The calcium-dependent protein kinase CPK16 regulates hypoxia-induced ROS production by phosphorylating the NADPH oxidase RBOHD in Arabidopsis.

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase respiratory burst oxidase homolog D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in the rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N-terminus of RBOHD at 4 serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16-RBOHD module shapes the ROS production during hypoxia and reoxygenation in Arabidopsis.

14-3-3 proteins contribute to autophagy by modulating SINAT-mediated degradation of ATG13.

In multicellular eukaryotes, autophagy is a conserved process that delivers cellular components to the vacuole or lysosome for recycling during development and stress responses. Induction of autophagy activates AUTOPHAGY-RELATED PROTEIN 1 (ATG1) and ATG13 to form a protein kinase complex that initiates autophagosome formation. However, the detailed molecular mechanism underlying the regulation of this protein complex in plants remains unclear. Here, we determined that in Arabidopsis thaliana, the regulatory proteins 14-3-3λ and 14-3-3κ redundantly modulate autophagy dynamics by facilitating SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA (SINAT)-mediated proteolysis of ATG13a and ATG13b. 14-3-3λ and 14-3-3κ directly interacted with SINATs and ATG13a/b in vitro and in vivo. Compared to wild-type (WT), the 14-3-3λ 14-3-3κ double mutant showed increased tolerance to nutrient starvation, delayed leaf senescence, and enhanced starvation-induced autophagic vesicles. Moreover, 14-3-3s were required for SINAT1-mediated ubiquitination and degradation of ATG13a. Consistent with their roles in ATG degradation, the 14-3-3λ 14-3-3κ double mutant accumulated higher levels of ATG1a/b/c and ATG13a/b than the WT upon nutrient deprivation. Furthermore, the specific association of 14-3-3s with phosphorylated ATG13a was crucial for ATG13a stability and formation of the ATG1-ATG13 complex. Thus, our findings demonstrate that 14-3-3λ and 14-3-3κ function as molecular adaptors to regulate autophagy by modulating the homeostasis of phosphorylated ATG13.

Phosphatidic acid modulates MPK3- and MPK6-mediated hypoxia signaling in Arabidopsis.

Phosphatidic acid (PA) is an important lipid essential for several aspects of plant development and biotic and abiotic stress responses. We previously suggested that submergence induces PA accumulation in Arabidopsis thaliana; however, the molecular mechanism underlying PA-mediated regulation of submergence-induced hypoxia signaling remains unknown. Here, we showed that in Arabidopsis, loss of the phospholipase D (PLD) proteins PLDα1 and PLDδ leads to hypersensitivity to hypoxia, but increased tolerance to submergence. This enhanced tolerance is likely due to improvement of PA-mediated membrane integrity. PA bound to the mitogen-activated protein kinase 3 (MPK3) and MPK6 in vitro and contributed to hypoxia-induced phosphorylation of MPK3 and MPK6 in vivo. Moreover, mpk3 and mpk6 mutants were more sensitive to hypoxia and submergence stress compared with wild type, and fully suppressed the submergence-tolerant phenotypes of pldα1 and pldδ mutants. MPK3 and MPK6 interacted with and phosphorylated RELATED TO AP2.12, a master transcription factor in the hypoxia signaling pathway, and modulated its activity. In addition, MPK3 and MPK6 formed a regulatory feedback loop with PLDα1 and/or PLDδ to regulate PLD stability and submergence-induced PA production. Thus, our findings demonstrate that PA modulates plant tolerance to submergence via both membrane integrity and MPK3/6-mediated hypoxia signaling in Arabidopsis.

Topological Lifshitz transition and one-dimensional Weyl mode in HfTe5.

