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Abstract The assessment of apple quality is pivotal in agricultural production management, and apple ripeness is a key determinant of apple quality. This paper proposes an approach for assessing apple ripeness from both structured and unstructured observation data, i.e., text and images. For structured text data, support vector regression (SVR) models optimized using the Whale Optimization Algorithm (WOA), Grey Wolf Optimizer (GWO), and Sparrow Search Algorithm (SSA) were utilized to predict apple ripeness, with the WOA-optimized SVR demonstrating exceptional generalization capabilities. For unstructured image data, an Enhanced-YOLOv8+, a modified YOLOv8 architecture integrating Detect Efficient Head (DEH) and Efficient Channel Attention (ECA) mechanism, was employed for precise apple localization and ripeness identification. The synergistic application of these methods resulted in a significant improvement in prediction accuracy. These approaches provide a robust framework for apple quality assessment and deepen the understanding of the relationship between apple maturity and observed indicators, facilitating more informed decision-making in postharvest management.

Abstract Aims Serum calcium level is widely used for evaluating disease severity, but its impact on clinical outcomes in patients with congestive heart failure (CHF) remains poorly understood. The aim of this study is to investigate the relationship between serum calcium levels and in‐hospital mortality in CHF patients. Methods and results We conducted a retrospective analysis utilizing clinical data from the Medical Information Mart for Intensive Care database, encompassing a cohort of 15 983 CHF patients. This cohort was stratified based on their serum calcium levels, with the primary objective being the determination of in‐hospital mortality. To assess the impact of admission serum calcium levels on in‐hospital mortality, we employed various statistical methodologies, including multivariable logistic regression models, a generalized additive model, a two‐piecewise linear regression model, and subgroup analysis. Comparative analysis of the reference group (Q3) revealed increased in‐hospital mortality in the first quintile (Q1, the group with the lowest blood calcium level) and the fifth quintile (Q5, the group with the highest blood calcium level), with fully adjusted odds ratios of 1.38 [95% confidence interval (CI): 1.13–1.68, P = 0.002] and 1.23 (95% CI: 1.01–1.5, P = 0.038), respectively. A U‐shaped relationship was observed between serum calcium levels and in‐hospital mortality, with the lowest risk occurring at a threshold of 8.35 mg/dL. The effect sizes and corresponding CIs below and above this threshold were 0.782 (95% CI: 0.667–0.915, P = 0.0023) and 1.147 (95% CI: 1.034–1.273, P = 0.0094), respectively. Stratified analyses confirmed the robustness of this correlation. Conclusions Our study identifies a U‐shaped association between serum calcium levels and in‐hospital mortality in CHF patients, with a notable inflection point at 8.35 mg/dL. Further investigation through prospective, randomized, and controlled studies is warranted to validate the findings presented in this study.

Abstract Liver metastasis is a common cause of death in colorectal cancer (CRC) patients, but epigenetic remodeling and metabolic reprogramming for CRC liver metastasis remain unclear. The study revealed that the Lyn/RUVBL1 complex is highly expressed in CRC and is closely correlated with liver metastasis. On the one hand, ATAC‐seq and HiCut suggested that Lyn/RUVBL1 regulates the expression of TRIB3 through the POL II‐mediated chromatin conformation of TRIB3 and thus the expression of β‐catenin. This promotes the proliferation and migration of CRC through β‐catenin‐mediated upregulation of MMP9 and VEGF. On the other hand, metabolomics revealed that Lyn/RUVBL1 regulates the expression of PGE2 through the enzyme COX2, thereby promoting arachidonic acid (AA) metabolism. CUT‐Tag showed that Lyn/RUVBL1 silencing reduces the H3K27ac level in the COX2 promoter. Then, it is found that COX2 is regulated by the transcription factor FOXA1. Lyn/RUVBL1 modulates AA metabolism by regulating the chromatin accessibility of FOXA1. AA metabolism promotes the metastasis of CRC by affecting β‐catenin nuclear translocation and upregulating MMP9 and VEGF. These findings suggest that the Lyn/RUVBL1 complex mediates epigenetic remodeling to regulate the metabolic reprogramming of AA, highlighting its role in promoting the metastasis of CRC.

Pulpitis, an inflammatory disease of dental pulp tissues, ultimately results in the loss of pulp defense properties. Existing clinical modalities cannot effectively promote inflamed pulp repair. Oxidative stress is a major obstacle inhibiting pulp repair. Due to their powerful antioxidative capacity, mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) exhibit potential for treating oxidative stress-related disorders. However, whether MSC-sEVs shield dental pulp tissues from oxidative damage is largely unknown. Here, we showed that dental follicle stem cell-derived sEVs (DFSC-sEVs) have antioxidative and prohealing effects on a rat LPS-induced pulpitis model by enhancing the survival, proliferation and odontogenesis of H2O2-injured dental pulp stem cells (DPSCs). Additionally, DFSC-sEVs restored the oxidative/antioxidative balance in DPSC mitochondria and had comparable effects on ameliorating mitochondrial dysfunction with the mitochondrion-targeted antioxidant Mito-Tempo. To improve the efficacy of DFSC-sEVs, we fabricated an intelligent and injectable hydrogel to release DFSC-sEVs by combining sodium alginate (SA) and the ROS sensor RhB-AC. The newly formed SA-RhB hydrogel efficiently encapsulates DFSC-sEVs and exhibits controlled release of DFSC-sEVs in a HClO/ClO− concentration-dependent manner, providing a synergistic antioxidant effect with DFSC-sEVs. These results suggest that DFSC-sEVs-loaded SA-RhB is a promising minimally invasive treatment for pulpitis by enhancing tissue repair in the pulp wound microenvironment.

