Restriction Factor Research Articles

Research on optimal carbon emissions in the production decision of the coal-fired power plant

PurposeThe coal-fired power plants have been confronted with new operation challenge since the unified carbon trading market was launched in China. To make the optimal decision for the carbon emissions and power production has already been an important subject for the plants. Most of the previous studies only considered the market prices of electricity and coal to optimize the generation plan. However, with the opening of the carbon trading market, carbon emission has become a restrictive factor for power generation. By introducing the carbon-reduction target in the production decision, this study aims to achieve both the environmental and economic benefits for the coal-fired power plants to positively deal with the operational pressure.Design/methodology/approachA dynamic optimization approach with both long- and short-term decisions was proposed in this study to control the carbon emissions and power production. First, the operation rules of carbon, electricity and coal markets are analyzed, and a two-step decision-making algorithm for annual and weekly production is presented. Second, a production profit model based on engineering constraints is established, and a greedy heuristics algorithm is applied in the Gurobi solver to obtain the amounts of weekly carbon emission, power generation and coal purchasing. Finally, an example analysis is carried out with five generators of a coal-fired power plant for illustration.FindingsThe results show that the joint information of the multiple markets of carbon, electricity and coal determines the real profitability of power production, which can assist the plants to optimize their production and increase the profits. The case analyses demonstrate that the carbon emission is reduced by 2.89% according to the authors’ method, while the annual profit is improved by 1.55%.Practical implicationsAs an important power producer and high carbon emitter, coal-fired power plants should actively participate in the carbon market. Rather than trade blindly at the end of the agreement period, they should deeply associate the prices of carbon, electricity and coal together and realize optimal management of carbon emission and production decision efficiently.Originality/valueThis paper offers an effective method for the coal-fired power plant, which is struggling to survive, to manage its carbon emission and power production optimally.

Diagnosis and Countermeasure Research on Restrictive Factors of Household Photovoltaic Development in Shunyi District

In order to mitigate climate change and global warming, and to balance the relationship between energy consumption and carbon emissions, China has put forward the “double carbon” goal, which will promote the construction of household photovoltaic as an important part of development. Distributed photovoltaic has the characteristics of high construction cost and long cost recovery cycle, which are unfavorable factors restricting large-scale promotion. and has been relying on national financial subsidies for a long time in the early stage of development. Under the incentive of high subsidies, the scale of China􀆳s distributed photovoltaic industry has expanded rapidly and maintained a high-speed development trend for many years. However, the large-scale development is accompanied by a surge in government subsidy funds. The high subsidy funds are difficult to be sustained, and the distributed photovoltaic industry is facing the overall trend of subsidy decline. This paper takes Shunyi District of Beijing, the first batch of pilot areas for rooftop distributed photovoltaic development in the whole county (city, district) in China, as an example. Through questionnaire survey, field interview and model analysis, this paper reveals the difficulties faced by household photovoltaic development in this area, identifies the main constraints and problems of photovoltaic development in this area, and quantitatively analyzes the influence degree of various factors. On this basis, based on the theoretical perspective of ‘cooperative governance’, this paper attempts to construct a G-P-M-S incentive system for household distributed photovoltaic development, which covers the government, public, market and society, and condenses the policy orientation of coordinating ‘cross-level’, ‘ cross-department’, ‘cross-subject’ and ‘policy tool integration’, and puts forward specific policy suggestions in light of the actual situation of Shunyi District, so as to provide support for Shunyi District to promote the development of photovoltaic industry and realize green and low-carbon transformation.

Personalizing Oncolytic Immunovirotherapy Approaches.

Development of successful cancer therapeutics requires exploration of the differences in genetics, metabolism, and interactions with the immune system among malignant and normal cells. The clinical observation of spontaneous tumor regression following natural infection with microorganismhas created the premise of their use as cancer therapeutics. Oncolytic viruses (OVs) originate from viruses with attenuated virulence in humans, well-characterized vaccine strains of known human pathogens, or engineered replication-deficient viral vectors. Their selectivity is based on receptor expression level and postentry restriction factors that favor replication in the tumor, while keeping the normal cells unharmed. Clinical trials have demonstrated a wide range of patient responses to virotherapy, with subgroups of patients significantly benefiting from OV administration. Tumor-specific gene signatures, including antiviral interferon-stimulated gene (ISG) expression profile, have demonstrated a strong correlation with tumor permissiveness to infection. Furthermore, the combination of OVs with immunotherapeutics, including anticancer vaccines and immune checkpoint inhibitors [ICIs, such as anti-PD-1/PD-L1 or anti-CTLA-4 and chimeric antigen receptor (CAR)-T or CAR-NK cells], could synergistically improve the therapeutic outcome. Creating response prediction algorithms represents an important step for the transition to individualized immunovirotherapy approaches in the clinic. Integrative predictors couldinclude tumor mutational burden (TMB), inflammatory gene signature, phenotype of tumor-infiltrating lymphocytes, tumor microenvironment (TME), and immune checkpoint receptor expression on both immune and target cells. Additionally, the gut microbiota has recently been recognized as a systemic immunomodulatory factor and could further be used in the optimization of individualized immunovirotherapy algorithms.