Landau band crossings typically stem from the intra-band evolution of electronic states in magnetic fields and enhance the interaction effect in their vicinity. Here in the extreme quantum limit of topological insulator HfTe5, we report the observation of a topological Lifshitz transition from inter-band Landau level crossings using magneto-infrared spectroscopy. By tracking the Landau level transitions, we demonstrate that band inversion drives the zeroth Landau bands to cross with each other after 4.5 T and forms a one-dimensional Weyl mode with the fundamental gap persistently closed. The unusual reduction of the zeroth Landau level transition activity suggests a topological Lifshitz transition at 21 T, which shifts the Weyl mode close to the Fermi level. As a result, a broad and asymmetric absorption feature emerges due to the Pauli blocking effect in one dimension, along with a distinctive negative magneto-resistivity. Our results provide a strategy for realizing one-dimensional Weyl quasiparticles in bulk crystals.

Causal relationship between gut microbiota and tuberculosis: a bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. RESULTS: In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. CONCLUSION: Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

ROS-Responsive Bola-Lipid Nanoparticles as a Codelivery System for Gene/Photodynamic Combination Therapy.

The nonviral delivery systems that combine genes with photosensitizers for multimodal tumor gene/photodynamic therapy (PDT) have attracted much attention. In this study, a series of ROS-sensitive cationic bola-lipids were applied for the gene/photosensitizer codelivery. Zn-DPA was introduced as a cationic headgroup to enhance DNA binding, while the hydrophobic linking chains may facilitate the formation of lipid nanoparticles (LNP) and the encapsulation of photosensitizer Ce6. The length of the hydrophobic chain played an important role in the gene transfection process, and 14-TDZn containing the longest chains showed better DNA condensation, gene transfection, and cellular uptake. 14-TDZn LNPs could well load photosensitizer Ce6 to form 14-TDC without a loss of gene delivery efficiency. 14-TDC was used for codelivery of p53 and Ce6 to achieve enhanced therapeutic effects on the tumor cell proliferation inhibition and apoptosis. Results showed that the codelivery system was more effective in the inhibition of tumor cell proliferation than individual p53 or Ce6 monotherapy. Mechanism studies showed that the production of ROS after Ce6 irradiation could increase the accumulation of p53 protein in tumor cells, thereby promoting caspase-3 activation and inducing apoptosis, indicating some synergistic effect. These results demonstrated that 14-TDC may serve as a promising nanocarrier for gene/PDT combination therapy.

Mortality and prognostic factors among inpatients with systemic lupus erythematosus in China: A 20-year retrospective study.

OBJECTIVE: To summarize the causes of death and clinical characteristics of systemic lupus erythematosus (SLE) hospitalized patients in the last 20 years to improve SLE survival rates by detecting critical SLE early. METHODS: In this case-control study, 218 SLE death cases were retrospectively analyzed from January 2002 to December 2022, with 110 SLE inpatients chosen at random as controls. The clinical symptoms, causes of death, and risk factors in patients with SLE were investigated. RESULTS: There were 218 deaths among 9538 patients with SLE, including 188 women and 30 men. The death rate fell steadily from 4.14% in 2002 to 1.96% in 2013 and remained at 1.84% from 2014 to 2022. The standardized mortality ratio (SMR) was 4.98 [95% CI (4.06-5.89)] from 2002 to 2012 and 3.39 [95% CI (2.74-4.04)] from 2013 to 2022. Infection, lupus-induced multiple organ failure syndrome (MODS), and neuropsychiatric lupus (NPLE) were the leading causes of death, accounting for 31.19%, 15.14%, and 11.47% of overall deaths. Age had a significant association with the major causes of death. Logistic regression analysis showed NPLE[OR = 10.772,95% CI (3.350,34.633), p < 0.001], lupus pulmonary involvement (LP)[OR = 3.844,95%CI (1.547,9.552), p = 0.004], pneumonia[OR = 3.439,95%CI(1.552,7.621), p = 0.002], thrombocytopenia[OR = 14.941,95%CI (4.088,54.604), p < 0.001], creatinine>177 µmol/L[OR = 8.644,95%CI (2.831,26.388), p < 0.001], glutamic transaminase(AST) > 60U/L[OR = 5.762,95%CI (2.200,15.088), p < 0.001], total bilirubin > 34 µmol/L[OR = 16.701,95%CI (3.349,83.294), p = 0.001], higher SLE Disease Activity Index (SLEDAI)[OR = 1.089,95%CI (1.032,1.149), p = 0.002] and SLE Damage Index (SDI)[OR = 3.690,95%CI (2.487,5.474), p < 0.001] correlated positively with death. CONCLUSION: From 2002 to 2013, the mortality rate among patients with SLE fell steadily but remained unchanged from 2014 to 2022. Patients with SLE had significantly higher SMR than the general population. Childhood-onset SLE had a poorer prognosis than adult-onset SLE. Infection, MODS, and NPLE were the three leading causes of death. Major organ involvement and high disease activity were risk factors for mortality.

