[The rs2564978(T) Allele Associated with Severe Influenza A Disrupts the Binding Site for Myeloid Differentiation Factor PU.1 and Reduces CD55/DAF Gene Promoter Activity in Macrophages].

The complement inhibitor CD55/DAF is expressed on many cell types. Dysregulation of CD55 expression is associated with increased disease severity in influenza A infection and vascular complications in pathologies that involve excessive activation of the complement system. A luciferase reporter system was used to functionally analyze the single nucleotide polymorphism rs2564978 in the U937 human promonocytic cell line. The polymorphism is in the promoter of the CD55 gene, and its minor allele T is associated with a severe course of influenza A(H1N1)pdm09. A decreased activity of the CD55 promoter carrying the minor rs2564978(T) allele was observed in activated U937 cells, which provide a cell model of human macrophages. Using bioinformatics resources, PU.1 was identified as a potential transcription factor that may bind to the CD55 promoter at the rs2564978 site in an allele-specific manner. The involvement of PU.1 in modulating CD55 promoter activity was verified by a PU.1 genetic knockdown with small interfering RNAs under specific monocyte activation conditions.

Modelling drought in South Africa: meteorological insights and predictive parameters.

South Africa has grappled with recurring drought scenarios for over two decades, leading to substantial economic losses. Droughts in the Western Cape between 2015 and 2018, especially in Cape Town was declared a national disaster, resulting in the strict water rationing and the "day zero" effect. This study presents a set of simulations for predicting drought over South Africa using Artificial Neural Network (ANN), using Standard Precipitation Index (SPI) as the drought indicator in line with the recommendations of the World Meteorological Organization (WMO). Furthermore, different meteorological variables and an aerosol parameter were used to develop the drought set in four distinct locations in South Africa for a 21-year period. That data used include relative humidity (rh), temperature (tp), soil wetness (sw), evapotranspiration (et), evaporation (ev) sea surface temperature (st), and aerosol optical depth (aa). The obtained R2 values for SPI3 ranged from 0.49 to 0.84 and from 0.22 to 0.84 for SPI6 at Spring Bok, Umtata 0.83 to 0.95 for SPI3, and 0.61 to 0.87 for SPI6; Cape Town displayed R2 values from 0.78 to 0.94 for SPI3 and 0.57 to 0.95 for SPI6, while Upington had 0.77-0.95 for SPI3, and 0.78-0.92 for SPI6. These findings underscore the significance of evapotranspiration (et) as a pivotal parameter in drought simulation. Additionally, the predictive accuracy of these parameter combinations varied distinctly across different locations, even for the same set of parameters. This implies that there is no single universal scheme for drought prediction. Hence, the results are important for simulating future drought scenarios at different parts of South Africa. Finally, this study shows that ANN is an effective tool that can be utilized for drought studies and simulations.

A novel approach to produce soy protein isolate: Direct enzymatic hydrolysis of high-temperature soybean meal using proteinase produced by microbial solid-state fermentation.

This study proposed a novel extraction method for soy protein isolate, which involved solid-state fermentation of high-temperature soybean meal. The proteinases secreted by microorganisms acted on the high-temperature soybean meal, making the SPI easier to extract. The study concludes that Bacillus amyloliquefaciens subsp. plantarum CICC 10265 could be used for solid-state fermentation of soybean meal, and the fermentation effect was good, with a yield of 41.91 % for SPI. Compared to the direct extraction of SPI from high-temperature soybean meal, the yield had increased by 130.19 %. Meanwhile, we also conducted research on the losses during the SPI extraction process. Through experiments, the study identified the patterns of protease activity changes and microbial colony growth during solid-state fermentation of soybean meal by Bacillus amyloliquefaciens subsp. plantarum CICC 10265. It was concluded that extracting SPI after 8 h of fermentation is more suitable. The experimental results indicated that the total amino acid content of SPI extracted from fermented soybean meal was 2.1 % higher compared to SPI extracted from low-temperature soybean meal. The extracted SPI also met the microbial standards.

Co-encapsulation of borage seed oil and peppermint oil blends within ultrasound-assisted soy protein isolate/purity gum ultra complex nanoparticles: Fabrication, structural interaction mechanisms, and in vitro digestion studies.