ObjectivesMast cell (MC) degranulation is a key process in allergic reactions and inflammatory responses. Aspartate aminotransferase 1 (AAT1)-derived endogenous sulfur dioxide (SO2) is an important regulator of MC function. However, the mechanism underlying its role in MC degranulation remains unclear. This study aimed to investigate the mechanism by which endogenous SO2 controlled MC degranulation.MethodsHMC-1 and Rat basophilic leukemia cell MC line (RBL-2H3) were used in the cell experiments. SO2 content was detected by in situ fluorescent probe. MC degranulation represented by the release rate of MC β-hexosaminidase was determined using a colorimetric assay. Sulfenylation of galectin-9 (Gal-9) in MCs and purified protein was detected using a biotin switch assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the exact sulfenylation sites of Gal-9 by SO2. Animal models of passive cutaneous anaphylaxis (PCA) and hypoxia-driven pulmonary vascular remodeling were used to investigate the effect of SO2 on mast cell activation in vivo. Site-directed mutation of Gal-9 was conducted to confirm the exact site of SO2 and support the significance of SO2/Gal-9 signal axis in the regulation of MC degranulation.ResultsDegranulation was increased in AAT1-knockdowned MCs, and SO2 supplementation reversed the increase in MC degranulation. Furthermore, deficiency of endogenous SO2 contributed to IgE-mediated degranulation in vitro. Besides, SO2 inhibited IgE-mediated and hypoxia-driven MC degranulation in vivo. Mechanistically, LC-MS/MS analysis and site-directed mutation results showed that SO2 sulfenylated Gal-9 at cysteine 74. Sulfenylation of the 74th cysteine of Gal-9 protein was required in the SO2-inhibited MC degranulation under both physiological and pathophysiological conditions.ConclusionThese findings elucidated that SO2 inhibited MC degranulation via sulfenylating Gal-9 under both physiological and pathophysiological conditions, which might provide a novel treatment approach for MC activation-related diseases.

Objective: Cardiomyocyte senescence is an important contributor to cardiovascular diseases and can be induced by stressors including DNA damage, oxidative stress, mitochondrial dysfunction, epigenetic regulation, etc. However, the underlying mechanisms for the development of cardiomyocyte senescence remain largely unknown. Sulfur dioxide (SO2) is produced endogenously by aspartate aminotransferase 2 (AAT2) catalysis and plays an important regulatory role in the development of cardiovascular diseases. The present study aimed to explore the effect of endogenous SO2 on cardiomyocyte senescence and the underlying molecular mechanisms. Approach and results: We interestingly found a substantial reduction in the expression of AAT2 in the heart of aged mice in comparison to young mice. AAT2-knockdowned cardiomyocytes exhibited reduced SO2 content, elevated expression levels of Tp53, p21Cip/Waf, and p16INk4a, enhanced SA-β-Gal activity, and elevated level of γ-H2AX foci. Notably, supplementation with a SO2 donor ameliorated the spontaneous senescence phenotype and DNA damage caused by AAT2 deficiency in cardiomyocytes. Mechanistically, AAT2 deficiency suppressed the sulphenylation of signal transducer and activator of transcription 3 (STAT3) facilitated its nuclear translocation and DNA-binding capacity. Conversely, a mutation in the cysteine (Cys) 259 residue of STAT3 blocked SO2-induced STAT3 sulphenylation and subsequently prevented the inhibitory effect of SO2 on STAT3-DNA-binding capacity, DNA damage, and cardiomyocyte senescence. Additionally, cardiomyocyte (cm)-specific AAT2 knockout (AAT2cmKO) mice exhibited a deterioration in cardiac function, cardiomegaly, and cardiac aging, whereas supplementation with SO2 donors mitigated the cardiac aging and remodeling phenotypes in AAT2cmKO mice. Conclusion: Downregulation of the endogenous SO2/AAT2 pathway is a crucial pathogenic mechanism underlying cardiomyocyte senescence. Endogenous SO2 modifies STAT3 by sulphenylating Cys259, leading to the inhibition of DNA damage and the protection against cardiomyocyte senescence.

Abstract Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta‐analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near‐infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta‐analysis. Overall, MCI patients exhibited reduced resting‐state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta‐analysis of two studies revealed a significant reduction in resting‐state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD] = −.56; p

With advanced digital technologies as the key support, many scholars and researchers have proposed various random warranty models by integrating mission cycles into the warranty stage. However, these existing warranty models are designed only from the manufacturer’s subjective perspective, ignoring certain consumer requirements. For instance, they overlook a wide range of warranty coverage, the pursuit of reliability improvement rather than mere minimal repair, and the need to limit the delay in repair. To address these consumer requirements, this paper proposes a novel random collaborative preventive maintenance warranty with repair-time threshold (RCPMW-RTT). This model incorporates terms that are jointly designed by manufacturers and consumers to meet specific consumer needs, thereby overcoming the limitations of existing warranty models. The introduction of a repair-time threshold aims to limit the time delay in repairing failures and to compensate for any losses incurred by consumers. Using probability theory, the RCPMW-RTT is evaluated in terms of cost and time, and relevant variants are derived by analyzing key parameters. As an exemplary representation of the RCPMW-RTT, two random replacement policies named the discrete random renewable back replacement (DRRBR) and the discrete random renewable front replacement (DRRFR) are proposed and modelled to ensure reliability after the expiration of the RCPMW-RTT. In both policies, product replacement is triggered either by the occurrence of the first extreme mission cycle or by reaching the limit on the number of non-extreme mission cycles, whichever comes first. Probability theory is used to present cost rates for both policies in order to determine optimal values for decision variables. Finally, numerical analysis is performed on the RCPMW-RTT to reveal hidden variation tendencies and mechanisms; numerical analysis is also performed on the DRRBR and the DRRFR. The numerical results show that the proposed random replacement policies are feasible and unique; the replacement time within the post-warranty coverage increases as the maintenance quality improves and the cost rate can be reduced by setting a smaller repair-time threshold.

