Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.

TRAF5 regulates intestinal mucosal Th1/Th17 cell immune responses via Runx1 in colitis mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease associated with CD4+ Th1 and Th17 cell immune responses. Tumour necrosis factor-associated factor 5 (TRAF5) deficiency has been shown to aggravate DSS-induced colitis. However, the potential role of TRAF5 in regulating CD4+ T cell immune responses in the pathogenesis of IBD remains unclear. TRAF5-/- CD4+ CD45RBhigh T cells and WT CD4+ CD45RBhigh T cells were transferred to Rag2-/- mice via intravenous (i.v.) tail injection, respectively, to establish a chronic colitis model. Adeno-associated virus (AAV)-mediated gene knockout technique was used to knock out runt-associated transcription factor 1 (Runx1) expression in vivo. Specific cytokines of Th1 and Th17 cells were detected by quantitative RT-PCR, immunohistochemistry, ELISA, and flow cytometry. In T-cell transfer colitis mice, the Rag2-/- mice reconstituted with TRAF5-/- CD4+ CD45RBhigh T cells showed more severe intestinal inflammation than the WT control group, which was characterised by increased expression of INF-γ, TNF-α, IL-17a. Furthermore, we found that the INF-γ+ CD4+ , IL17a+ CD4+ , and INF-γ+ IL17a+ CD4+ T cells in the intestinal mucosa of Rag2-/- mice reconstituted with TRAF5-/- CD4+ CD45RBhigh T cells were significantly higher than those of the WT control group by flow cytometry. Mechanistically, knockout Runx1 inhibited the differentiation of TRAF5-/- CD4+ T cells into Th1 and Th17 cells in the intestinal mucosa of T-cell transfer colitis mice. TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 to participate in the pathogenesis of colitis. Thus targeting TRAF5 in CD4+ T cells may be a novel treatment for IBD.

Characterization of wheat Wrab18 gene promoter and expression analysis under abiotic stress.

BACKGROUND: Promoters play key roles in plant gene expression in complex and varied natural environments. The type and amount of cis-acting elements in the promoter sequence tend to indicate the response of genes to induction factors. WRAB18 is a group III member of the late embryogenesis abundant (LEA) protein family that performs multiple functions in plant stress physiology. To elucidate the particularly biological effects of WRAB18 on stress, exploration of its promoter sequence is necessary. METHODS AND RESULTS: In this study, the full-length and promoter sequences of Wrab18 were isolated from the Zhengyin 1 cultivar of Triticum aestivum. The gene sequences and cis-acting elements in the promoter were analyzed using the Plant Promoter Database and bioinformatics methods. The results showed that Wrab18 possessed one intron with 100 bp, the promoter sequence contained various stress-related cis-acting elements, and the functionality of the promoter was checked using green fluorescent protein (GFP) marker protein expression by transient assay in Nicotiana benthamiana. Furthermore, based on promoter prediction analysis, quantitative real-time fluorescent PCR results confirmed the response of gene expression levels to stress factors. CONCLUSIONS: In summary, the promoter sequence of Wrab18 plays a role in plant stress responses, contains multiple cis-acting elements, and provides insights into the role of WRAB18 in plant resilience to stress. This study has guiding significance for further studies of gene function and mechanism of action, and lays a theoretical foundation for improving wheat quality.

The Anti-Apoptotic Role of COX-2 during In Vitro Infection of Human Intestinal Cell Line by Giardia duodenalis and the Potential Regulators.