Genome-wide screens connect HD82 loss-of-function to purine analog resistance in African trypanosomes.

Nucleoside analogs have been used extensively as anti-infective agents, particularly against viral infections, and have long been considered promising anti-parasitic agents. These pro-drugs are metabolized by host-cell, viral, or parasite enzymes prior to incorporation into DNA, thereby inhibiting DNA replication. Here, we report genes that sensitize African trypanosomes to nucleoside analogs, including the guanosine analog, ganciclovir. We applied ganciclovir selective pressure to a trypanosome genome-wide knockdown library, which yielded nucleoside mono- and diphosphate kinases as hits, validating the approach. The two most dominant hits to emerge, however, were Tb927.6.2800 and Tb927.6.2900, which both encode nuclear proteins; the latter of which is HD82, a SAMHD1-related protein and a putative dNTP triphosphohydrolase. We independently confirmed that HD82, which is conserved among the trypanosomatids, can sensitize Trypanosoma brucei to ganciclovir. Since ganciclovir activity depends upon phosphorylation by ectopically expressed viral thymidine kinase, we also tested the adenosine analog, ara-A, that may be fully phosphorylated by native T. brucei kinase(s). Both Tb927.6.2800 and HD82 knockdowns were resistant to this analog. Tb927.6.2800 knockdown increased sensitivity to hydroxyurea, while dNTP analysis indicated that HD82 is indeed a triphosphohydrolase with dATP as the preferred substrate. Our results provide insights into nucleoside/nucleotide metabolism and nucleoside analog metabolism and resistance in trypanosomatids. We suggest that the product of 6.2800 sensitizes cells to purine analogs through DNA repair, while HD82 does so by reducing the native purine pool.IMPORTANCEThere is substantial interest in developing nucleoside analogs as anti-parasitic agents. We used genome-scale genetic screening and discovered two proteins linked to purine analog resistance in African trypanosomes. Our screens also identified two nucleoside kinases required for pro-drug activation, further validating the approach. The top novel hit, HD82, is related to SAMHD1, a mammalian nuclear viral restriction factor. We validated HD82 and localized the protein to the trypanosome nucleus. HD82 appears to sensitize trypanosomes to nucleoside analogs by reducing native pools of nucleotides, providing insights into both nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.

MODEL-BASED OPTIMIZATION OF ICVs’ CONTROL FOR PRODUCERS, INJECTORS, AND WAG-CO2 CYCLES SIZE IN A CARBONATE RESERVOIR UNDER UNCERTAINTY

Life cycle management of oil fields involves complex decisions, with many variables to be considered. In some fields of the Brazilian pre-salt, this task is even more challenging given the ultra-deep water location, with an expressive amount of gas (including CO2) production. This feature becomes a restricting factor for oil production in these types of fields, and a proper management is essential to overcome this issue, improving both production and economic returns. Therefore, Water-Alternate-Gas (WAG) is often used as an Enhanced Oil Recovery- EOR mechanism, providing a better mobility control, improving reservoir sweep and oil recovery. Moreover, WAG can be an alternative for recycling the produced gas, providing an adequate destination (mainly for CO2) and avoiding environmental problems. In this case, we name the method as WAG-CO2. Moreover, Interval Control Valves (ICVs) are also a good alternative to deal with these fields, since they work as flow control devices and allow for a better balance of the fluid flow in the reservoir. In this work, we evaluate the impact of the use of ICVs in producers, injectors, along with WAG cycles size to improve the performance of a developed field. The work consists of two parts. In Part I, using a single simulation model, we performed (1) six hierarchical optimization approaches to verify if the order in which the optimization occurs influences the final results, and (2) a joint optimization of all parameters for comparison purposes. The final strategies are simulated in a reference case (representing the “true response” of the field) to evaluate how the achieved control rules would behave in a real field. In Part II, we considered a probabilistic procedure, applying one of the hierarchical approaches in several representative models (RMs) expressing uncertain scenarios. In this case, we compared nominal optimization of individual RMs against a robust optimization (in which all RMs are optimized simultaneously). The study is applied to the benchmark case SEC1_2022, a synthetic model analogous to a pre-salt field. The results show an expressive increase in the economic return of the field with a proper operation of the ICVs and size of the WAG-CO2 cycles, despite the platform being restricted by gas production capacity. This result occurred because of a better balance in fluid flow through the reservoir and among wells. Moreover, in the first part of the work, all hierarchical approaches presented very similar results in terms of NPV, so the order of the optimization steps did not significantly affect the results. The non-hierarchical approach presented a slightly better result, but still close to those obtained in the hierarchical approaches. Furthermore, the most impacting variable was the ICV for producers, followed by ICV for injectors and, then, WAG-CO2 cycles. Similar tendencies were observed in the second part of the work, with higher expected economic return for the robust optimization.