Background: Evidence regarding the relationship between dietary calcium intake and severe abdominal aortic calcification (AAC) is limited. Therefore, this study aimed to investigate the association between dietary calcium intake and severe AAC in American adults based on data from the National Health and Nutrition Examination Survey (NHANES). Methods: The present cross-sectional study utilized data from the NHANES 2013–2014, a population-based dataset. Dietary calcium intake was assessed using two 24-h dietary recall interviews. Quantification of the AAC scores was accomplished utilizing the Kauppila score system, whereby severe AAC was defined as having an AAC score greater than 6. We used multivariable logistic regression models, a restricted cubic spline analysis, and a two-piecewise linear regression model to show the effect of calcium intake on severe AAC. Results: Out of the 2640 individuals examined, 10.9% had severe AAC. Following the adjustment for confounding variables, an independent association was discovered between an augmented intake of dietary calcium and the incidence of severe AAC. When comparing individuals in the second quartile (Q2) of dietary calcium intake with those in the lowest quartile (Q1), a decrease in the occurrence of severe AAC was observed (odds ratio: 0.66; 95% confidence interval: 0.44–0.99). Furthermore, the relationship between dietary calcium intake and severe AAC demonstrated an L-shaped pattern, with an inflection point observed at 907.259 mg/day. Subgroup analyses revealed no significant interaction effects. Conclusion: The study revealed that the relationship between dietary calcium intake and severe AAC in American adults is L-shaped, with an inflection point of 907.259 mg/day. Further research is required to confirm this association.

Parkinson’s disease (PD) is featured by movement impairments, including tremors, bradykinesia, muscle stiffness, and imbalance. PD is also associated with many non-motor symptoms, such as cognitive impairments, dementia, and mental disorders. Previous studies identify the associations between PD progression and factors such as α-synuclein aggregation, mitochondrial dysfunction, inflammation, and cell death. The cannabinoid type-2 receptor (CB2 receptor) is a transmembrane G-protein-coupled receptor and has been extensively studied as part of the endocannabinoid system. CB2 receptor is recently emerged as a promising target for anti-inflammatory treatment for neurodegenerative diseases. It is reported to modulate mitochondrial function, oxidative stress, iron transport, and neuroinflammation that contribute to neuronal cell death. Additionally, CB2 receptor possesses the potential to provide feedback on electrophysiological processes, offering new possibilities for PD treatment. This review summarized the mechanisms underlying PD pathogenesis. We also discussed the potential regulatory role played by CB2 receptor in PD.

Abstract Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway‐associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway‐related intermediate metabolites and elevates NADP+/NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR‐212‐5p to upregulate c‐Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR‐212‐5p/c‐Met axis plays a key role in oxidative pentose phosphate pathway‐mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer.

ABSTRACT Bacteria-diatom interactions in the ocean are diverse but usually studied in static conditions, which limits our understanding of their importance in marine ecosystems and biogeochemical cycles. Here, we explored the dynamic interactions between an ubiquitous marine bacterium Alteromonas sp. and a diatom Thalassiosira pseudonana under different nutrient conditions. In oligotrophic conditions, minor shifts in nutrients qualitatively altered the interactions from mutualism during early exponential growth to weak parasitism during the late stationary phase. Organic matter-activated Alteromonas chemotactically swam toward, attached on, and dramatically broke down T. pseudonana cells, leading to an aggressive parasitic behavior with a 95% algicidal rate. Meanwhile, inorganic matter-activated T. pseudonana showed amensalism against Alteromonas, resulting in an ephemeral decrease of bacterial abundance by 27%. Interestingly, when both organics and inorganics were sufficient, Alteromonas suppressed diatom growth by inhibiting the cell division, while the surviving T. pseudonana restored proliferation with a significantly smaller cell size inconducive to bacterial attachment, demonstrating an intense competition. The results further indicated that the algicidal effect of Alteromonas was controlled by the cell-specific protease activity and the number of attached bacteria on the diatom cell surface, both of which were related to nutrient conditions. Since the nature and intensity of bacteria-diatom interaction depend on the composition and richness of nutrients, it mechanistically explains the tripartite relationship among bacterial proliferation, nutrient viability, and algal demise during blooms. The algicidal behavior of copiotrophs also potentially enhances the contribution of a microbial carbon pump to carbon sequestration in the ocean. IMPORTANCE As the major producers and consumers, phytoplankton and bacteria play central roles in marine ecosystems and their interactions show great ecological significance. Whether mutualistic or antagonistic, the interaction between certain phytoplankton and bacterial species is usually seen as a derivative of intrinsic physiological properties and rarely changes. This study demonstrated that the interactions between the ubiquitously co-occurring bacteria and diatom, Alteromonas and Thalassiosira pseudonana, varied with nutrient conditions. They overcame hardship together in oligotrophic seawater but showed antagonistic effects against each other under nutrient amendment. The contact-dependent algicidal behavior of Alteromonas based on protease activity solved the paradox among bacterial proliferation, nutrient viability, and algal demise haunting other known non-contact-dependent algicidal processes and might actually trigger the collapse of algal blooms in situ. The chemotactic and swarming movement of Alteromonas might also contribute greatly to the breakdown of “marine snow,” which could redirect the carbon sequestration pathway in the ocean.

Lithium (Li) is vital to the world economy as an irreplaceable element in new-generation sustainable energy applications. Quantifying Li levels in clay minerals, a key new resource, supports extensive mineralization surveys. The major limitation in these analyses is complete decomposition, which often requires the use of strong acids and is labor-intensive, particularly in batch processing. This paper presents a partial extraction strategy for quantifying Li and multiple elements, employing ammonium hydrogen fluoride to extract from clay minerals while avoiding the use of various strong acids. Following extraction, the efficiency for Li reaches 98.61%, with values ranging from 62.68% to 91.43% for multiple elements including three major elements (Ca, Fe, Mg) and eleven trace elements (Be, Co, Cr, Cu, Ga, Mn, Ni, P, Rb, Sr, V), demonstrating favorable precision (RSD below 7.34%). This approach offers a promising tool for a simple and efficient batch analysis in the survey of mineralization in Li-bearing clay deposits.

