Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.

Introduction: Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Methods: Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Results: Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. Conclusion: The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. Clinical trial registration: http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.

TaMYB-CC5 gene specifically expressed in root improve tolerance of phosphorus deficiency and drought stress in wheat.

Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat.

[Clinical Characteristics and Prognosis of Myelodysplastic Syndromes Patients with RUNX1 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes (MDS) with RUNX1 gene mutation. METHODS: Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology, the Second Affiliated Hospital of Air Force Military Medical University from October 1, 2015 to October 31, 2022 were retrospectively analyzed. Gene mutation detection was performed by second-generation sequencing technology, and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed. RESULTS: A total of 30 cases (16.95%) of RUNX1 gene mutations were detected, including 15 missense mutations (50.0%), 9 frameshift deletion mutations (30.0%), 4 splice site mutations (13.3%), 1 insertion mutation (3.3%), and 1 nonsense mutation (3.3%). Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis (range: 62.25-78.50 years old). There were no significantly differences between RUNX1 mutations and wild type patients in age distribution, gender, peripheral blood white blood cell count, hemoglobin level, bone marrow and peripheral blood blasts ratio, IPSS-R cytogenetics, IPSS-R stage, etc. (P >0.05). However, there were statistically significant differences in platelet count and whether complicated karyotype. Compared with patients without RUNX1 gene mutation, patients with RUNX1 gene mutation had lower platelet count (P =0.018), and were less likely to have complicatedkaryotype at initial diagnosis (P =0.01). Cox proportional hazards model analysis showed that when other covariates remained unchanged, the higher the platelet count, the better the survival of patients (HR=0.995, 95%CI : 0.990-0.999, P =0.036); In the IPSS-M prognostic stratification, keeping other covariates unchanged, the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group (HR=0.149, 95%CI : 0.031-0.721, P =0.018; HR=0.026, 95%CI : 0.003-0.234, P =0.001). Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time (P < 0.001). Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group. RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients. CONCLUSION: RUNX1 gene mutation is an adverse prognostic factor in MDS patients, especially in the IPSS-M prognosis stratification group of low-risk, medium-low risk, medium-high risk and WHO classification of early patients.

Structurally Diverse Stilbenoids as Potent α-Glucosidase Inhibitors with Antidiabetic Effect from Morus alba.

Fifteen stilbenoid derivatives, including five previously undescribed ones (albaphenols A-E, 1-5) with diverse scaffolds, were obtained from the well-known agricultural economic tree Morus alba. Their structures, including absolute stereochemistries, were fully characterized by detailed interpretation of spectroscopic data and quantum chemical computational analyses of nuclear magnetic resonance (NMR) and electric circular dichroism (ECD). Albaphenol A (1) features an unprecedented rearranged carbon skeleton incorporating a novel 2-oxaspiro[bicyclo[3.2.1]octane-6,3'-furan] motif; albaphenol C (3) is likely derived from a cometabolite through an interesting intramolecular transesterification reaction; and albaphenol E (5) bears a cleavage-reconnection scaffold via a dioxane ring. All of the compounds exhibited significant inhibition against the diabetic target α-glucosidase, with low to submicromole IC50 values (0.70-8.27 µM), and the binding modes of selected molecules with the enzyme were further investigated by fluorescence quenching, kinetics, and molecular docking experiments. The antidiabetic effect of the most active and abundant mulberrofuran G (6) was further assessed in vivo in diabetic mice, revealing potent antihyperglycemic activity and comparable antidiabetic efficacy to the clinical drug acarbose.

Lipases are differentially regulated by hormones to maintain free fatty acid homeostasis for insect brain development.

BACKGROUND: Free fatty acids (FFAs) play vital roles as energy sources and substrates in organisms; however, the molecular mechanism regulating the homeostasis of FFA levels in various circumstances, such as feeding and nonfeeding stages, is not fully clarified. Holometabolous insects digest dietary triglycerides (TAGs) during larval feeding stages and degrade stored TAGs in the fat body during metamorphosis after feeding cessation, which presents a suitable model for this study. RESULTS: This study reported that two lipases are differentially regulated by hormones to maintain the homeostasis of FFA levels during the feeding and nonfeeding stages using the lepidopteran insect cotton bollworm Helicoverpa armigera as a model. Lipase member H-A-like (Lha-like), related to human pancreatic lipase (PTL), was abundantly expressed in the midgut during the feeding stage, while the monoacylglycerol lipase ABHD12-like (Abhd12-like), related to human monoacylglycerol lipase (MGL), was abundantly expressed in the fat body during the nonfeeding stage. Lha-like was upregulated by juvenile hormone (JH) via the JH intracellular receptor methoprene-tolerant 1 (MET1), and Abhd12-like was upregulated by 20-hydroxyecdysone (20E) via forkhead box O (FOXO) transcription factor. Knockdown of Lha-like decreased FFA levels in the hemolymph and reduced TAG levels in the fat body. Moreover, lipid droplets (LDs) were small, the brain morphology was abnormal, the size of the brain was small, and the larvae showed the phenotype of delayed pupation, small pupae, and delayed tissue remodeling. Knockdown of Abhd12-like decreased FFA levels in the hemolymph; however, TAG levels increased in the fat body, and LDs remained large. The development of the brain was arrested at the larval stage, and the larvae showed a delayed pupation phenotype and delayed tissue remodeling. CONCLUSIONS: The differential regulation of lipases expression by different hormones determines FFAs homeostasis and different TAG levels in the fat body during the feeding larval growth and nonfeeding stages of metamorphosis in the insect. The homeostasis of FFAs supports insect growth, brain development, and metamorphosis.

Prenylated Flavanone Enantiomers with α-Glucosidase Inhibitory Activity from the Root Bark of Morus alba.

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target a-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

[Study on related influencing factors on the occurrence of redundant sign in the cauda equina in lumbar spinal stenosis].

OBJECTIVE: To analyze the relational factors influencing the formation of cauda equina redundant nerve roots (RNRs) of the lumbar spinal stenosis. METHODS: Clinical data of 116 patients with lumbar spinal stenosis treated from January 2016 to June 2019 were retrospectively analyzed. The patients were divided into redundant nerve roots(RNRs) group and non-RNRs group based on the presence or absence of RNRs on sagittal T2-weighted MRI. In the non-RNRs group, there were 74 patients, including 38 males and 36 females with an average age of (62.00±10.41) years old, the body mass index (BMI) was (23.09±2.22) kg·m-2;the maximum stenosis segment was L2-L3 in 12 cases, L3-L4 in 38, L4-L5 in 20, and L5S1 in 4, respectively. In the RNRs group, there were 42 patients, including 18 males and 24 females with an average age of (63.36±8.73) years old, the BMI was (22.63±2.60) kg·m-2;the maximum stenosis segment was L2-L3 in 3 cases, L3-L4 in 9, L4-L5 in 27 and L5S1 in 3, respectively. MRI was performed in the supine position to observe the conshape and morphology of the redundant nerve in the sagittal position. The preoperative low back and leg pain visual analogue scale(VAS), and preoperative Oswestry disability index(ODI) were analyzed, and the rate of spondylolisthesis and ligamentum flavum hypertrophy were compared. Simultaneously, the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, median sagittal diameter at the inter-vertebral space level(DIW-MSD), median sagittal diameter at the pedicel level(DV-MSD), range of motion(ROM) of the stenotic segment were measured and analyzed. RESULTS: Among the 116 patients with lumbar spinal stenosis, 42 patients developed RNRs, with an incidence of 36.2%. There were no significant differences in gender, age, BMI, preoperative VAS for lumbar and leg pain and ODI between two groups(P>0.05). There were statistically significant differences regard to the duration of symptoms and the rate of spondylolisthesis and ligamentum flavum hypertrophy (P<0.05);the inter-vertebral height, intervertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD, ROM of the stenotic segment were also significantly different between two groups(P<0.05). However, there was no significant difference in DV-MSD between two groups(P>0.05). CONCLUSION: The inter-vertebral height, inter-vertebral foramen height, inter-vertebral height+vertebral height, DIW-MSD and ROM of the stenotic segment were the crucial factors related to RNRs in lumbar spinal stenosis.

[Differences in Soil Fertility and Bacterial Community Structure Between Carbon Inputs such as Biochar and Organic Fertilizer and Their Relationship].

