significantly impacted the zooplankton assemblage in the central Yellow Sea (CYSA), resulting in notable distinctions from the Shandong coastal assemblage (SCA) and Jiangsu coastal assemblage (JCA). Compared to the SCA and JCA (comprising 45 and 34 taxa, with abundances of 119.4 ± 114.6 ind·m-3 and 82.8 ± 62.1 ind·m-3, respectively), the CYSA exhibited higher species richness and abundance (with 51 taxa and 144.4 ± 103.4 ind·m-3, respectively). This study documented a total of 11 warm-water species, showing a decreasing trend in both species richness and abundance from south to north. The CYSA was characterized by the predominance of medium‒sized, current‒feeding, omnivorous‒herbivorous broadcast spawners, whereas the SCA and the JCA were predominantly dominated by giant‒sized, ambush‒feeding carnivores. The Qingdao-Shidao anticyclonic eddy in the southern of Shandong Province led to a significant increase in the abundance of zooplankton, potentially impacting Yellow Sea fishery resource. This research contributed to a deeper understanding of how YSWC influence the zooplankton community and offered fresh insights into the effects of YSWC on zooplankton function traits and functional groups.

Elevated pCO2 may increase the edible safety risk of clams exposed to toxic Alexandrium spp.

Toxic harmful algal blooms (HABs) have received increasing attention owing to their threat to the health of aquatic life and seafood consumers. This study evaluated the impacts of elevated atmospheric partial pressure of CO2 (pCO2) on the production of paralytic shellfish toxins (PSTs) in different Alexandrium spp. strains, together with its further effects on the bioaccumulation/elimination dynamics of PSTs in bivalves contaminated with PSTs from toxic dinoflagellates. Our results showed that elevated pCO2 stimulated the growth of the two Alexandrium spp. (A. catenella and A. pacificum) isolated from the northern and southern coastal areas of China, respectively, and affected PST production including content and toxicity of the two strains differently. Further PSTs bioaccumulation/elimination in PSTs-contaminated Manila clam, Ruditapes philippinarum under high pCO2 also occurred. It is worth noting the biotransformation of neosaxitoxin (NEO) with high toxicity through trophic transfer with effect of elevated pCO2. When in microalgae cultured under the control (410 ppm) and elevated pCO2 conditions (495 and 850 ppm), the proportion of NEO in the PST content produced by A. catenella was reduced from 11.1 to 6.4 and 2.6 %, while the proportion of NEO in A. pacificum was increased from 3.1 to 3.6 and 4.7 %, respectively. NEO accounted for >50 % of total PST contents in clams, which were biotransformed via transfer from dinoflagellates and higher pCO2 enhanced this biotransformation leading to increased NEO accumulation. The negatively affected elimination of PSTs, especially NEO, in clams fed with A. catenella or A. pacificum, indicates that the detoxification of PSTs-contaminated clams may be more difficult under elevated pCO2. This study provides reference for developing models to assess the safety of bivalves under the co-stress of environmental change and toxic HABs, suggesting that ocean acidification may lead to the higher safety risk of Manila clams exposed to toxic HAB dinoflagellates.

[The regulation of Akt signaling on axonal density after hypoxic-ischemic brain injury in neonatal rat].

OBJECTIVE: To investigate the activity of protein kinase B (Akt) and its downstream protein, glycogen synthase kinase-3beta (GSK-3beta) under hypoxia-ischemia (HI), and the possible regulation for axonal density. METHODS: Postnatal day 10 SD rats were suffered the right common carotid artery ligation and 8% mixture of oxygen and nitrogen hypoxia 2.5 h to produce HI model. The expression of total and phosphorylated Akt and GSK-3beta was detected by western blot after HI. After pretreatment of Akt inhibitor, wortmannin or LY294002, Western blot detect the expression of total and phosphorylated of Akt, GSK-3beta at 4 h and 24 h after HI. After pretreatment of wortmannin, axonal density was determined by Bielschowsky silver impregnation, and histological injury was evaluated by hematoxylin and eosin (HE) staining. RESULTS: The expression of total Akt and GSK-3beta remained unchanged after HI. p-Akt protein significantly decreased at 0.5 h, increased at 2 h and reached the highest at 4 h, returned to baseline at 8 h, declined at 24 and 48 h after HI, and finally returned to baseline again at 72 h compared with that of sham controls, p-GSK-3beta protein decreased at 0. 5 h, increased at 2 h, reached the highest at 4 h, returned to baseline at 8 and decreased at 24 h, reached the lowest at 48 h, and returned to baseline at 72 h. Wortmannin or LY294002 intervention didn't change the expression of total Akt and GSK-3beta, while decrease the p-Akt and p-GSK-3beta expression. HI cause decreased axonal density, and the histological injury of brain. Wortmannin pretreatment could aggravate the histological injury and decrease axonal density after HI. CONCLUSION: The Akt pathway is involved in axonal density and histological brain injury after HI in neonatal rat.