A new generation of metal chillers to control the solidification structure of Al-4.5 wt%Cu alloy

This paper introduces and examines a new generation of chillers for judicious control of the solidification structure of cast metals and alloys. This innovative chiller makes use of the absorption of the latent heat of melting of a Phase Change Material (PCM) incorporated in the chiller. In this work, Al-4.5 wt%Cu melt was cast in sand molds fitted with a traditional solid steel chiller as well as this new type of chiller consisted of a steel container filled with a given amount of pure zinc as PCM. Effects of the PCM fitted chiller on the thermal history, solidification and structure of the castings were studied by experimental and computer simulation investigations. The optimum casting parameters and mold and chillers dimensions were selected using ProCast simulation software. Use of the PCM fitted chiller resulted in faster columnar-equiaxed transition, 27 %, 54 % and 40 % reduction in the length of the columnar zone and the primary and the secondary dendrite arm spacings, respectively, and about 30 % improvement in the hardness. Thermal gradients and cooling rates at different points of the PCM fitted casting were generally more than those in the traditionally chilled casting. Use of the PCM fitted chiller eliminated the formation of the feathery grains and reduced the formation of the undesired Fe-rich phases close to the chiller due to different thermal history of the castings. Segregation pattern and change of Growth Restriction Factor (GRF) along the castings were studied and related to the cooling and growth conditions experienced by each casting.

Factors associated with grazing behavior in candidates for bariatric surgery at a hospital in the Amazon.

To assess grazing behavior and associated factors in candidates for bariatric surgery monitored at a public hospital that is a reference in the care of people with severe obesity. Cross-sectional analytical study, with candidates for bariatric surgery of both genders, treated in a public hospital in the Amazon. To assess grazing behavior, the Repetitive Eating Questionnaire was used, and to investigate patterns of eating behavior, the Three Factor Eating Questionnaire was used, which assesses: Emotional Eating, Cognitive Restriction and Uncontrolled Eating. Sociodemographic information was obtained through self-report and the description of medication use through the medical record. Body mass index (BMI) was also calculated by measuring weight and height. The SPSS program, v. 21.0 was used. The study was approved by the Research Ethics Committee. A total of 205 participants were evaluated, with a mean age of 37.5 ± 8.6 years, the majority (93.7%) being women and the majority (59.5%) was not also using medication to lose weight. About 66.3% of the participants had compulsive grazing. The factor with the highest score was cognitive restriction (p < 0.001). Individuals who used weight loss drugs had higher scores in the cognitive restriction factor (p = 0.015) and lower scores for uncontrolled eating (p = 0.008), compulsive grazing (p = 0.021) and non-compulsive grazing (p = 0.034). Linear regression showed that emotional eating and uncontrolled eating were predictors of both compulsive grazing and non-compulsive grazing behavior. It was observed that grazing behavior, cognitive restriction, emotional eating and uncontrolled eating are present and correlated in the studied patients. In addition, the use of weight loss drugs seems to help reduce dysfunctional eating behaviors in patients with severe obesity.

Antiviral Activity of Zinc Finger Antiviral Protein (ZAP) in Different Virus Families.

The CCCH-type zinc finger antiviral protein (ZAP) in humans, specifically isoforms ZAP-L and ZAP-S, is a crucial component of the cell's intrinsic immune response. ZAP acts as a post-transcriptional RNA restriction factor, exhibiting its activity during infections caused by retroviruses and alphaviruses. Its function involves binding to CpG (cytosine-phosphate-guanine) dinucleotide sequences present in viral RNA, thereby directing it towards degradation. Since vertebrate cells have a suppressed frequency of CpG dinucleotides, ZAP is capable of distinguishing foreign genetic elements. The expression of ZAP leads to the reduction of viral replication and impedes the assembly of new virus particles. However, the specific mechanisms underlying these effects have yet to be fully understood. Several questions regarding ZAP's mechanism of action remain unanswered, including the impact of CpG dinucleotide quantity on ZAP's activity, whether this sequence is solely required for the binding between ZAP and viral RNA, and whether the recruitment of cofactors is dependent on cell type, among others. This review aims to integrate the findings from studies that elucidate ZAP's antiviral role in various viral infections, discuss gaps that need to be filled through further studies, and shed light on new potential targets for therapeutic intervention.