This study aimed at co-encapsulating borage seed oil (BSO)- and peppermint oil (PO) blends in ultrasound-assisted complex nanoparticles stabilized by soy protein isolate (SPI) and purity gum ultra (PGU) in different ratios: SPI/PGU-1:0 (NP1), 0:1 (NP2), 1:1 (NP3), 1:3 (NP4), and 3:1 (NP5). The BSO- and PO-loaded SPI/PGU complex nanoparticles (BP-loaded SPNPs) coded as NP4 (SPI-PGU-1:3) revealed a zeta potential of -33.27 mV, a PDI of 0.14, and the highest encapsulation efficiency (81.38 %). The main interactions observed among SPI, PGU, BSO, PO, and a blend of BSO and PO, as determined by FTIR and molecular docking, involved hydrophobic effects, electrostatic attraction, and H-bonding. These interactions played crucial roles in the production of BP-loaded SPNPs. XRD results validated the alterations in the structure of BP-loaded SPNPs caused by varying proportions of SPI and PGU. The thermal capacity of BP-loaded SPNPs (NP4), as determined by TGA, exhibited the lowest amount of weight loss compared to other BP-loaded SPNPs. Morphological results revealed that NP4 and NP5 exhibited a spherical surface and two distinguishable layers, indicating successful coating of PGU onto the droplet surface. In addition, BP-loaded SPNPs (NP4) exhibited a higher antioxidant effect due to their improved progressive release and prolonged release of co-encapsulated BSO and PO during in vitro digestion. The comprehensive investigation of the co-encapsulation of BSO and PO in complex nanoparticles, dietary supplements, and double-layered emulsified systems provides valuable insights into the development of functional foods.

Decreased PU.1 expression in mature B cells induces lymphomagenesis.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, accounting for 30% of non-Hodgkin lymphomas. Although comprehensive analysis of genetic abnormalities has led to the classification of lymphomas, the exact mechanism of lymphomagenesis remains elusive. The Ets family transcription factor, PU.1, encoded by Spi1, is essential for the development of myeloid and lymphoid cells. Our previous research illustrated the tumor suppressor function of PU.1 in classical Hodgkin lymphoma and myeloma cells. In the current study, we found that patients with DLBCL exhibited notably reduced PU.1 expression in their lymphoma cells, particularly in the non-germinal center B-cell-like (GCB) subtype. This observation suggests that downregulation of PU.1 may be implicated in DLBCL tumor growth. To further assess PU.1's role in mature B cells in vivo, we generated conditional Spi1 knockout mice using Cγ1-Cre mice. Remarkably, 13 of the 23 knockout mice (56%) showed splenomegaly, lymphadenopathy, or masses, with some having histologically confirmed B-cell lymphomas. In contrast, no wild-type mice developed B-cell lymphoma. In addition, RNA-seq analysis of lymphoma cells from Cγ1-Cre Spi1F/F mice showed high frequency of each monoclonal CDR3 sequence, indicating that these lymphoma cells were monoclonal tumor cells. When these B lymphoma cells were transplanted into immunodeficient recipient mice, all mice died within 3 weeks. Lentiviral-transduced Spi1 rescued 60% of the recipient mice, suggesting that PU.1 has a tumor suppressor function in vivo. Collectively, PU.1 is a tumor suppressor in mature B cells, and decreased PU.1 results in mature B-cell lymphoma development.

A comprehensive analysis and comparison of SPI and SPEI for spatiotemporal drought evaluation.

Assessing drought is crucial for effective water resources management and the development of mitigation strategies. Drought indices serve as indispensable tools in this evaluation process, and choosing an appropriate index is vital for accurate drought assessment. The characteristics and classification of drought depend entirely on the chosen index. Based on the existing literature, the Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) are the most commonly and widely used indices, and there is a significant need for a comprehensive comparison between SPI and SPEI to understand their differences and implications for drought assessment. This research aims to compare SPI and SPEI based on drought indices, characteristics, and classifications using the innovative drought classification matrix (IDCM) for spatiotemporal drought evaluation, and the comparison process is done for events and monthly scales. Also, it aims to investigate the comparison between SPEI obtained from in situ meteorological stations and from the SPEI database. The application and the comparison are presented for Istanbul city between 1951 and 2020. The results show similar variations and high correlation (more than 0.65) between SPI and SPEI. For drought characteristics, there is no consistent relationship between SPI and SPEI at the drought event scale. The outcomes revealed that approximately 60% of the months exhibit consistent drought classifications between the two indices. Finally, it shows a significant difference between SPEI based on in situ meteorological stations and satellite data. The comparison between SPI and SPEI based on different aspects is necessary and essential for drought studies and water resources management.

circE2F1-encoded peptide inhibits circadian machinery essential for nucleotide biosynthesis and tumor progression via repressing SPIB/E2F1 axis.