The effects of meteorological factors and air pollutants on the incidence of tuberculosis in people living with HIV/AIDS in subtropical Guangxi, China.

BACKGROUND: Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. METHOD: Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. RESULTS: A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507-0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116-1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425-0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135-0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322-0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells < 200 cells/µL subgroup, temperature, precipitation, and PM10 had a significant hysteretic effect on TB incidence, while temperature and precipitation had a significant cumulative lag effect. However, these effects were not observed in the CD4(+) T cells ≥ 200 cells/µL subgroup. CONCLUSION: For PLWHA in subtropical Guangxi, temperature and precipitation had a significant cumulative effect on TB incidence among PLWHA, while air pollutants had little effect. Moreover, the influence of meteorological factors on the incidence of TB also depends on the immune status of PLWHA.

Influence of Family-Learned Fear-of-Pain on Patients.

BACKGROUND: Fear-of-pain is a common feeling of patients and their family who experience or witness severe or chronic pain. Fear-of-pain may disturb patient's recovery, and also influence family support to assist patients' recovery. AIM: This study is to measure the level of family support for each patient; evaluate the extent of the supporting families' fear-of-pain; and identify possible interventions in family support and family fear-of-pain. METHODS: This cross-sectional descriptive research involved 77 participants in the orthopedics department of a tertiary hospital by convenience sampling. The online questionnaire includes general information, and scales of fear-of-pain, pain anxiety, pain vigilance and awareness, pain catastrophizing, and family support. T-test, Pearson correlation analysis and Spearman correlation analysis were used to analyze data. RESULTS: Most participants reported that they experienced a moderate-to-high level of fear-of-pain, pain anxiety, pain vigilance and awareness. A total of 15.6% of participants are at risk of pain catastrophizing. The family's pain vigilance and awareness, and fear-of-pain were often similar to those of the patient, and their levels of pain anxiety and catastrophizing were often higher than the patient's. Family support and families' fear-of-pain affect patients' feelings of pain and families' behavior in decision-making for patient recovery, necessitating the development of interventions for patients' families. CONCLUSIONS: Family members can develop the fear-of-pain from witnessing painful experiences and may exhibit fear-avoidance behaviors in deciding on patients' rehabilitation plan. Family support, including the type of relationship with families, and length of time family spent with the patient, had an effect on patients' pain and fear-of-pain.

Pain Sensitivity and Acute Postoperative Pain in Patients Undergoing Abdominal Surgery: The Mediating Roles of Pain Self-Efficacy and Pain Catastrophizing.