Latitudinal transition of epipelagic mesozooplankton in the northwestern Pacific in winter.

The northwestern Pacific (NWP) is a hotspot of marine biodiversity study, and zooplankton is a crucial secondary producer in the marine ecosystem. It is of utmost importance to do extensive study on the distribution of zooplankton community in the NWP. The distribution of epipelagic zooplankton community in the 143-146°E section between the equator and 36°N in winter was examined in this study. The findings indicated that the Kuroshio extension, the North Pacific Subtropical Gyre, the North Equatorial Current and the North Equatorial Countercurrent were the four main ocean currents in the NWP that regulated the latitudinal transition of epipelagic mesozooplankton and split the sample section into four station groups. The key factors influencing zooplankton's geographic distribution were temperature, primary productivity, and current movement. In general, as latitude increased, zooplankton abundance and biomass first decreased and subsequently flourished in the NWP. Diversity indexes and indicator species also revealed the difference across the communities in four station groups. The body length of zooplankton declined gradually from north to south under the combined influence of temperature and primary production, with the minimum in the oligotrophic subtropical zone and a sub-peak in the high primary production area near the equator. Additionally, the abundance of zooplankton was higher in the winter than in the summer due to seasonal fluctuations in the properties of the ocean currents. This study elucidated the control effects of ocean currents on the latitudinal distribution of zooplankton, supplemented records of the geographic distribution and body length characteristics of zooplankton communities in the NWP, and provided the basis for further research on the ecological role of zooplankton communities and the global changes of marine ecosystems.

Trait-based approach revealed the seasonal variation of mesozooplankton functional groups in the South Yellow Sea.

Functional traits determine the fitness of organisms and mirror their ecological functions. Although trait-based approaches provide ecological insights, it is underexploited for marine zooplankton, particularly with respect to seasonal variation. Here, based on four major functional traits, including body length, feeding type, trophic group, and reproduction mode, we quantified the seasonal variations of mesozooplankton functional groups in the South Yellow Sea (SYS) in the spring, summer, and autumn of 2018. Strong seasonal dynamics were identified for all traits but patterns varied among traits. Small zooplankton (47.7-88.6%), omnivores-herbivores (81.3-97.6%), and free spawners (54.8-92.5%) dominated in three seasons, while ambush feeders and current feeders dominated in spring (45.7%), and autumn (73.4%), respectively. Cluster analysis of the functional traits showed that the mesozooplankton in the SYS can be classified into eight functional groups. The biogeographic and seasonal variations of functional groups can be partially explained by environmental drivers. Group 1, represented by omnivores-herbivores, was the most dominant functional group, the abundance of which peaked in spring and was positively correlated with chlorophyll a concentration, indicating its close association with phytoplankton dynamics. The contribution of giant, active ambush carnivores, passive ambush carnivore jellyfish, current omnivores-detritivores, and parthenogenetic cladocerans increased with sea surface temperature. The proportion of giant, active ambush carnivores and active ambush omnivore-carnivore copepods decreased with salinity in autumn. This study presents a new perspective for understanding the dynamics of zooplankton and paves the way for further research on the functional diversity of zooplankton in the SYS. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00156-9.

CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway.

CXCL8-CXCR1/CXCR2 signaling pathways might form complex crosstalk among different cell types within the ovarian tumor microenvironment, thereby modulating the behaviors of different cells. This study aimed to investigate the expression pattern of CXCL8 in the ovarian tumor microenvironment and its impact on both endothelial-to-mesenchymal transition (EndMT) and ferroptosis of endothelial cells. The human monocytic cell line THP-1 and the human umbilical vein endothelial cell line PUMC-HUVEC-T1 were used to conduct in vitro studies. Erastin was used to induce ferroptosis. Results showed that tumor-associated macrophages are the major source of CXCL8 in the tumor microenvironment. CXCL8 treatment promoted the nucleus entrance of NF-κB p65 and p65 phosphorylation via CXCR2 in endothelial cells, suggesting activated NF-κB signaling. Via the NF-κB signaling pathway, CXCL8 enhanced TGF-ß1-induced EndMT of PUMC-HUVEC-T1 cells and elevated their expression of SLC7A11 and GPX4. These trends were drastically weakened in groups with CXCR2 knockdown or SB225002 treatment. TPCA-1 reversed CXCL8-induced upregulation of SLC7A11 and GPX4. CXCL8 protected endothelial cells from erastin-induced ferroptosis. However, these protective effects were largely canceled when CXCR2 was knocked down. In summary, CXCL8 can activate the NF-κB signaling pathway in endothelial cells in a CXCR2-dependent manner. The CXCL8-CXCR2/NF-κB axis can enhance EndMT and activate SLC7A11 and GPX4 expression, protecting endothelial cells from ferroptosis.