Circadian clock dominates a variety of biological activities, while its roles and regulatory mechanisms in neuroblastoma (NB), a pediatric extracranial malignancy, still remain largely elusive. Herein, through comprehensive analyses of public datasets, E2F transcription factor 1 (E2F1) and its circular RNA (circE2F1)-encoded 99-amino acid peptide (E2F1-99aa) were identified as vital regulators of circadian machinery essential for purine and pyrimidine biosynthesis during NB progression. Mechanistically, through interaction with Spi-B transcription factor (SPIB), E2F1 was transactivated to up-regulate circadian machinery genes (CRY1 and TIMELESS), resulting in relief of CLOCK/BMAL1-repressed transcription of enzymes (DHODH, PAICS, or PPAT) essential for de novo purine and pyrimidine biosynthesis. The biogenesis of circE2F1 was repressed by eukaryotic translation initiation factor 4A3 (EIF4A3), while E2F1-99aa or its truncated peptide competitively bound to SPIB, leading to decrease in SPIB-E2F1 interaction, circadian machinery and nucleotide biosynthetic gene expression, purine or pyrimidine biosynthesis, tumorigenesis, and aggresiveness of NB cells. In clinical NB cases, high EIF4A3, E2F1 or SPIB expression was correlated with low survival possibility of patients, while lower circE2F1 or E2F1-99aa levels were associated with advanced stages and tumor progression. These results indicate that circE2F1-encoded peptide inhibits circadian machinery essential for nucleotide biosynthesis and tumor progression via repressing SPIB/E2F1 axis.

Single-strand DNA-binding protein suppresses illegitimate recombination in Escherichia coli, acting in synergy with RecQ helicase.

Single-strand DNA-binding proteins SSB/RPA are ubiquitous and essential proteins that bind ssDNA in bacteria/eukaryotes and coordinate DNA metabolic processes such as replication, repair, and recombination. SSB protects ssDNA from degradation by nucleases, while also facilitating/regulating the activity of multiple partner proteins involved in DNA processes. Using Spi- assay, which detects aberrantly excised λ prophage from the E. coli chromosome as a measure of illegitimate recombination (IR) occurrence, we have shown that SSB inhibits IR in several DSB resection pathways. The conditional ssb-1 mutation produced a higher IR increase at the nonpermissive temperature than the recQ inactivation. A double ssb-1 recQ mutant had an even higher level of IR, while showing reduced homologous recombination (HR). Remarkably, the ssb gene overexpression complemented recQ deficiency in suppressing IR, indicating that the SSB function is epistatic to RecQ. Overproduced truncated SSBΔC8 protein, which binds to ssDNA, but does not interact with partner proteins, only partially complemented recQ and ssb-1 mutations, while causing an IR increase in otherwise wild-type bacteria, suggesting that ssDNA binding of SSB is required but not sufficient for effective IR inhibition, which rather entails interaction with RecQ and likely some other protein(s). Our results depict SSB as the main genome caretaker in E. coli, which facilitates HR while inhibiting IR. In enabling high-fidelity DSB repair under physiological conditions SSB is assisted by RecQ helicase, whose activity it controls. Conversely, an excess of SSB renders RecQ redundant for IR suppression.

Assessment of meteorological drought impacts on rainfed agriculture using remote sensing-derived biomass productivity.