BBIBP-CorV exerts efficient protection against SARS-CoV-2 infection. However, waning vaccine-induced humoral immune responses after two-dose vaccination have significantly undermined durable immuno-protection. In this study, we have demonstrated that although anti-spike (S) antibody responses in BBIBP-CorV vaccinees exhibited three serotypes after 6 months, including de novo sero-negative, sero-positive, and sero-decay features, S-specific interferon-γ release as well as Th1 cytokine production in CD4+ and CD8+ T cells were comparable, especially in vaccinees without detectable neutralizing antibodies. Notably, regardless of dramatic increases in humoral immunity after booster vaccination, T cell responses targeting S protein from either wild type or Omicron remained stable before and after booster vaccination in all three serotype vaccinees. No severe cases were observed even in the sero-decay group during the Omicron epidemic in Shanghai. Our results thus illustrate that unlike fluctuating humoral responses, viral-specific T cell responses are extremely stable after booster vaccination. Sustained T cell responses might be dedicated to the rapid restoration of antibody responses after booster vaccination.

PurposeHelicobacter pylori infection is a well-established etiological factor for gastric inflammation and a significant risk factor for the development of gastric cancer. However, the precise relationship between dietary zinc intake and seropositivity for Helicobacter pylori remains uncertain.MethodsThis cross-sectional observational study utilized data from the United States National Health and Nutrition Examination Survey conducted between 1999 and 2000. The study cohort comprised 2,884 adults aged 20 years or older who provided comprehensive 24-h dietary recall data. The presence of Helicobacter pylori infection was confirmed using serum analysis and lgG protein enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression models and generalized additive model (GAM) were employed to explore the potential association between dietary zinc intake and Helicobacter pylori seropositivity.ResultsAdditionally, subgroup analysis was performed to evaluate the robustness of the primary findings. Of the 1,281 participants, 47.8% were male and the average age was 49.5 years. In the fully adjusted model, a statistically significant inverse association between dietary zinc intake and Helicobacter pylori seropositivity was observed [quartile variable, Q4 vs. Q1, odds ratio (OR): 0.72, 95% confidence interval (CI): 0.57–0.91, p = 0.007]. Furthermore, the relationship between dietary zinc intake and Helicobacter pylori seropositivity exhibited an L-shaped pattern, indicating a saturation effect. The results of sensitivity analysis remained consistent and reliable.ConclusionTherefore, this study suggests that higher dietary zinc intake may be associated with a lower prevalence of Helicobacter pylori seropositivity. Notably, this association follows an L-shaped pattern, with a threshold point estimated at 24.925 mg/day.

Variants of SARS-CoV-2 present the potential for differential response and performance to delivered vaccine regimens. Here the authors characterise the neutralising antibody response to the inactivated SARS-CoV-2 vaccine BBIBP-CorV and assess functionality against a range of key SARS-CoV2 variants.

As the exploration and exploitation of deep-sea oil and gas, along with promising polymetallic nodule&sulfides mining, have been developing toward ultra-deep waters, some innovative concepts of marine cable configuration suitable for ultra-deepwater are proposed, such as stepped cable, hybrid cable and double-stepped cable. For deep-water cables with complex configurations, the structural responses become more complicated due to their non-uniform structural properties. Because the distributed buoyancy modules along cable length might introduce more significant local bending segments. Moreover, the impacts of moving boundary, caused by the motions of top vessel and bottom mining vehicle, should be considered. Through combing the finite element simulations with the hydrodynamic models, the dynamic response analysis approach of ultra-deepwater cables is established in this study. Then the double-stepped cable responses, including axial tension, displacement along with the change of overall configurations caused by moving top vessel and bottom mining vehicle, are calculated. Moreover, wave propagation behaviors during cable response are comprehensively examined, and the influences of non-uniform structural properties on cable response and wave propagation are analyzed using the wave propagation theory of structure with axially varying properties based on the Bessel function. The results show that the presented double-stepped cable can provide suitable configurations during the dynamic response, which has good compliance performance and can effectively buffer its response caused by moving boundary excitation. Finally, we found that the response spatial-temporal evolutions present some interesting phenomena, such as the axially non-uniform characteristics lead to non-monotonic changes in response amplitude and wavelength, with local peaks occurring in the low-tension region, owing to the distributed buoyancy modules, along with axially-varying and discontinuous structural properties. And, there exists significant mixed effect coming from both standing waves and traveling waves.

Impaired iron homeostasis has been proven to be one of the critical contributors to the pathology of Parkinson’s disease (PD). Ferritin is considered an intracellular protein responsible for storing cytosolic iron. Recent studies have found that ferritin can be secreted from cells independent of the classical endoplasmic reticulum–Golgi system. However, the precise mechanisms underlying the secretion of ferritin in the brain were not elucidated. In the present study, we demonstrated that the primary cultured astrocytes do have the ability to secrete ferritin, which is enhanced by iron treatment. Increased ferritin secretion was accompanied by increased protein expression of ferritin response to iron stimulation. Further study showed that iron-induced expression and secretion of ferritin could be inhibited by CQ or 3-MA pretreatment. In addition, the knockdown of transient receptor potential mucolipin 1 (TRPML1) antagonized iron-induced ferritin secretion, accompanied by further increased intracellular protein levels of ferritin. Further study demonstrated that ferritin colocalized with LAMP1 in iron-treated astrocytes. On the contrary, ras-associated protein 27a (Rab27a) knockdown further enhanced iron-induced ferritin secretion and decreased intracellular protein levels of ferritin. Furthermore, we also showed that the secretory autophagy protein tripartite motif containing 16 (TRIM16) and sec22b decreased in iron-treated astrocytes. These results suggested that astrocytes might secrete ferritin via TRPML1-mediated exocytosis. This provides new evidence for the mechanisms underlying the secretion of ferritin in primary cultured astrocytes under a high iron environment.

