Review on Hydroxyurea Usage in Young Children with Sickle Cell Disease: Examining Hemoglobin Induction, Potential Benefits, Responses, Safety, and Effectiveness

Sickle cell disease (SCD) is a prevalent condition, particularly in the countries of sub-Saharan Africa, where the presence of specific genes associated with Malaria contributes to its high prevalence. Patients with sickle cell disease frequently experience painful episodes necessitating hospitalization, and their hemoglobin levels are typically lower than those of the general population. There are different treatment options available to manage complications, such as transfusing blood, hydroxyurea, and strong anti-pains. However, with all these treatments, patients still commonly experience pain crises and suffer from organ damage. Hydroxyurea, the sole approved medication for sickle cell anemia in developed and developing countries, is widely used in children despite being primarily indicated for adults. Multiple studies have demonstrated the efficacy of hydroxyurea in inducing HbF production in young children with SCD. Elevated HbF levels have been associated with improved clinical outcomes, including a reduction in vaso-occlusive crises, acute chest syndrome, and the need for blood transfusions. Furthermore, increased HbF levels have been shown to ameliorate disease-related organ damage, such as pulmonary hypertension and sickle cell retinopathy. The response to hydroxyurea treatment in young children with SCD is variable. Some patients achieve substantial increases in HbF levels and experience significant clinical benefits, while others may have a more modest response. Factors influencing the response include baseline HbF levels, genetic modifiers, treatment adherence, and dose optimization. Safety is a crucial consideration when using hydroxyurea in young children. Studies have shown that hydroxyurea is generally well-tolerated, with the most common adverse effects being myelosuppression, gastrointestinal symptoms, and dermatological manifestations. However,long-term effects and potential risks, such as renal dysfunction and reproductive impacts, require further investigation. The effectiveness of hydroxyurea in young children with SCD has been demonstrated in various clinical trials and observational studies. These studies have shown a significant reduction in disease-related complications and improved quality of life. However, optimal dosing, treatment duration, and long-term outcomes are still areas of ongoing research. This review focuses on recent studies investigating the benefits, effectiveness, responses, and safety of hydroxyurea in pediatric individuals diagnosed with sickle cell disease.

Leaf Morphology Genes SRL1 and RENL1 Co-Regulate Cellulose Synthesis and Affect Rice Drought Tolerance

The morphological development of rice(Oryza sativa L.)leaves is closely related to plant architecture,physiological activities,and resistance.However,it is unclear whether there is a co-regulatory relationship between the morphological development of leaves and adaptation to drought environment.In this study,a drought-sensitive,roll-enhanced,and narrow-leaf mutant(renl1)was induced from a semi-rolled leaf mutant(srl1)by ethyl methane sulfonate(EMS),which was obtained from Nipponbare(NPB)through EMS.Map-based cloning and functional validation showed that RENL1 encodes a cellulose synthase,allelic to NRL1/OsCLSD4.The RENL1 mutation resulted in reduced vascular bundles,vesicular cells,cellulose,and hemicellulose contents in cell walls,diminishing the water-holding capacity of leaves.In addition,the root system of the renl1 mutant was poorly developed and its ability to scavenge reactive oxygen species(ROS)was decreased,leading to an increase in ROS after drought stress.Meanwhile,genetic results showed that RENL1 and SRL1 synergistically regulated cell wall components.Our results revealed a theoretical basis for further elucidating the molecular regulation mechanism of cellulose on rice drought tolerance,and provided a new genetic resource for enhancing the synergistic regulation network of plant type and stress resistance,thereby realizing simultaneous improvement of multiple traits in rice.

Transcription factor CabHLH035 promotes cold resistance and homeostasis of reactive oxygen species in pepper

Plant basic helix-loop-helix(bHLH)transcription factors(TFs)play central roles in various abiotic stresses.However,its role in plant cold resistance is largely unknown.Previously,we characterised CaNAC035 in pepper,which positively regulates tolerance to cold,salt and drought stresses tolerance.Here,we identified CabHLH035,a CaNAC035-interacting protein in pepper.To explore its functions in cold stress tolerance,we silenced the gene in pepper via virus-induced gene silencing(VIGS)and overexpressed the gene in Arabidopsis.The results showed that CabHLH035 expression was induced by cold treatment,and silencing of CabHLH035 decreased cold stress tolerance.Conversely,overexpression of CabHLH035 in Arabidopsis increased cold stress tolerance.To investigate homologs genes of C-repeat binding factor(CBF)pathway proteins and reactive oxygen species(ROS)marker gene expression blocking by CabHLH035,we performed yeast one-hybrid(Y1H),dual luciferase and electrophoretic mobility shift assay experiments.The results showed that CabHLH035 bound to the region upstream of the CaCBF1A and CaAPX promoters.Additionally,CaCBF1A bound to the CaDHN4 promoter.Taken together,our results showed that CabHLH035 plays a crucial role in cold stress tolerance and its potential as a target for breeding cold-resistant crops.The findings provide a basis for studying the functions and regulatory network of cold stress tolerance in pepper.

