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Ubiquitin‐conjugating enzyme (UBC) is a crucial component of the ubiquitin‐proteasome system, which contributes to plant growth and development. While some UBCs have been identified as potential regulators of abiotic stress responses, the underlying mechanisms of this regulation remain poorly understood. Here, we report a cotton (Gossypium hirsutum) UBC gene, GhUBC10‐2, which negatively regulates the salt stress response. We found that the gain of function of GhUBC10‐2 in both Arabidopsis (Arabidopsis thaliana) and cotton leads to reduced salinity tolerance. Additionally, GhUBC10‐2 interacts with glutathione S‐transferase (GST) U17 (GhGSTU17), forming a heterodimeric complex that promotes GhGSTU17 degradation. Intriguingly, GhUBC10‐2 can be self‐polyubiquitinated, suggesting that it possesses E3‐independent activity. Our findings provide new insights into the PTM of plant GST‐mediated salt response pathways. Furthermore, we found that the WRKY transcription factor GhWRKY13 binds to the GhUBC10‐2 promoter and suppresses its expression under salt conditions. Collectively, our study unveils a regulatory module encompassing GhWRKY13–GhUBC10‐2–GhGSTU17, which orchestrates the modulation of reactive oxygen species homeostasis to enhance salt tolerance. Summary statement: GhUBC10‐2 negatively regulates salt tolerance by targeting glutathione S‐transferase U17 (GhGSTU17) for its degradation. GhWRKY13 binds the W‐box of the GhUBC10‐2 promoter to repress GhUBC10‐2 transcription. The GhWRKY13–GhUBC10‐2–GhGSTU17 module offers a guidance for cotton breeding. [ABSTRACT FROM AUTHOR]

Objective: The BRAFV600E mutation is the universal genetic mutation in papillary thyroid microcarcinoma (PTMC). The present study is to estimate the role of the BRAFV600E mutation in the clinical outcome of PTMC with intermediate to high recurrence risk after radioactive iodine (RAI) therapy, which is considered to be an indolent tumor. Methods: We conducted a single-center retrospective study. Between May 2016 and March 2019, PTMC patients with known BRAFV600E status who received RAI therapy were reviewed at the Second Hospital of Shandong University. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The association between the BRAFV600E mutation and clinicopathological characteristics, response to RAI therapy, and recurrence after a period of follow-up were analyzed. Propensity score matching (PSM) and logistic regression were used to control confounding variables. Results: Of the 322 patients with intermediate to high recurrence risk in PTMC, the mean age of the patients were 43.7 ± 12.2 years, and 72.1% were women. BRAFV600E mutation was found in 64.9% (209/322). After PSM, 112 pairs of patients were matched, and except for multifocality (P = 0.001), extrathyroidal invasion (P = 0.003) and tumor size (P = 0.03), there was no significant difference in all baseline characteristics between the two groups. An excellent response (ER) to RAI therapy was observed in 273 patients (84.7%). At the end of the study, 17(5.2%) and 6(1.8%) patients showed structural incomplete response (SIR) and biochemical incomplete response (BIR) status. The proportion of patients who achieved ER status in the BRAFV600E mutation positive and negative groups was 86.6% and 81.4%, respectively. Kaplan–Meier analyses showed that the BRAFV600E mutation was not related to lower ER reached time. The median follow-up was 51 months. Conclusions: We found the BRAFV600E mutation was associated with multifocality, extrathyroidal invasion, and tumor size in papillary thyroid microcarcinoma. However, the BRAFV600E mutation had no significant association with clinical outcomes in patients with intermediate to high recurrence risk after RAI therapy. Furthermore, the extra-thyroid uptake results and distant metastasis had been proven to be independent factor predicting the clinical response. Registration number: ChiCTR2200062911 [ABSTRACT FROM AUTHOR]

Phosphatases are important regulators of protein phosphorylation and various cellular processes, and they serve as counterparts to kinases. In this study, our comprehensive analysis of oomycete complete proteomes unveiled the presence of approximately 3833 phosphatases, with most species estimated to have between 100 and 300 putative phosphatases. Further investigation of these phosphatases revealed a significant increase in protein serine/threonine phosphatases (PSP) within oomycetes. In particular, we extensively studied the metallo‐dependent protein phosphatase (PPM) within the PSP family in the model oomycete Phytophthora sojae. Our results showed notable differences in the expression patterns of PPMs throughout 10 life stages of P. sojae, indicating their vital roles in various stages of oomycete pathogens. Moreover, we identified 29 PPMs in P. sojae, and eight of them possessed accessory domains in addition to phosphate domains. We investigated the biological function of one PPM protein with an extra PH domain (PPM1); this protein exhibited high expression levels in both asexual developmental and infectious stages. Our analysis confirmed that PPM1 is indeed an active protein phosphatase, and its accessory domain does not affect its phosphatase activity. To delve further into its function, we generated knockout mutants of PPM1 and validated its essential roles in mycelial growth, sporangia and oospore production, as well as infectious stages. To the best of our knowledge, this study provides the first comprehensive inventory of phosphatases in oomycetes and identifies an important phosphatase within the expanded serine/threonine phosphatase group in oomycetes. [ABSTRACT FROM AUTHOR]

