Extracellular RIPK3 Acts as a Danger-Associated Molecular Pattern to Exaggerate Cardiac Ischemia/Reperfusion Injury.

BACKGROUND: Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease. Currently, there is no effective therapy for reducing cardiac I/R injury. Damage-associated molecular patterns are endogenous molecules released after cellular damage to exaggerate tissue inflammation and injury. RIPK3 (receptor-interacting protein kinase 3), a well-established intracellular mediator of cell necroptosis and inflammation, serves as a circulating biomarker of multiple diseases. However, whether extracellular RIPK3 also exerts biological functions in cardiac I/R injury remains totally unknown. METHODS: Patients with acute myocardial infarction receiving percutaneous coronary intervention (PCI) were recruited independently in the discovery cohort (103 patients) and validation cohort (334 patients), and major adverse cardiovascular events were recorded. Plasma samples were collected before and after PCI (6 and 24 h) for RIPK3 concentration measurement. Cultured neonatal rat ventricular myocytes, macrophages and endothelial cells, and in vivo mouse models with myocardial injury induced by I/R (or hypoxia/reoxygenation) were used to investigate the role and mechanisms of extracellular RIPK3. Another cohort including patients with acute myocardial infarction receiving PCI and healthy volunteers was recruited to further explore the mechanisms of extracellular RIPK3. RESULTS: In the discovery cohort, elevated plasma RIPK3 levels after PCI are associated with poorer short- and long-term outcomes in patients with acute myocardial infarction, as confirmed in the validation cohort. In both cultured cells and in vivo mouse models, recombinant RIPK3 protein exaggerated myocardial I/R (or hypoxia/reoxygenation) injury, which was alleviated by the RIPK3 antibody. Mechanistically, RIPK3 acted as a damage-associated molecular pattern and bound with RAGE (receptor of advanced glycation end-products), subsequently activating CaMKII (Ca2+/calmodulin-dependent kinase II) to elicit the detrimental effects. The positive correlation between plasma RIPK3 concentrations and CaMKII phosphorylation in human peripheral blood mononuclear cells was confirmed. CONCLUSIONS: We identified the positive relationship between plasma RIPK3 concentrations and the risk of major adverse cardiovascular events in patients with acute myocardial infarction receiving PCI. As a damage-associated molecular pattern, extracellular RIPK3 plays a causal role in multiple pathological conditions during cardiac I/R injury through RAGE/CaMKII signaling. These findings expand our understanding of the physiological and pathological roles of RIPK3, and also provide a promising therapeutic target for myocardial I/R injury and the associated complications.

The RNA helicase LOS4 regulates pre-mRNA splicing of key genes (EIN2, ERS2, CTR1) in the ethylene signaling pathway.

KEY MESSAGE: The Arabidopsis RNA helicase LOS4 plays a key role in regulating pre-mRNA splicing of the genes EIN2, CTR1, and ERS2 in ethylene signaling pathway. The plant hormone ethylene plays diverse roles in plant growth, development, and responses to stress. Ethylene is perceived by the membrane-bound ethylene receptors complex, and then triggers downstream components, such as EIN2, to initiate signal transduction into the nucleus, leading to the activation of ethylene-responsive genes. Over the past decades, substantial information has been accumulated regarding gene cloning, protein-protein interactions, and downstream gene expressions in the ethylene pathway. However, our understanding of mRNA post-transcriptional processing and modification of key genes in the ethylene signaling pathway remains limited. This study aims to provide evidence demonstrating the involvement of the Arabidopsis RNA helicase LOS4 in pre-mRNA splicing of the genes EIN2, CTR1, and ERS2 in ethylene signaling pathway. Various genetic approaches including RNAi gene silencing, CRISPR-Cas9 gene editing, and amino acid mutations were employed in this study. When LOS4 was silenced or knocked down, the ethylene sensitivity of etiolated seedlings was significantly enhanced. Further investigation revealed errors in the EIN2 pre-mRNA splicing when LOS4 was knocked down. In addition, aberrant pre-mRNA splicing was observed in the ERS2 and CTR1 genes in the pathway. Biochemical assays indicated that the los4-2 (E94K) mutant protein exhibited increased ATP binding and enhanced ATP hydrolytic activity. Conversely, the los4-1 (G364R) mutant had reduced substrate RNA binding and lower ATP binding activities. These findings significantly advanced our comprehension of the regulatory functions and molecular mechanisms of RNA helicase in ethylene signaling.