BACKGROUND: Inadequately managed postoperative pain remains a common issue. Examining factors like pain sensitivity, pain catastrophizing, and pain self-efficacy can help improve postoperative pain management. While these factors have been identified as potential predictors of acute postoperative pain, their effects have been inconsistent. Few studies have explored the interactions between these factors. AIM: To investigate the influence of preoperative pain sensitivity, pain catastrophizing, and pain self-efficacy on acute postoperative pain in abdominal surgery patients and to determine the mediating roles of pain catastrophizing and pain self-efficacy in the relationship between pain sensitivity and acute postoperative pain, as per the gate control theory. METHODS: A total of 246 patients were enrolled in this study. General information was collected before surgery, and the Pain Sensitivity Questionnaire (PSQ), Pain Catastrophizing Scale (PCS), and Pain Self-Efficacy Questionnaire (PSEQ) were administered. After surgery, patients' average pain scores over the 24 hours were reported using the Numerical Rating Scale (NRS). Correlation analyses and a structural equation model were used to examine the relationships among these variables. RESULTS: NRS scores over 3 during the 24 hours post-surgery were reported by 21.54% of patients. Postoperative acute pain was found to be associated with pain sensitivity (rs = 0.463, p < .001), pain catastrophizing (rs = 0.328, p < .001), and pain self-efficacy (rs = -0.558, p < .001). A direct effect on postoperative acute pain was exerted by pain sensitivity (effect = 0.250, p = .001), along with indirect effects through: (A) pain catastrophizing (effect = 0.028, p = .001); (B) pain self-efficacy (effect = 0.132, p = .001); and (C) the chain mediation of pain self-efficacy and pain catastrophizing (effect = 0.021, p = .008). CONCLUSIONS: The severity of postoperative acute pain can be predicted by pain self-efficacy and pain catastrophizing, and the connection between moderate pain sensitivity and postoperative acute pain severity is mediated by them. Therefore, intervention programs aimed at boosting pain self-efficacy and reducing pain catastrophizing can enhance postoperative pain outcomes for abdominal surgery patients.

Development of a nomogram for predicting acute pain among patients after abdominal surgery: A prospective observational study.

AIMS: To develop a nomogram to provide a screening tool for recognising patients at risk of post-operative pain undergoing abdominal operations. BACKGROUND: Risk prediction models for acute post-operative pain can allow initiating prevention strategies, which are valuable for post-operative pain management and recovery. Despite the increasing number of studies on risk factors, there were inconsistent findings across different studies. In addition, few studies have comprehensively explored predictors of post-operative acute pain and built prediction models. DESIGN: A prospective observational study. METHODS: A total of 352 patients undergoing abdominal operations from June 2022 to December 2022 participated in this investigation. A nomogram was developed for predicting the probability of acute pain after abdominal surgery according to the results of binary logistic regression. The nomogram's predictive performance was assessed by discrimination and calibration. Internal validation was performed via Bootstrap with 1000 re-samplings. RESULTS: A total of 139 patients experienced acute post-operative pain following abdominal surgery, with an incidence of 39.49%. Age <60, marital status (unmarried, divorced, or widowed), consumption of intraoperative remifentanil >2 mg, indwelling of drainage tubes, poor quality sleep, high pain catastrophizing, low pain self-efficacy, and PCIA not used were predictors of inadequate pain control in patients after abdominal surgery. Using these variables, we developed a nomogram model. All tested indicators showed that the model has reliable discrimination and calibration. CONCLUSIONS: This study established an online dynamic predictive model that can offer an individualised risk assessment of acute pain after abdominal surgery. Our model had good differentiation and calibration and was verified internally as a useful tool for risk assessment. RELEVANCE TO CLINICAL PRACTICE: The constructed nomogram model could be a practical tool for predicting the risk of experiencing acute post-operative pain in patients undergoing abdominal operations, which would be helpful to realise personalised management and prevention strategies for post-operative pain. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were adopted in this study. PATIENT OR PUBLIC CONTRIBUTION: Before the surgery, research group members visited the patients who met the inclusion criteria and explained the purpose and scope of the study to them. After informed consent, they completed the questionnaire. The patients' pain scores (VAS) were regularly assessed and documented by the bedside nurse for the first 3 days following surgery. Other information was obtained from medical records.

Improved encapsulation efficiency and storage stability of lutein by soy protein isolate nanocarriers with thermal and trypsin treatments.

