WRKY47 transcription factor modulates leaf senescence through regulating PCD-associated genes in Arabidopsis.

Transcription factors play crucial roles in almost all physiological processes including leaf senescence. Cell death is a typical symptom appearing in senescing leaves, which is also classified as developmental programmed cell death (PCD). However, the link between PCD and leaf senescence still remains unclear. Here, we found a WRKY transcription factor WRKY47 positively modulates age-dependent leaf senescence in Arabidopsis (Arabidopsis thaliana). WRKY47 was expressed preferentially in senescing leaves. A subcellular localization assay indicated that WRKY47 was exclusively localized in nuclei. Overexpression of WRKY47 showed precocious leaf senescence, with less chlorophyll content and higher electrolyte leakage, but loss-of-function mutants of WRKY47 delayed this biological process. Through qRT-PCR and dual luciferase reporter assays, we found that WRKY47 could activate the expression of senescence-associated genes (SAGs) and PCD-associated genes to regulate leaf senescence. Furthermore, through electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-qPCR, WRKY47 was found to bind to W-box fragments in promoter regions of BFN1 (Bifunctional Nuclease 1) and MC6 (Metacaspase 6) directly. In general, our research revealed that WRKY47 regulates age-dependent leaf senescence by activating the transcription of two PCD-associated genes.

The casein in sheep milk processed by cold plasma technology: Phosphorylation degree, functional properties, oxidation characteristics, and structure.

Cold plasma is a nonthermal process used for modification of proteins. The objective of this study was to investigate the effect of cold plasma technology on the phosphorylation degree, functional and oxidation properties, and structure of casein in sheep milk. Cold plasma treatment for 3-4 min significantly increased the phosphorylation degree and enhanced functional properties, including water-holding capacity, solubility, foaming capacity and stability. Besides, plasma treatment time profoundly influenced protein oxidation, and treatment for 2 and 3 min could be the preferred conditions to minimize protein change. The protein conformation became unstable with the extension of treatment time. Particle size, polymer dispersity index, and microscopy images confirmed alterations in the protein structure following 3 min of processing. Consequently, using cold plasma treatment at 10 kHz 20 kV for 3 min could be suggested for milk protein modification, providing a basis for the application of high-quality caseins in food processing.

Gallic Acid Alleviates Psoriasis Keratinization and Inflammation by Regulating BRD4 Expression.

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.

Sucralose triggers insulin resistance leading to follicular dysplasia in mice.

Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.

Photothermophoretic Splitting of Gold Nanoparticles for Plasmonic Nanopores and Nanonets Sensing.

Optical processing of single plasmonic nanoparticles reinvents the way of high-density information storage, high-performance sensing, and high-definition displays. However, such laser-fabricated nanoplasmonics with well-defined hot spots remain elusive due to the diffraction limit of light. Here we show Au nanoparticle (NP) decorated nanopores can be facilely generated with photothermal splitting of single Au NPs embedded in a silica matrix. The extremely high local temperature induced by plasmonic heating renders gradients of the temperature and surface tension around the Au NP, which drives the nanoscale thermophoretic and Marangoni flow of molten Au/silica. As a result, a nanopore decorated with fragmented Au NPs is formed in the silica film, which presents much stronger surface-enhanced Raman scattering as compared to a single Au NP due to the emergence of hot spots. This strategy can be used to generate plasmonic nanopores of various sizes in the silicon nitride (SiNx) films, which further transforms into nanonets at ambient conditions via light-induced reconstruction of silicon nitride membrane. These nanonets can serve as a robust platform for single particle trapping and analysis.

A Comparative Study of Organizational Grief Support and Burnout among Nursing Home Staff.