Alkali-activated fly ash (AAF) and alkali-activated slag (AAS) mortars were exposed to the sewage environment with acidophilic sulfur oxidizing bacteria and high concentration H2S to study their interaction. It was found that when they suffered the biogenic sulfuric acid attack, both the AAF and calcium aluminate cement (CAC) mortars had a strong inhibition effect on the growth and activity of microorganisms. There are more aluminum ions dissolved from AAF mortar into sewage, and its structure was characterized by the increase in 100-1000 nm pores. Still, a hard high silicon skeleton was formed to keep the apparent intact. However, CAC mortar had a higher killing rate for the bacteria in the attached biofilm. For AAS mortar, the formation of excessive gypsum increased the macropores content and was more conducive to the growth of biofilm, thereby accelerating the penetration of corrosive medium and the deterioration of mortar. [ABSTRACT FROM AUTHOR]

Purpose: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. Methods: The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography–mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. Results: Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. Conclusions: This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Cotton fiber is a model tissue for studying microtubule-associated proteins (MAPs). The Xklp2 (TPX2) proteins that belong to the novel MAPs member mainly participate in the formation and development of microtubule (MT). However, there is a lack of studies concerning the systematic characterization of the TPX2 genes family in cotton. Therefore, the identification and portrayal of G. hirsutum TPX2 genes can provide key targets for molecular manipulation in the breeding of cotton fiber improvement. Result: In this study, TPX2 family genes were classified into two distinct subclasses TPXLs and MAP genes WAVE DAMPENED2-LIKE (WDLs) and quite conservative in quantity. GhWDL3 was significantly up-regulated in 15 days post anthesis fibers of ZRI-015 (an upland cotton with longer and stronger fiber). GhWDL3 promotes all stem hairs to become straight when overexpressed in Arabidopsis, which may indirectly regulate cotton fiber cell morphology during fiber development. Virus induced gene silencing (VIGS) results showed that GhWDL3 inhibited fiber cell elongation at fiber development periods through regulating the expression of cell wall related genes. Conclusion: These results reveal that GhWDL3 regulated cotton fiber cell elongation and provide crucial information for the further investigation in the regulatory mechanisms/networks of cotton fiber length. [ABSTRACT FROM AUTHOR]

Both Streptococcus equi subsp. zooepidemicus (SEZ) and canine influenza virus (CIV) are two important pathogens causing infectious respiratory disease in dogs and are frequently codetected in respiratory secretions. However, the clinical significance of viral/bacterial coinfection remains unknown. This study investigated the pathogenic characteristics of infection with CIV and SEZ alone or in combination in mice. Our data indicated that the severity of the disease is related to the challenge order of CIV and SEZ. Coinfection of CIV and SEZ induced higher weight loss in mice than single infection, except for the VB group (viral followed by secondary bacterial infection). Compared with the concurrent or sequential infection groups of CIV and SEZ, mice in the CIV–SEZ preincubation group exhibited more obvious weight loss, higher mortality, and significantly enhanced burden of SEZ and CIV in tissues. Interestingly, viral and bacterial preincubation before coinfection caused typical pulmonary fibrosis in mice. Correspondingly, transforming growth factor (TGF)-β was upregulated, and its canonical small mother against decapentaplegic (Smad) 2/3 signaling was noticeably induced. Further investigation indicated that the activity of the viral neuraminidase (NA) enzyme upon sialic acid was considerably increased due to the direct interaction of CIV with SEZ, which may be related to the activation of the TGF-β signaling pathway. These findings implicate an unexpected contribution of the direct interaction between CIV and SEZ to synergistic pathogenicity. [ABSTRACT FROM AUTHOR]