Assessing drought impacts is necessary for pursuing sustainable development goals relevant to food security and land degradation. Data availability is a major restriction and remote sensing has been promoted for this purpose. Version 3 of WaPOR has been released in 2023, which provides global coverage of remote sensing-derived water productivity indicators and could allow improved analysis of drought impacts, but validation is still needed. This study explores the utility of remote sensing-derived productivity data from WaPOR as a proxy indicator for agricultural drought impacts. The analysis utilized (1) production surveys, (2) meteorological measurements for drought analysis, and (3) remote sensing-derived gross and net biomass water productivities (GBWP & NBWP) and total biomass production (TBP). All layers were analyzed against the Standardized Precipitation and Standardized Precipitation Evapotranspiration Indices (SPI and SPEI) over drought-vulnerable locations in Irbid and Madaba governorates in Jordan. Strong and significant correlations (R2 0.5-0.8, P < 0.05) were obtained between drought intensities and GBWP and NBWP layers, particularly in the May-Sep periods. These correlations were higher than previously tested remotely sensed indicators for agricultural drought impacts. Water productivity and biomass production averages were lower during drier periods and higher during wet periods, but pairwise testing did not reveal significant differences. There is sufficient evidence that WaPOR data demonstrates behavior that reflects agricultural response to drought, and further assessment in other agroclimatic zones is recommended. This could potentially allow for enhanced evaluation of management strategies, decision support, and policy recommendations for drought mitigation.

Characterization of a Bacterial Keratinolytic Protease for Effective Degradation of Chicken Feather Waste into Feather Protein Hydrolysates.

BACKGROUND: Chicken feathers contribute to large quantities of keratinaceous wastes that pose serious environmental problems and must be catered to properly. Chicken feathers are also a potential source of vital proteins, peptides, and amino acids, which could be used as low-cost animal feeds. Therefore, there has been increasing interest in keratinase-producing microbes for reprocessing and using keratinous biomaterials. METHODS: Among the five isolated keratinolytic microorganisms, one microbe, Bacillus XT 01, produced a significant amount of enzyme activity, which was partially characterized. The potential of this protease-producing microbe was investigated for converting feather keratin waste to valuable protein hydrolysate. RESULTS: Maximum keratinase production was observed after 5 days of incubating Bacillus XT 01 at an optimum temperature of 45 °C and pH 8.5. Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and zymogram of ammonium sulfate precipitated culture supernatant showed the presence of several proteolytic enzymes with molecular weights between 30 and 60 kDa. The Bacillus strain caused almost complete feather degradation (98%) after 7 days of incubation at 45 °C in a shake culture medium. Antioxidant and reducing activities of the feather protein hydrolysate (FPH) elevated with increased cultivation time. Investigation of the effect of feather protein hydrolysate on plants indicated improved plant growth regarding the agronomic parameters, such as plant height, number of trifoliate leaves, number of pods, pod length, number of seeds per pod, and root length, which increased by 30.84%, 49.32%, 70.90%, 53.27%, 60.03%, and 54.71%, respectively. CONCLUSIONS: The prospective of Bacillus XT 01 for degrading feather waste keratin to highly valued hydrolyzed feather protein offers effectiveness in the poultry industry and ultimately decreases environmental pollution hazards.

The role of lipoprotein­associated phospholipase A2 in inflammatory response and macrophage infiltration in sepsis and the regulatory mechanisms.

Lipoproteinassociated phospholipase A2 (Lp-PLA2), encoded by the phospholipase A2 group VII (Pla2g7) gene, has been pertinent to inflammatory responses. This study investigates the correlation between Lp-PLA2 and inflammatory injury in septic mice and explores its regulatory mechanism. Lp-PLA2 was found to be upregulated in the serum of septic mice induced by cecal ligation and puncture and in the culture supernatant of RAW264.7 cells following lipopolysaccharide and adenosine triphosphate treatments. The contents of Lp-PLA2 were positively correlated with increased concentrations of proinflammatory cytokines in patients with sepsis. Both animal and cellular models showed increased concentrations of proinflammatory cytokines. Spi-1 proto-oncogene (Spi1), highly expressed in these models, was found to activate Pla2g7 transcription. Knockdown of Pla2g7 or Spi1 reduced the proinflammatory cytokine production, mitigated organ damage in mice, and suppressed macrophage migration in vitro. Retinoblastoma binding protein 6 (Rbbp6), poorly expressed in both models, was found to reduce Spi1 protein stability through ubiquitination modification. Rbbp6 overexpression similarly suppressed inflammatory activation of RAW264.7 cells, which was counteracted by Pla2g7 or Spi1 upregulation. In summary, this study demonstrates that the Pla2g7 loss and Spi1 upregulation participate in inflammatory responses in sepsis by elevating the Lp-PLA2 levels.

LncRNA018392 promotes the proliferation of Liaoning cashmere goat skin fibroblasts by upregulating CSF1R through binding to SPI1.