Differences in leaf cuticular wax induced by whole-genome duplication in autotetraploid sour jujube

Drought-resistant plants exhibit strong water retention capability.In this regard,the autotetraploid sour jujube leaves exhibit better water retention than diploid leaves.Morphological comparisons and physiological comparisons of diploid and autotetraploid leaves showed that the autotetraploid leaves had thicker leaf cuticles and more leaf wax accumulation than the diploid leaves,which could reduce cuticle permeability and improve the drought tolerance of leaves.In this study,the cuticular wax crystalloids on the adaxial and abaxial sides of young and mature jujube leaves were observed in the two ploidy types,and unique cuticular wax crystalloids covering a large area of the cuticle on autotetraploid sour jujube leaves may provide an advantage in reducing leaf non-stomata transpiration and improving plant drought tolerance.Based on the transcriptome,115 differentially expressed genes between diploids and autotetraploids were further analyzed and found to be involved in the accumulation of cuticular wax components,including terpenoids,fatty acids,and lipids,as well as ABC transporter and wax biosynthetic process.Finally,14 genes differentially expressed between glossy autotetraploid leaves and nonglossy diploid leaves,such as LOC107414787,LOC107411574 and LOC107413721,were screened as candidate genes by qRT-PCR analysis.This findings provided insights into how polyploidization improved drought tolerance.

An Environment‑Tolerant Ion‑Conducting Double‑Network Composite Hydrogel for High‑Performance Flexible Electronic Devices

High-performance ion-conducting hydrogels(ICHs)are vital for developing flexible electronic devices.However,the robustness and ion-conducting behavior of ICHs deteriorate at extreme tempera-tures,hampering their use in soft electronics.To resolve these issues,a method involving freeze–thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network(DN)ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol)(PMP DN ICH)system.The well-designed ICH exhibits outstanding ionic conductivity(63.89 mS cm^(-1) at 25℃),excellent temperature resistance(-60–80℃),prolonged stability(30 d at ambient temperature),high oxidation resist-ance,remarkable antibacterial activity,decent mechanical performance,and adhesion.Additionally,the ICH performs effectively in a flexible wireless strain sensor,thermal sensor,all-solid-state supercapacitor,and single-electrode triboelectric nanogenerator,thereby highlighting its viability in constructing soft electronic devices.The highly integrated gel structure endows these flexible electronic devices with stable,reliable signal output performance.In particular,the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm^(-2)(current density,1 mA cm^(-2))and excellent environmental adaptability.This study paves the way for the design and fabrication of high-performance mul-tifunctional/flexible ICHs for wearable sensing,energy-storage,and energy-harvesting applications.

The ABA synthesis enzyme allele OsNCED2^(T)promotes dryland adaptation in upland rice

Upland rice shows dryland adaptation in the form of a deeper and denser root system and greater drought resistance than its counterpart,irrigated rice.Our previous study revealed a difference in the frequency of the OsNCED2 gene between upland and irrigated populations.A nonsynonymous mutation(C to T,from irrigated to upland rice)may have led to functional variation fixed by artificial selection,but the exact biological function in dryland adaptation is unclear.In this study,transgenic and association analysis indicated that the domesticated fixed mutation caused functional variation in OsNCED2,increasing ABA levels,root development,and drought tolerance in upland rice under dryland conditions.OsNCED2-overexpressing rice showed increased reactive oxygen species-scavenging abilities and transcription levels of many genes functioning in stress response and development that may regulate root development and drought tolerance.OsNCED2^(T)-NILs showed a denser root system and drought resistance,promoting the yield of rice under dryland conditions.OsNCED2^(T)may confer dryland adaptation in upland rice and may find use in breeding dryland-adapted,water-saving rice.

