Environmental DNA-based biodiversity profiling along the Houdong River in north-eastern Taiwan.

Background: This paper describes two datasets: species occurrences, which were determined by environmental DNA (eDNA) metabarcoding and their associated DNA sequences, originating from a research project which was carried out along the Houdong River (), Jiaoxi Township, Yilan, Taiwan. The Houdong River begins at an elevation of 860 m and flows for approximately 9 km before it empties into the Pacific Ocean. Meandering through mountains, hills, plains and alluvial valleys, this short river system is representative of the fluvial systems in Taiwan. The primary objective of this study was to determine eukaryotic species occurrences in the riverine ecosystem through the use of the eDNA analysis. The second goal was, based on the current dataset, to establish a metabarcoding eDNA data template that will be useful and replicable for all users, particularly the Taiwan community. The species occurrence data are accessible at the Global Biodiversity Information Facility (GBIF) portal and its associated DNA sequences have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI, respectively. A total of 12 water samples from the study yielded an average of 1.5 million reads. The subsequent species identification from the collected samples resulted in the classification of 432 Operational Taxonomic Units (OTUs) out of a total of 2,734. Furthermore, a total of 1,356 occurrences with taxon matches in GBIF were documented (excluding 4,941 incertae sedis, accessed 05-12-2023). These data will be of substantial importance for future species and habitat monitoring within the short river, such as assessment of biodiversity patterns across different elevations, zonations and time periods and its correlation to water quality, land uses and anthropogenic activities. Further, these datasets will be of importance for regional ecological studies, in particular the freshwater ecosystem and its status in the current global change scenarios. New information: The datasets are the first species diversity description of the Houdong River system using either eDNA or traditional monitoring processes.

First Report of Plumed Cockscomb (Celosia argentea var. plumosa) Stem Blight Caused by Phytophthora nicotianae in Taiwan.

Celosia spp. is a widely cultivated ornamental plant in gardens or parks in Taiwan. In September 2021, withering leaves and grayish-brown lesions were observed on the lower stem of plumed cockscombs (C. argentea var. plumosa) in Taichung City, with an incidence of about 22% in 136 plants after continuous precipitation, impacting the aesthetic value of the landscape. Symptomatic plants were collected, surface disinfected with 70% EtOH for ~20 sec., blotted dried, and excised diseased tissues (~ 3×3 mm2) were placed on 2% water agar. Four representative isolates were obtained after purification and the colonies were white with aerial and non-septated hyphae on V8 agar for 7 days. Sporangia were ovoid, ellipsoid or obpyriform, papillate, (26.3-55.9) 38.0 × 29.0 (20.1-40.6) µm (n = 200) (Ahonsi et al. 2007). Chlamydospores were spherical, terminal or intercalary, 26.0 (15.1-40.4) µm (n = 200). All isolates belong to A2 mating type with amphigynous antheridia and plerotic oospores, 21.0 (17.7-25.7) µm (n = 200), resembling the descriptions of Phytophthora (Erwin & Ribeiro 1996). For molecular identification, sequences of the ITS, ß-tubulin (ß-tub), and EF-1α regions of all isolates were amplified using ITS1/ITS4, TUBUF2/TUBUR1, and ELONGF1/ELONGR1 primers, respectively (White et al. 1990; Kroon et al. 2004). BLAST analyses of isolates cap1-2 (ITS: OQ581785; ß-tub: OQ590022; EF-1α: OQ590026), cap1-3 (ITS: OQ581786; ß-tub: OQ590023; EF-1α: OQ590027), cap2-1 (ITS: OQ581787; ß-tub: OQ590024; EF-1α: OQ590028), and cap2-2 (ITS: OQ581788; ß-tub: OQ590025; EF-1α: OQ590029) showed 100% of ITS identity, 99.5 to 99.9% of ß-tub identity, and 99.4 to 99.6% of EF-1α identity with Phytophthora nicotianae (ITS: MG865551; ß-tub: MH493987; EF-1α: MH359043). Phylogenetic trees were constructed using concatenated ITS, ß-tub, and EF-1α sequences based on maximum likelihood with a GTR+G model in MEGA X and Bayesian inference method in Geneious Prime 2022.2. All isolates were clustered in P. nicotianae with similar topology, thereby were identified as P. nicotianae. To confirm pathogenicity, 7 to 10-day-old seedlings and 6-week-old plumed cockscomb plants were inoculated in separate trials and each experiment was conducted twice. For each seedling, the lower stem was inoculated with 50 µl of zoospore suspension (104 zoospores/ml), 3 plants per isolate, and then incubated at 30±2℃ with 12 h light. For adult plants, each was inoculated with mycelial plugs from one V8 plate of 10-day-old P. nicotianae, 5 plants per isolate, and incubated at 25±2℃ in a greenhouse. Control plants were inoculated with sterile water and V8 agar plugs, respectively. Stem and root rot were observed on seedlings 4 days after inoculation while wilting and lower stem browning were observed on adult plants 2 months after inoculation. All control plants remained healthy at the end of repeated trials and identical pathogens were re-isolated only from symptomatic plants, thus fulfilling Koch's rules. P. nicotianae has been reported causing root rot and stem necrosis not only on cockscomb (C. plumosa Hort. ex Burvenich) in Argentina (Frezzi 1950), but also infecting several ornamental plants recently in Taiwan (Ann et al. 2018). To our knowledge, this is the first report of stem blight caused by P. nicotianae on plumed cockscombs in Taiwan. This finding suggests limited options for landscaping and the host preference of the isolates obtained in this study should warrant further studies.