Both the Positioned Supplemental or Night-Interruptional Blue Light and the Age of Leaves (or Tissues) Are Important for Flowering and Vegetative Growth in Chrysanthemum.

In this study, the effects of supplemental or night interruptional blue light (S-BL or NI-BL) positioning on morphological growth, photoperiodic flowering, and expression of floral genes in Chrysanthemum morifolium were investigated. Blue light-emitting diodes (LEDs) at an intensity of 30 µmol·m-2·s-1 photosynthetic photon flux density (PPFD) were used for 4 h either (1) to supplement the white LEDs at the end of the 10 h short-day (SD10 + S-BL4) and 13 h long-day conditions (LD13 + S-BL4), or (2) to provide night interruption in the SD10 (SD10 + NI-BL4) and LD13 (LD13 + NI-BL4). The S-BL4 or NI-BL4 was positioned to illuminate either the shoot tip, the youngest leaf (vigorously growing the third leaf from the shoot tip), or the old leaf (the third leaf from the stem base). In the text, they will be denoted as follows: SD10 + S-BL4-S, -Y, or -O; SD10 + NI-BL4-S, -Y, or -O; LD13 + S-BL4-S, -Y, or -O; LD13 + NI-BL4-S, -Y, or -O. Normally, the LD13 conditions enhanced more vegetative growth than the SD10 periods. The growth of leaves, stems, and branches strongly responded to the S-BL4 or NI-BL4 when it was targeted onto the shoot tip, followed by the youngest leaf. The SD10 + S-BL4 or +NI-BL4 on the old leaf obviously suppressed plant extension growth, resulting in the smallest plant height. Under LD13 conditions, the flowering-related traits were significantly affected when the S-BL4 or NI-BL4 was shed onto the youngest leaf. However, these differences do not exist in the SD10 environments. At the harvest stage, other than the non-flowered LD13 treatment, the LD13 + S-BL4 irradiating the youngest leaf induced the most flowers, followed by the shoot tip and old leaf. Moreover, LD13 + NI-BL4 resulted in the latest flowering, especially when applied to the shoot tip and old leaf. However, the SD10 + S-BL4 or + NI-BL4 irradiated the shoot tip, youngest leaf, or old leaf all significantly earlier and increased flowering compared to the SD10 treatment. Overall: (1) Generally, vegetative growth was more sensitive to photoperiod rather than lighting position, while, during the same photoperiod, the promotion of growth was stronger when the light position of S-BL4 or NI-BL4 was applied to the shoot tip or the youngest leaf. (2) The photoperiodic flowering of these short-day plants (SDPs) comprehensively responded to the photoperiod combined with blue light positioning. Peculiarly, when they were exposed to the LD13 flowering-inhibited environments, the S-BL4 or NI-BL4 shed onto the leaves, especially the youngest leaves, significantly affecting flowering.

Cohort Profile: the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde, China (Speed-Shunde Cohort).

AIMS: The objective of the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde (Speed-Shunde cohort) was to evaluate the incidence of cardiovascular-kidney-metabolic (CKM) syndrome and metabolic-associated multimorbidity, such as diabetes, hypertension, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD) in Shunde, Foshan, Guangdong, China. Additionally, the study sought to identify the potential determinants that may impact the development of these conditions and the potential consequences that may result. METHODS AND RESULT: In the Speed-Shunde cohort, data were gathered via questionnaires, physical measurements, and laboratory analyses encompassing demographic data, behavioral tendencies, anthropometric assessments, controlled attenuation parameters and liver stiffness measurement utilizing vibration-controlled transient elastography (VCTE), as well as serum and urine detection (such as oral 75g glucose tolerance tests, hemoglobin A1c levels, lipid profiles, liver and renal function tests, urinary microalbumin and creatinine levels, etc.). The baseline data were gathered from October 2021 to September 2022 from over 10,000 Chinese community-based adults and the follow-up surveys would be conducted every two or three years. Blood and urine samples were obtained and stored for future omics data acquisition. Initial analyses revealed the prevalence and risk factors associated with metabolic-associated multimorbidity. CONCLUSIONS: The Speed-Shunde Cohort study is a longitudinal community-based cohort with comprehensive CKM health and metabolic-associated multimorbidity assessment. It will provide valuable insights into these conditions' development, progression, and interrelationships, potentially informing future prevention and treatment strategies.