MIR1868 negatively regulates rice cold tolerance at both the seedling and booting stages

Low temperature causes rice yield losses of up to 30%–40%,therefore increasing its cold tolerance is a breeding target.Few genes in rice are reported to confer cold tolerance at both the vegetative and reproductive stages.This study revealed a rice-specific 24-nt miRNA,miR1868,whose accumulation was suppressed by cold stress.Knockdown of MIR1868 increased seedling survival,pollen fertility,seed setting,and grain yield under cold stress,whereas its overexpression conferred the opposite phenotype.Knockdown of MIR1868 increased reactive oxygen species(ROS)scavenging and soluble sugar content under cold stress by increasing the expression of peroxidase genes and sugar metabolism genes,and its overexpression produced the opposite effect.Thus,MIR1868 negatively regulated rice cold tolerance via ROS scavenging and sugar accumulation.

Alkali Tolerance of Concrete Internal Curing Agent Based on Sodium Carboxymethyl Starch

Internal curing agents (ICA) based on super absorbent polymer have poor alkali tolerance and reduce the early strength of concrete.An alkali tolerate internal curing agent (CAA-ICA) was designed and prepared by using sodium carboxymethyl starch (CMS) with high hydrophilicity,acrylic acid (AA) containing anionic carboxylic group and acrylamide (AM) containing non-ionic amide group as the main raw materials.The results show that the ratio of CAA-ICA alkali absorption solution is higher than that existing ICA,which solves the low water absorption ratio of the ICA in alkali environment.The water absorption ratio of CAA-ICA in saturated Ca(OH)_(2) solution is 95.8 g·g^(-1),and the alkali tolerance coefficient is 3.4.The application of CAA-ICA in cement-based materials can increase the internal relative humidity and miniaturize the pore structure.The compressive strength of mortar increases up to 12.95%at 28 d,which provids a solution to overcome the reduction of the early strength.

Drought-Tolerant Rice at Molecular Breeding Eras:An Emerging Reality

Rice(Oryza sativa L.)stands as the most significantly influential food crop in the developing world,with its total production and yield stability affected by environmental stress.Drought stress impacts about 45%of the world’s rice area,affecting plants at molecular,biochemical,physiological,and phenotypic levels.The conventional breeding method,predominantly employing single pedigree selection,has been widely utilized in breeding numerous drought-tolerant rice varieties since the Green Revolution.With rapid progress in plant molecular biology,hundreds of drought-tolerant QTLs/genes have been identified and tested in rice crops under both indoor and field conditions.Several genes have been introgressed into elite germplasm to develop commercially accepted drought-tolerant varieties,resulting in the development of several drought-tolerant rice varieties through marker-assisted selection and genetically engineered approaches.This review provides up-to-date information on proof-of-concept genes and breeding methods in the molecular breeding era,offering guidance for rice breeders to develop drought-tolerant rice varieties.

Abiotic stress treatment reveals expansin like A gene OfEXLA1 improving salt and drought tolerance of Osmanthus fragrans by responding to abscisic acid

Sweet osmanthus(Osmanthus fragrans) is a having general approval aromatic tree in China that is widely applied to landscaping and gardening. However, the evergreen tree adaptability is limited by many environmental stresses. Currently, limited information is available regarding the genetic analysis and functional identification of expansin genes in response to abiotic stress in sweet osmanthus. In this study, a total of 29 expansin genes were identified and divided into four groups by genome-wide analysis from the sweet osmanthus genome. Transcriptome and quantitative Real-time PCR analysis showed that the cell wall-localized protein expansin-like A(OfEXLA1) gene was significantly induced by salt and drought treatment. Histochemical GUS staining of transgenic Arabidopsis lines in which GUS activity was driven with the OfEXLA1 promoter, GUS activity was significantly induced by salt, drought, and exogenous abscisic acid(ABA). In yeast, we found OfEXLA1overexpression significantly improved the population of cells compared with wild-type strains after NaCl and polyethylene glycol(PEG)treatment. Additionally, OfEXLA1 overexpression not only promoted plant growth, but also improved the salt and drought tolerance in Arabidopsis. To gain insight into the role of ABA signaling in the regulation of OfEXLA1 improving abiotic tolerance in sweet osmanthus, four differentially expressed ABA Insensitive 5(ABI5)-like genes(OfABL4, OfABL5, OfABL7, and OfABL8) were identified from transcriptome, and dualluciferase(dual-LUC) and yeast one hybrid(Y1H) assay showed that OfABL4 and OfABL5 might bind to OfEXLA1 promoter to accumulate the OfEXLA1 expression by responding to ABA signaling to improve abiotic tolerance in sweet osmanthus. These results provide the information for understanding the molecular functions of expansin-like A gene and molecular breeding of sweet osmanthus in future.