An Apriori algorithm-based association rule analysis to identify acupoint combinations for treating uremic pruritus.

Objective: Uremic pruritus (UP) is a prevalent and troublesome condition affecting individuals with end-stage renal failure, which results in intense pruritus, depression, as well as poor quality of sleep, significantly impacting their quality of life. According to previous studies, acupuncture and acupoint stimulation have been shown to provide additional benefits in treating UP in dialysis patients. In addition, using acupoints combination may yield superior effectiveness compared to utilizing a singular acupoint. To investigate the potential correlations between acupoint combinations, an association-rule analysis was employed. Materials and Methods: Apriori algorithms stand out as highly potent techniques for identifying associations in databases; this study utilized an association rule mining to examine the association rules of key acupoint groupings that could be employed for treating UP. Results: The analysis utilized information derived from the meta-analysis encompassing 40 randomized controlled trials that used acupuncture to treat UP. In total, 64 acupoints were analyzed, and 71 association rules were found. The following acupoint combinations: Auricular shenmen (TF4), Quchi (LI11), and Geshu (BL17); Auricular heart (Extra14), Sanyinjiao (SP6), and Auricular lung (CO14); and Auricular heart (Extra14), Xuehai (SP10), and Auricular lung (CO14) showed the strongest associations. Conclusion: Acupoints involving Auricular shenmen (TF4), Quchi (LI11), Geshu (BL17), Auricular heart (Extra14), Sanyinjiao (SP6), Auricular lung (CO14), and Xuehai (SP10) can be regarded as the core combination of acupuncture points for managing UP.

Comparative efficacy of acupuncture point stimulation treatments for dialysis patients with uremic pruritus: a systematic review and network meta-analysis.

Background: Uremic pruritus (UP) is a common complication of chronic kidney disease that causes sleep disturbances and increases all-cause mortality. Currently, the first-line medications for UP exhibit inadequate pruritus control with adverse effects. Various acupuncture point stimulation treatments (APSTs) have been shown to be effective as adjuvant therapies in UP, and a network meta-analysis can offer relative efficacy estimates for treatments for which head-to-head studies have not been performed. Methods: We conducted a random-effects network meta-analysis on a consistency model to compare the different APSTs for UP. The primary outcomes were the mean visual analog scale (VAS) score and effectiveness rate (ER). Results: The network meta-analysis retrieved 27 randomized controlled trials involving 1969 patients. Compared with conventional treatment alone, combination treatment with acupuncture (mean difference, -2.63; 95% confidence interval, -3.71 to -1.55) was the most effective intervention in decreasing VAS scores, followed by acupoint injection and massage (mean difference, -2.04; 95% confidence interval, -3.96 to -0.12). In terms of the ER, conventional treatment with acupuncture and hemoperfusion (risk ratio, 14.87; 95% confidence interval, 2.18 to 101.53) was superior to other therapeutic combinations. Considering the VAS score and ER, combination treatment with acupoint injection and massage showed benefits in treating UP. Conclusion: Our network meta-analysis provided relative efficacy data for choosing the optimal adjuvant treatment for UP. Combined treatment with acupuncture was more effective than conventional treatment only and was the most promising intervention for treating UP.Systematic review registration: PROSPERO (CRD42023425739: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023425739).