Prolonged Post-Harvest Preservation in Lettuce (Lactuca sativa L.) by Reducing Water Loss Rate and Chlorophyll Degradation Regulated through Lighting Direction-Induced Morphophysiological Improvements.

To investigate the relationship between the lighting direction-induced morphophysiological traits and post-harvest storage of lettuce, the effects of different lighting directions (top, T; top + side, TS; top + bottom, TB; side + bottom, SB; and top + side + bottom, TSB; the light from different directions for a sum of light intensity of 600 µmol·m-2·s-1 photosynthetic photon flux density (PPFD)) on the growth morphology, root development, leaf thickness, stomatal density, chlorophyll concentration, photosynthesis, and chlorophyll fluorescence, as well as the content of nutrition such as carbohydrates and soluble proteins in lettuce were analyzed. Subsequently, the changes in water loss rate, membrane permeability (measured as relative conductivity and malondialdehyde (MDA) content), brittleness (assessed by both brittleness index and ß-galactosidase (ß-GAL) activity), and yellowing degree (evaluated based on chlorophyll content, and activities of chlorophyllase (CLH) and pheophytinase (PPH)) were investigated during the storage after harvest. The findings indicate that the TS treatment can effectively reduce shoot height, increase crown width, enhance leaves' length, width, number, and thickness, and improve chlorophyll fluorescence characteristics, photosynthetic capacity, and nutrient content in lettuce before harvest. Specifically, lettuce's leaf thickness and stomatal density showed a significant increase. Reasonable regulation of water loss in post-harvested lettuce is essential for delaying chlorophyll degradation. It was utilized to mitigate the increase in conductivity and hinder the accumulation of MDA in lettuce. The softening speed of leafy vegetables was delayed by effectively regulating the activity of the ß-GAL. Chlorophyll degradation was alleviated by affecting CLH and PPH activities. This provides a theoretical basis for investigating the relationship between creating a favorable light environment and enhancing the post-harvest preservation of leafy vegetables, thus prolonging their post-harvest storage period through optimization of their morphophysiological phenotypes.

Synergistic Effects of Silicon and Aspartic Acid on the Alleviation of Salt Stress in Celery (Apium graveliens L.) "Si Ji Xiao Xiang Qin".

Salinity is one of the primary abiotic stresses that seriously hampers plant quality and productivity. It is feasible to reduce or reverse the negative effects of salt through the supplementation of silicon (Si) and aspartic acid (Asp). However, the question of how exogenous Si and Asp induce salt tolerance in celery remains incipient. Thus, this study was performed to determine the synergistic effects of Si and Asp on the alleviation of salt stress in celery. To this end, the celery plants were cultivated in a controlled regime (light for 14 h at 22 °C; darkness for 10 h at 16 °C) and treated with one of five treatments (CK, 100 mM NaCl, 100 mM NaCl + 75 mg/L Si, 100 mM NaCl + 100 mg/L Asp, and 100 mM NaCl + 75 mg/L Si + 100 mg/L Asp). Results showed that solely NaCl-treated celery plants developed salt toxicity, as characterized by decreased growth, declined photosynthetic ability, disturbed nutritious status and internal ion balance, and a boosted antioxidant defense system (Improved antioxidant enzymes and reduced ROS accumulation). In contrast, these adverse effects of NaCl were ameliorated by the additions of Si and Asp, regardless of Si, Asp, or both. Moreover, the mitigatory impacts of the co-application of Si and Asp on salt stress were more pronounced compared to when one of them was solely applied. Collectively, exogenous Si and Asp alleviate the degree of salt stress and thereby improve the salt tolerance of celery.

Corrigendum: Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022.

[This corrects the article DOI: 10.3389/fgene.2024.1395988.].

Awake fiberoptic intubation of a patient with severe multiple trauma in prone position: a case report.