Quantum generative adversarial networks based on a readout error mitigation method with fault tolerant mechanism

Readout errors caused by measurement noise are a significant source of errors in quantum circuits,which severely affect the output results and are an urgent problem to be solved in noisy-intermediate scale quantum(NISQ)computing.In this paper,we use the bit-flip averaging(BFA)method to mitigate frequent readout errors in quantum generative adversarial networks(QGAN)for image generation,which simplifies the response matrix structure by averaging the qubits for each random bit-flip in advance,successfully solving problems with high cost of measurement for traditional error mitigation methods.Our experiments were simulated in Qiskit using the handwritten digit image recognition dataset under the BFA-based method,the Kullback-Leibler(KL)divergence of the generated images converges to 0.04,0.05,and 0.1 for readout error probabilities of p=0.01,p=0.05,and p=0.1,respectively.Additionally,by evaluating the fidelity of the quantum states representing the images,we observe average fidelity values of 0.97,0.96,and 0.95 for the three readout error probabilities,respectively.These results demonstrate the robustness of the model in mitigating readout errors and provide a highly fault tolerant mechanism for image generation models.

Control Strategies for Digital Twin Systems

With the continuous breakthrough in information technology and its integration into practical applications, industrial digital twins are expected to accelerate their development in the near future. This paper studies various control strategies for digital twin systems from the viewpoint of practical applications.To make full use of advantages of digital twins for control systems, an architecture of digital twin control systems, adaptive model tracking scheme, performance prediction scheme, performance retention scheme, and fault tolerant control scheme are proposed. Those schemes are detailed to deal with different issues on model tracking, performance prediction, performance retention, and fault tolerant control of digital twin systems. Also, the stability of digital twin control systems is analysed. The proposed schemes for digital twin control systems are illustrated by examples.

Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management.However,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more attention.Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain normal.The approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced tolerance.The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up.No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation.With the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT recipients.Cellular strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells.The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical practice.Here,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

The BEL1-like transcription factor GhBLH5-A05 participates in cotton response to drought stress

Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.

Boosting oxygen reduction activity and CO_(2) resistance on bismuth ferrite-based perovskite cathode for low-temperature solid oxide fuel cells below 600℃

Developing efficient and stable cathodes for low-temperature solid oxide fuel cells(LT-SOFCs) is of great importance for the practical commercialization.Herein,we propose a series of Sm-modified Bi_(0.7-x)Sm_xSr_(0.3)FeO_(3-δ) perovskites as highly-active catalysts for LT-SOFCs.Sm doping can significantly enhance the electrocata lytic activity and chemical stability of cathode.At 600℃,Bi_(0.675)Sm_(0.025)Sr_(0.3)FeO_(3-δ)(BSSF25) cathode has been found to be the optimum composition with a polarization resistance of 0.098 Ω cm^2,which is only around 22.8% of Bi_(0.7)Sr_(0.3)FeO_(3-δ)(BSF).A full cell utilizing BSSF25 displays an exceptional output density of 790 mW cm^(-2),which can operate continuously over100 h without obvious degradation.The remarkable electrochemical performance observed can be attributed to the improved O_(2) transport kinetics,superior surface oxygen adsorption capacity,as well as O_(2)p band centers in close proximity to the Fermi level.Moreover,larger average bonding energy(ABE) and the presence of highly acidic Bi,Sm,and Fe ions restrict the adsorption of CO_(2) on the cathode surface,resulting in excellent CO_(2) resistivity.This work provides valuable guidance for systematic design of efficient and durable catalysts for LT-SOFCs.

Assessment of molecular markers and marker-assisted selection for drought tolerance in barley(Hordeum vulgare L.)