BACKGROUND AND OBJECTIVES: The purpose of this study was to examine the relationship between dimensions of grief support (recognition of the relationship, acknowledgement of the loss, and inclusion of the griever) and aspects of burnout (emotional exhaustion, depersonalization, and personal accomplishment) among nursing home staff. RESEARCH DESIGN AND METHODS: Data was collected from 553 nursing home (NH) workers from 37 nursing home facilities in 5 states during fall 2022. Responses to the Maslach Burnout Inventory (MBI) and Grief Support Health Care Scale (GSHCS) were analyzed for this study. RESULTS: The study found that recognizing the relationship with deceased patients led to a decrease in exhaustion and depersonalization among workers, while simultaneously enhancing their sense of personal accomplishment. Including the griever in the support process lowered all burnout sub-scales for nursing home staff. Acknowledging the loss was associated with higher levels of personal accomplishment. Registered nurses, nurse practitioners, and physicians experienced higher levels of exhaustion and depersonalization compared to other nursing home staff. Behavioral health workers had the highest personal accomplishment, while direct support workers reported the lowest. DISCUSSION AND IMPLICATIONS: These findings have important implications for improving the well-being of nursing home staff, emphasizing the importance of organizational grief support, and tailored interventions to address burnout among different healthcare provider roles in nursing homes.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK.

The efficient clinical treatment of oral squamous cell carcinoma (OSCC) is still a challenge that demands the development of effective new drugs. Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors, however, not much is known about the influence of phenformin on OSCC cells. We found that phenformin suppresses OSCC cell proliferation, and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro. RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4 (DNA damage inducible transcript 4) and NIBAN1 (niban apoptosis regulator 1). We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy. Further, the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4 (activation transcription factor 4), which was induced by phenformin treatment in OSCC cells. Mechanistically, these results revealed that phenformin triggers endoplasmic reticulum (ER) stress to activate PERK (protein kinase R-like ER kinase), which phosphorylates the transitional initial factor eIF2, and the increased phosphorylation of eIF2 leads to the increased translation of ATF4. In summary, we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth. Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Fluorescent Molybdenum Disulfide Quantum Dots for Sensitive Detecting Curcumin in Food Samples through FRET Mechanism.

A selective and sensitive fluorometric assay was developed for specific determination of curcumin (Cur) based on fluorescence resonance energy transfer (FRET) between molybdenum disulfide quantum dots (MoS2 QDs) and Cur. The MoS2 QDs were prepared via a one-step hydrothermal protocol using sodium molybdate dihydrate, L-cysteine (Cys) as precursors, and sodium cholate (SC) as a modification agent. The as-prepared MoS2 QDs possessed maximum fluorescence emission at 460 nm with a 20% of fluorescence quantum yield (FQY). It was found that the fluorescence of MoS2 QDs could be quantitatively quenched by Cur through FRET mechanism. Therefore, Cur could be detected in the range of 0.1-20 µg mL- 1 with a detection limit of 5 ng mL- 1. Additionally, the developed MoS2 QDs based fluorescent assay has been successfully applied for real food sample analysis with satisfactory results.

The Laccase Family Gene CsLAC37 Participates in Resistance to Colletotrichum gloeosporioides Infection in Tea Plants.

Fungal attacks have become a major obstacle in tea plantations. Colletotrichum gloeosporioides is one of the most devastating fungal pathogens in tea plantations that can severely affect tea yield and quality. However, the molecular mechanism of resistance genes involved in anthracnose is still largely unknown in tea plants. Here, we found that the laccase gene CsLAC37 was involved in the response to fungal infection based on a transcriptome analysis. The full-length CDS of CsLAC37 was cloned, and its protein sequence had the closest relationship with the Arabidopsis AtLAC15 protein compared to other AtLACs. Tissue-specific expression analysis showed that CsLAC37 had higher expression levels in mature leaves and stems than in the other tissues. Subcellular localization showed that the CsLAC37 protein was predominantly localized in the cell membrane. The expression levels of CsLAC37 were upregulated at different time points under cold, salt, SA, and ABA treatments. qRT-PCR confirmed that CsLAC37 responded to both Pestalotiopsis-like species and C. gloeosporioides infections. Functional validation showed that the hydrogen peroxide (H2O2) content increased significantly, and POD activity decreased in leaves after antisense oligonucleotide (AsODN) treatment compared to the controls. The results demonstrated that CsLAC37 may play an important role in resistance to anthracnose, and the findings provide a theoretical foundation for molecular breeding of tea varieties with resistance to fungal diseases.

Thin-Film-Assisted Photothermal Deformation of Gold Nanoparticles: A Facile and In-Situ Strategy for Single-Plate-Based Devices.