BACKGROUND: Fiberoptic-guided intubation is considered as "gold standard" of difficult airway management. Management of the airway in prone position in patients with severe trauma presenting with penetrating waist and hip injury poses a major challenge to the anesthesiologist. CASE PRESENTATION: A man presented with severe multiple trauma and hemorrhagic shock as a result of an industrial accident with several deformed steel bars penetrating the left lower waist and hip. It was decided to schedule an exploratory laparotomy following extracting the deformed steel bars. Successful administration of awake fiberoptic nasotracheal intubation, performed in a prone position under airway blocks and appropriate sedation, allowed for the procedure. The exploratory laparotomy revealed damage to multiple organs, which were repaired sequentially during a 7-hour surgical operation. The patient's recovery was uneventful, and he was discharged from the hospital one month after the surgery. CONCLUSIONS: Awake fiberoptic nasotracheal intubation, along with airway blocks and appropriate sedation, can be a viable option in patients with severe multiple trauma in the prone position.

Disease spectrum, prevalence, genetic characteristics of inborn errors of metabolism in 21,840 hospitalized infants in Chongqing, China, 2017-2022.

Inborn errors of metabolism (IEMs) are uncommon. Although some studies have explored the distribution and characteristics of IEMs in newborns, the impact of these disorders on hospitalized newborns remains unclear. In this study, we gathered data from 21,840 newborn patients admitted for various medical conditions at the Children's Hospital of Chongqing Medical University from January 2017 and December 2022. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography-mass spectrometry (GC-MS/MS), and genetic analysis were used to elucidate the disease spectrum, incidence rate, and genetic characteristics of IEMs in hospitalized newborns. The results revealed that the incidence of IEMs in hospitalized newborns was 1/377 (58/21,840), with a higher incidence in full-term infants (1/428) than in premature infants (1/3,120). Among the diagnosed genetic metabolic diseases, organic acid metabolism disorders (1/662), amino acid metabolism disorders (1/950), and fatty acid oxidation disorders (1/10,920) were the most prevalent. Methylmalonic acidemia (MMA), especially the isolated form, emerged as the most common IEM, while neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and ornithine transcarbamylase deficiency (OTCD) were prevalent in premature infants. Of the 58 confirmed cases of IEMs, 72 variants were identified, of which 31.94% (23/72) had not been reported previously. This study contributes to understanding the incidence and clinical features of IEMs in hospitalized newborns, offering more efficient strategies for screening and diagnosing these disorders.

Lung-Gut Microbiota and Tryptophan Metabolites Changes in Neonatal Acute Respiratory Distress Syndrome.

Purpose: Neonatal Acute Respiratory Distress Syndrome (NARDS) is a severe respiratory crisis threatening neonatal life. We aim to identify changes in the lung-gut microbiota and lung-plasma tryptophan metabolites in NARDS neonates to provide a differentiated tool and aid in finding potential therapeutic targets. Patients and Methods: Lower respiratory secretions, faeces and plasma were collected from 50 neonates including 25 NARDS patients (10 patients with mild NARDS in the NARDS_M group and 15 patients with moderate-to-severe NARDS in the NARDS_S group) and 25 control patients screened based on gestational age, postnatal age and birth weight. Lower airway secretions and feces underwent 16S rRNA gene sequencing to understand the microbial communities in the lung and gut, while lower airway secretions and plasma underwent LC-MS analysis to understand tryptophan metabolites in the lung and blood. Correlation analyses were performed by comparing differences in microbiota and tryptophan metabolites between NARDS and control, NARDS_S and NARDS_M groups. Results: Significant changes in lung and gut microbiota as well as lung and plasma tryptophan metabolites were observed in NARDS neonates compared to controls. Proteobacteria and Bacteroidota were increased in the lungs of NARDS neonates, whereas Firmicutes, Streptococcus, and Rothia were reduced. Lactobacillus in the lungs decreased in NARDS_S neonates. Indole-3-carboxaldehyde decreased in the lungs of NARDS neonates, whereas levels of 3-hydroxykynurenine, indoleacetic acid, indolelactic acid, 3-indole propionic acid, indoxyl sulfate, kynurenine, and tryptophan decreased in the lungs of the NARDS_S neonates. Altered microbiota was significantly related to tryptophan metabolites, with changes in lung microbiota and tryptophan metabolites having better differentiated ability for NARDS diagnosis and grading compared to gut and plasma. Conclusion: Significant changes occurred in the lung-gut microbiota and lung-plasma tryptophan metabolites of NARDS neonates. Alterations in lung microbiota and tryptophan metabolites were better discriminatory for the diagnosis and grading of NARDS.