AbstractTo realize the safe disposal of solid waste containing heavy metals, sewage sludge jointly with slag and metakaolin was used to prepare alkali-activated materials (AAMs), and the effect mechanism of polycarboxylate acid superplasticizer (PCE), naphthalene superplasticizer (NS) and aliphatic superplasticizer (AS) in AAMs were studied. The results showed that both the fluidity and strength of AAMs decreased with the addition of sludge. For the NaOH + Na2SiO3 activated mortar specimen, the incorporation of sludge can reduce their fluidity and strength from 206 mm and 80.25 MPa to 193 mm and 42.43 MPa, respectively. However, the addition of superplasticizers into sludge-containing AAMs leads to a reduction of 3–9% of the fluidity. Interestingly, it can enhance the strength of the AAMs, especially the NS and AS, which increase the strength by approximately 25%. This is attributed to the increase of particle dispersion by superplasticizers. However, the free water released in the process is reabsorbed by the sludge, which increases the local alkali concentration and promotes the activation of the activity. The dispersed sludge particles can play the role of physical filling, making the structure denser. HIGHLIGHTSSludge is adverse effects on both the fluidity and strength of alkali-activated materials (AAMs).The addition of superplasticizers (SPs) increases the strength of AAM with sludge.SPs do not affect improving the fluidity of AAMs with sludge, even slightly bad.The dispersion effect of SPs on the sludge is beneficial to promote its activity in AAMs.Sludge is adverse effects on both the fluidity and strength of alkali-activated materials (AAMs).The addition of superplasticizers (SPs) increases the strength of AAM with sludge.SPs do not affect improving the fluidity of AAMs with sludge, even slightly bad.The dispersion effect of SPs on the sludge is beneficial to promote its activity in AAMs. [ABSTRACT FROM AUTHOR]

Purpose: Investigate the oxylipin profiles in the aqueous humor of primary open-angle glaucoma (POAG) patients., Methods: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to a liquid chromatography/mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted., Results: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified five differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The five oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk area ratio in the POAG patients. In addition, 15-kPGF2α was moderately and positively correlated with the mean deviation (MD) of visual field defect, and LTB4 was moderately and negatively correlated with macular thickness., Conclusions: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in the arachidonic acid metabolism pathway could play a role in POAG, and anti-inflammatory therapies could be potential treatment strategies for POAG.

Cotton (Gossypium) fiber length, a key trait determining fiber yield and quality, is highly regulated by a class of recently identified phytohormones, strigolactones (SLs). However, the underlying molecular mechanisms of SL signaling involved in fiber cell development are largely unknown. Here, we show that the SL signaling repressors MORE AXILLARY GROWTH2-LIKE7 (GhSMXL7) and GhSMXL8 negatively regulate cotton fiber elongation. Specifically, GhSMXL7 and GhSMXL8 inhibit the polyubiquitination and degradation of the gibberellin (GA)-triggered DELLA protein (GhSLR1). Biochemical analysis revealed that GhSMXL7 and GhSMXL8 physically interact with GhSLR1, which interferes with the association of GhSLR1 with the E3 ligase GA INSENSITIVE2 (GhGID2), leading to the repression of GA signal transduction. GhSMXL7 also interacts with the transcription factor GhHOX3, preventing its binding to the promoters of essential fiber elongation regulatory genes. Moreover, both GhSMXL7 and GhSMXL8 directly bind to the promoter regions of the AUXIN RESPONSE FACTOR (ARF) genes GhARF18-10A, GhARF18-10D, and GhARF19-7D to suppress their expression. Cotton plants in which GhARF18-10A, GhARF18-10D, and GhARF19-7D transcript levels had been reduced by virus-induced gene silencing (VIGS) displayed reduced fiber length compared with control plants. Collectively, our findings reveal a mechanism illustrating how SL integrates GA and auxin signaling to coordinately regulate plant cell elongation at the single-cell level., Competing Interests: Conflict of interest statement. The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The optimal plant height is crucial in modern agriculture, influencing lodging resistance and facilitating mechanized crop production. Upland cotton (Gossypium hirsutum) is the most crucial fiber crop globally, but the knowledge of the genetic basis underlying plant height still needs to be discovered. Here we conducted a genome-wide association study (GWAS) to identify the major locus controlling plant height (PH1) in upland cotton. The locus encodes gibberellin 2-oxidase 1A (GhPH1), with a 1,133 bp-length structural variation (PAV PH1 ) located approximately 16 kb upstream of it. The presence or absence of PAV PH1 confers a differential expression of GhPH1, consequently leading to changes in plant height. Further analysis revealed that a gibberellin-regulating transcription factor (GhGARF) recognizes a specific 'CATTTG' motif on the GhPH1 promoter and PAV PH1 . This binding event down-regulates GhPH1, indicating that PAV PH1 functions as a distant upstream silencer. Intriguingly, we found that the critical repressor of the strigolactone (SL) signaling pathway, DWARF53 (D53), directly interacts with GhGARF and inhibits its binding to targets. Moreover, our study uncovers a previously unrecognized GA-SL crosstalk mechanism mediated by the GhD53-GhGARF-GhPH1/PAV PH1 module, crucial in regulating the plant height of upland cotton. These findings shed light on the genetic basis and gene interaction network underlying plant height and provide valuable insights for developing semi-dwarf cotton varieties through precise modulation of GhPH1 expression., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer is the second most common cancer in humans. Its therapy procedures such as breast biopsy can cause anxiety and persistent pain in patients. Virtual reality (VR) has been applied to promote comfort in various populations. However, the effectiveness of VR in relieving pain and anxiety in patients undergoing breast cancer treatment is unclear., Purpose: This study was designed to examine the effect of VR on anxiety and pain in people undergoing treatment for breast cancer., Methods: PubMed, Cochrane, Embase, Scopus, Web of Science, and MEDLINE databases were searched for studies involving VR, pain, and anxiety in patients with breast cancer published up to March 2022. The Cochrane Handbook for Systems quality evaluation standard 6.3.0 was followed to assess risk of bias in the identified studies, with the results reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Subsequently, a meta-analysis of the included data was conducted using RevMan 5.3 software., Results: Six randomized controlled trials and one quasi-experimental study were included. The strength of the evidence ranged from moderate to high. Although VR was found to ameliorate anxiety in patients with breast cancer, only three studies showed statistically significant changes. All of the included studies reported statistically significant improvement in pain levels. In addition, two of the studies reported cybersickness symptoms as a common side effect of VR., Conclusions: VR has an important role to play in alleviating pain in patients with breast cancer. However, evidence demonstrating VR's importance in alleviating anxiety symptoms in this population is insufficient. Studies conducted with larger sample sizes and high-quality research methodologies will be necessary to clarify this issue. Clinical nurses should address the potential side effects of VR., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

In view of the safety concerns of probiotics, more and more attention is paid to the beneficial effects of dead probiotics cells. Herein, we investigated and compared the alleviation effects of viable Bifidobacterium longum subsp. infantis B8762 ( B. infantis B8762) and its heat-killed cells on dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) rats. Four groups of rats ( n = 12 per group) were included: normal control, DSS-induced colitis rats without bacterial administration (DSS), DSS-induced colitis rats with viable B. infantis B8762 administration (VB8762), and DSS-induced colitis rats with dead B. infantis B8762 administration (DB8762). Our results showed that both VB8762 and DB8762 administration exerted significant protective effects on DSS-induced IBD rats, as evidenced by a reduction in mortality, disease activity index score, body weight loss, as well as decreased histology score, which were companied by a significant decrease in serum pro-inflammatory factors compared with DSS group, and a stronger effect on modulating the fecal microbiota alpha-diversity and beta-diversity compared with DSS group. Additionally, the fecal metabolome results showed that both VB8762 and DB8762 interventions indeed altered the fecal metabolome profile and related metabolic pathways of DSS-induced IBD rats. Therefore, given the alleviation effects on colitis, the DB8762 can be confirmed to be a postbiotic. Overall, our findings suggested that VB8762 and DB8762 had similar ability to alleviate IBD although with some differences. Due to the minimal safety concern of postbiotics, we propose that the postbiotic DB8762 could be a promising alternative to probiotics to be applied in the prevention and treatment of IBDs.IMPORTANCEInflammatory bowel disease (IBD) has emerged as a global disease because of the worldwide spread of western diets and lifestyles during industrialization. Up to now, many probiotic strains are used as a modulator of gut microbiota or an enhancer of gut barrier to alleviate or cure IBD. However, there are still many issues of using probiotics, which were needed to be concerned about, for instance, safety issues in certain groups like neonates and vulnerable populations, and the functional differences between viable and dead microorganisms. Therefore, it is of interest to investigate the beneficial effects of dead probiotics cells. The present study proved that both viable Bifidobacterium longum subsp. infantis B8762 and heat-killed cells could alleviate dextran sodium sulfate-induced colitis in rats. The findings help to support that some heat-killed probiotics cells can also exert relevant biological functions and can be used as a postbiotic., Competing Interests: The authors declare no conflict of interest.

Objective: The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy., Method: We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases., Results: A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts ( P <0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders., Conclusions: In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Cao, Wang, Zhu, Sun, Song, Zhang and Han.)