Manufacturing high strength Ti alloy with in-situ Cu alloying via directed energy deposition and evaluation of material properties

In recent years, researchers have increasingly focused on alloy design in additive manufacturing (AM) to adjust the microstructure and improve the mechanical properties. The microstructure of columnar grains, strong texture, and chemical inhomogeneity in designed alloy exhibit anisotropic properties, which negatively affect the mechanical properties of the materials. One such material affected by this problem is titanium (Ti), which is known for its exceptional mechanical properties. Unlike other alloys, titanium lacks grain refiners that can ameliorate the columnar structure. Consequently, numerous studies are currently underway to refine the Ti grain through the addition of solute elements. In this study, Ti6Al4V with Cu element was deposited using the directed energy deposition (DED) process to investigate the feasibility of Ti6Al4V-xCu and analyze the effect of Cu addition. Ti6Al4V with Cu addition was successfully deposited and exhibited evenly distributed composition. In addition, finer grains were more created than the deposited Ti6Al4V by converting columnar to equiaxed grain due to the high cooling rate facilitated by high restriction factor Q of Cu. The deposited Ti6Al4V–4Cu of mechanical properties exhibited a 19 % increase in ultimate tensile strength, a 19 % increase in hardness at the top, and reduced elongation compared to the deposited Ti6Al4V, owing to the precipitation of Ti2Cu, grain refinement, and solid solution of Cu. However, although the hardness of the deposited Ti6Al4V–7Cu exhibited a 36 % increase in hardness at the top, Ti2Cu precipitate was generated significantly, which adversely exhibited a 26 % decrease in ultimate tensile strength compared to the deposited Ti6Al4V.

Exogenous abscisic acid improves grain filling capacity under heat stress by enhancing antioxidative defense capability in rice

BackgroundHeat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress.ResultsRice plants were pretreated with distilled water, 50 μM ABA and 10 μM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2– and H2O2) by 15.0–25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4–16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress.ConclusionTaken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

Citrullination profile analysis reveals peptidylarginine deaminase 3 as an HSV-1 target to dampen the activity of candidate antiviral restriction factors.

Herpes simplex virus 1 (HSV-1) is a neurotropic virus that remains latent in neuronal cell bodies but reactivates throughout an individual's life, causing severe adverse reactions, such as herpes simplex encephalitis (HSE). Recently, it has also been implicated in the etiology of Alzheimer's disease (AD). The absence of an effective vaccine and the emergence of numerous drug-resistant variants have called for the development of new antiviral agents that can tackle HSV-1 infection. Host-targeting antivirals (HTAs) have recently emerged as promising antiviral compounds that act on host-cell factors essential for viral replication. Here we show that a new class of HTAs targeting peptidylarginine deiminases (PADs), a family of calcium-dependent enzymes catalyzing protein citrullination, exhibits a marked inhibitory activity against HSV-1. Furthermore, we show that HSV-1 infection leads to enhanced protein citrullination through transcriptional activation of three PAD isoforms: PAD2, PAD3, and PAD4. Interestingly, PAD3-depletion by specific drugs or siRNAs dramatically inhibits HSV-1 replication. Finally, an analysis of the citrullinome reveals significant changes in the deimination levels of both cellular and viral proteins, with the interferon (IFN)-inducible proteins IFIT1 and IFIT2 being among the most heavily deiminated ones. As genetic depletion of IFIT1 and IFIT2 strongly enhances HSV-1 growth, we propose that viral-induced citrullination of IFIT1 and 2 is a highly efficient HSV-1 evasion mechanism from host antiviral resistance. Overall, our findings point to a crucial role of citrullination in subverting cellular responses to viral infection and demonstrate that PAD inhibitors efficiently suppress HSV-1 infection in vitro, which may provide the rationale for their repurposing as HSV-1 antiviral drugs.