Distributions and Trends of the Global Burden of DKD Attributable to Lead Exposure: A Systematic Analysis of GBD from 1990 to 2019.

Long-term exposure to lead is associated with an increased risk of diabetic kidney disease (DKD). However, limited data exist on global trends in DKD burden attributable to lead exposure, especially across diverse regions categorized by socioeconomic level. We aimed to assess the spatiotemporal changes in DKD burden attributable to lead exposure from 1990 to 2019 across 204 countries and regions with varying socio-demographic index (SDI) metrics. This retrospective analysis utilized data from the Global Burden of Disease Study 2019 (GBD2019) database. We estimated the burden of DKD attributable to lead exposure using the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year rate (ASDR), accounting for sex, age, nationality, and SDI. The annual percentage change (APC) and average annual percentage change (AAPC) were calculated using the Joinpoint model to evaluate trends in the ASMR and ASDR attributable to lead exposure from 1990 to 2019. Gaussian process regression was used to model the relationship between the SDI and ASMR/ASDR. Globally, the burden of DKD attributable to lead exposure has significantly increased since 1990, especially among elderly men and in regions such as Asia, Central Latin America, North Africa, the Middle East, and low-SDI regions. In 2019, the ASMR and ASDR of DKD attributable to lead exposure were 0.68 (95% CI: 0.40, 0.98) per 100,000 people and 15.02 (95% CI: 8.68, 22.26) per 100,000 people, respectively. From 1990 to 2019, the global ASMR and ASDR attributable to lead-associated DKD changed by 15.45% and -1.78%, respectively. The global AAPCs of the ASMR and ASDR were 0.55 (95% CI: 0.45, 0.65) and -0.01 (95% CI: -0.12, 0.1), respectively. Significant declining trends were observed in the high-income Asia Pacific region, eastern sub-Saharan Africa, North Africa, the Middle East, and other regions with high SDIs. Over this 30-year study period, the global burden of DKD attributable to lead exposure has increased, particularly in regions with low SDI. Lead exposure remains a significant concern in the global burden of diabetic kidney disease.

Flowering and Runnering of Seasonal Strawberry under Different Photoperiods Are Affected by Intensity of Supplemental or Night-Interrupting Blue Light.

The strawberry (Fragaria × ananassa Duch.) "Sulhyang" is a typical seasonal flowering (SF) strawberry that produces flower buds in day lengths shorter than a critical limit (variable, but often defined as <12 h). There is a trade-off between photoperiod-controlled flowering and gibberellin (GA) signaling pathway-mediated runnering. Some related genes (such as CO, FT1, SOC1, and TFL1) participating in light signaling and circadian rhythm in plants are altered under blue light (BL). Sugars for flowering and runnering are mainly produced by photosynthetic carbon assimilation. The intensity of light could affect photosynthesis, thereby regulating flowering and runnering. Here, we investigated the effect of the intensity of supplemental blue light (S-BL) or night-interrupting blue light (NI-BL) in photoperiodic flowering and runnering regulation by applying 4 h of S-BL or NI-BL with either 0, 10, 20, 30, or 40 µmol·m-2·s-1 photosynthetic photon flux density (PPFD) in a 10 h short-day (SD10) (SD10 + S-BL4 or + NI-BL4 (0, 10, 20, 30, or 40)) or 14 h long-day (LD14) conditions (LD14 + S-BL4 or + NI-BL4 (0, 10, 20, 30, or 40)). Approximately 45 days after the photoperiodic light treatment, generally, whether S-BL or NI-BL, BL (20) was the most promotive in runnering, leading to more runners in both the LD and SD conditions. For flowering, except the treatment LD14 + S-BL, BL (20) was still the key light, either from BL (20) or BL (40), promoting flowering, especially when BL acted as the night-interrupting light, regardless of the photoperiod. At the harvest stage, larger numbers of inflorescences and runners were observed in the LD14 + NI-BL4 treatment, and the most were observed in the LD14 + NI-BL (20). Moreover, the SD10 + NI-BL4 was slightly inferior to the LD14 + NI-BL4 in increasing the numbers of inflorescences and runners, but it caused earlier flowering. Additionally, the circadian rhythm expression of flowering-related genes was affected differently by the S-BL and NI-BL. After the application of BL in LD conditions, the expression of an LD-specific floral activator FaFT1 was stimulated, while that of a flowering suppressor FaTFL1 was inhibited, resetting the balance of expression between these two opposite flowering regulators. The SD runnering was caused by BL in non-runnering SD conditions associated with the stimulation of two key genes that regulate runner formation in the GA pathway, FaGRAS32 and FaGA20ox4. In addition, the positive effects of BL on enhancing photosynthesis and carbohydrate production also provided an abundant energy supply for the flowering and runnering processes.