Abstract Background Pulpitis is a common dental disease characterized by sustained inflammation and impaired pulp self-repair. Mesenchymal stem cell-based minimally invasive vital pulp therapy (MSC-miVPT) is a potential treatment method, but its application is limited by the difficulty in acquiring MSCs. We recently revealed the immunomodulatory effects of rat dental follicle stem cells (rDFSCs) on acute lung injury. The present study focused on the paracrine effects of rDFSCs on the inflammation and regeneration of rat injured dental pulp to detect whether DFSCs are a potential candidate for MSC-miVPT. Methods Conditioned medium from rDFSCs (rDFSC-CM) was applied to lipopolysaccharide (LPS)-induced inflammatory rat dental pulp cells (rDPCs). The inflammation and regeneration of rDPCs were detected by RT-qPCR, Western blotting, immunofluorescence staining, Cell Counting Kit-8 (CCK-8) assay, flow cytometry, wound-healing assay, and Masson’s staining. The effects of rDFSC-CM on inflamed rat dental pulp were further evaluated by hematoxylin-eosin and immunohistochemical staining. Results rDFSC-CM downregulated the ERK1/2 and NF-κB signaling pathways, which resulted in suppression of the expression of IL-1β, IL-6, and TNF-α and promotion of the expression of IL-4 and TGF-β, and these findings lead to the attenuation of rDPC inflammation. rDFSC-CM enhanced the in vitro proliferation, migration, and odontogenic differentiation of inflammatory rDPCs and their in vivo ectopic dentinogenesis. Furthermore, rDFSC-CM inhibited inflammatory cell infiltration in rat pulpitis and triggered Runx2 expression in some of the odontoblast-like cells surrounding the injured site, and these effects were conducive to the repair of inflamed dental pulp. Conclusions rDFSC-CM exhibits therapeutic potential by rescuing the regeneration of the inflamed rat dental pulp through an immunomodulatory mechanism, indicating the application prospects of DFSCs in biological regenerative endodontics.

The hull (palea and lemma) is the specific organ of grass florets. Although many genes related to the hull development have been cloned, the genetic mechanisms behind the development are still unclear, and the evolutionary relationship has different explanations and heated arguments between the palea and lemma. In this study, we found a specific mr1 mutant with a reduced palea, showing an enlarged mrp and degraded bop. Phenotype observations and molecular evidences showed that the bop was converted to the mrp-like organ. Our findings first reveal that the bop and mrp are homologous structures, and the palea and lemma are the same whorl floral organs. MR1 may prevent the transformation of the bop into mrp by regulating the expressions of hull identity genes. Meantime, the mr1 mutant showed altered grain size and grain quality, with defective physical and chemical contents. MR1 was controlled by a single recessive gene and was finally located on chromosome 1, with a physical distance of 70 kb. More work will be needed for confirming the target gene of MR1, which would contribute to our understanding of grain formation and the origin between the lemma, bop, and mrp.

Lithium metal batteries (LMBs) are a dazzling star in electrochemical energy storage thanks to their high energy density and low redox potential. However, LMBs have a deadly lithium dendrite problem. Among the various methods for inhibiting lithium dendrites, gel polymer electrolytes (GPEs) possess the advantages of good interfacial compatibility, similar ionic conductivity to liquid electrolytes, and better interfacial tension. In recent years, there have been many reviews of GPEs, but few papers discussed the relationship between GPEs and solid electrolyte interfaces (SEIs). In this review, the mechanisms and advantages of GPEs in inhibiting lithium dendrites are first reviewed. Then, the relationship between GPEs and SEIs is examined. In addition, the effects of GPE preparation methods, plasticizer selections, polymer substrates, and additives on the SEI layer are summarized. Finally, the challenges of using GPEs and SEIs in dendrite suppression are listed and a perspective on GPEs and SEIs is considered.

A conventional way to monitor severe convective weather is using the composite reflectivity of radar as an indicator. For oceanic areas without radar deployment, reconstruction from satellite data is useful. However, those reconstruction models built on a land dataset are not directly applicable to the ocean due to different underlying surfaces. In this study, we built reconstruction models based on U-Net (named STR-UNet) for different underlying surfaces (land, coast, offshore, and sea), and evaluated their applicability to the ocean. Our results suggest that the comprehensive use of land, coast, and offshore datasets should be more suitable for reconstruction in the ocean than using the sea dataset. The comprehensive performances (in terms of RMSE, MAE, POD, CSI, FAR, and BIAS) of the Land-Model, Coast-Model, and Offshore-Model in the ocean are superior to those of the Sea-Model, e.g., with RMSE being 5.61, 6.08, 5.06, and 7.73 in the oceanic area (Region B), respectively. We then analyzed the importance of different types of features on different underlying surfaces for reconstruction by using interpretability methods combined with physical meaning. Overall, satellite cloud-related features are most important, followed by satellite water-related features and satellite temperature-related features. For the transition of the model from land to coast, then offshore, the importance of satellite water-related features gradually increases, while the importance of satellite cloud-related features and satellite temperature-related features gradually decreases. It is worth mentioning that in the offshore region, the importance of satellite water-related features slightly exceeds the importance of satellite cloud-related features. Finally, based on the performance of the case, the results show that the STR-UNet reconstruction models we established can accurately reconstruct the shape, location, intensity, and range of the convective center, achieving the goal of detecting severe convective weather where a radar is not present.