Optical-induced shape transformation of single nanoparticles on substrates has shown benefits of simplicity and regularity for single-particle device fabrication and on-chip integration. However, most of the existing strategies are based on wet chemical growth and etching, which could lead to surface contamination with limited local selectivity and device compatibility. Shape deformation via the photothermal effect can overcome these issues but has limited versatility and tunability largely due to the high surface tension of the molten droplet. Here we show gold nanoparticles (Au NPs) can drastically transform into nanoplates under the irradiation of a continuous wave laser (446 nm). We reveal the dielectric thin film underneath the molten Au is critical in deforming the NP into faceted nanoplate under the drive of photothermophoretic forces, which is sufficient to counteract the surface tension of the molten droplet. Both experimental evidence and simulations support this thin-film-assisted photothermal deformation mechanism, which is local selective and generally applicable to differently shaped Au NPs. It provides a facile and robust strategy for single-plate-based device applications.

Strip loaded waveguide amplifiers based on erbium-doped nanocomposites with 17†dB internal net gain.

We propose a strip loaded amplifier employing SU-8 as the loaded waveguide and nanoparticles (NPs)-polymethyl methacrylate (PMMA) as the cladding layer. By leveraging the undoped SU-8 loaded waveguide, the polymer waveguide amplifier accomplished remarkably low transmission losses, reaching as low as 1.8 dB/cm at 1530 nm. We prepared NPs-PMMA nanocomposite by utilizing NaLu0.1Y0.7F4: Er3+, Yb3+ @NaLuF4 core-shell nanoparticles, which exhibited a significantly enhanced lifetime of 6.15 ms. An internal net gain of up to 17.7 dB was achieved on a strip loaded waveguide with a length as short as 0.5 cm when the on-chip pump power was 77 mW. Signal enhancement (SE) was measured at different wavelengths, revealing that the strip loaded waveguide exhibited broadband SE ranging from 1510 nm to 1570 nm, covering the C-band. To the best of our knowledge, this work has achieved the highest gain results reported thus far on a polymer matrix and provides an efficient method for optical amplification in passive devices on silicon and Si3N4 platforms, leveraging the ease of integration of polymer materials with diverse photonic platforms.

Toward Bicalutamide Analogues with High Structural Diversity Using Catalytic Asymmetric Oxohydroxylation.

A catalytic enantioselective synthesis of bicalutamide derivatives with promising potentials in prostate cancer treatment has been disclosed. The key intermediates, α-hydroxy-ß-keto esters, were efficiently constructed through cinchoninium-mediated asymmetric oxohydroxylation of easily accessible alkenes with potassium permanganate. Good yields and high levels of asymmetric induction are achieved. This method provides a new synthetic route to bicalutamide analogues with high structural diversity, which will beneficially support subsequent structure-activity relationship studies and boost prostate cancer drug development.

A preliminary report on the exploration of salivary bacterial diversity by the multiplex SNaPshot assay.

Salivary bacterial community composition is associated with the host's internal and environmental factors, which have potential applications in forensic practice. The 16S rRNA gene sequencing is the most commonly used strategy for detecting salivary bacterial diversity; however, its platforms are not compatible with capillary electrophoresis (CE) platforms commonly used for forensic applications. Therefore, we attempted to detect the salivary bacterial diversity using a single nucleotide polymorphism (SNP) assay. Salivary bacterial diversity varies among diverse geographic locations, making it a potential supplementary biomarker for forensic geographic sourcing. To evaluate the performance of the multiplex SNaPshot assay, saliva samples from three geographic locations in China were analyzed using the multiplex SNaPshot assay and 16S rRNA gene sequencing. We screened SNPs from two high-relative-abundance salivary genera (Streptococcus and Veillonella) to construct a multiplex SNaPshot system that can be used on the CE platform. The stability and sensitivity of the multiplex SNaPshot system were also tested. A random forest classification model was used to classify samples from different regions to explore the ability of salivary bacteria to discriminate between geographic sources. Six bacterial SNPs were screened and a multiplex SNaPshot system was constructed. The stability results showed that the typing of salivary stains that were placed indoors for different days was not affected in this study. Two-thirds of mocked salivary stain samples showed more than 90% of typing results obtained for salivary stain samples with an input of 0.1 µl saliva. The results of principal coordinate analysis based on salivary bacterial diversity showed significant differences between samples from the three different geographic locations. The accuracy of the random forest classification was 66.67% based on the multiplex SNaPshot assay and 83.33% based on the 16S rRNA gene sequencing. In conclusion, this is the first attempt to detect salivary bacterial diversity using a multiplex SNaPshot bacterial SNP assay. The geographic difference in human salivary bacterial community composition was significant, as revealed by the multiplex SNaPshot assay; however, its performance in discriminating geographic sources was lower than that of 16S rRNA gene sequencing. This strategy based on bacterial SNP loci may favor the detection of human bacterial diversity in common forensic laboratories but requires further exploration in larger sample sizes and more bacterial SNP loci.