Associations Between Individual and Combined Metal Exposures in Whole Blood and Kidney Function in U.S. Adults Aged 40 Years and Older.

The effects of metal exposure on kidney function have been reported in previous literature. There is limited and inconsistent information on the associations between individual and combined exposures to metals and kidney function among the middle-aged and older population. The aim of this study was to clarify the associations of exposure to individual metals with kidney function while accounting for potential coexposure to metal mixtures and to evaluate the joint and interactive associations of blood metals with kidney function. A total of 1669 adults aged 40 years and older were enrolled in the present cross-sectional study using the 2015-2016 National Health and Nutrition Examination Survey (NHANES). Single-metal and multimetal multivariable logistic regression models, quantile G-computation, and Bayesian kernel machine regression models (BKMR) were fitted to explore the individual and joint associations of whole blood metals [lead (Pb), cadmium (Cd), mercury (Hg), cobalt (Co), manganese (Mn), and selenium (Se)] with the odds of decreased estimated glomerular filtration rate (eGFR) and albuminuria. A decreased eGFR was defined as an eGFR ≤ 60 mL/min per 1.73 m2, and albuminuria was categorized as a urinary albumin-creatinine ratio (UACR) of ≥ 30.0 mg/g. The results from quantile G-computation and BKMR indicated positive associations between exposure to the metal mixture and the prevalence of decreased eGFR and albuminuria (all P values < 0.05). These positive associations were mainly driven by blood Co, Cd, and Pb. Furthermore, blood Mn was identified as an influential element contributing to an inverse correlation with kidney dysfunction within metal mixtures. Increasing blood Se levels were negatively associated with the prevalence of decreased eGFR and positively associated with albuminuria. In addition, a potential pairwise interaction between Mn-Co on decreased eGFR was identified by BKMR analysis. Findings from our study suggested a positive association between exposure to the whole blood metal mixture and decreased kidney function, with blood Co, Pb, and Cd being the main contributors to this association, while Mn demonstrated an inverse relationship with renal dysfunction. However, as our study was cross-sectional in nature, further prospective studies are warranted to better understand the individual and combined effects of metals on kidney function.

Refined composite moving average fluctuation dispersion entropy and its application on rolling bearing fault diagnosis.

Vibration signal analysis based on multiscale entropy is one of the important means to realize rotating machinery fault diagnosis. However, the length of the time series will be shortened during the coarse-graining process with the increase of the scale factor, which makes the calculated entropy values unstable. This inherent drawback of the coarse-graining method limits its application in fault feature extraction. This paper presents a novel feature extraction method for vibration signals called refined composite moving average fluctuation dispersion entropy (RCMAFDE). It is verified by simulation experiments that RCMAFDE has high stability of entropy values under different time series lengths as well as different disturbances. The RCMAFDE was applied to the fault diagnosis of rolling bearings, and a new fault diagnosis method of rolling bearings was proposed by combining RCMAFDE and kernel extreme learning machine (KELM) optimized by the chaos sparrow search optimization algorithm (CSSOA). First, the vibration signal is preprocessed to form a sample set, and then, the fault feature vector is calculated by RCMAFDE. Finally, the feature vector set is input into the CSSOA-KELM model for training and testing, and the fault diagnosis result is output. To demonstrate the effectiveness and feasibility of the fault diagnosis method, two publicly available datasets and a self-collected dataset are used for experimental validation. The experimental results show that the proposed fault diagnosis method can extract the nonlinear dynamic complexity information of vibration signals more effectively compared with the comparison methods and obtain the highest fault identification accuracy under different datasets.

Nickel chloride promotes lung cancer invasion and metastasis by up-regulating the expression of E3 ubiquitin ligase TRIM31 through the IL-6/STAT3 signaling axis.