Objectives: The study was designed to explore the role of endogenous gaseous signaling molecule sulfur dioxide (SO2) in the control of cardiomyocyte apoptosis and its molecular mechanisms.Methods: Neonatal mouse cardiac myocytes (NMCMs) and H9c2 cells were used in the cell experiments. The endogenous SO2 pathway including SO2 level and the expression of SO2-generating enzyme aspartate aminotransferase 1/2 (AAT1/2) were detected in NMCMs. The apoptosis of cardiomyocytes was examined by a TUNEL assay. The cleavage and the activity of apoptotic proteins caspase9 and caspase3 were measured. The content of ATP, the opening of mitochondrial permeability transition pore (mPTP), and the cytochrome c (cytc) leakage were detected by immunofluorescence. The sulphenylation of cyclophilin-D (CypD) was detected by biotin switch analysis. The four CypD mutant plasmids in which cysteine sites were mutated to serine were constructed to identify the SO2-affected site in vitro.Results: ISO down-regulated the endogenous SO2/AAT pathway of cardiomyocytes in association with a significant increase in cardiomyocyte apoptosis, demonstrated by the increases in apoptosis, cleaved-caspase3/caspase3 ratio, and caspase3 activity. Furthermore, ISO significantly reduced ATP production in H9c2 cells, but the supplement of SO2 significantly restored the content of ATP. ISO stimulated mPTP opening, resulting in an increase in the release of cytc, which further increased the ratio of cleaved caspase9/caspase9 and enhanced the protein activity of caspase9. While, the supplementation of SO2 reversed the above effects. Mechanistically, SO2 did not affect CypD protein expression, but sulphenylated CypD and inhibited mPTP opening, resulting in an inhibition of cardiomyocyte apoptosis. The C104S mutation in CypD abolished SO2-induced sulphenylation of CypD, and thereby blocked the inhibitory effect of SO2 on the mPTP opening and cardiomyocyte apoptosis.Conclusion: Endogenous SO2 sulphenylated CypD at Cys104 to inhibit mPTP opening, and thus protected against cardiomyocyte apoptosis.

Objective: This study aimed to determine the communicational pattern of gaseous signaling molecules sulfur dioxide (SO2) and nitric oxide (NO) between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), and elucidate the compensatory role and significance of endogenous SO2 in the development of hypertension due to NO deficiency. Approach and results: Blood pressure was monitored by the tail-cuff and implantable physiological signal telemetry in L-nitro-arginine methyl ester (l-NAME)-induced hypertensive mice, and structural alterations of mouse aortic vessels were detected by the elastic fiber staining method. l-NAME-treated mice showed decreased plasma NO levels, increased SO2 levels, vascular remodeling, and increased blood pressure, and application of l-aspartate-β-hydroxamate, which inhibits SO2 production, further aggravated vascular structural remodeling and increased blood pressure. Moreover, in a co-culture system of HAECs and HASMCs, NO from HAECs did not influence aspartate aminotransferase (AAT)1 protein expression but decreased AAT1 activity in HASMCs, thereby resulting in the inhibition of endogenous SO2 production. Furthermore, NO promoted S-nitrosylation of AAT1 protein in HASMCs and purified AAT1 protein. Liquid chromatography with tandem mass spectrometry showed that the Cys192 site of AAT1 purified protein was modified by S-nitrosylation. In contrast, dithiothreitol or C192S mutations in HASMCs blocked NO-induced AAT1 S-nitrosylation and restored AAT1 enzyme activity. Conclusion: Endothelium-derived NO inhibits AAT activity by nitrosylating AAT1 at the Cys192 site and reduces SO2 production in HASMCs. Our findings suggest that SO2 acts as a compensatory defense system to antagonize vascular structural remodeling and hypertension when the endogenous NO pathway is disturbed.

ABSTRACTSince the first report of the coronavirus disease (COVID-19) in late December 2019, the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now widely spread to more than 187 countries and regions. However, it is unclear whether there has been cryptic transmission before these early officially confirmed cases, we therefore retrospectively screened for the SARS-CoV-2 RNA in 1271 nasopharyngeal swab samples, as well as the prevalence of IgM, IgG, and total antibodies against SARS-CoV-2 in 357 matched serum samples collected from hospitalized patients with influenza-like illness between 1 December 2018 and 31 March 2020 in Shanghai Ruijin Hospital. The onset date of the earliest COVID-19 case in this study was 25 January 2020. Before this time point, the presence of SARS-CoV-2 was not observed, which limited the possibility that SARS-CoV-2 has already spread among the population before the large-scale outbreak. Additionally, among 6662 patients with influenza-like illness from 1 December 2017 to 31 March 2020, the overall number of patients positive for influenza and other respiratory viruses during the COVID-19 period decreased significantly when compared with that in the same period of the last two years, reflecting that public health interventions can effectively control the spread of common respiratory viruses.

BackgroundDisruption of the blood–brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis.MethodTwenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge.ResultssCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls.ConclusionOur data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis.

Sulfur dioxide (SO2) has emerged as a physiological relevant signaling molecule that plays a prominent role in regulating vascular functions. However, molecular mechanisms whereby SO2 influences its upper-stream targets have been elusive. Here we show that SO2 may mediate conversion of hydrogen peroxide (H2O2) to a more potent oxidant, peroxymonosulfite, providing a pathway for activation of H2O2 to convert the thiol group of protein cysteine residues to a sulfenic acid group, aka cysteine sulfenylation. By using site-centric chemoproteomics, we quantified >1000 sulfenylation events in vascular smooth muscle cells in response to exogenous SO2. Notably, ~42% of these sulfenylated cysteines are dynamically regulated by SO2, among which is cysteine-64 of Smad3 (Mothers against decapentaplegic homolog 3), a key transcriptional modulator of transforming growth factor β signaling. Sulfenylation of Smad3 at cysteine-64 inhibits its DNA binding activity, while mutation of this site attenuates the protective effects of SO2 on angiotensin II-induced vascular remodeling and hypertension. Taken together, our findings highlight the important role of SO2 in vascular pathophysiology through a redox-dependent mechanism.

Nedd4 family interacting protein 1 (Ndfip1) is an adaptor of Nedd4-family ubiquitin ligases. Experimental results showed that Ndfip1 had a potential neuroprotective effect in neurology diseases. However, the neuroprotective effect and the underlying mechanisms of Ndfip1 in Parkinson's disease (PD) have not yet been fully elucidated. Therefore, in this study, we explored the neuroprotective effect of Ndfip1 against mitochondrial complex I inhibitor rotenone in a human dopaminergic neuroblastoma SH-SY5Y cell line and further elucidated its possible underlying mechanisms. Our results showed that rotenone could induce the up-regulation of α-synuclein (α-syn) in both mRNA and protein levels. The expression of Ndfip1 decreased at 24 h after rotenone treatment. Further study showed that high expression of Ndfip1 could protect SH-SY5Y cells against rotenone-induced neurotoxicity and antagonize the rotenone-induced increase in α-syn protein levels. In addition, high expression of Ndfip1 inhibited rotenone-induced increase in the protein levels of caspase-3 and decrease in tyrosine hydroxylase (TH). Further study showed that Ndfip1 did not affect the protein expression of iron regulatory protein 1 (IRP1), transferrin receptor 1 (TfR1), while antagonized the increase in protein levels of P62 and ferritin L caused by rotenone. Our findings provide specific identification of Ndfip1 proteins to inhibit the increase of α-syn in rotenone-induced SH-SY5Y cells. Ndfip1 might be a new theoretical drug target for the prevention and treatment of PD.

Background: The sudden outbreak of COVID-19 has caused mental stress on healthcare workers (HCW). This study aimed to assess their psychological health status at the peak of COVID-19 and to identify some coping strategies.Methods: A cross-sectional survey study was conducted during the outbreak of COVID-19. The survey was completed by 908/924 HCW (response rate 98.27%) in government-designated hospitals in Guangdong, China. A quality of life (QoL) scale, the Zung Self-Rating Anxiety Scale (SAS), and the Zung Self-Rating Depression Scale (SDS) were used to evaluate their psychological status. Logistic regression models were used to identify the occupational factors related to anxiety or depression.Results: A total of 221 (24.34%) respondents had varying levels of anxiety, and 299 (32.93%) of them had depression. The mean SAS (42.9) and SDS (47.8) scores of HCW indicated that they were in the normal range for both anxiety and depression. Contact with COVID-19 cases or suspected cases, worry about suffering from COVID-19, worry about their family, and dismission during the COVID-19 period were significant work-related contributing factors to the psychological health problems of HCW (all p

Background/Aims: Increasing evidence has demonstrated the novel roles of mesenchymal stem cells (MSCs) in immunotherapy. However, difficulty in acquiring these cells and possible ethical issues limited their application. Recently, we have isolated a unique MSC population from dental follicles with potent stem cell-like properties. This study focused on the effects of dental follicle stem cells (DFSCs) on macrophage activation and polarization to determine their role in immunomodulation and to test if DFSCs are a promising cell source for MSC-based immunotherapy. Methods: Rat acute lung injury (ALI) models induced by Lipopolysaccharide (LPS) were applied to test the immune-modulatory effects of DFSC/DFSC-CM in vivo. The pulmonary permeability was determined by the dry / wet weight ratios of the left upper lung lobe. The lung histopathological damage was graded on a 0 to 4+ scale. And the inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were tested by ELISA. Then we established LPS-induced inflamed macrophage models in vitro. Inflammatory cytokine production and polarization marker expression were measured by RT-qPCR, ELISA, western blot and flow cytometric analysis in macrophages following DFSC-CM treatment. The paracrine factors in DFSC-CM were revealed by a RayBiotech Protein Array. Thereafter, neutralization studies were performed to confirm the potential immune regulators in DFSC-CM. Results: The DFSC/DFSC-CM not only attenuated histopathological damage and pulmonary permeability, but also downregulated pro-inflammatory cytokines MCP-1, IL-1, IL-6 and TNF-α, and upregulated anti-inflammatory cytokine IL-10 in BALF. Immunofluorescence staining revealed the increased expression of macrophage M2 marker Arg-1. Further in vitro study revealed that macrophages switched to an anti-inflammatory M2 phenotype when co-cultured with DFSC-CM, characterized by suppressed production of pro-inflammatory cytokines MCP-1, IL-1, IL-6, TNF-α and M1-polarizing markers iNOS and CD86; and increased expression of the anti-inflammatory cytokine IL-10 and the M2-polarizing markers Arg-1 and CD163. A RayBiotech Protein Array revealed 42 differentially expressed (> 2-fold) paracrine factors in DFSC-CM compared with the serum-free Ham’s F-12K medium, among which TGF-β3 and Thrombospondin-1 (TSP-1) were upregulated by 18- and 105-fold, respectively. Neutralization studies confirmed the immunoregulatory roles of TGF-β3 and TSP-1 in macrophage activation and polarization. Conclusion: These results indicated that DFSCs can reprogram macrophages into the anti-inflammatory M2 phenotype, the paracrine factors TGF-β3 and TSP-1 may be one of the underlying mechanisms. This study supports the hypothesis that DFSCs are promising for MSC-based immunotherapy.

