LncRNAs as potential prognosis/diagnosis markers and factors driving drug resistance of osteosarcoma, a review.

Osteosarcoma is a common malignancy that often occurs in children, teenagers and young adults. Although the treatment strategy has improved, the results are still poor for most patients with metastatic or recurrent osteosarcomas. Therefore, it is necessary to identify new and effective prognostic biomarkers and therapeutic targets for diseases. Human genomes contain lncRNAs, transcripts with limited or insufficient capacity to encode proteins. They have been implicated in tumorigenesis, particularly regarding the onset, advancement, resistance to treatment, recurrence and remote dissemination of malignancies. Aberrant lncRNA expression in osteosarcomas has been reported by numerous researchers; lncRNAs have the potential to exhibit either oncogenic or tumor-suppressing behaviors and thus, to govern the advancement of this skeletal cancer. They are suspected to influence osteosarcoma cell growth, replication, invasion, migration, remote dissemination and programmed cell death. Additionally, they have been recognized as clinical markers, and may participate in the development of multidrug resistance. Therefore, the study of lncRNAs in the growth, metastasis, treatment and prognosis of osteosarcoma is very important for the active prevention and treatment of osteosarcoma. Consequently, this work reviews the functions of lncRNAs.

Consistent Thermal Conductivities of Spring-Like Structured Polydimethylsiloxane Composites under Large Deformation.

Flexible and highly thermally conductive materials with consistent thermal conductivity (λ) during large deformation are urgently required to address the heat accumulation in flexible electronics. In this study, spring-like thermal conduction pathways of silver nanowire (S-AgNW) fabricated by 3D printing are compounded with polydimethylsiloxane (PDMS) to prepare S-AgNW/PDMS composites with excellent and consistent λ during deformation. The S-AgNW/PDMS composites exhibit a λ of 7.63 W m-1 K-1 at an AgNW amount of 20 vol%, which is ≈42 times that of PDMS (0.18 W m-1 K-1) and higher than that of AgNW/PDMS composites with the same amount and random dispersion of AgNW (R-AgNW/PDMS) (5.37 W m-1 K-1). Variations in the λ of 20 vol% S-AgNW/PDMS composites are less than 2% under a deformation of 200% elongation, 50% compression, or 180° bending, which benefits from the large deformation characteristics of S-AgNW. The heat-transfer coefficient (0.29 W cm-2 K-1) of 20 vol% S-AgNW/PDMS composites is ≈1.3 times that of the 20 vol% R-AgNW/PDMS composites, which reduces the temperature of a full-stressed central processing unit by 6.8 °C compared to that using the 20 vol% R-AgNW/PDMS composites as a thermally conductive material in the central processing unit.

EBF1-COX4I2 signaling axis promotes a myofibroblast-like phenotype in cancer-associated fibroblasts (CAFs) and is associated with an immunosuppressive microenvironment.

Immunotherapy has limited response rates in colorectal cancer (CRC) due to an immunosuppressive tumor microenvironment (TME). Combining transcriptome sequencing, clinical specimens, and functional experiments, we identified a unique group of CAF subpopulations (COX4I2 + ) with inhibited mitochondrial respiration and enhanced glycolysis. Through bioinformatics predictions and luciferase reporter assays, we determined that EBF1 can upstreamly regulate COX4I2 transcription. COX4I2 + CAFs functionally and phenotypically resemble myofibroblasts, are important for the formation of the fibrotic TME, and are capable of activating the M2 phenotype of macrophages. In vitro experiments demonstrated that COX4I2 + CAFs promote immunosuppressive TME by blocking CD8 + T cell infiltration and inducing CD8 + T cell dysfunction. Using multiple independent cohorts, we also found a strong correlation between the immunotherapy response rate of CRC patients and COX4I2 expression in their tumors. Our results identify a CAF subpopulation characterized by activation of the EBF1-COX4I2 axis, and this group of CAFs can be targeted to improve cancer immunotherapy outcomes.

Early detection of gray blight in tea leaves and rapid screening of resistance varieties by hyperspectral imaging technology.

BACKGROUND: Gray blight (GB) is a significant disease of tea leaves, posing a severe threat to both the yield and quality. In this study, the process of leaf infection by a pathogenic isolate of the GB disease (DDZ-6) was simulated. Hyperspectral images of normal leaves, infected leaves without symptoms, and infected leaves with mild and moderate symptoms were collected. Combining convolution neural network (CNN), long short-term memory (LSTM), and support vector machine (SVM) algorithms, the early detection model of GB disease, and the rapid screening model of resistant varieties were established. The generality of this method was verified by collecting datasets under field conditions. RESULTS: The visible red-light band demonstrated a pronounced responsiveness to GB disease, with three sensitive bands identified through rigorous screening processes utilizing uninformative variable elimination (UVE), competitive adaptive reweighted sampling (CARS), and the successive projections algorithm (SPA). The 693, 727, and 766 nm bands emerged as highly sensitive indicators of GB. Under ideal conditions, the CARS-LSTM model excelled in early detection of GB, achieving an accuracy of 92.6%. However, under field conditions, the combination of 693 and 727 nm bands integrated with a CNN provided the most effective early detection model, attaining an accuracy of 87.8%. For screening tea varieties resistant to GB, the SPA-LSTM model excelled, achieving an accuracy of 82.9%. CONCLUSION: This study provides a core algorithm for a GB disease instrument with detection capabilities, which is of great importance for the early prevention of GB disease in tea plantations. © 2024 Society of Chemical Industry.

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.

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.

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 were collected from 553 nursing home workers from 37 nursing home facilities in 5 states during fall of 2022. Responses to the Maslach Burnout Inventory and Grief Support Health Care Scale 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 subscales 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, whereas 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.

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.

Occurrence and distribution of antibiotic resistance genes in urban rivers with black-odor water of Harbin, China.

Antibiotic resistance gene contamination in polluted rivers remains a widely acknowledged environmental issue. This study focused on investigating the contamination conditions of antibiotic resistance genes (ARGs) in Harbin's urban black-odor rivers, specifically Dongfeng Ditch and Hejia Ditch. The research employed a SmartChip Real-Time PCR System to explore the types, abundance, and distribution of ARGs in diverse habitats, such as surface water and sediment. Additionally, the study examined the correlation of ARGs with mobile genetic elements (MGEs) and various environmental factors. It was found that antibiotic resistance genes were prevalent in both water and sediment within the black-odor ditches. The dominant types of ARGs identified included aminoglycoside, sulfonamide, multidrug-resistant, and ß-lactam ARGs. Notably, the top four ARGs, in terms of relative abundance, were sul1, fox5, qacEdelta1-01 and aadA1. Most categories of ARGs have significant positive connections with MGEs, indicating that the enrichment and spreading of ARGs in rivers are closely related to MGEs. Based on the correlation analysis, it is found that environmental factors such as dissolved oxygen (DO), ammonia nitrogen (NH4-N), and phosphate (PO4-P) played a substantial role in influencing the variations observed in ARGs. By employing a risk assessment framework based on the human association, host pathogenicity, and mobility of ARGs, the identification of seven high-risk ARGs was achieved. In addition, it is important to assess the environmental risk of ARGs from multiple perspectives (abundance,detection rateand mobility). This study provides a significant reference regarding the presence of ARGs contamination in urban inland black-odor rivers, essential for assessing the health risks associated with ARGs and devising strategies to mitigate the threat of antibiotic resistance.

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.

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.

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.

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.

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.

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.

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.