BACKGROUND: Liaoning cashmere goat is recognized as a valuable genetic resource breed, with restrictions on genetic outflow in China. Hair follicle development in the cashmere goat is influenced by melatonin and long non-coding RNAs (lncRNAs). However, the role of lncRNAs in facilitating melatonin-promoted cashmere growth remains poorly understood. Previous studies have identified a new lncRNA, lncRNA018392, which is involved in the melatonin-promoted proliferation of cashmere skin fibroblasts. METHOD: Flow cytometry and CCK-8 assays confirmed that silencing lncRNA018392 negates the effects of melatonin on cell proliferation, and that proliferation was reduced when the gene CSF1R, located near lncRNA018392, was inhibited. Further investigation using a dual-luciferase reporter assay showed that lncRNA018392 could positively regulate the promoter of CSF1R. RESULTS: Results from RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq) revealed that lncRNA018392 interacts with the transcription factor SPI1, with CSF1R being a downstream target gene regulated by SPI1. This interaction was confirmed by ChIP-PCR, which demonstrated SPI1's binding to CSF1R. CONCLUSIONS: This study found that the melatonin-responsive lncRNA018392 accelerates the cell cycle and promotes cell proliferation by recruiting SPI1 to upregulate the expression of the neighboring gene CSF1R. These findings provide a theoretical foundation for elucidating the molecular mechanisms of cashmere growth and for the molecular breeding of cashmere goats.

Multifractal characterization of meteorological to agricultural drought propagation over India.

Agricultural drought affects the regional food security and thus understanding how meteorological drought propagates to agricultural drought is crucial. This study examines the temporal scaling trends of meteorological and agricultural drought data over 34 Indian meteorological sub-divisions from 1981 to 2020. A maximum Pearson's correlation coefficient (MPCC) derived between multiscale Standardised Precipitation Index (SPI) and monthly Standardised Soil Moisture Index (SSMI) time series was used to assess the seasonal as well as annual drought propagation time (DPT). The multifractal characteristics of the SPI time series at a time scale chosen from propagation analysis as well as the SSMI-1 time series were further examined using Multifractal Detrended Fluctuation Analysis (MF-DFA). Results reveal longer average annual DPT in arid and semi-arid regions like Saurashtra and Kutch (~ 6 months), Madhya Maharashtra (~ 5 months), and Western Rajasthan (~ 6 months), whereas, humid regions like Arunachal Pradesh, Assam and Meghalaya, and Kerala exhibit shorter DPT (~ 2 months). The Hurst Index values greater/less than 0.5 indicates the existence of long/short-term persistence (LTP/STP) in the SPI and SSMI time series. The results of our study highlights the inherent connection among drought propagation time, multifractality, and regional climate variations, and offers insights to enhance drought prediction systems in India.

Cytosolic serpins act in a cytoprotective feedback loop that limits ESX-1-dependent death of Mycobacterium marinum-infected macrophages.

Serine protease inhibitors (serpins) constitute the largest family of protease inhibitors expressed in humans, but their role in infection remains largely unexplored. In infected macrophages, the mycobacterial ESX-1 type VII secretion system permeabilizes internal host membranes and causes leakage into the cytosol of host DNA, which induces type I interferon (IFN) production via the cyclic GMP-AMP synthase (cGAS) and stimulator of IFN genes (STING) surveillance pathway, and promotes infection in vivo. Using the Mycobacterium marinum infection model, we show that ESX-1-mediated type I IFN signaling in macrophages selectively induces the expression of serpina3f and serpina3g, two cytosolic serpins of the clade A3. The membranolytic activity of ESX-1 also caused leakage of cathepsin B into the cytosol where it promoted cell death, suggesting that the induction of type I IFN comes at the cost of lysosomal rupture and toxicity. However, the production of cytosolic serpins suppressed the protease activity of cathepsin B in this compartment and thus limited cell death, a function that was associated with increased bacterial growth in infected mice. These results suggest that cytosolic serpins act in a type I IFN-dependent cytoprotective feedback loop to counteract the inevitable toxic effect of ESX-1-mediated host membrane rupture. IMPORTANCE: The ESX-1 type VII secretion system is a key virulence determinant of pathogenic mycobacteria. The ability to permeabilize host cell membranes is critical for several ESX-1-dependent virulence traits, including phagosomal escape and induction of the type I interferon (IFN) response. We find that it comes at the cost of lysosomal leakage and subsequent host cell death. However, our results suggest that ESX-1-mediated type I IFN signaling selectively upregulates serpina3f and serpina3g and that these cytosolic serpins limit cell death caused by cathepsin B that has leaked into the cytosol, a function that is associated with increased bacterial growth in vivo. The ability to rupture host membranes is widespread among bacterial pathogens, and it will be of interest to evaluate the role of cytosolic serpins and this type I IFN-dependent cytoprotective feedback loop in the context of human infection.

SPI1-mediated transcriptional activation of CEP55 promotes the malignant growth of triple-negative breast cancer and M2 macrophage polarization.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of three receptors commonly targeted in breast cancer treatment. In this study, the research focused on investigating the role of centrosomal protein 55 (CEP55) in TNBC progression and its interaction with the transcription factor Spi-1 proto-oncogene (SPI1). METHODS: Various techniques including qRT-PCR, western blotting, and immunohistochemistry assays were utilized to examine gene expression patterns. Functional assays such as wound-healing assay, transwell invasion assay, 5-Ethynyl-2'-deoxyuridine assay, and metabolic assays were conducted to assess the impact of CEP55 on the behaviors of TNBC cells. CD163-positive macrophages were quantified by flow cytometry. The chromatin immunoprecipitation assay and dual-luciferase reporter assay were performed to assess the association of SPI1 with CEP55. A xenograft mouse model experiment was used to analyze the impact of SPI1 on tumor development in vivo. RESULTS: CEP55 and SPI1 expression levels were significantly upregulated in TNBC tissues and cells. The depletion of CEP55 led to decreased TNBC cell migration, invasion, proliferation, glucose metabolism, and M2 macrophage polarization, indicating its crucial role in promoting TNBC progression. Moreover, SPI1 transcriptionally activated CEP55 in TNBC cells, and its overexpression was associated with accelerated tumor growth in vivo. Further, CEP55 overexpression relieved SPI1 silencing-induced inhibitory effects on TNBC cell migration, invasion, proliferation, glucose metabolism, and M2 macrophage polarization. CONCLUSION: SPI1-mediated transcriptional activation of CEP55 plays a key role in enhancing TNBC cell migration, invasion, proliferation, glucose metabolism, and M2 macrophage polarization. These insights provide valuable information for potential targeted therapies to combat TNBC progression by modulating the SPI1-CEP55 axis.

Exploring climate shifts in the Ganga-Brahmaputra basin based on rainfall and temperature variability.

Climate change has a significant impact on the Ganga-Brahmaputra (GB) basin, the major food belt of India, which frequently experiences flooding and varied incidences of drought. The current study examines the changing trend of rainfall and temperature in the GB basin over a period of 30 years to identify areas at risk with an emphasis on the Paris Agreement's mandate to keep increasing temperatures below 2 °C. The maximum temperature anomaly in the middle Ganga plains recorded an increase of more than 1.5 °C year-1 in 1999, 2005, and 2009. Some extreme events were observed in the Brahmaputra basin during 1999, 2009, and 2010, where a prominent temperature increase of 1.5 °C year-1 was observed. The minimum temperature revealed an increasing trend for the G-B basin with an anomalous increase of 0.04 to 0.06 °C year-1. The rainfall variability across the Ganga basin shows a rising tendency over the lower Ganga region while the Brahmaputra basin showed a downward trend. To identify the statistical relation between the Global climatic oscillations and regional climate, Standardized Precipitation Index (SPI) and Niño 3.4 were used. The wet and dry period estimation shows a rise in flood conditions in the Ganga basin whereas, in the Brahmaputra basin, an increase in drought frequency was observed. The correlation based on Niño 3.4 and SPI3 presents a negative relation for the monsoon season in the G-B basin revealing a situation of drought occurrence (SPI3 below 0) with increased Nino 3.4 values (El Niño above + 0.4C).

Development of a Data Model to Predict Nursing Workload Using Routine Clinical Data.

The effective management of human resources in nursing is fundamental to ensuring high-quality care. The necessary staffing levels can be derived from the nursing-related health status. Our approach is based on the use of artificial intelligence (AI) and machine learning (ML) to recognize key workload-driving predictors from routine data in the first step and derive recommendations for staffing levels in the second step. The precedent analysis was a multi-center study with data provided by three hospitals. The SPI (Self Care Index = sum score of 10 functional/cognitive items of the epaAC (epaAC = nursing assessment tool for AcuteCare (abbreviated from the German-language effiziente Pflege-Analyse AcuteCare))) was identified as a strong predictor of nursing workload. The SPI alone explains the variance in minutes with an adjusted R2 of 40% to 66%. With the addition of further predictors such as "fatigue" or "pain intensity", the adjusted R2 can be increased by up to 17%. The resulting model can be used as a foundation for data-based personnel controlling using AI-based prediction models.

The SPI1/SMAD5 cascade in the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells: a mechanism study.

BACKGROUND: Dysregulation of osteogenic differentiation is a crucial event during osteoporosis. The bioactive phytochemical icariin has become an anti-osteoporosis candidate. Here, we elucidated the mechanisms underlying the promoting function of icariin in osteogenic differentiation. METHODS: Murine pre-osteoblast MC3T3-E1 cells were stimulated with dexamethasone (DEX) to induce osteogenic differentiation, which was evaluated by an Alizarin Red staining assay and ALP activity measurement. The mRNA amounts of SPI1 and SMAD5 were detected by real-time quantitative PCR. Expression analysis of proteins, including osteogenic markers (OPN, OCN and RUNX2) and autophagy-associated proteins (LC3, Beclin-1, and ATG5), was performed by immunoblotting. The binding of SPI1 and the SMAD5 promoter was predicted by the Jaspar2024 algorithm and confirmed by chromatin immunoprecipitation (ChIP) experiments. The regulation of SPI1 in SMAD5 was examined by luciferase assays. RESULTS: During osteogenic differentiation of MC3T3-E1 cells, SPI1 and SMAD5 were upregulated. Functionally, SPI1 overexpression enhanced autophagy and osteogenic differentiation of MC3T3-E1 cells, while SMAD5 downregulation exhibited opposite effects. Mechanistically, SPI1 could enhance SMAD5 transcription and expression. Downregulation of SMAD5 also reversed SPI1 overexpression-induced autophagy and osteogenic differentiation in MC3T3-E1 cells. In MC3T3-E1 cells under DEX stimulation, icariin increased SMAD5 expression by upregulating SPI1. Furthermore, icariin could attenuate SPI1 depletion-imposed inhibition of autophagy and osteogenic differentiation of MC3T3-E1 cells. CONCLUSION: Our findings demonstrate that the SPI1/SMAD5 cascade, with the ability to enhance osteogenic differentiation, underlies the promoting effect of icariin on osteogenic differentiation of MC3T3-E1 cells.

The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway.

INTRODUCTION: Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated. OBJECTIVES: This research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma. METHODS: The amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules. RESULTS: The upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4. CONCLUSION: Our findings provide evidence for the role of VSIG4 as an oncogene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.

Characteristics of soy films as affected by transglutaminase cross-linking and inclusions of pectin and protein enhancers.

Previously, we showed that water extract (soymilk, except pH was increased to 8 from 6.5) of whole soybean could be used directly as a raw material for producing edible soy films by deposition of the film-forming solution (soy extract with enhancers). However, the strength of such soy films needed improvement because they were weak. The purpose of this study was to investigate how transglutaminase (TG) cross-linking reactions and film enhancers, including pectin (low- and high-methoxyl pectin), whey protein isolate (WPI), and soy protein isolate (SPI), improve the physical properties of soy films. Soy films prepared with TG had tensile strength (TS) of 3.01 MPa and puncture strength (PS) of 0.78 MPa, which were higher by as much as 51% and 30% than that of soy films without TG treatment, respectively. Pectin showed significant effects on the mechanical properties of TG-added soy films in terms of TS, PS, and % elongation. On the other hand, only TS and PS were increased by the addition of WPI or SPI. Heat curing had a significant effect on soy film's physical properties. TG treatment significantly reduced film solubility when soaked in water and various levels of acid (vinegar) and base (baking soda) solutions. Under the experimental conditions of 35 unit TG and 28 min of reaction, the degrees of cross-linking were evidenced by the disappearance of individual protein subunits, except the basic subunit of glycinin, and the reduction of 21% of lysine residues of the proteins. HIGHLIGHTS: Edible soy films were made with transglutaminase and about 21% lysine cross-linked. The mechanical strength of soy films was increased by incorporating film enhancers. Transglutaminase enhanced the mechanical properties of soy films.