Nickel compounds are widely used in industries and daily life as important industrial products. Long-term exposure to nickel compounds has been associated with increased incidence and poor prognosis of lung cancer. However, the molecular mechanism by which exposure to nickel compounds induces the malignant phenotype of lung cancer cells remains unclear. In this study, we confirmed that nickel chloride (NiCl2) exposure promotes invasion and metastasis through IL-6/STAT3 both in vitro and vivo. Mechanistically, we found that NiCl2 mediated the transcriptional regulation of E3 ubiquitin ligase TRIM31 by SATAT3 phosphorylation, and promoted its up-regulation. Overexpression TRIM31 is an independent risk factor for lung cancer patients, and it promotes the invasion and metastasis of lung cancer cells. In addition, E3 ubiquitination ligase TRIM31 binds to its substrate TP53 protein in the RING region and accelerates TP53 protein ubiquitination and degradation. Functional recovery experiments showed that NiCl2 exposure promotes the invasion and metastasis ability of lung cancer and ubiquitination-mediated degradation of TP53 protein through the STAT3/TRIM31 axis. These findings reveal the role and mechanism of NiCl2 in lung cancer progression, indicating that STAT3 and TRIM31 may be promising targets for the treatment of lung cancer.

Comparative Analysis of Vaccine Inequity and COVID-19 Transmission Amid the Omicron Variant Among Countries - Six Countries, Asia-Pacific Region, 2022.

What is already known about this topic?: The coronavirus disease 2019 (COVID-19) persists as a significant global public health crisis. The predominant strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), notably the Omicron variant, continues to undergo mutations. While vaccination is heralded as the paramount solution to cease the pandemic, challenges persist in providing equitable access to COVID-19 vaccines. What is added by this report?: The distribution of vaccine coverage exhibited disparities between high-income and middle-income countries, with middle-income countries evidencing lower levels of vaccination. The data further suggested that countries with lesser vaccination levels tended to display a higher case fatality rate. Findings indicated that an increase in population-wide vaccination was effective in mitigating COVID-19 related mortalities. What are the implications for public health practice?: The findings of this research underscore the pressing necessity for equitable access to vaccines to effectively mitigate the COVID-19 pandemic within the Asia-Pacific region.

Difference between Day and Night Temperature (DIF) and Light Intensity Affect Growth and Photosynthetic Characteristics of Panax ginseng Meyer Sprouts.

Panax ginseng sprouts (PGS) have the advantage of requiring short-term cultivation while maintaining higher ginsenoside contents than traditional ginseng seedlings. It is feasible to improve their yield capacity by manipulating physical factors such as temperature and light. This study therefore investigated the effects of the DIF (difference between day and night temperature) and LI (light intensity) on the growth and photosynthetic characteristics of PGS. To this end, four DIF treatments (18/22 °C, 20/20 °C, 22/22 °C, 22/18 °C), corresponding to two LI regimes (20 PPFD, 200 PPFD), were applied on one-year-old ginseng rootlets in closed-type plant production systems (CPPSs). The PGS had distinctly different responses to the eight treatments. In particular, we found that negative DIF considerably hampered the growth and development of roots, shoots, leaves, and photosynthesis, regardless of the LI considered. The PGS treated with 20/20 °C combined with 20 PPFD displayed the best root growth, shoot development, leaf area, as well as optimal photosynthetic ability. On the other hand, we further showed that the root growth rate was positively correlated with the stem diameter, leaf traits, and photosynthetic ability, whereas it was negatively correlated with the petiole length, stem length, and shoot length. Collectively, 20/20 °C combined with 20 PPFD was the optimal condition in the current study, and may be regarded as a successful strategy for large-scale productions of PGS.

Top and Side Lighting Induce Morphophysiological Improvements in Korean Ginseng Sprouts (Panax ginseng C.A. Meyer) Grown from One-Year-Old Roots.