BACKGROUND: Encapsulation of bioactive compounds within protein-based nanoparticles has garnered considerable attention in the food and pharmaceutical industries because of its potential to enhance stability and delivery. Soy protein isolate (SPI) has emerged as a promising candidate, prompting the present study aiming to modify its properties through controlled thermal and trypsin treatments for improved encapsulation efficiency (EE) of lutein and its storage stability. RESULTS: The EE of lutein nanoparticles encapsulated using SPI trypsin hydrolysates (SPIT) with three varying degrees of hydrolysis (4.11%, 6.91% and 10.61% for SPIT1, SPIT2 and SPIT3, respectively) increased by 12.00%, 15.78% and 18.59%, respectively, compared to SPI. Additionally, the photostability of SPIT2 showed a remarkable increase of 38.21% compared to SPI. The superior encapsulation efficiency and photostability of SPIT2 was attributed to increased exposure of hydrophobic groups, excellent antioxidant activity and uniform particle stability, despite exhibiting lower binding affinity to lutein compared to SPI. Furthermore, in SPIT2, the protein structure unfolded, with minimal impact on overall secondary structure upon lutein addition. CONCLUSION: The precise application of controlled thermal and trypsin treatments to SPI has been shown to effectively produce protein nanoparticles with substantially improved encapsulation efficiency for lutein and enhanced storage stability of the encapsulated lutein. These findings underscore the potential of controlled thermal and trypsin treatments to modify protein properties effectively and offer significant opportunities for expanding the applications of protein-based formulations across diverse fields. © 2024 Society of Chemical Industry.

[Mechanism of Huachansu Injection against colorectal cancer based on network pharmacology and cellular experimental].

This study aimed to elucidate the mechanism of Huachansu Injection(HCSI) against colorectal cancer(CRC) using network pharmacology, molecular docking technology, and cellular experimental. This research group initially used LC-MS/MS to detect the content of 16 bufadienolides in HCSI. Ten bufadienolide components were selected based on a content threshold of greater than 10 ng·mL~(-1). Their potential targets were further predicted using the SwissTargetPrediction database. CRC-related targets were obtained through GeneCards, OMIM, TTD, and PharmGKB databases. The intersection targets of HCSI in the treatment of CRC were obtained through Venny. The "active component-target-disease" network and target protein-protein interaction(PPI) network were constructed via Cytoscape software. Core targets were screened based on the degree values. Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed on these key targets. Molecular docking was conducted using AutoDock software on major bufadienolide active components and key targets. Different concentrations of HCSI, psi-bufarenogin(BUF), and bufotalin(BFT) were tested for their effects on cell viability, migration, and apoptosis rates in CRC HCT116 cells. Western blot was conducted to detect the expression of proteins related to the PI3K/Akt/mTOR signaling pathway in HCT116 cells. Eight main active components of HCSI, including arenobufagin, BUF, and BFT, as well as 20 key targets of HCSI in combating CRC, such as EGFR, IL6, and mTOR, were identified. Based on KEGG pathway enrichment and molecular docking results, the PI3K/Akt/mTOR signaling pathway was selected for further verification. Cellular experimental demonstrated that HCSI, BUF, and BFT significantly inhibited the proliferation and migration abilities of HCT116 cells, induced apoptosis in these cells, and downregulated the expression of PI3K/Akt/mTOR pathway-related proteins. This result suggests that HCSI, BUF, and BFT may exert their anti-CRC effects by regulating the PI3K/Akt/mTOR signaling pathway through targets such as mTOR and PIK3CA. This study provides theoretical evidence for exploring the active ingredients and mechanism of HCSI against CRC.

Impact of high-power short-duration atrial fibrillation ablation technique on the incidence of silent cerebral embolism: a prospective randomized controlled study.

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

MYB30 integrates light signals with antioxidant biosynthesis to regulate plant responses during postsubmergence recovery.