Machine learning algorithms to predict colistin-induced nephrotoxicity from electronic health records in patients with multidrug-resistant gram-negative infection.

OBJECTIVES: Colistin-induced nephrotoxicity prolongs hospitalisation and increases mortality. The study aimed to construct machine learning models to predict colistin-induced nephrotoxicity in patients with multidrug-resistant Gram-negative infection. METHODS: Patients receiving colistin from three hospitals in the Clinical Research Database were included. Data were divided into a derivation cohort (2011-2017) and a temporal validation cohort (2018-2020). Fifteen machine learning models were established by categorical boosting, light gradient boosting machine and random forest. Classifier performances were compared by the sensitivity, F1 score, Matthews correlation coefficient (MCC), area under the receiver operating characteristic (AUROC) curve, and area under the precision-recall curve (AUPRC). SHapley Additive exPlanations plots were drawn to understand feature importance and interactions. RESULTS: The study included 1392 patients, with 360 (36.4%) and 165 (40.9%) experiencing nephrotoxicity in the derivation and temporal validation cohorts, respectively. The categorical boosting with oversampling achieved the highest performance with a sensitivity of 0.860, an F1 score of 0.740, an MCC of 0.533, an AUROC curve of 0.823, and an AUPRC of 0.737. The feature importance demonstrated that the days of colistin use, cumulative dose, daily dose, latest C-reactive protein, and baseline haemoglobin were the most important risk factors, especially for vulnerable patients. A cutoff colistin dose of 4.0 mg/kg body weight/d was identified for patients at higher risk of nephrotoxicity. CONCLUSIONS: Machine learning techniques can be an early identification tool to predict colistin-induced nephrotoxicity. The observed interactions suggest a modification in dose adjustment guidelines. Future geographic and prospective validation studies are warranted to strengthen the real-world applicability.

AMPK activation modulates IL-36-induced inflammatory responses by regulating IκBζ expression in the skin.

BACKGROUND AND PURPOSE: The interleukin (IL)-36 pathway is a critical player in the pathogenesis of pustular psoriasis. However, therapies targeting this pathway are limited or unaffordable (e.g. the anti-IL-36 receptor antibody). AMP-activated protein kinase (AMPK), a regulator of cellular energy and metabolism, is known to participate in inflammatory diseases. However, its role in IL-36-induced skin inflammation remains unclear. Therefore, we sought to investigate the role of AMPK signals in regulating IL-36-induced responses in the skin. EXPERIMENTAL APPROACH: IL-36-stimulated primary normal human epidermal keratinocytes (NHEKs) and IL-36-injected (intradermally) BALB/c mice served as the cell and animal models, respectively. Additionally, 5-aminoimidazole-4-carboxamide riboside (AICAR) and A769662 served as AMPK activators. KEY RESULTS: AICAR and A769662 significantly suppressed the IL-36-induced IL-8 (CXCL8) and CCL20 production from NHEKs. IL-36-induced IκBζ protein expression was prominently reduced and IKK/IκBα phosphorylation was attenuated by AICAR and A769662. Conversely, AMPKα knockdown increased IκBζ protein expression and IKK/IκBα phosphorylation in IL-36-treated NHEKs. Furthermore, AICAR and A769662 enhanced IL-36-induced-IκBζ protein degradation via the proteasome-dependent but not the lysosome-dependent pathway. Pretreatment of NHEKs with IL-36 slightly suppressed the AICAR- and A769662-triggered phosphorylation of AMPK and acetyl-CoA carboxylase. In the mouse model, topical application of AICAR significantly reduced ear swelling, redness, epidermal thickening, neutrophil infiltration and inflammatory and antimicrobial peptide gene expression. CONCLUSION AND IMPLICATIONS: AMPK activation suppresses IL-36-induced IL-8 and CCL20 release by regulating IκBζ expression in keratinocytes and reduces IL-36-induced skin inflammation in mice, suggesting that AMPK activation is a potential strategy for treating patients with IL-36-mediated inflammatory skin disorders.

Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor.