The protozoan parasite Giardia duodenalis inhabits the upper small intestine of mammals, including humans, and causes a disease known as giardiasis, which can lead to diarrhea, abdominal cramps, and bloating. G. duodenalis was known as a causative factor of intestinal epithelial cell (IEC) apoptosis. Cyclooxygenase-2 (COX-2) has been identified as an influencing factor of pathogen infection by participating in immune response, while its role in host defense against Giardia infection is not clear. Here, we initially observed the involvement of COX-2 in the regulation of Giardia-induced IEC apoptosis. Inhibition of COX-2 activity could promote Giardia-induced reduction of IEC viability, increase of reactive oxygen species (ROS) production, and decrease of nitric oxide (NO) release, which would exacerbate IEC apoptosis. In addition, during Giardia-IEC interactions, COX-2 inhibition was able to accelerate caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage and inhibit the expressions of some anti-apoptotic proteins like cIAP-2 and survivin. In contrast, COX-2 overexpression could reduce Giardia-induced IEC apoptosis. We further investigated the regulatory mechanisms affecting COX-2 expression in terms of anti-apoptosis. The results showed that p38/ERK/AKT/NF-κB signaling could regulate COX-2-mediated ROS/NO production and anti-IEC apoptosis during Giardia infection. We also found that COX-2-mediated anti-IEC apoptosis induced by Giardia was related to Toll-like receptor 4 (TLR4)-dependent activation of p38-NF-κB signaling. Collectively, this study identified COX-2 as a promoter for apoptotic resistance during Giardia-IEC interactions and determined the potential regulators, furthering our knowledge of anti-Giardia host defense mechanisms.

High-spatiotemporal-resolution estimation of solar energy component in the United States using a new satellite-based model.

Diffuse solar radiation (Rd), known as an important component of global solar radiation (Rg), is a key parameter for solar energy related applications and ecosystem photosynthesis. Some meteorological models have been developed to estimate Rd with acceptable accuracy, but their spatial scales are often small due to the limited meteorological station number. Satellite-based models provide accurate and large-scale Rg estimates. However, remote sensing estimations of Rd are often with low spatial resolutions and large uncertainties, because their methods were based on inaccurate surface and atmospheric parameters. To address these challenges, the high-spatiotemporal-resolution (half-hourly and 1-km) Rd in the United States was estimated using the top-of-atmosphere (TOA) data from the new-generation geostationary satellite Geostationary Operational Environmental Satellites (GOES-16) and the method iterative random forest (RF). The results showed that the iterative RF model had higher accuracy than the simple RF and artificial neural network (ANN) models, and using TIR (thermal infrared) bands can improve models' accuracy. The best model can estimate half-hourly Rd with the accuracy R2 = 0.88, RMSE = 37.81 W/m2, and MBE = 0.01 W/m2. Compared with the previous 0.01-degree (∼11-km) Rd product Earth Polychromatic Imaging Camera (EPIC), the GOES-16 estimated 1-km Rd had similar spatial patterns. Moreover, based on the GOES-16 estimated half-hourly and 1-km Rd in the United States, the spatiotemporal heterogeneity of Rd was quantitatively observed. The proposed approach can be used to produce more high-spatiotemporal-resolution Rd products, and these products are very helpful for many solar-related research topics and industrial applications.

The immunophilin CYCLOPHILIN28 affects PSII-LHCII supercomplex assembly and accumulation in Arabidopsis thaliana.

In plant chloroplasts, photosystem II (PSII) complexes, together with light-harvesting complex II (LHCII), form various PSII-LHCII supercomplexes (SCs). This process likely involves immunophilins, but the underlying regulatory mechanisms are unclear. Here, by comparing Arabidopsis thaliana mutants lacking the chloroplast lumen-localized immunophilin CYCLOPHILIN28 (CYP28) to wild-type and transgenic complemented lines, we determined that CYP28 regulates the assembly and accumulation of PSII-LHCII SCs. Compared to the wild type, cyp28 plants showed accelerated leaf growth, earlier flowering time, and enhanced accumulation of high molecular weight PSII-LHCII SCs under normal light conditions. The lack of CYP28 also significantly affected the electron transport rate. Blue native-polyacrylamide gel electrophoresis analysis revealed more Lhcb6 and less Lhcb4 in M-LHCII-Lhcb4-Lhcb6 complexes in cyp28 versus wild-type plants. Peptidyl-prolyl cis/trans isomerase (PPIase) activity assays revealed that CYP28 exhibits weak PPIase activity and that its K113 and E187 residues are critical for this activity. Mutant analysis suggested that CYP28 may regulate PSII-LHCII SC accumulation by altering the configuration of Lhcb6 via its PPIase activity. Furthermore, the Lhcb6-P139 residue is critical for PSII-LHCII SC assembly and accumulation. Therefore, our findings suggest that CYP28 likely regulates PSII-LHCII SC assembly and accumulation by altering the configuration of P139 of Lhcb6 via its PPIase activity.

Characterization of the complete mitochondrial genome of Notocotylus sp. (Trematoda, Notocotylidae) and its phylogenetic implications.

The parasite genus Notocotylus comprises at least 50 species colonizing mainly aquatic birds and to a lesser extent some mammals, particularly rodents. Here trematode specimens isolated from a wild black swan were characterized and identified to belong to the genus Notocotylus via morphological and molecular analyses. Phylogenetic position of the isolate among other trematodes was determined based on the ribosomal internal transcribed spacer (ITS) 1 and 2. The complete mitochondrial (mt) genome of the isolate was amplified, sequenced, assembled, analyzed, and annotated. The isolate has an AT-rich mt genome (14,317 bp in length) that comprises 12 protein-coding genes (PCGs), 22 transfer RNA genes, and two ribosomal RNA genes. The Notocotylus isolate identified in this study has relatively high mt genome sequence identity and identical gene content and arrangement to a known Notocotylidae species, Ogmocotyle sikae. The isolate formed a genetic clade with O. sikae in phylogenetic analysis of the concatenated PCG amino acid sequences. Compared to the ITS, the trematode mt genome appears more informative for resolving high-level phylogenies. To the best of our knowledge, this is the first study exploring the complete mt genome for the genus Notocotylus, and it offers a novel genomic resource that has important implications for trematode phylogenetics.

Prevalence and subtype diversity of Blastocystis in human and nonhuman primates in North China.

Blastocystis is of public health concern due to its global distribution in diverse animals including humans. Here, fecal specimens sampled from human and nonhuman primates were examined for Blastocystis by PCR and sequence analysis of the small subunit ribosomal RNA gene. Among age cohorts, the parasite was positive only for three of 126 (2.4%) adults admitted to a hospital in Harbin, Heilongjiang province, with a less common human subtype (ST), ST5, determined. Blastocystis was identified in 7.0% of nonhuman primates (NHPs), giving an infection rate of 6.8% (4/59) to zoo NHPs in Harbin and 7.1% (9/126) to lab NHPs in Beijing. No significant prevalence differences by macaque species, age, gender, and sample source were observed. Among the subtypes found in NHPs, seven belonged to ST1, three to ST2, one to ST3, and the remaining two to mixed ST1/ST3 and ST2/ST3. Although the data here showed no direct evidence linking human infections to Blastocystis of NHP origin, individuals might acquire colonization of ST5 from livestock sources judged by occurrence of this subtype also in cattle in Harbin and pigs and sheep in unspecified cities of Heilongjiang as noted in previous reports. In addition, given the nonrigid (but sometimes, perhaps cryptic) host specificity of ST1, ST2, and ST3 and their dominant role in human affections globally as discussed in a previous NHP report by Alfellani et al. (Parasitology 140:966-971, 2013a), precautions should be taken to minimize the possible transmission of those subtypes from NHPs to humans in North China.

Evaluation of protective immunity induced by DNA vaccination with genes encoding Toxoplasma gondii GRA17 and GRA23 against acute toxoplasmosis in mice.

Toxoplasma gondii, an obligatory intracellular protozoan, can cause serious public health problems and economic losses worldwide. Two novel dense granule proteins (GRA17 and GRA23) were recently identified as T. gondii-secreted proteins which are localized to the parasitophorous vacuole membrane (PVM) and can mediate the movement of small molecules between the host cell and parasitophorous vacuole (PV). In the present study, we evaluated the protective immunity induced by DNA vaccination with genes encoding GRA17 and GRA23 against acute toxoplasmosis in mice. Eukaryotic expressing plasmids pVAX-TgGRA17 and pVAX-TgGRA23 were constructed. Then, BALB/c mice were intramuscularly immunized with pVAX-TgGRA17, pVAX-TgGRA23, or pVAX-TgGRA17 + pVAX-TgGRA23 followed by challenge infection with the highly virulent RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii were examined by cytokine and serum antibody measurements, lymphocyte proliferation assays, flow cytometry of lymphocytes and the survival time after challenge. Our results showed that mice immunized with pVAX-TgGRA17, pVAX-TgGRA23, or pVAX-TgGRA17 + pVAX-TgGRA23 induced specific humoral and cellular responses, with higher level of IgG antibody, increased levels of Th1-type cytokines IFN-γ and IL-12 (p70), and CD3+CD4+CD8- and CD3+CD8+CD4- T cells, as well as prolonged survival time (9.1 ± 0.32 days for pVAX-TgGRA17, 10.8 ± 0.79 days for pVAX-TgGRA23, and 12.6 ± 2.55 days for pVAX-TgGRA17 + pVAX-TgGRA23) compared to the blank control (7.11 ± 0.33 days), PBS control (7.22 ± 0.44 days), and pVAX I control (7.11 ± 0.33 days). These results demonstrated that both TgGRA17 and TgGRA23 are potential vaccine candidates, TgGRA23 has a better immunogenicity, and co-immunization of pVAX-TgGRA17 and pVAX-TgGRA23 induces better protective efficacy.

The dehydrin wzy2 promoter from wheat defines its contribution to stress tolerance.

Dehydrins (DHNs), which are stress-related proteins, are important for plant survival under various abiotic and biotic stresses. To elucidate the regulatory mechanisms of wheat-derived DHNs under these stresses, we characterized the DHN wzy2 promoter of the wheat cultivar Zhengyin 1 and studied its contribution to stress tolerance. Sequence analysis indicated that the wzy2 gene contains one 109-bp intron inserted in the nucleotide sequence encoding the S-motif and characterized by a GT-AG border. The wzy2 promoter was revealed to contain several potential stress-related cis-acting regulatory elements, including elements responsive to abscisic acid (ABA; ABREs), anoxia (GC motifs), low temperature (LTREs), auxin (TGA elements), methyl jasmonate (MeJA; TGACG motifs), and gibberellin (TATC boxes). Quantitative real-time PCR analysis showed that transcript accumulation occurred in response to low temperature, anoxia, indoleacetic acid, MeJA, ABA, and gibberellin (GA) treatments. Histochemical analysis of GUS expression demonstrated that wzy2 promoter activity could be upregulated by low temperature, anoxia, ABA, and GA treatments. Interestingly, wzy2 promoter element-driven ß-glucuronidase expression was first observed in meristemoids rather than calli of wheat seeds subjected to anoxia. Taken together, these results indicate that YSK2-type wzy2 can be induced directly by ABA, low temperature, anoxia, and GA treatments and indirectly by drought, implying that different cis-acting elements interact in stress response cross talk.

Corrigendum: Specific TLR-mediated HSP70 activation plays a potential role in host defense against the intestinal parasite Giardia duodenalis.

[This corrects the article DOI: 10.3389/fmicb.2023.1120048.].

Dynamic regulation of EXO1 promotes the progression from liver fibrosis to HCC through TGF-ß1/Smad signaling feedback loop.

BACKGROUND: HSCs are the main stromal cells in the process of liver fibrosis and accelerate HCC progression. Previous studies determined that highly expressed exonuclease 1 (EXO1) increases the malignant behavior of HCC cells and is closely related to liver cirrhosis. This study aimed to explore the roles and mechanisms of EXO1 in the development of liver cirrhosis and HCC. METHODS: We fully demonstrated that EXO1 expression was positively correlated with liver fibrosis and cirrhotic HCC by combining bioinformatics, hepatic fibrosis mouse models, and human HCC tissues. The role of EXO1 in a murine HCC model induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated by employing an adeno-associated virus-mediated EXO1 knockdown technique. RESULTS: The knockdown of EXO1 promoted a regression of HCC in AKT/Ras mice and reduced the degree of liver fibrosis. Downregulated EXO1 inhibited LX-2 cell activation and inhibited the proliferation and migration of HCC cells. Moreover, conditioned medium of LX-2 cells with EXO1 overexpression increased the proliferation and migration of HCC cells, which was attenuated after EXO1 knockout in LX-2 cells. EXO1 knockdown attenuated the role of LX-2 in promoting HepG2 xenograft growth in vivo. Mechanistically, EXO1 promotes the activation of the downstream TGF-ß-smad2/3 signaling in LX-2 and HCC cells. Interestingly, increased TGF-ß-smad2/3 signaling had a feedback effect on EXO1, which sustains EXO1 expression and continuously stimulates the activation of HSCs. CONCLUSIONS: EXO1 forms a positive feedback circuit with TGF-ß-Smad2/3 signaling and promotes the activation of HSCs, which accelerates HCC progression. Those findings indicate EXO1 may be a promising target for the diagnosis and treatment of cirrhotic HCC.

Specific TLR-mediated HSP70 activation plays a potential role in host defense against the intestinal parasite Giardia duodenalis.

Giardia duodenalis, an important flagellated noninvasive protozoan parasite, infects the upper small intestine and causes a disease termed giardiasis globally. Few members of the heat shock protein (HSP) family have been shown to function as potential defenders against microbial pathogens, while such information is lacking for Giardia. Here we initially screened and indicated that in vitro Giardia challenge induced a marked early upregulation of HSP70 in intestinal epithelial cells (IECs). As noted previously, apoptotic resistance, nitric oxide (NO)-dependent cytostatic effect and parasite clearance, and epithelial barrier integrity represent effective anti-Giardia host defense mechanisms. We then explored the function of HSP70 in modulating apoptosis, NO release, and tight junction (TJ) protein levels in Giardia-IEC interactions. HSP70 inhibition by quercetin promoted Giardia-induced IEC apoptosis, viability decrease, NO release reduction, and ZO-1 and occludin downregulation, while the agonist celastrol could reverse these Giardia-evoked effects. The results demonstrated that HSP70 played a previously unrecognized and important role in regulating anti-Giardia host defense via attenuating apoptosis, promoting cell survival, and maintaining NO and TJ levels. Owing to the significance of apoptotic resistance among those defense-related factors mentioned earlier, we then elucidated the anti-apoptotic mechanism of HSP70. It was evident that HSP70 could negatively regulate apoptosis in an intrinsic way via direct inhibition of Apaf-1 or ROS-Bax/Bcl-2-Apaf-1 axis, and in an extrinsic way via cIAP2-mediated inhibition of RIP1 activity. Most importantly, it was confirmed that HSP70 exerted its host defense function by downregulating apoptosis via Toll-like receptor 4 (TLR4) activation, upregulating NO release via TLR4/TLR2 activation, and upregulating TJ protein expression via TLR2 activation. HSP70 represented a checkpoint regulator providing the crucial link between specific TLR activation and anti-Giardia host defense responses. Strikingly, independent of the checkpoint role of HSP70, TLR4 activation was proven to downregulate TJ protein expression, and TLR2 activation to accelerate apoptosis. Altogether, this study identified HSP70 as a potentially vital defender against Giardia, and revealed its correlation with specific TLR activation. The clinical importance of HSP70 has been extensively demonstrated, while its role as an effective therapeutic target in human giardiasis remains elusive and thus needs to be further clarified.

ROS-AMPK/mTOR-dependent enterocyte autophagy is involved in the regulation of Giardia infection-related tight junction protein and nitric oxide levels.

Giardia duodenalis, a cosmopolitan noninvasive protozoan parasite of zoonotic concern and public health importance, infects the upper portions of the small intestine and causes one of the most common gastrointestinal diseases globally termed giardiasis, especially in situations lacking safe drinking water and adequate sanitation services. The pathogenesis of giardiasis is complex and involves multiple factors from the interaction of Giardia and intestinal epithelial cells (IECs). Autophagy is an evolutionarily conserved catabolic pathway that involves multiple pathological conditions including infection. Thus far, it remains uncertain if autophagy occurs in Giardia-infected IECs and if autophagic process is associated with the pathogenic factors of giardiasis, such as tight junction (TJ) barrier defects and nitric oxide (NO) release of IECs. Here Giardia-in vitro exposed IECs showed upregulation of a series of autophagy-related molecules, such as LC3, Beclin1, Atg7, Atg16L1, and ULK1, and downregulation of p62 protein. IEC autophagy induced by Giardia was further assessed by using autophagy flux inhibitor, chloroquine (CQ), with the ratio of LC3-II/LC3-I significantly increased and downregulated p62 significantly reversed. Inhibition of autophagy by 3-methyladenine (3-MA) rather than CQ could markedly reverse Giardia-induced downregulation of TJ proteins (claudin-1, claudin-4, occludin, and ZO-1; also known as epithelial cell markers) and NO release, implying the involvement of early-stage autophagy in TJ/NO regulation. We subsequently confirmed the role of ROS-mediated AMPK/mTOR signaling in modulating Giardia-induced autophagy, TJ protein expression, and NO release. In turn, impairment of early-stage autophagy by 3-MA and late-stage autophagy by CQ both exhibited an exacerbated effect on ROS accumulation in IECs. Collectively, we present the first attempt to link the occurrence of IEC autophagy with Giardia infection in vitro, and provides novel insights into the contribution of ROS-AMPK/mTOR-dependent autophagy to Giardia infection-related downregulation of TJ protein and NO levels.