Submergence is an abiotic stress that limits agricultural production world-wide. Plants sense oxygen levels during submergence and postsubmergence reoxygenation and modulate their responses. Increasing evidence suggests that completely submerged plants are often exposed to low-light stress, owing to the depth and turbidity of the surrounding water; however, how light availability affects submergence tolerance remains largely unknown. Here, we showed that Arabidopsis thaliana MYB DOMAIN PROTEIN30 (MYB30) is an important transcription factor that integrates light signaling and postsubmergence stress responses. MYB DOMAIN PROTEIN30 protein abundance decreased upon submergence and accumulated during reoxygenation. Under submergence conditions, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a central regulator of light signaling, caused the ubiquitination and degradation of MYB30. In response to desubmergence, however, light-induced MYB30 interacted with MYC2, a master transcription factor involved in jasmonate signaling, and activated the expression of the VITAMIN C DEFECTIVE1 (VTC1) and GLUTATHIONE SYNTHETASE1 (GSH1) gene families to enhance antioxidant biosynthesis. Consistent with this, the myb30 knockout mutant showed increased sensitivity to submergence, which was partially rescued by overexpression of VTC1 or GSH1. Thus, our findings uncover the mechanism by which the COP1-MYB30 module integrates light signals with cellular oxidative homeostasis to coordinate plant responses to postsubmergence stress.

The role of iTr35 cells in the inflammatory response and fibrosis progression of systemic sclerosis.

OBJECTIVE: To evaluate the role of induced immunosuppressive T regulatory (iTr) 35 cells in SSc-related inflammation and fibrosis. METHODS: Sixty-eight SSc patients were enrolled in this study. Subsets of iTr35 and Tr1 were measured by flow cytometry. IL-35 and IL-10 levels were measured using ELISA. Expressions of iTr35, Tr1, fibrosis-related genes and proteins associated with signalling pathways were determined using immunofluorescence, western blot and immunohistochemistry assays. RESULTS: In peripheral blood, the proportions of the iTr35 cells were higher and Tr1 cells were lower than the control group. Similarly, IL-35 expression was increased, while IL-10 levels were decreased. In fibroblasts from skin tissue, the expression levels of EBI3, IL-12Ap35, Foxp3 and IL-10 were decreased, but collagen I, TGF-ß, alpha smooth muscle actin (α-SMA) and fibronectin levels were increased. Phosphorylated STAT3/6 were increased, but iTr35 and Tr1 cell levels were significantly decreased. When CD4+ cells were incubated with both recombinant human (rh)IL-35 and rhIL-10, the cell numbers of iTr35 and Tr1 were greater than the same type of cells treated with rhIL-35 or rhIL-10 alone. However, the viability of conventional CD4+ T cells was decreased by gradually increasing iTr35 cells. Moreover, iTr35 cells affected α-SMA expression through the STAT3/6 signalling pathway. CONCLUSION: Both iTr35 and Tr1 cells are involved in SSc-related inflammation and fibrosis. IL-35 can induce iTr35 cells, showing a synergistic effect with IL-10. We also found that iTr35 cells can inhibit T cell proliferation and differentiation via the STAT3/6 signalling pathway, thereby causing fibrosis.

SINAT E3 Ubiquitin Ligases Mediate FREE1 and VPS23A Degradation to Modulate Abscisic Acid Signaling.