Evaluation of sewage sludge effects on soil fertility and silage maize growth

Different methods are being tried all over the world for the safe disposal of sewage sludge. One of these methods is to evaluate the waste in plant production by applying it to the soil. In this study, the potential of using stabilized and dried sewage sludge in silage maize cultivation was investigated. Silage maize was grown by applying the sewage sludge to the soil at different rates [0 t ha-1 (SS0-Control), 20 t ha-1 (SS2), 40 t ha-1 (SS4), 60 t ha-1 (SS6), and 80 t ha-1 (SS8)]. Thus, the material's effects on soil fertility and plant growth were examined. According to the results, the sewage sludge enriched the soil, which contains restrictive factors in terms of fertility and on which maize growth is carried out, with humus and nutrients. However, it was observed that the material does not cause salinity problems in the soil. It was determined that sewage sludge positively affected the growth of silage maize but could not provide sufficient nutrition for the plant in terms of macronutrients. Considering the economic benefits and environmental risks, applying the sewage sludge with a maximum of 60 t ha-1 in silage maize growth is appropriate. However, it would be incredibly beneficial to support the material with chemical fertilizers to increase the silage yield and quality of the plant.

Tetherin Restricts SARS-CoV-2 despite the Presence of Multiple Viral Antagonists.

Coronavirus infection induces interferon-stimulated genes, one of which encodes Tetherin, a transmembrane protein inhibiting the release of various enveloped viruses from infected cells. Previous studies revealed that SARS-CoV encodes two Tetherin antagonists: the Spike protein (S), inducing lysosomal degradation of Tetherin, and ORF7a, altering its glycosylation. Similarly, SARS-CoV-2 has also been shown to use ORF7a and Spike to enhance virion release in the presence of Tetherin. Here, we directly compare the abilities and mechanisms of these two viral proteins to counteract Tetherin. Therefore, cell surface and total Tetherin levels upon ORF7a or S expression were investigated using flow cytometry and Western blot analysis. SARS-CoV and SARS-CoV-2 S only marginally reduced Tetherin cell surface levels in a cell type-dependent manner. In HEK293T cells, under conditions of high exogenous Tetherin expression, SARS-CoV-2 S and ORF7a reduced total cellular Tetherin levels much more efficiently than the respective counterparts derived from SARS-CoV. Nevertheless, ORF7a from both species was able to alter Tetherin glycosylation. The ability to decrease total protein levels of Tetherin was conserved among S proteins from different SARS-CoV-2 variants (α, γ, δ, ο). While SARS-CoV-2 S and ORF7a both colocalized with Tetherin, only ORF7a directly interacted with the restriction factor in a two-hybrid assay. Despite the presence of multiple Tetherin antagonists, SARS-CoV-2 replication in Caco-2 cells was further enhanced upon Tetherin knockout. Altogether, our data show that endogenous Tetherin restricts SARS-CoV-2 replication and that the antiviral activity of Tetherin is only partially counteracted by viral antagonists with differential and complementary modes of action.

Elucidating the promoting mechanism of nitrogen in the columnar-to-equiaxed transition of steel ingot

Based on the behavior of heat and mass transfer ahead of the advancing columnar front, combined with the nucleation and growth of dendrites, as well as the blocking mechanism of columnar-to-equiaxed transition (CET), the promoting mechanism of nitrogen in the CET of steel ingot was elucidated. It was found that the CET moves from the center to the edge of the ingot as the nitrogen content increases, resulting in a decrease in the columnar dendrite zone and an increase in the equiaxed dendrite zone. The occurrence of this phenomenon can be attributed to two factors. On the one hand, an increase in nitrogen content leads to an increase in critical nucleation supercooling and incubation time of dendrites, causing a decrease in the number of dendrites nucleation. Additionally, the higher nitrogen content reduces the restriction effect of solute on the growth of columnar dendrites, leading to an increase in dendrite size. On the other hand, within the constitutional supercooling (CS) zone ahead of the advancing columnar front, both the CS and temperature gradient decrease with increasing nitrogen content, while the CS increases and the temperature gradient decreases with the distance from the advancing columnar front. Consequently, the nitrogen solute primarily influences the nucleation and growth of columnar and equiaxed dendrites, as well as the length, temperature gradient, and growth restriction factor Qc of the CS zone, resulting in changes in the heat and mass transfer behavior ahead of the advancing columnar front, thereby promoting CET.