Nowadays, not only the roots, but also leaves and flowers of ginseng are increasingly popular ingredients in supplements for healthcare products and traditional medicine. The cultivation of the shade-loving crop, ginseng, is very demanding in terms of the light environment. Along with the intensity and duration, light direction is another important factor in regulating plant morphophysiology. In the current study, three lighting directions-top (T), side (S), or top + side (TS)-with an intensity of 30 ± 5 µmol·m-2·s-1 photosynthetic photon flux density (PPFD) were employed. Generally, compared with the single T lighting, the composite lighting direction, TS, was more effective in shaping the ginseng with improved characteristics, including shortened, thick shoots; enlarged, thick leaves; more leaf trichomes; earlier flower bud formation; and enhanced photosynthesis. The single S light resulted in the worst growth parameters and strongly inhibited the flower bud formation, leading to the latest flower bud observation. Additionally, the S lighting acted as a positive factor in increasing the leaf thickness and number of trichomes on the leaf adaxial surface. However, the participation of the T lighting weakened these traits. Overall, the TS lighting was the optimal direction for improving the growth and development traits in ginseng. This preliminary research may provide new ideas and orientations in ginseng cultivation lodging resistance and improving the supply of ginseng roots, leaves, and flowers to the market.

Identification of C2H2 zinc finger genes through genome-wide association study and functional analyses of LkZFPs in response to stresses in Larix kaempferi.

BACKGROUND: C2H2 zinc finger proteins (C2H2-ZFPs), one of the largest transcription factors, play a variety of roles in plant development and growth as well as stress response. While, the evolutionary history and expression profile of the C2H2-ZFP genes in Larix kaempferi (LkZFPs) have not been reported so far. RESULTS: In this study, the whole genome of the LkZFPs was identified and characterized, including physicochemical properties, phylogenetic relationships, conservative motifs, the promoter cis-elements and Gene Ontology (GO) annotation. We identified 47 LkZFPs and divided them into four subfamilies based on phylogenetic analysis and conserved motifs. Subcellular localization prediction showed that most of the LkZFPs were located in the nucleus. Promoter cis-element analysis suggested that the LkZFPs may be involved in the regulation of stress responses. Moreover, Real-time quantitative PCR (RT-qPCR) results showed that Q-type LkZFP genes were involved in the response to abiotic stress, such as salt, drought and hormone stresses. Subcellular localization results showed that LkZFP7 and LkZFP37 were located in the nucleus, LkZFP32 was located in both cytoplasm and nucleus. CONCLUSION: The identification and functional analysis of LkZFPs suggested that some LkZFP genes might play important roles in coping with both biological and abiotic stresses. These results could further increase understanding of the function of the LkZFPs, and provide some research direction and theoretical support.

Progression from different blood glucose states to cardiovascular diseases: a prospective study based on multi-state model.

AIMS: To quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cardiovascular death, and the effects of risk factors on the rates of transition. METHODS AND RESULTS: We used data from the Jinchang Cohort of 42 585 adults aged 20-88 free of coronary heart disease (CHD) and stroke at baseline. A multistate model was applied for analysing the progression of CVD and its relation to various risk factors. During a median follow-up of 7 years, 7498 participants developed pre-diabetes, 2307 developed T2DM, 2499 developed CVD, and 324 died from CVD. Among 15 postulated transitions, transition from comorbid CHD and stroke to cardiovascular death had the highest rate (157.21/1000 person-years), followed by transition from stroke alone to cardiovascular death (69.31/1000 person-years) and transition from pre-diabetes to normoglycaemia (46.51/1000 person-years). Pre-diabetes had a sojourn time of 6.77 years, and controlling weight, blood lipids, blood pressure, and uric acid within normal limits may promote reversion to normoglycaemia. Among transitions to CHD alone and stroke alone, transition from T2DM had the highest rate (12.21/1000 and 12.16/1000 person-years), followed by transition from pre-diabetes (6.81/1000 and 4.93/1000 person-years) and normoglycaemia (3.28/1000 and 2.39/1000 person-years). Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions. CONCLUSION: Pre-diabetes was the optimal intervention stage in the disease trajectory. The derived transition rates, sojourn time, and influence factors could provide scientific support for the primary prevention of both T2DM and CVD.

Former single-outcome studies on the relationship between glycaemia and cardiovascular disease (CVD) may ignore the complexity and multi-transformations across the multiple stages from normoglycaemia to CVD in real-world setting. We aimed to quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes, CVD, and cardiovascular death. Pre-diabetes was the optimal intervention stage in the disease trajectory. Transitions from CVD to death had much higher rates than other transitions. Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions.