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Objective This study evaluates the long-term trends in Multiple Myeloma (MM) incidence, mortality, and Age-Period-Cohort (APC) effects in the BRICS nations (Brazil, Russia, India, China, and South Africa). Methods Data on age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and 95% uncertainty intervals (UIs), were obtained from the Global Burden of Disease Study 2021. Joinpoint regression model was used to estimate the average annual percentage change (AAPC) and annual percentage change (APC) trends from 1992 to 2021, and the Age-Period-Cohort model evaluated nonlinear impacts of age, period, and cohort effects. Projections to 2046 were calculated using Bayesian APC modeling. Results From 1992 to 2021, MM incidence and death cases in the BRICS nations increased nearly four to fivefold, with ASIR and ASMR nearly doubling. China and India had lower ASIR and ASMR than other BRICS countries despite accounting for over half of cases and deaths. South Africa consistently had the highest ASIR and ASMR in both 1992 and 2021. China experienced a significant increase in ASIR (AAPC 4.92%, p  < 0.001) and ASMR (AAPC 4.07%, p  < 0.001) over the past three decades. MM incidence and mortality increased with aging, and the age effect on MM was more pronounced among individuals aged greater than 40 years. Birth cohorts’ impact on MM varied greatly between BRICS, with China suffering the largest risk increase among those born after the 1970s. Projections indicate ASIR and ASMR will reach 2.44 and 1.82 per 100,000 by 2046, continuing to rise across the BRICS nations. Conclusions MM burden is rapidly increasing in the BRICS, closely tied to population aging. Targeted strategies addressing each country’s unique challenges are essential as the burden continues to grow.

The complete nucleotide sequences of the chloroplast (cp) and mitochondrial (mt) genomes of resurrection plant Boea hygrometrica (Bh, Gesneriaceae) have been determined with the lengths of 153,493 bp and 510,519 bp, respectively. The smaller chloroplast genome contains more genes (147) with a 72% coding sequence, and the larger mitochondrial genome have less genes (65) with a coding faction of 12%. Similar to other seed plants, the Bh cp genome has a typical quadripartite organization with a conserved gene in each region. The Bh mt genome has three recombinant sequence repeats of 222 bp, 843 bp, and 1474 bp in length, which divide the genome into a single master circle (MC) and four isomeric molecules. Compared to other angiosperms, one remarkable feature of the Bh mt genome is the frequent transfer of genetic material from the cp genome during recent Bh evolution. We also analyzed organellar genome evolution in general regarding genome features as well as compositional dynamics of sequence and gene structure/organization, providing clues for the understanding of the evolution of organellar genomes in plants. The cp-derived sequences including tRNAs found in angiosperm mt genomes support the conclusion that frequent gene transfer events may have begun early in the land plant lineage.

Sucrose-metabolizing enzymes in plant leaves have hitherto been investigated mainly in temperate plants, and rarely conducted in tandem with gene expression and sugar analysis. Here, we investigated the sugar content, gene expression, and the activity of sucrose-metabolizing enzymes in the leaves of , a tropical tree widely cultivated for natural rubber. Sucrose, fructose and glucose were the major sugars detected in leaves at four developmental stages (I to IV), with starch and quebrachitol as minor saccharides. Fructose and glucose contents increased until stage III, but decreased strongly at stage IV (mature leaves). On the other hand, sucrose increased continuously throughout leaf development. Activities of all sucrose-cleaving enzymes decreased markedly at maturation, consistent with transcript decline for most of their encoding genes. Activity of sucrose phosphate synthase (SPS) was low in spite of its high transcript levels at maturation. Hence, the high sucrose content in mature leaves was not due to increased sucrose-synthesizing activity, but more to the decline in sucrose cleavage. Gene expression and activities of sucrose-metabolizing enzymes in leaves showed striking differences compared with other plants. Unlike in most other species where vacuolar invertase predominates in sucrose cleavage in developing leaves, cytoplasmic invertase and sucrose synthase (cleavage direction) also featured prominently in . Whereas SPS is normally responsible for sucrose synthesis in plant leaves, sucrose synthase (synthesis direction) was comparable or higher than that of SPS in leaves. Mature leaves had an unusually high sucrose:starch ratio of about 11, the highest reported to date in plants.

The para rubber tree ( Hevea brasiliensis ) is the world’s sole commercial source of natural rubber, a vital industrial raw material. However, the narrow genetic diversity of this crop poses challenges for rubber breeding. Here, we generate high-quality de novo genome assemblies for three H. brasiliensis cultivars, two H. brasiliensis wild accessions, and three other Hevea species ( H. nitida , H. pauciflora , and H. benthamiana ). Through analyzing genomes of 94 Hevea accessions, we identify five distinct lineages that do not align with their previous species delineations. We discover multiple accessions with hybrid origins between these lineages, indicating incomplete reproductive isolation between them. Only two out of four wild lineages have been introduced to commercial rubber cultivars. Furthermore, we reveal that the rubber production traits emerged following the development of a large REF/SRPP gene cluster and its functional specialization in rubber-producing laticifers within this genus. These findings would enhance rubber breeding and benefit research communities. The para rubber tree is the world’s sole commercial source of natural rubber. Here, the authors assemble the pangenome based on five genomes of H. brasiliensis and three genomes of other Hevea species, and reveal species delineation and rubber trait evolution through phylogenomic analyses.

Ferroptosis is an iron-dependent form of regulated cell death and is characterized by high concentrations of intracellular lipid peroxide and a redox imbalance in the cells. Ferroptosis shows distinct morphological and biological features compared with other prominent mechanisms of programmed cell death. The distinct characteristics of ferroptosis include the dysfunction of the lipid peroxide repair enzyme glutathione peroxidase 4, the presence of ferrous iron overload, and the lipid peroxidation of polyunsaturated fatty acids. Several other metabolic pathways (including iron, lipid, and amino acid metabolism) and ferritinophagy, as well as transcription factors, can modulate ferroptosis. However, to date, the molecular mechanism of ferroptosis has not been elucidated. This review outlines the discovery, characterization, regulatory mechanisms, and crosstalk of ferroptosis. Further, we have noted the controversial elements in the ferroptosis-related mechanisms. Our inferences may provide a partial reference for developing strategies to regulate ferroptosis.

The Holland wind model remains limitations on the accurate surface wind estimation of tropical cyclone (TC) and the storm surge modelling. This study investigates the influence of TC moving speeds on the attenuation effect of Holland surface wind and proposes a weakening factor to correct Holland surface wind. Then the corrected surface wind fields are combined with ERA5 to produce the improved hybrid surface wind fields to simulate total water levels. The significant linear correlation (R 2 = 0.54) between TC moving speeds and the weakening factor shows that the slower the TC moves, the greater attenuation rate the surface wind speeds need. The improved Hybrid wind fields (Hybrid_f) have the best agreement with ground observations, with the Skills and RMSEs in the range of 0.65-0.93 and 2.3-6.9 m/s. The total water levels of storm surge simulated by the Hybrid_f have the best agreement with gauge measurements, with the Skills and RMSEs in the range of 0.72-0.99 and 0.16-0.51 m. In particular, the improved surface wind fields for TCs with slower movement substantially mitigate the severe reduction of water levels. These findings offer valuable insights for optimizing the surface wind fields to improve storm surge modeling and other applications.

Understanding groundwater–surface water interaction is essential for water resource management and watershed ecological protection. However, the existing studies often emphasize the tracer role of hydrogeochemical methods (including hydrochemistry and isotopes) while underestimating the importance of analyzing watershed hydraulic characteristics, thus neglecting the indications of the driving mechanisms (hydraulic head difference) for the water exchange. Taking the Songhua River in the Sanjiang Plain as an example, this study combines hydraulic, hydrochemical, and isotopic methods to clarify the groundwater–surface water interactions from both a driving mechanism perspective and a hydrogeochemical characterization perspective within the water cycle. The results indicate that human exploitation has caused river water to infiltrate into groundwater, converting the section into a losing river, where surface water consistently exhibits a hydraulic tendency to recharge the aquifer. The influence zone of the river extends up to 3.5 km from the riverbank, with an average recharge rate from the river reaching 78.04% within this area. This recharge mixes and dilutes the adjacent groundwater, impacting its hydrogeochemical characteristics. This study enhances the understanding of combined methods for groundwater–surface water interaction and provides a scientific basis for water resource management and pollution control strategies in the local agricultural regions.

Acute lymphoblastic leukemia (ALL) is the most common malignant hematological diseases in children. An immunosuppressive microenvironment, particularly regulatory T cell (Treg) infiltration, has been documented to be highly associated with childhood ALL. This present study, based on genetic factors, was aimed at investigating the mutations potentially involved in the immunosuppressive microenvironment in childhood ALL. After whole-exome sequencing was used on DNA extracted from the T cells of ALL bone marrow samples, we found the FOXC1 H446HG induced a increased Treg while decreased cytotoxic T lymphocyte (CTL) in bone marrow. The mutation of FOXC1 in T cell promoted the proliferation of leukemia cells in vitro and in vivo. CpG islands formed by insertion mutation led to an abnormal increase in exon methylation and were associated with the suppression of FOXC1. Decreased FOXC1 attenuated the transcription of HDAC1, thus resulting in the activation of KLF10 through increasing H3K27 acetylation in the promoter region. In conclusion, the de novo insertion mutation in FOXC1 induced suppression of FOXC1, thereby promoting a Treg/CTL shift in the ALL immune microenvironment. The FOXC1 H446HG mutation might be a potential therapeutic target for ALL in the future.

BackgroundThe prognosis of MYCN positive NB is poor, and there is no targeted drug for N-myc at present. This study aims to screen out hub genes closely related to MYCN , analyze the relationship between hub genes and NB microenvironment, and provide basis for molecular targeted therapy of MYCN positive NB.MethodsWe combined the microarray data of GSE45547 (n=649) and GSE49710 (n=498), screened the DEGs between MYCN positive (n=185) and MYCN negative NB (n=951), performed WGCNA, Lasso regression and Roc analyses on the merged matrix, and obtained the hub genes related to MYCN in the training group. We performed ssGSEA on the experimental group to calculate the infiltration level of 28 kinds of immune cells in each sample, compared the differences of immune cell infiltration between MYCN positive and MYCN negative group. The influences of hub genes on the distribution of each immune cell were also analyzed by ssGSEA. The expression differences of the three hub genes were verified in the E-MTAB-8248 cohort (n=223), and the correlation between hub genes and prognosis of NB was calculated by Kaplan-Meier method in GSE62564 (n=498) and the validation group. We also verified the expression differences of hub genes by qRT-PCR in SK-N-BE(2), SKNDZ, Kelly and SH-SY5Y cell lines.ResultsHere were 880 DEGs including 420 upregulated and 460 downregulated genes in MYCN positive NB in the training group. Overlap of the DEGs and WGCNA networks identified four shared genes, namely, ZNF695 , CHEK1 , C15ORF42 and EXO1 , as candidate hub genes in MYCN positive NB. Three core genes, ZNF695 , CHEK1 and C15ORF42 , were finally identified by Lasso regression and Roc analyses. ZNF695 , CHEK1 and C15ORF42 were highly expressed in MYCN positive NB tissues and cell lines. These three genes were closely related to the prognosis of children with NB. Except that Activated CD4 T cell and Type2 T helper cell increased, the infiltration levels of the other 26 cells decreased significantly in MYCN positive NB tissues. The infiltration levels of Type2 T helper cell and Activated CD4 T cell were also significantly positively correlated with the expression levels of the three hub genes.ConclusionZNF695 , CHEK1 and C15ORF42 are highly expressed in MYCN positive NB, and their expression levels are negatively correlated with the prognosis of children with NB. The infiltration levels of Activated CD4 T cell and Type2 T helper cell increased in the microenvironment of MYCN positive NB and were significantly positively correlated with the expression levels of the three hub genes. The results of this study provide that ZNF695 , CHEK1 and C15ORF42 may be potential prognostic markers and immunotherapy targets for MYCN positive NB.