HIV-1 Restriction in Systemic Lupus Erythematosus Involves Iron Homeostasis

INTRODUCTION: Over the past two decades, there has been a growing emphasis on host restriction factors. However, a comprehensive understanding of their role in modulating HIV-1 infection in vivo requires further detailed investigation. Intracellular iron levels can affect HIV-1 replication by influencing expression of host cell viral restriction factors. Systemic Lupus Erythematosus (SLE) is characterized by upregulation of interferon response and the coexistence of SLE and HIV infection is rare. In lupus nephritis, deregulation of proteins involved in iron homeostasis have also been identified, with hepcidin suggested to play a role in disease severity . Hif1α, a protein regulated by hypoxia and under iron depletion, and reported to block HIV transcription, is upregulated in SLE. High levels of IL-10 and IL-16 which inhibits HIV infection are upregulated in SLE. APOBECs and oxysterols and Interferon Regulating Factors (IRFs) are also known to be upregulated in SLE. The current study is aimed to investigate ex vivo HIV-1 infection in peripheral blood mononuclear cells (PBMCs) derived from individuals SLE and identify factors that contributed to this inhibition. METHODS: We utilized replication deficient VSVg-pseudotype HIV-1 and replication competent HIV-IIIB to infect SLE PBMCs. Real-time PCR was conducted to determine the upregulation of genes involved in HIV-1 replication. RNA-seq of PBMCs were done to identify altered restriction factors. RESULTS: We investigated one round of HIV-1 infection in peripheral blood mononuclear cells (PBMCs) obtained from individuals with Systemic Lupus Erythematosus (SLE) and compared them to control PBMCs. We found that the HIV-1 infection in SLE-derived PBMCs was significantly reduced, as indicated by lower mRNA levels of Gag and Nef, two essential viral proteins. Our ongoing study, which focused on the inhibition of HIV-1 replication ex vivo in Sickle Cell Disease (SCD), revealed interesting findings. RNA sequencing of PBMCs from individuals with SCD showed an upregulation of APOBEC3A, APOBEC3B, and CH25H, which are known restriction factors against HIV-1. Given these intriguing results, we decided to analyze the RNA expression of these restriction factors in SLE-derived PBMCs. Surprisingly, we found a significant increase in the mRNA levels of APOBEC3A, APOBEC3B, and CH25H in SLE-derived PBMCs as well. This suggests that the enhanced expression of these restriction factors could be contributing to the reduced HIV-1 infection observed in SLE-derived PBMCs. Additionally, we explored the RNA expression of HIF-1α and TFR1, which are iron-regulated factors, and found that their mRNA levels were upregulated in SLE-derived PBMCs. Furthermore, we observed an upregulation of interferon regulatory factors, including IL-10, IFN-β, and IRF-7, which are involved in immune responses and antiviral defense mechanisms. Interestingly IRF-7 was upregulated in SCD PBMCs too. DISSUCION: The ongoing study in our lab on SCD and the study reported here are known for deregulated iron metabolism. Interestingly on one hand PBMCs derived from both inhibit HIV-1 and on other have some common restriction factors, iron regulated genes and IRF upregulated. Iron-regulated factors, such as TFR1, HIF-1α and ferroportin have been associated with antiviral effects. Modulating the expression or activity of these factors could influence HIV infection. CONCLUSIONs: Taken together, our findings indicate that SLE-derived PBMCs exhibit a distinct gene expression profile that may confer protection against HIV-1 infection. The upregulation of APOBEC3A, APOBEC3B, CH25H, HIF-1α, TFR1, and interferon regulatory factors could collectively contribute to the observed reduction in HIV-1 replication in SLE-derived PBMCs. Further investigation is needed to fully understand the mechanisms underlying these observations and their implications for HIV-1 pathogenesis under altered intracellular iron levels influencing HIV-1 replication by modulating host cell factors. Acknowledgments This work was supported by NIH Research Grants 1R01HL125005, 5U54MD007597, P30AI087714 and P50AI150476. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The experiences of older adults with cognitive impairment in using falls prevention alarms in hospital: A qualitative descriptive study.

Bed and chair sensor alarms are commonly used for falls prevention in hospitals, despite questionable efficacy. Research analysing older adults' experiences of alarms is scarce, and adults with cognitive impairment are consistently excluded. The aim of this study was to explore how older adults with cognitive impairment perceive and experience falls prevention alarms in hospital. A qualitative descriptive design investigated older adults' experiences of alarms in a Geriatric Evaluation and Management ward in Melbourne. Patients were included if they had been provided an alarm. Semi-structured interviews were the primary method of data collection with two observation sessions and medical record analyses completed to enable triangulation of findings. Data were subjected to thematic analysis, and the Person-Environment-Occupation framework was chosen to add insight into the complexities of older adults' experiences of alarms. All 11 participants had a level of cognitive impairment with delirium, confusion, or impulsiveness recorded in their medical file. Two overarching themes were identified: communication and collaboration with staff and rationalisation of alarm use. Participants' perceived staff were focussed on falls prevention but experienced a lack of communication about the purpose of alarms. Participants wanted an individualised approach to alarms. Some were comforted with the thought of alarms alerting staff, making them feel well cared for and believed alarms were a useful 'back-up'. Others found alarms uncomfortable, frustrating, and restricting. Application of the Person-Environment-Occupation framework provided insight into how enabling and restrictive factors can impact whether the alarm is experienced positively or negatively. Seven unwitnessed falls occurred during the participants' admissions. Thirty-four per cent of alarm triggers observed were considered false alerts. Older adults commonly reported negative experiences using bed/chair sensor alarms. Occupational therapists have the training to collaborate with people with cognitive impairment and assess the usefulness of alarms in reducing falls, based on how they interact with the older adult's unique person, environment, and occupation domains.