Care stressors and perceived stress among family caregivers of Chinese older adults with disabilities: The mediation effect of resilience.

OBJECTIVES: Guided by the Stress Process Model, this study examined the mediating effect of resilience on the relationship between care stressors and perceived caregiving stress. METHODS: Data were based on 234 older adults with disabilities and their caregivers from 6 urban districts and 6 rural counties from Jinan, China. Descriptive analysis, analysis of variance, ordinary least squares regression, and mediation analysis were performed. RESULTS: Perceived stress among family caregivers of Chinese older adults with disabilities was affected by the physical and mental health of both themselves and the care recipients, as well as care intensity and financial difficulties. Resilience played a partial mediating role in the associations among three stressors (i.e. older adults' disability levels, number of chronic diseases, and caregivers' self-reported mental) and perceived caregiving stress. CONCLUSIONS: Enhanced resilience aids caregivers' adaptation to their roles, suggesting the need for societal, spiritual, emotional, and behavioral resilience training.

Meta-analysis on the impact of immune senescence: Unravelling the interplay in cutaneous wound healing and lung cancer progression.

The primary objective of this meta-analysis was to provide the comprehensive understanding of the intricate correlation that existed between immune senescence and its effects on the advancement of lung cancer as well as recovery of cutaneous wounds. By conducting this systematic review of six rigorous studies utilizing databases such as PubMed and Web of Science, this research examined the multitude of facets pertaining to immune aging and consequences it bear on the health outcomes. The incorporated studies encompassed wide range of geographical and methodological viewpoints, with the specific emphasis on non-small-cell lung cancer and diverse scenarios related to wound recovery. This analysis synthesized discoveries regarding therapeutic responses, cellular and molecular mechanisms and impact of lifestyle factors on immune senescence. The findings suggested that immune senescence has substantial impact on the effectiveness of treatments for lung cancer and cutaneous wounds healing process; therefore, targeted therapies and holistic approaches may be able to mitigate these effects. By following the revised PRISMA guidelines, this meta-analysis guarantee thorough and ethically sound methodology for amalgamating pre-existing literature. The study concluded by emphasizing the critical nature of comprehending immune senescence in the context of clinical practice and proposed avenues for further investigation to enhance health results among the elderly.

The emerging roles of irisin in vascular calcification.

Vascular calcification is a common accompanying pathological change in many chronic diseases, which is caused by calcium deposition in the blood vessel wall and leads to abnormal blood vessel function. With the progress of medical technology, the diagnosis rate of vascular calcification has explosively increased. However, due to its mechanism's complexity, no effective drug can relieve or even reverse vascular calcification. Irisin is a myogenic cytokine regulating adipose tissue browning, energy metabolism, glucose metabolism, and other physiological processes. Previous studies have shown that irisin could serve as a predictor for vascular calcification, and protect against hypertension, diabetes, chronic kidney disease, and other risk factors for vascular calcification. In terms of mechanism, it improves vascular endothelial dysfunction and phenotypic transformation of vascular smooth muscle cells. All the above evidence suggests that irisin plays a predictive and protective role in vascular calcification. In this review, we summarize the association of irisin to the related risk factors for vascular calcification and mainly explore the role of irisin in vascular calcification.