Hotspots and trends in ophthalmology in recent 5 years: Bibliometric analysis in 2017-2021.

Purpose: The purpose of this study was to investigate the hotspots and research trends of ophthalmology research. Method: Ophthalmology research literature published between 2017 and 2021 was obtained in the Web of Science Core Collection database. The bibliometric analysis and network visualization were performed with the VOSviewer and CiteSpace. Publication-related information, including publication volume, citation counts, countries, journals, keywords, subject categories, and publication time, was analyzed. Results: A total of 10,469 included ophthalmology publications had been cited a total of 7,995 times during the past 5 years. The top countries and journals for the number of publications were the United States and the Ophthalmology. The top 25 global high-impact documents had been identified using the citation ranking. Keyword co-occurrence analysis showed that the hotspots in ophthalmology research were epidemiological characteristics and treatment modalities of ocular diseases, artificial intelligence and fundus imaging technology, COVID-19-related telemedicine, and screening and prevention of ocular diseases. Keyword burst analysis revealed that "neural network," "pharmacokinetics," "geographic atrophy," "implementation," "variability," "adverse events," "automated detection," and "retinal images" were the research trends of research in the field of ophthalmology through 2021. The analysis of the subject categories demonstrated the close cooperation relationships that existed between different subject categories, and collaborations with non-ophthalmology-related subject categories were increasing over time in the field of ophthalmology research. Conclusions: The hotspots in ophthalmology research were epidemiology, prevention, screening, and treatment of ocular diseases, as well as artificial intelligence and fundus imaging technology and telemedicine. Research trends in ophthalmology research were artificial intelligence, drug development, and fundus diseases. Knowledge from non-ophthalmology fields is likely to be more involved in ophthalmology research.

Publication delays and associated factors in ophthalmology journals.

Introduction: This study aimed to evaluate the publication delays and correlative factors of peer-reviewed ophthalmology journals. Methods: The ophthalmology journals listed in the Journal Citation Report 2020 were retrieved from the Web of Science database. The first original research article of each journal issue from January to December 2020 was extracted, and its submission, final revision, acceptance, and publication dates were obtained. Information on impact factors, advance online publication (AOP) status, open access (OA) rate and acceptance rate in 2020 was also collected. The correlations between publication delays and potential associated factors were analyzed. Results: A total of 58 ophthalmology journals were included and information on 685 articles was collected. The median times from submission to acceptance, from acceptance to publication, and from submission to publication were 118.0 (IQR, 74.0-185.0) days, 31.0 (IQR, 15.0-64.0) days, and 161.0 (IQR, 111.0-232.0) days, respectively. A higher impact factor was correlated with shorter delays of acceptance and publication (P < 0.05). There was a positive correlation between acceptance rates and publication delays (r = 0.726, P = 0.007). Forty-seven (81.03%) journals provided AOP. There was no statistically significant difference for impact factors and publication delays between journal with and without AOP (all P > 0.05). No correlation between OA rate and publication delays or impact factors was detected (all P > 0.05). Conclusions: Journals with higher impact factors and lower acceptance rates tend to have quicker publication processes. No significant associations were detected between publication delays and AOP or OA rate.

Giardia duodenalis and Its Secreted PPIB Trigger Inflammasome Activation and Pyroptosis in Macrophages through TLR4-Induced ROS Signaling and A20-Mediated NLRP3 Deubiquitination.

The extracellular protozoan parasite Giardia duodenalis is a well-known and important causative agent of diarrhea on a global scale. Macrophage pyroptosis has been recognized as an important innate immune effector mechanism against intracellular pathogens. Yet, the effects of noninvasive Giardia infection on macrophage pyroptosis and the associated molecular triggers and regulators remain poorly defined. Here we initially observed that NLRP3 inflammasome-mediated pyroptosis was activated in Giardia-treated macrophages, and inhibition of ROS, NLRP3, or caspase-1 could block GSDMD cleavage, IL-1ß, IL-18 and LDH release, and the cell viability reduction. We also confirmed that Giardia-induced NLRP3 inflammasome activation was involved in its K63 deubiquitination. Thus, six candidate deubiquitinases were screened, among which A20 was identified as an effective regulator. We then screened TLRs on macrophage membranes and found that upon stimulation TLR4 was tightly correlated to ROS enhancement, A20-mediated NLRP3 deubiquitination, and pyroptotic signaling. In addition, several Giardia-secreted proteins were predicted as trigger factors via secretome analysis, of which peptidyl-prolyl cis-trans isomerase B (PPIB) independently induced macrophage pyroptosis. This was similar to the findings from the trophozoite treatment, and also led to the TLR4-mediated activation of NLRP3 through K63 deubiquitination by A20. Collectively, the results of this study have significant implications for expanding our understanding of host defense mechanisms after infection with G. duodenalis.

Chromophoric dissolved organic matter in inland waters: Present knowledge and future challenges.

Chromophoric dissolved organic matter (CDOM) plays an important role in the biogeochemical cycle and energy flow of aquatic ecosystems. Thus, systematic and comprehensive understanding of CDOM dynamics is critically important for aquatic ecosystem management. CDOM spans multiple study fields, including analytical chemistry, biogeochemistry, water color remote sensing, and global environmental change. Here, we thoroughly summarize the progresses of recent studies focusing on the characterization, distribution, sources, composition, and fate of CDOM in inland waters. Characterization methods, remote sensing estimation, and biogeochemistry cycle processes were the hotspots of CDOM studies. Specifically, optical, isotope, and mass spectrometric techniques have been widely used to characterize CDOM abundance, composition, and sources. Remote sensing is an effective tool to map CDOM distribution with high temporal and spatial resolutions. CDOM dynamics are mainly determined by watershed-related processes, including rainfall discharge, groundwater, wastewater discharges/effluents, and biogeochemical cycling occurring in soil and water bodies. We highlight the underlying mechanisms of the photochemical degradation and microbial decomposition of CDOM, and emphasize that photochemical and microbial processes of CDOM in inland waters accelerate nutrient cycling and regeneration in the water column and also exacerbate global warming by releasing greenhouse gases. Future study directions to improve the understanding of CDOM dynamics in inland waters are proposed. This review provides an interdisciplinary view and new insights on CDOM dynamics in inland waters.

Monitoring dissolved organic carbon by combining Landsat-8 and Sentinel-2 satellites: Case study in Saginaw River estuary, Lake Huron.

Dissolved organic carbon (DOC) in aquatic environments is an important cycled pool of organic matter on the Earth. Satellite remote sensing provides a useful tool to determine spatiotemporal distribution of water quality parameters. Previous DOC remote sensing studies in inland water suffered from either low spatial resolution or low temporal frequency. In this study, we evaluated the potential of jointly using Landsat-8 and Sentinel-2 with high spatial resolution to estimate DOC concentrations in Saginaw River plume regions of Lake Huron. Firstly, CDOM (colored dissolved organic matter) was estimated from images using the known models and then DOC can be derived in terms of the good correlations between DOC and CDOM. The results show that Landsat-8 and Sentinel-2 had acceptable accuracy and good consistency in DOC estimation so that jointly using them can improve the observation frequency. In different seasons from 2013 to 2018, DOC was typically higher in spring and autumn but lower in summer. Monthly spatiotemporal variations of DOC in 2018 were also observed. The image-derived DOC spatiotemporal variations show that DOC was covaried with Saginaw River discharge (r = 0.82) and also weakly and negatively correlated with water temperature (r = -0.6). This study demonstrated that using Landsat-8 and Sentinel-2 together can offer the potential applications for monitoring DOC and water quality dynamic in complex inland water.