Outcomes of Allogenic Hematopoietic Stem Cell Transplantation in Patients Aged 70 Years and Older

Background: Allogeneic hematopoietic cell transplantation (Allo-HCT) is a highly effective method of achieving prolonged disease control for many types of blood cancers. However, historically, older adults were not considered eligible candidates for Allo-HCT due to concerns about increased toxicity and mortality. This is a significant issue, as the proportion of cancer patients with comorbidities, disability, and geriatric syndromes increases by 3-5% for every 5-year increase in age beyond 65 years. This systematic review aims to address this gap in literature by analyzing survival prognosis in patients aged 70 years and above who have undergone Allo-HCT. Methods: As per the preferred reporting items for systemic reviews and meta-analysis (PRISMA) guidelines, a comprehensive literature search was performed on 3 databases (PubMed, Cochrane Register of Controlled Trials and Clinicaltrials.gov) using MeSH terms and keywords for “Hematopoietic Stem Cell Transplantation” AND “Outcome Assessment” AND “&amp;gt;70 years old” from the date of inception to Feb 13, 2023. Our research produced 101 articles. After excluding irrelevant and review articles during primary and secondary screening, six original studies reporting outcomes of Allo-HCT in patients over 70 years were included. The methodological quality of the included studies was evaluated using NIH quality assessment tool. Inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% confidence Interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2). Results: A total of 2292 patients aged 70 years or more were included for this systematic review and meta-analysis. (Table 1) The median age was 71.75 (70-84) years and 67.5% (n=1547) patients were male. Median follow-up time was 22.1 (5-37.1) months. The underlying diagnosis was acute myeloid leukemia (AML) 63% (n=1445), myelodysplastic syndrome (MDS) 20.9% (n=480), non-Hodgkin lymphoma (NHL) 5% (n=115), acute lymphocytic leukemia (ALL) 4.2% (n=96), and chronic lymphocytic leukemia (CLL) 3.1 % (n=71). The source of stem cells was peripheral blood, bone marrow, and cord blood in 90.2% (n=2068), 6.2% (n=142), and 3.1% (n=70) of the patients, respectively. Myeloablative conditioning (MAC) was used in 17.8% of patients, reduced-intensity conditioning (RIC) was used in 77.4% of patients, and a non-myeloablative conditioning regimen (NMA) was used in 4.6% of patients. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) of the included patients was 0 (25.7%), 1-2 (30.1%), and 3 or more (44.2%). The pooled overall survival (OS) at a median of 2 years (1-3) was 41.8% (95% CI 0.34-0.49, I2=88%, p&amp;lt;0.01, n=2292). The pooled progression-free survival (PFS) was 36.4% (95% CI 0.31-0.43, I2=75%, p&amp;lt;0.01, n=1979) at a median of 2 (1-2) years while the pooled incidence of relapse and non-relapse mortality (NRM) was 33.7% (95% CI 0.29-0.38, I2=69%, p&amp;lt;0.01, n=2292) and 28.7% (95% CI 0.22-0.36, I2=88%, p&amp;lt;0.01, n=2292), respectively. The pooled incidence of acute graft versus host disease (GvHD) grade II-IV at a median of 6 months (3-24) and grade III-IV at median of 4.5 months (3-24) was 25.8% (95% CI 0.20-0.31, I2=84%, p&amp;lt;0.01, n=2270) and 11.1% (95% CI 0.10-0.13, I2=2%, p=0.39, n=1979), respectively, while the pooled incidence of chronic GvHD at a median of 1.5 years (1-2) was 33.6% (95% CI 0.28-0.40, I2=84%, p&amp;lt;0.01, n=2292). Conclusion: Our meta-analysis shows that allo-HCT offers promising outcomes for elderly patients aged 70 or greater, and should be considered more frequently for those with transplant eligible disease. It also shows that age can be a restrictive factor due to co-existing comorbidities and poor performance status. Several other factors such as the availability of matched donors, conditioning regimen can play a role in the final outcome of disease progression and associated adverse effects such as GVHD.