Lung cancer is considered the number one cause of cancer-related deaths worldwide. Although current treatments initially reduce the lung cancer burden, relapse occurs in most cases; the major causes of mortality are drug resistance and cancer stemness. Recent investigations have provided evidence that shikonin generates various bioactivities related to the treatment of cancer. We used shikonin to treat multi-resistant non-small lung cancer cells (DOC-resistant A549/D16, VCR-resistant A549/V16 cells) and defined the anti-cancer efficacy of shikonin. Our results showed shikonin induces apoptosis in these ABCB1-dependent and independent chemoresistance cancer sublines. Furthermore, we found that low doses of shikonin inhibit the proliferation of lung cancer stem-like cells by inhibiting spheroid formation. Concomitantly, the mRNA level and protein of stemness genes (Nanog and Oct4) were repressed significantly on both sublines. Shikonin reduces the phosphorylated Akt and p70s6k levels, indicating that the PI3K/Akt/mTOR signaling pathway is downregulated by shikonin. We further applied several signaling pathway inhibitors that have been used in anti-cancer clinical trials to test whether shikonin is suitable as a sensitizer for various signaling pathway inhibitors. In these experiments, we found that low doses shikonin and dual PI3K-mTOR inhibitor (BEZ235) have a synergistic effect that inhibits the spheroid formation from chemoresistant lung cancer sublines. Inhibiting the proliferation of lung cancer stem cells is believed to reduce the recurrence of lung cancer; therefore, shikonin's anti-drug resistance and anti-cancer stem cell activities make it a highly interesting molecule for future combined lung cancer therapy.

Highly effective ashless and non-corrosive dimercaptobenzothiadiazole as multifunctional lubricant additives in naphthenic base oil.

The conventional medium chain chlorinated paraffin (MCCP) and zinc dialkyl dithiophosphate (ZDDP) additives have greatly enhanced the extreme pressure (EP) and anti-wear (AW) performance of the metalworking fluids. However, chlorine- and zinc-containing additives are restricted in use due to eco-toxicity issue. Herein, ashless and non-corrosive dimercaptobenzothiadiazole derivatives, namely bis-2,5-benzylsulfanyl-[1,3,4]thiadiazole (BBST) and bis-2,5-octylsulfanyl-[1,3,4]thiadiazole (BOST) consist of three sulfur atoms have been synthesized and evaluated. The performance of BBST shows a weld load (PD) of 3089 N and AW value of 5 mm2, which represents an improvement of 3.1 and 7.4 folds over naphthenic base oil (NBO). In addition, BBST also outperformed BOST, MCCP, and ZDDP in terms of its weld load and AW properties. Based on XPS analysis and molecular electrostatic potential maps (MEPS), BBST exhibits superior tribology performance due to the interaction between the sulfur (S), nitrogen (N), and π-electrons of the benzene ring with the metal surface. The formation of FeS, Fe2O3 and Fe⋯N coordinate bonds contributes to the creation of an excellent tribofilm.

Comparative efficacy of Chinese herbal medicines for dialysis patients with uremic pruritus: A systematic review and network meta-analysis.

Introduction: Uremic pruritus is common in dialysis patients and reduces their quality of life. Chinese herbal medicine has been effective in patients with this condition. Methods: We conducted a random-effects network meta-analysis to compare the efficacies of different Chinese herbal medicine treatments for uremic pruritus. Outcome measures including the overall effective rates, visual analog scale scores, C-reactive protein levels, and adverse drug reactions were analyzed. Results: The network meta-analysis retrieved 25 randomized controlled trials. Compared with conventional treatments alone, combination treatments with Xiao-Yang-Ke-Li was the most effective intervention in decreasing visual analog scale scores (mean difference -2.98, 95% mean difference -5.05 to -0.91) and levels of C-reactive protein (mean difference -5.01, 95% mean difference -7.27 to -2.75). Conventional treatment combined with Si-Wu Tang was superior to other therapeutic combinations when overall effective rates were determined. The best visual analog scale scores and overall effective rates were achieved by adjunctive treatment with the Touxie-Jiedu-Zhiyang decoction followed by uremic clearance granules; these treatments were the most beneficial for uremic pruritis. Conclusion: Our network meta-analysis provided the relative efficacies of different adjunctive Chinese herbal formulas. Adjunctive treatment with the Touxie-Jiedu-Zhiyang decoction was the best treatment for improving overall effective rates and reducing visual analog scores of uremic pruritus in dialysis patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=357656; Identifier: CRD42022357656.

Impact of Type D Personality, Role Strain, and Diabetes Distress on Depression in Women With Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND: Women with diabetes face a significantly elevated risk of developing depression. Clarifying the factors associated with depression is critical to designing more timely interventions for this vulnerable population. PURPOSE: This study was developed to examine the impact of Type D personality, diabetes-care-related role strain, and diabetes-related distress on depression in women with Type 2 diabetes. METHODS: A cross-sectional design was used. Convenience sampling was used to recruit 298 women aged 20-64 years who had been diagnosed with Type 2 diabetes for over 6 months from three outpatient endocrine clinics in Taiwan. Demographic and disease characteristics and Type D personality (negative affectivity and social inhibition), diabetes-care-related role strain, and diabetes-related distress and depression status information were collected using self-reported questionnaires and medical records. The important factors of influence on depression were examined using hierarchical multiple regression. RESULTS: On the basis of the results of the hierarchical multiple regression analysis, age, negative affectivity, diabetes-care-related role strain, and diabetes-related distress were identified as significantly associated with depression, with negative affectivity explaining most (43.4%) of the variance in depression, followed by diabetes-care-related role strain and diabetes-related distress, which respectively explained 3% and 2.5% of the variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The negative affectivity associated with the Type D personality was shown to be more significantly associated with depression than diabetes-related psychosocial factors such as diabetes-related distress and diabetes-care-related role strain. Timely assessment of negative affectivity and the provision of brief mindfulness intervention to reduce negative affectivity may be useful in preventing depression in women with Type 2 diabetes, whereas addressing diabetes-related distress and diabetes-care-related role strain should not be neglected when providing comprehensive depression-preventing interventions to young women with diabetes.

Responses of medaka (Oryzias latipes) ammonia production and excretion to overcome acidified environments.

Anthropogenic acidification of water is an on-going environmental disaster for freshwater fishes. Fishes rely on ammonia excretion to eliminate the excess acid and mitigate the harmful effects; however, it remains largely unknown how ammoniagenesis occurs and is coordinated with ammonia excretion upon acidic stress. Medaka (Oryzias latipes) was used to examine the effects of acidic stress on ammonia production and excretion. We reveal an undiscovered ammonia-producing cell type that is rich in glutaminase (GLS) and located adjacent to the ammonia-excreting ionocytes, Na+/H+ exchanger (NHE) cells, in the gills. The gills, comparing with other ammoniagenetic organs, is the quickest to respond to the acidic stress by triggering GLS-dependent ammonia production. The unique division of labor between GLS and NHE cells in the gills allows medaka to simultaneously upregulate GLS activity and ammonia excretion shortly after exposure to acidic environments. Pharmacological experiment with a GLS inhibitor abolished the activated ammonia excretion, further suggesting the essential role of the unique feature in the responses to acidic stress. Our study shades light on a novel physiological mechanism to timely and efficiently mitigate adverse effects of acidification, providing a new way to assess the impact of on-going environmental acidification on fish.

Curcumin Induces Apoptosis of Chemoresistant Lung Cancer Cells via ROS-Regulated p38 MAPK Phosphorylation.

This study aimed to challenge chemoresistance by curcumin (CUR) with drug-selected human lung cancer A549 sublines that continuously proliferate in the present of docetaxel (DOC) and vincristine (VCR). Their sensitivities to CUR were measured by MTT assay and the particular intracellular reactive oxygen species (ROS) was detected by fluorescence activated cell sorting (FACS) analysis. Apoptosis was analyzed by Annexin V assay of the flow cytometry. Inhibitors and RNA interference were used to examine the signaling pathway regulated by the kinases. The obtained data demonstrated that CUR induces chemoresistant cell apoptosis by generating ROS and application of N-acetylcysteine (NAC) blocks ROS production, resulting in apoptosis suppression. Phosphorylation of extracellular regulated kinase (ERK), p38 MAPK, and eIF-2α were increased but c-Jun N-terminal kinase (JNK) did not increase when chemoresistant cells were treated with CUR. Downregulation of ERK and p38 MAPK phosphorylation by their inhibitors had no effect on CUR-induced apoptosis. Interestingly, the knockdown of p38 MAPK with shRNA significantly reduced CUR-induced apoptosis on the chemoresistant sublines. Phosphorylation of the eIF-2α protein was inhibited when p38 MAPK was knocked down in DOC-resistant A549 cells, but a high level of phosphorylated eIF-2α protein remained on the VCR-resistant A549 cells when p38 MAPK was knocked down. These data confirmed that CUR-augmented ROS potently induced apoptosis via upregulated p38 MAPK phosphorylation. Therefore, activated p38 MAPK is considered a pro-apoptotic signal for CUR-induced apoptosis of chemoresistant human lung cancer cells.

Thioredoxin-interacting protein regulates keratinocyte differentiation: Implication of its role in psoriasis.

Thioredoxin-interacting protein (TXNIP), also known as Vitamin-D upregulated protein-1 (VDUP-1), interacts with thioredoxin to regulate redox responses and participates in diverse disorders including metabolic, cardiovascular, inflammatory and malignant diseases. Psoriasis is characterized by chronic skin inflammation and an aberrant pattern of keratinocyte differentiation. Clinically, psoriasis is associated with various cardiometabolic comorbidities but studies on TXNIP's biological role in skin disorders are limited. In this study, we investigated TXNIP expression in psoriasis and its regulation in normal human epidermal keratinocytes (NHEKs), and then explored how TXNIP regulated skin keratinocyte differentiation to determine its role in psoriasis pathogenesis. Our immunohistochemical study demonstrated extensive TXNIP expression in the upper and lower epidermis of psoriasis compared to predominant TXNIP expression in the basal layer of normal skin. 1, 25-dihydroxyvitamin D3  suppressed but TGF-α and EGF enhanced TXNIP expression in NHEKs. An inducer of keratinocyte differentiation, phorbol 12-myristate 13-acetate (PMA), also diminished TXNIP expression, which was reversed by PKC-δ knockdown. TXNIP knockdown reduced PMA-induced involucrin and transglutaminse-1 expression, and increased p63 expression in NHEKs but did not significantly affect cell proliferation. H2 O2 -induced ROS production and EGFR phosphorylation decreased in NHEKs with TXNIP knockdown. Furthermore, PMA-induced PKC-δ phosphorylation, TGF-α, and EGF-triggered EGFR phosphorylation were attenuated by TXNIP knockdown. Our results unraveled the regulation and function of TXNIP expression in skin keratinocytes and the cross-regulation between TXNIP and EGFR signaling. These findings imply a role of TXNIP in psoriasis and provide insight into the possible impact of TXNIP regulators on the skin or psoriasis.

Ethylene Response Factor109 Attunes Immunity, Photosynthesis, and Iron Homeostasis in Arabidopsis Leaves.

Iron (Fe) is an essential micronutrient element for all organisms including plants. Chlorosis of young leaves is a common symptom of Fe deficiency, reducing the efficiency of photosynthesis, and, ultimately, crop yield. Previous research revealed strong responsiveness of the putative key transcription factor ERF109 to the Fe regime. To elucidate the possible role of ERF109 in leaf Fe homeostasis and photosynthesis, we subjected Arabidopsis thaliana erf109 knockout lines and Col-0 wild-type plants to transcriptome profiling via RNA-seq. The transcriptome profile of Fe-sufficient erf109 leaves showed a 71% overlap with Fe-deficient Col-0 plants. On the other hand, genes that were differentially expressed between Fe-deficient and Fe-sufficient Col-0 plants remained unchanged in erf109 plants under conditions of Fe deficiency. Mutations in ERF109 increased the expression of the clade Ib bHLH proteins bHLH38, bHLH39, bHLH101, the nicotianamine synthase NAS4, and the Fe storage gene FER1. Moreover, mutations in ERF109 led to significant down-regulation of defense genes, including CML37, WRKY40, ERF13, and EXO70B2. Leaves of erf109 exhibited increased Fe levels under both Fe-sufficient and Fe-deficient conditions. Reduced Fv/Fm and Soil Plant Analysis Development (SPAD) values in erf109 lines under Fe deficiency indicate curtailed ability of photosynthesis relative to the wild-type. Our findings suggest that ERF109 is a negative regulator of the leaf response to Fe deficiency. It further appears that the function of ERF109 in the Fe response is critical for regulating pathogen defense and photosynthetic efficiency. Taken together, our study reveals a novel function of ERF109 and provides a systematic perspective on the intertwining of the immunity regulatory network and cellular Fe homeostasis.

PARP-1 regulates inflammasome activity by poly-ADP-ribosylation of NLRP3 and interaction with TXNIP in primary macrophages.

Poly(ADP-ribose) polymerase-1 (PARP-1) plays an essential role in DNA repair by catalyzing the polymerization of ADP-ribose unit to target proteins. Several studies have shown that PARP-1 can regulate inflammatory responses in various disease models. The intracellular Nod-like receptor NLRP3 has emerged as the most crucial innate immune receptor because of its broad specificity in mediating immune response to pathogen invasion and danger signals associated with cellular damage. In our study, we found NLRP3 stimuli-induced caspase-1 maturation and IL-1ß production were impaired by PARP-1 knockout or PARP-1 inhibition in bone marrow-derived macrophages (BMDM). The step 1 signal of NLRP3 inflammasome activation was not affected by PARP-1 deficiency. Moreover, ATP-induced cytosolic ROS production was lower in Parp-1-/- BMDM, resulting in the decreased inflammasome complex assembly. PARP-1 can translocate to cytosol upon ATP stimulation and trigger the PARylation modification on NLRP3, leading to NLRP3 inflammasome assembly. PARP-1 was also a bridge between NLRP3 and thioredoxin-interacting protein (TXNIP) and participated in NLRP3/TXNIP complex formation for inflammasome activation. Overall, PARP-1 positively regulates NLRP3 inflammasome activation via increasing ROS production and interaction with TXNIP and NLRP3, leading to PARylation of NLRP3. Our data demonstrate a novel regulatory mechanism for NLRP3 inflammasome activation by PARP-1. Therefore, PARP-1 can serve as a potential target in the treatment of IL-1ß associated inflammatory diseases.

Spleen tyrosine kinase regulates keratinocyte inflammasome activation and skin inflammation induced by UVB irradiation.

UVB can induce inflammatory responses contributing to diverse skin damage. UVB-triggered inflammasome activation of human keratinocytes underlies UVB-induced skin sunburn reaction. Pleiotropic functions of spleen tyrosine kinase (Syk) have rendered it as a potential therapeutic target. In immunocytes, Syk modulates immunoreceptor signaling and NLRP3 inflammasome activation. In skin, Syk mediates EGFR signaling, regulates keratinocyte differentiation and is involved in inflammatory disorders. However, roles of Syk in UVB-induced inflammasome activation in keratinocytes remain elusive. We investigated roles of keratinocyte Syk in UVB-triggered photo-responses. Primary normal human epidermal keratinocytes (NHEKs) isolated from skin were used. Syk knockdown or Syk inhibitor R406 was applied to investigate functions of keratinocyte Syk in UVB photobiology. The possible in vivo role of Syk was evaluated by checking UVB-induced skin damage in R406-treated mice. UVB was able to induce Syk phosphorylation in NHEKs that could be regulated by reactive oxygen species (ROS) generation and EGFR. Syk knockdown or Syk inhibitor (R406) treatment reduced UVB-triggered apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) crosslinking, procaspase-1 cleavage, active IL-1ß formation, and gasdermin D activation, indicating roles of Syk in UVB-triggered inflammasome activation in keratinocytes. UVB-induced production of IL-8, TNF-α, ROS, and phosphorylation of JNK and p38 were attenuated after Syk knockdown or inhibition. R406 ameliorated UVB-induced mouse skin damage, including erythema and transepidermal water loss (TEWL). Thus, Syk participated in UVB-induced inflammasome activation and inflammatory response in vitro and in vivo, suggesting potential photo-protective effects of Syk inhibition in UVB-induced skin inflammation.

Critical roles of irradiance in the regulation of UVB-induced inflammasome activation and skin inflammation in human skin keratinocytes.

UVB dosage is generally regarded as the most critical factor that determines the severity of UVB-induced skin erythema. However, recent studies have demonstrated that different UV irradiances induce varying biological responses in mouse skin even at constant UV doses. UVB-induced inflammasome activation is particularly observed in human skin keratinocytes, which are classified as immunocompetent cells, but not in mouse skin keratinocytes, which do not express sufficient inflammasome complex components. In human skin UVB-induced sunburn reactions, NLRP1 inflammasome activation critically mediates the inflammatory responses. Here, we employed primary human skin keratinocytes to explore the impact of different irradiances of a constant UVB dosage on inflammasome activation and related inflammatory responses. Our findings indicated that low-irradiance UVB induced relatively stronger NLRP1 inflammasome activation, which manifested as more active IL-1ß, IL-18 release, and enhanced procaspase-1 cleavage compared to high-irradiance UVB at the same dose. Irradiance did not influence cell lysis or the expression of inflammasome complex proteins including NLRP1, proIL-1ß, proIL-18, procaspase-1, and ASC. The UVB-induced TNF-α and cyclooxygenase-2 expression was also relatively higher in keratinocytes exposed to low-irradiance UVB. Low-irradiance UVB also increased reactive oxygen species production. UVB-triggered signaling analysis revealed that low-irradiance UVB resulted in more prominent p38 and JNK activation. Therefore, our findings indicated that, in addition to the role of total dosage, irradiance crucially modulates UVB-elicited inflammation in human skin keratinocytes, thus providing novel insights into human skin photobiology.