In plants, the ubiquitin-proteasome system, endosomal sorting, and autophagy are essential for protein degradation; however, their interplay remains poorly understood. Here, we show that four Arabidopsis (Arabidopsis thaliana) E3 ubiquitin ligases, SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA1 (SINAT1), SINAT2, SINAT3, and SINAT4, regulate the stabilities of FYVE DOMAIN PROTEIN REQUIRED FOR ENDOSOMAL SORTING1 (FREE1) and VACUOLAR PROTEIN SORTING23A (VPS23A), key components of the endosomal sorting complex required for transport-I, to modulate abscisic acid (ABA) signaling. GFP-SINAT1, GFP-SINAT2, and GFP-SINAT4 primarily localized to the endosomal and autophagic vesicles. SINATs controlled FREE1 and VPS23A ubiquitination and proteasomal degradation. SINAT overexpressors showed increased ABA sensitivity, ABA-responsive gene expression, and PYRABACTIN RESISTANCE1-LIKE4 protein levels. Furthermore, the SINAT-FREE1/VPS23A proteins were codegraded by the vacuolar pathway. In particular, during recovery post-ABA exposure, SINATs formed homo- and hetero-oligomers in vivo, which were disrupted by the autophagy machinery. Taken together, our findings reveal a novel mechanism by which the proteasomal and vacuolar turnover systems regulate ABA signaling in plants.

Proposal for Observing Yang-Lee Criticality in Rydberg Atomic Arrays.

Yang-Lee edge singularities (YLES) are the edges of the partition function zeros of an interacting spin model in the space of complex control parameters. They play an important role in understanding non-Hermitian phase transitions in many-body physics, as well as characterizing the corresponding nonunitary criticality. Even though such partition function zeroes have been measured in dynamical experiments where time acts as the imaginary control field, experimentally demonstrating such YLES criticality with a physical imaginary field has remained elusive due to the difficulty of physically realizing non-Hermitian many-body models. We provide a protocol for observing the YLES by detecting kinked dynamical magnetization responses due to broken PT symmetry, thus enabling the physical probing of nonunitary phase transitions in nonequilibrium settings. In particular, scaling analyses based on our nonunitary time evolution circuit with matrix product states accurately recover the exponents uniquely associated with the corresponding nonunitary CFT. We provide an explicit proposal for observing YLES criticality in Floquet quenched Rydberg atomic arrays with laser-induced loss, which paves the way towards a universal platform for simulating non-Hermitian many-body dynamical phenomena.

Omnifarious fruit polyphenols: an omnipotent strategy to prevent and intervene diabetes and related complication?

Diabetes mellitus is a metabolic syndrome which cannot be cured. Recently, considerable interest has been focused on food ingredients to prevent and intervene in complications of diabetes. Polyphenolic compounds are one of the bioactive phytochemical constituents with various biological activities, which have drawn increasing interest in human health. Fruits are part of the polyphenol sources in daily food consumption. Fruit-derived polyphenols possess the anti-diabetic activity that has already been proved either from in vitro studies or in vivo studies. The mechanisms of fruit polyphenols in treating diabetes and related complications are under discussion. This is a comprehensive review on polyphenols from the edible parts of fruits, including those from citrus, berries, apples, cherries, mangoes, mangosteens, pomegranates, and other fruits regarding their potential benefits in preventing and treating diabetes mellitus. The signal pathways of characteristic polyphenols derived from fruits in reducing high blood glucose and intervening hyperglycemia-induced diabetic complications were summarized.

Food phenolics stimulate adipocyte browning via regulating gut microecology.

Fat browning has piqued the interest of researchers as a potential target for treating obesity and related metabolic disorders. Recruitment of brown adipocytes leads to enhanced energy dissipation and reduced adiposity, thus facilitating the maintenance of metabolic homeostasis. Evidence is increasing to support the crucial roles of polyphenols and gut microecology in turning fat "brown". However, it is not clear whether the intestinal microecology is involved in polyphenol-mediated regulation of adipose browning, so this concept is worthy of exploration. In this review, we summarize the current knowledge, mostly from studies with murine models, supporting the concept that the effects of food phenolics on brown fat activation and white fat browning can be attributed to their regulatory actions on gut microecology, including microbial community profile, gut metabolites, and gut-derived hormones. Furthermore, the potential underlying pathways involved are also discussed. Basically, understanding gut microecology paves the way to determine the underlying roles and mechanisms of food phenolics in adipose browning.