This review updates the present status of the field of molecular markers and marker-assisted selection(MAS),using the example of drought tolerance in barley.The accuracy of selected quantitative trait loci(QTLs),candidate genes and suggested markers was assessed in the barley genome cv.Morex.Six common strategies are described for molecular marker development,candidate gene identification and verification,and their possible applications in MAS to improve the grain yield and yield components in barley under drought stress.These strategies are based on the following five principles:(1)Molecular markers are designated as genomic‘tags’,and their‘prediction’is strongly dependent on their distance from a candidate gene on genetic or physical maps;(2)plants react differently under favourable and stressful conditions or depending on their stage of development;(3)each candidate gene must be verified by confirming its expression in the relevant conditions,e.g.,drought;(4)the molecular marker identified must be validated for MAS for tolerance to drought stress and improved grain yield;and(5)the small number of molecular markers realized for MAS in breeding,from among the many studies targeting candidate genes,can be explained by the complex nature of drought stress,and multiple stress-responsive genes in each barley genotype that are expressed differentially depending on many other factors.

Emerging Trends in Damage Tolerance Assessment:A Review of Smart Materials and Self-Repairable Structures

The discipline of damage tolerance assessment has experienced significant advancements due to the emergence of smart materials and self-repairable structures.This review offers a comprehensive look into both traditional and innovative methodologies employed in damage tolerance assessment.After a detailed exploration of damage tolerance concepts and their historical progression,the review juxtaposes the proven techniques of damage assessment with the cutting-edge innovations brought about by smart materials and self-repairable structures.The subsequent sections delve into the synergistic integration of smart materials with self-repairable structures,marking a pivotal stride in damage tolerance by establishing an autonomous system for immediate damage identification and self-repair.This holistic approach broadens the applicability of these technologies across diverse sectors yet brings forth unique challenges demanding further innovation and research.Additionally,the review examines future prospects that combine advanced manufacturing processes with data-centric methodologies,amplifying the capabilities of these‘intelligent’structures.The review culminates by highlighting the transformative potential of this union between smart materials and self-repairable structures,promoting a sustainable and efficient engineering paradigm.

Immunology demystified: A guide for transplant hepatologists

Liver transplantation has become standard practice for treating end-stage liver disease.The success of the procedure relies on effective immunosuppressive medications to control the host's immune response.Despite the liver's inherent capacity to foster tolerance,the early post-transplant period is marked by significant immune reactivity.To ensure favorable outcomes,it is imperative to identify and manage various rejection types,encompassing T-cell-mediated,antibody-mediated,and chronic rejection.However,the approach to prescribing immunosuppressants relies heavily on clinical judgment rather than evidencebased criteria.Given that the majority of patients will require lifelong immunosuppression as the mechanisms underlying operational tolerance are still being investigated,healthcare providers must possess an understanding of immune responses,rejection mechanisms,and the pathways targeted by immunosuppressive drugs.This knowledge enables customization of treatments and improved patient care,even though a consensus on an optimal immunosuppressive regimen remains elusive.

Pros and cons of live kidney donation in prediabetics: A critical review and way forward

There is shortage of organs,including kidneys,worldwide.Along with deceased kidney transplantation,there is a significant rise in live kidney donation.The prevalence of prediabetes(PD),including impaired fasting glucose and impaired glucose tolerance,is on the rise across the globe.Transplant teams frequently come across prediabetic kidney donors for evaluation.Prediabetics are at risk of diabetes,chronic kidney disease,cardiovascular events,stroke,neuropathy,retinopathy,dementia,depression and nonalcoholic liver disease along with increased risk of all-cause mortality.Unfortunately,most of the studies done in prediabetic kidney donors are retrospective in nature and have a short follow up period.There is lack of prospective long-term studies to know about the real risk of complications after donation.Furthermore,there are variations in recommendations from various guidelines across the globe for donations in prediabetics,leading to more confusion among clinicians.This increases the responsibility of transplant teams to take appropriate decisions in the best interest of both donors and recipients.This review focuses on pathophysiological changes of PD in kidneys,potential complications of PD,other risk factors for development of type 2 diabetes,a review of guidelines for kidney donation,the potential role of diabetes risk score and calculator in kidney donors and the way forward for the evaluation and selection of prediabetic kidney donors.

Reliability Analysis of Varietal Hypercube

Connectivity is a vital metric to explore fault tolerance and reliability of network structure based on a graph model. Let be a connected graph. A connected graph G is called supper-κ (resp. supper-λ) if every minimum vertex cut (edge cut) of G is the set of neighbors of some vertex in G. The g-component connectivity of a graph G, denoted by , is the minimum number of vertices whose removal from G results in a disconnected graph with at least g components or a graph with fewer than g vertices. The g-component edge connectivity can be defined similarly. In this paper, we determine the g-component (edge) connectivity of varietal hypercube for small g.