Estrogen-related receptor γ2 controls NaCl uptake to maintain ionic homeostasis.

Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that Errγ2 may play a crucial role in ion uptake. In situ hybridization showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl- transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl- cotransporter (Ncc), the number of Ncc ionocytes, Na+/Cl- influxes of ionocytes, and whole-body Na+/Cl- contents. In FW with low Na+ and low Cl-, the expression levels of mRNA for Na+/H+ exchanger 3 (Nhe3) and Ncc were both decreased in Errγ2 morphants. Treating embryos with DY131, an agonist of Errγ, increased the whole-body Na+/Cl- contents and ncc mRNA expression in Errγ2 morphants. As such, medaka Errγ2 may control Na+/Cl- uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

The Impact of Self-Stigma, Role Strain, and Diabetes Distress on Quality of Life and Glycemic Control in Women With Diabetes: A 6-Month Prospective Study.

PURPOSES: Women with diabetes (WD) are more severely impacted by the consequence of suboptimal diabetes control. This study aims to examine the impact of demographic and disease characteristics, baseline self-stigma, role strain, diabetes distress on Hemoglobin A1C (A1C) levels, quality of life (D-QoL) and 6-month A1C levels in younger WD. METHODS: This study was a 6-month prospective study. In total, 193 WD aged 20-64 years were selected by convenience sampling from three outpatient clinics in Taiwan. Demographic and disease characteristics, self-stigma, role strain, diabetes distress, A1C levels, and D-QoL were collected at baseline. A1C levels were further collected 6 months later. Structural equation modeling was conducted to test the hypothesized model. RESULTS: The final model supported that higher baseline D-QoL directly associated with lower concurrent A1C levels and indirectly associated with lower 6-month A1C levels through baseline A1C levels. Higher baseline self-stigma, role strain, and diabetes distress directly associated with lower baseline D-QoL, and indirectly associated with higher 6-month A1C levels through D-QoL. CONCLUSION: Improving self-stigma, role strain, and diabetes distress should be considered as promising strategies to improve D-QoL in young WD. D-QoL plays a mediation role between baseline self-stigma, role strain, diabetes distress and subsequent glycemic control in younger WD. Enhancing baseline D-QoL is fundamental to improve subsequent glycemic control.

PARP-1 involves in UVB-induced inflammatory response in keratinocytes and skin injury via regulation of ROS-dependent EGFR transactivation and p38 signaling.

UV irradiation can injure the epidermis, resulting in sunburn, inflammation, and cutaneous tissue disorders. Previous studies demonstrate that EGFR in keratinocytes can be activated by UVB and contributes to inflammation. Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme and plays an essential role in DNA repair under moderate stress. In this study, we set out to understand how PARP-1 regulates UVB irradiation-induced skin injury and interplays with EGFR to mediate the inflammation response. We found that PARP-1 deficiency exacerbated the UVB-induced inflammation, water loss, and back skin damage in mice. In human primary keratinocytes, UVB can activate PARP-1 and enhance DNA damage upon PARP-1 gene silencing. Moreover, PARP-1 silencing and PARP inhibitor olaparib can suppress UVB-induced COX-2 and MMP-1 expression, but enhance TNF-α and IL-8 expression. In addition, EGFR silencing or EGFR inhibition by gefitinib can decrease UVB-induced COX-2, TNF-α, and IL-8 expression, suggesting EGFR activation via paracrine action can mediate UVB-induced inflammation responses. Immunoblotting data revealed that PARP-1 inhibition decreases UVB-induced EGFR and p38 activation. Pharmacological inhibition of p38 also dramatically led to the attenuation of UVB-induced inflammatory gene expression. Of note, genetic ablation of PARP-1 or EGFR can attenuate UVB-induced ROS production, and antioxidant NAC can attenuate UVB-induced EGFR-p38 signaling axis and PARP-1 activation. These data suggest the regulatory loops among EGFR, PARP-1, and ROS upon UVB stress. PARP-1 not only serves DNA repair function but also orchestrates interactions to EGFR transactivation and ROS production, leading to p38 signaling for inflammatory gene expression in keratinocytes.