APOBEC3G Is a p53-Dependent Restriction Factor in Respiratory Syncytial Virus Infection of Human Cells Included in the p53/Immune Axis.

Identifying and understanding genetic factors that influence the propagation of the human respiratory syncytial virus (RSV) can lead to health benefits and possibly augment recent vaccine approaches. We previously identified a p53/immune axis in which the tumor suppressor p53 directly regulates the expression of immune system genes, including the seven members of the APOBEC3 family of DNA cytidine deaminases (A3), which are innate immune sentinels against viral infections. Here, we examined the potential p53 and A3 influence in RSV infection, as well as the overall p53-dependent cellular and p53/immune axis responses to infection. Using a paired p53 model system of p53+ and p53- human lung tumor cells, we found that RSV infection activates p53, leading to the altered p53-dependent expression of A3D, A3F, and A3G, along with p53 site-specific binding. Focusing on A3G because of its 10-fold-greater p53 responsiveness to RSV, the overexpression of A3G can reduce RSV viral replication and syncytial formation. We also observed that RSV-infected cells undergo p53-dependent apoptosis. The study was expanded to globally address at the transcriptional level the p53/immune axis response to RSV. Nearly 100 genes can be directly targeted by the p53/immune axis during RSV infection based on our p53BAER analysis (Binding And Expression Resource). Overall, we identify A3G as a potential p53-responsive restriction factor in RSV infection. These findings have significant implications for RSV clinical and therapeutic studies and other p53-influenced viral infections, including using p53 adjuvants to boost the response of A3 genes.

Patterns of Evolution of TRIM Genes Highlight the Evolutionary Plasticity of Antiviral Effectors in Mammals.

The innate immune system of mammals is formed by a complex web of interacting proteins, which together constitute the first barrier of entry for infectious pathogens. Genes from the E3-ubiquitin ligase tripartite motif (TRIM) family have been shown to play an important role in the innate immune system by restricting the activity of different retrovirus species. For example, TRIM5 and TRIM22 have both been associated with HIV restriction and are regarded as crucial parts of the antiretroviral machinery of mammals. Our analyses of positive selection corroborate the great significance of these genes for some groups of mammals. However, we also show that many species lack TRIM5 and TRIM22 altogether. By analyzing a large number of mammalian genomes, here we provide the first comprehensive view of the evolution of these genes in eutherians, showcasing that the pattern of accumulation of TRIM genes has been dissimilar across mammalian orders. Our data suggest that these differences are caused by the evolutionary plasticity of the immune system of eutherians, which have adapted to use different strategies to combat retrovirus infections. Altogether, our results provide insights into the dissimilar evolution of a representative family of restriction factors, highlighting an example of adaptive and idiosyncratic evolution in the innate immune system.

Spatial Distribution of Major Fish Species Catches and Their Relationship with Environmental Factors in the Beibu Gulf, South China Sea

This study focused on major fish species caught from different ecological habitats to analyze the habitat changes in economically important fish in the Beibu Gulf. The maximum entropy model was constructed based on the data from 26 voyages obtained through the otter trawl fishery stock surveys conducted in the Beibu Gulf from 2006 to 2018. A total of 10 taxa of major fish catches, belonging to 4 families, 1 genus, and 5 species, were analyzed for their distribution characteristics in potential habitats during various ecological periods, specifically the withered and high-water periods, as well as their relationships with crucial environmental factors. During both the withered and high-water periods, the average area under the curve was 0.927, and all models had values exceeding 0.9. Salinity was identified as the principal factor during both periods. The salinity niche of Acropoma japonicum and the primary productivity niche of Sciaenidae were identified as the most restricted factors. The total distribution area of potentially suitable regions for major fish catches extended between 106°30′–109°45′ E and 17°30′–20°45′ N, and the area was lesser during the withered period. During the withered period, the distribution areas of Sciaenidae, Leiognathidae, and Saurida increased, while the distribution area of Trachurus japonicus increased during the high-water period. Sciaenidae and Trachurus japonicus exhibited the highest rates of change at 6.22% and 10.92%, respectively. This indicates that the high-water period may expand the range of suitable habitats for large catches that have an ideal habitat status in the Beibu Gulf. Therefore, it is crucial to anticipate the potential fish habitats in the Beibu Gulf and clarify their spatial distribution patterns.