The current study examined a multiple mediator model based on the control-value theory. A sample of 433 Chinese junior middle school students participated in questionnaires assessing teacher-student relationships (TSRs), academic emotions, academic value (AV), and academic self-efficacy (ASE). English test scores were collected as an indicator of students' English academic performance. The results indicated the following: (a) for academic enjoyment, the TSR has an effect on academic achievement through the chain intermediary of AV and ASE; (b) for academic relaxation, the TSR has an effect on English academic achievement through the single intermediary of academic relaxation and the chain intermediary of AV, ASE, and academic relaxation; (c) for academic anxiety, the TSR has an effect on English academic achievement through the single intermediary of AV, the single intermediary of academic anxiety, and the chain intermediary of AV, ASE, and academic anxiety; (d) for academic boredom, the TSR has an effect on English academic achievement through the single intermediary of academic boredom. These findings enrich the relevant research on the control-value theory and provide important insights for improving students' English academic achievement.

Endogenous hydrogen sulfide (H2S) and sulfur dioxide (SO2) are regarded as important regulators to control endothelial cell function and protect endothelial cell against various injuries. In our present study, we aimed to investigate the effect of endogenous H2S on the SO2 generation in the endothelial cells and explore its significance in the endothelial inflammation in vitro and in vivo. The human umbilical vein endothelial cell (HUVEC) line (EA.hy926), primary HUVECs, primary rat pulmonary artery endothelial cells (RPAECs), and purified aspartate aminotransferase (AAT) protein from pig heart were used for in vitro experiments. A rat model of monocrotaline (MCT)-induced pulmonary vascular inflammation was used for in vivo experiments. We found that endogenous H2S deficiency caused by cystathionine-γ-lyase (CSE) knockdown increased endogenous SO2 level in endothelial cells and enhanced the enzymatic activity of AAT, a major SO2 synthesis enzyme, without affecting the expressions of AAT1 and AAT2. While H2S donor could reverse the CSE knockdown-induced increase in the endogenous SO2 level and AAT activity. Moreover, H2S donor directly inhibited the activity of purified AAT protein, which was reversed by a thiol reductant DTT. Mechanistically, H2S donor sulfhydrated the purified AAT1/2 protein and rescued the decrease in the sulfhydration of AAT1/2 protein in the CSE knockdown endothelial cells. Furthermore, an AAT inhibitor l-aspartate-β-hydroxamate (HDX), which blocked the upregulation of endogenous SO2/AAT generation induced by CSE knockdown, aggravated CSE knockdown-activated nuclear factor-κB pathway in the endothelial cells and its downstream inflammatory factors including ICAM-1, TNF-α, and IL-6. In in vivo experiment, H2S donor restored the deficiency of endogenous H2S production induced by MCT, and reversed the upregulation of endogenous SO2/AAT pathway via sulfhydrating AAT1 and AAT2. In accordance with the results of the in vitro experiment, HDX exacerbated the pulmonary vascular inflammation induced by the broken endogenous H2S production in MCT-treated rat. In conclusion, for the first time, the present study showed that H2S inhibited endogenous SO2 generation by inactivating AAT via the sulfhydration of AAT1/2; and the increased endogenous SO2 generation might play a compensatory role when H2S/CSE pathway was downregulated, thereby exerting protective effects in endothelial inflammatory responses in vitro and in vivo.

Lipases are the most widely employed enzymes in commercial industries. The catalytic mechanism of most lipases involves a step called “interfacial activation”. As interfacial activation can lead to a significant increase in catalytic activity, it is of profound importance in developing lipase immobilization methods. To obtain a potential biocatalyst for industrial biodiesel production, an effective strategy for enhancement of catalytic activity and stability of immobilized lipase was developed. This was performed through the combination of interfacial activation with hybrid magnetic cross-linked lipase aggregates. This biocatalyst was investigated for the immobilization of lipase from Rhizomucor miehei (RML). Under the optimal conditions, the activity recovery of the surfactant-activated magnetic RML cross-linked enzyme aggregates (CLEAs) was as high as 2058%, with a 20-fold improvement over the free RML. Moreover, the immobilized RML showed excellent catalytic performance for the biodiesel reaction at a yield of 93%, and more importantly, could be easily separated from the reaction mixture by simple magnetic decantation, and retained more than 84% of its initial activities after five instances of reuse. This study provides a new and versatile approach for designing and fabricating immobilized lipase with high activation and stability.

One process of layer-by-layer sol-gel deposition without sulfurization was developed. The CZTS films with 1.2 μm and the sulfur ratio of ~48% were prepared and their characteristics were measured. The as-deposited and annealed films are of Kesterite structure. The as-deposited films do not present obvious electric conduction type. However, the annealed 9-LAY-ANN film is p-type conduction and has sheet resistance of 4.08 kΩ/□ and resistivity of 4.896 × 10−1 Ω·cm. The optic energy gap is 1.50 eV for as-deposited films and is 1.46 eV after being annealed. The region deposited by using Lo-Con solution is more compact than that by the Hi-Con solution from SEM morphology images.

The utilization of renewable biomass resources to produce high-value chemicals by enzymatic processes is beneficial for alternative energy production, due to the accelerating depletion of fossil fuels. As immobilization techniques can improve enzyme stability and reusability, a novel magnetic cross-linked cellulase aggregate has been developed and applied for biomass bioconversion. The crosslinked aggregates could purify and immobilize enzymes in a single operation, and could then be combined with magnetic nanoparticles (MNPs), which provides easy separation of the materials. The immobilized cellulase showed a better activity at a wider temperature range and pH values than that of the free cellulase. After six cycles of consecutive reuse, the immobilized cellulase performed successful magnetic separation and retained 74% of its initial activity when carboxylmethyl cellulose (CMC) was used as the model substrate. Furthermore, the structure and morphology of the immobilized cellulase were studied by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the immobilized cellulase was shown to hydrolyze bamboo biomass with a yield of 21%, and was re-used in biomass conversion up to four cycles with 38% activity retention, which indicated that the immobilized enzyme has good potential for biomass applications.