The potato planting area of Guizhou Province ranks second in China. However, due to factors such as climatic conditions and unbalanced fertilization, soil organic matter in potato fields is consumed rapidly and has a large deficit, which affects soil biological function and soil fertility. Biochar and organic fertilizer are effective ways to supplement foreign aid organic matter to improve soil quality. However, the differences in soil fertility and microbial community structure and their relationships under the conditions of organic fertilizer or biochar combined with chemical fertilizer are not clear. In this study, three treatments of conventional fertilization （NPK）, increased application of biochar （NPKB）, and increased application of organic fertilizer （NPKO） were set up to investigate the characteristics of potato rhizosphere soil, bacterial community composition, and diversity； to analyze the effects of these factors on the soil integrated fertility index； and to explore the direct and indirect effects of IFI on soil fertility and bacterial community structure differences between treatments and their driving factors. The results showed that soil pH, available phosphorus （AP）, available potassium （AK）, total nitrogen （TN）, organic carbon （SOC）, and C/N ratio were significantly higher in the NPKB and NPKO treatments than in the NPK treatment （P<0.05）. Soil IFI was greatest for NPKO, followed by NPKB and least for the NPK treatment. A total of 8 214 ASVs were obtained from all the soil samples, belonging to 26 phyla, 75 classes, 165 orders, 176 families, and 251 genera （excluding unidentified fungi）. Proteobacteria, Actinobacteria, and Chloroflexi were the dominant phyla, accounting for 54.85% of all ASVs. Compared to that in the NPK and NPKB treatments, the NPKO treatment had the highest bacterial diversity and number of significantly different taxa, and soil AN, AP, AK, SOC, TN, and IFI were significant correlates of bacterial diversity index （P<0.05）. Additionally, pH, TN, and SOC were significant influencers of bacterial taxa differences （P<0.05）, with importance ranked as TN （70.59%） > SOC （49.42%） > pH （27.08%）. Structural equations suggested that pH-related soil properties and bacterial community diversity were the direct pathways influencing IFI, and soil pH-related soil characteristics could also indirectly affect IFI by affecting bacterial Shannon diversity. These results indicate that soil fertility and bacterial community structure were significantly different and correlated between the biochar and organic fertilizer addition treatments and that pH and bacterial community diversity were the key factors influencing IFI, with the NPKO treatment in particular having the best effect on improving IFI. Considering the effect of soil fertilization and the functional group of bacteria, NPKO is the recommended combination for the best synergistic effect of soil fertilization, that is, N 150 kg·hm-2+P2O5 135 kg·hm-2+K2O 135 kg·hm-2+organic fertilizer 6.6 t·hm-2.

Exotic plants introduction changed soil nutrient cycle and symbiotic relationship with arbuscular mycorrhizal fungi in wetland ecological projects.

In the process of applying exotic plants to wetland ecological restoration, insufficiently evaluated alien species may exhibit strong competitiveness and fecundity. Once introduced, they can displace native flora, disrupt the original ecological balance, diminish biodiversity, and even induce ecosystem dysfunction. Furthermore, exotic plants have the potential to alter soil microbial community structure, including the composition and activity of beneficial symbiotic microorganisms such as arbuscular mycorrhizal fungi (AMF), thereby impacting soil nutrient cycling and interplant nutrient competition. Here, we conducted three consecutive years of sampling experiments to investigate the succession of AMF communities associated with the invasive plant Spartina alterniflora along an initial introduction chronosequence, and to identify the key environmental factors influencing its response to S. alterniflora invasion. Our findings reveal that early-stage invasion by S. alterniflora alters the composition of soil AMF communities with unclassified_c__Glomeromycetes and Glomus-viscosum-VTX00063 consistently dominating. Additionally, as the duration of introduction increases, the diversity of rhizosphere soil AMF significantly decreases, while its evenness remains relatively stable. It's indicated that soil ω, AN, AK and N/P ratio were the main influencing factors of the integral AMF community. Notably, soil available phosphorus (AP) emerges as a positive influence on the important AMF taxa. The results confirm the mutual feedback effect between the invasion of the perennial herb S. alterniflora and AMF, in which specific AMF assist in nutrient absorption to promote S. alterniflora growth, potentially facilitating its rapid and successful invasion of new habitats. Given the likely differential effects of AMF communities on various plant species, our findings could contribute to anticipating future AMF-mediated effects during the introduction of alien plants.

Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac.

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors' knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.

Effectiveness and safety of vascular intervention plus lenvatinib versus vascular intervention alone for hepatocellular carcinoma patients with portal vein tumor thrombus: a retrospective comparative study.

Background: This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes. Methods: We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model. Results: The median follow-up duration was 20.07 months (interquartile range: 6.41-25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely. Conclusion: The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.

Impairment in acquisition of conditioned fear in people with depressive symptoms.

Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.

Aberrant Splicing of COL4A5 Intronic Variant Contribute to the Pathogenesis of X-Linked Alport Syndrome: A Case Series.

Introduction: X-linked Alport syndrome (XLAS) is caused by pathogenic variants in COL4A5 which lead to abnormalities of the glomerular basement membrane (GBM) structural and is characterized by progressive kidney disease, hearing loss, and ocular abnormalities. The aim of this study was to identify gene mutations in a Chinese family with XLAS by whole-exome sequencing (WES) and verified the pathogenicity of the mutation in vitro experiments. Case Presentation: A five-generation pedigree with a total of 49 family members originating from Hainan province of China was investigated in this study. The proband was a 23-year-old male who developed microscopic hematuria, proteinuria and end-stage kidney disease (ESKD) at age 17. WES identified a novel splicing mutation c.321+5G>A of COL4A5, which cause exon skip. Further co-segregation analysis confirmed that this mutation exists in relatives who had renal abnormalities using Sanger sequencing. According to American College of Medical Genetics and Genomics guidelines (ACMG), the mutation was determined to be of uncertain significance (VUS). In vitro splicing experiments have shown that the COL4A5 variant induces aberrant mRNA splicing and transcript deletion. Conclusion: We identified a novel intronic COL4A5 pathogenic mutation (c.321+5G>A) in a Chinese XLAS family and described the phenotypes of affected relatives. This study expands the mutation spectrum of COL4A5 gene in XLAS and demonstrates the importance of gene screening for AS.

Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

Emodin alleviates intestinal ischemia/reperfusion-induced lung injury by upregulating HO-1 expression via PI3K/AkT pathway.

BACKGROUND: Emodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. METHODS: Intestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. RESULTS: Our data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. CONCLUSION: In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.

Ecological and evolutionary processes involved in shaping microbial habitat generalists and specialists in urban park ecosystems.

Microbiomes are integral to ecological health and human well-being; however, their ecological and evolutionary drivers have not been systematically investigated, especially in urban park ecosystems. As microbes have different levels of tolerance to environmental changes and habitat preferences, they can be categorized into habitat generalists and specialists. Here, we explored the ecological and evolutionary characteristics of both prokaryotic and microeukaryotic habitat generalists and specialists from six urban parks across five habitat types, including moss, soil, tree hole, water, and sediment. Our results revealed that different ecological and evolutionary processes maintained and regulated microbial diversity in urban park ecosystems. Under ecological perspective, community assembly of microbial communities was mainly driven by stochastic processes; however, deterministic processes were higher for habitat specialists than generalists. Microbial interactions were highly dynamic among habitats, and habitat specialists played key roles as module hubs in intradomain networks. In aquatic interdomain networks, microeukaryotic habitat specialists and prokaryotic habitat specialists played crucial roles as module hubs and connectors, respectively. Furthermore, analyzing evolutionary characteristics, our results revealed that habitat specialists had a much higher diversification potential than generalists, while generalists showed shorter phylogenetic branch lengths as well as larger genomes than specialists. This study broadens our understanding of the ecological and evolutionary features of microbial habitat generalists and specialists in urban park ecosystems across multi-habitat. IMPORTANCE: Urban parks, as an important urban greenspace, play essential roles in ecosystem services and are important hotspots for microbes. Microbial diversity is driven by different ecological and evolutionary processes, while little is currently known about the distinct roles of ecological and evolutionary features in shaping microbial diversity in urban park ecosystems. We explored the ecological and evolutionary characteristics of prokaryotic and microeukaryotic habitat generalists and specialists in urban park ecosystems based on a representative set of different habitats. We found that different ecological and evolutionary drivers jointly maintained and regulated microbial diversity in urban park microbiomes through analyzing the community assembly process, ecological roles in hierarchical interaction, and species diversification potential. These findings significantly advance our understanding regarding the mechanisms governing microbial diversity in urban park ecosystems.

Mapping of Long-Wavelength Phonon Contribution in the Thermal Transport of Alloyed Semiconductor Superlattices.

The mapping of long-wavelength phonons is important to understand and manipulate the thermal transport in multilayered structures, but it remains a long-standing challenge due to the collective behaviors of phonons. In this study, an experimental demonstration of mapping the long-wavelength phonons in an alloyed Al0.1Ga0.9As/Al0.9Ga0.1As superlattice system is reported. Multiple strategies to filter out the short- to mid-wavelength phonons are used. The phonon mean-free-path-dependent thermal transport properties directly demonstrate both the suppression effect of the ErAs nanoislands and the contribution of long-wavelength phonons. The contribution from phonons with mean free path longer than 1 µm is clearly demonstrated. A model based on the Boltzmann transport equation is proposed to calculate and describe the thermal transport properties, which depicts a clear physical picture of the transport mechanisms. This method can be extended to map different wavelength phonons and become a universal strategy to explore their thermal transport in various application scenarios.

Plant-LncPipe: a computational pipeline providing significant improvement in plant lncRNA identification.

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline.

Production of Promising Heat-Labile Enterotoxin (LT) B Subunit-Based Self-Assembled Bioconjugate Nanovaccines against Infectious Diseases.

Nanoparticles (NPs) have been widely utilized in vaccine design. Although numerous NPs have been explored, NPs with adjuvant effects on their own have rarely been reported. We produce a promising self-assembled NP by integrating the pentameric Escherichia coli heat-labile enterotoxin B subunit (LTB) (studied as a vaccine adjuvant) with a trimer-forming peptide. This fusion protein can self-assemble into the NP during expression, and polysaccharide antigens (OPS) are then loaded in vivo using glycosylation. We initially produced two Salmonella paratyphi A conjugate nanovaccines using two LTB subfamilies (LTIB and LTIIbB). After confirming their biosafety in mice, the data showed that both nanovaccines (NP(LTIB)-OPSSPA and NP(LTIIbB)-OPSSPA) elicited strong polysaccharide-specific antibody responses, and NP(LTIB)-OPS resulted in better protection. Furthermore, polysaccharides derived from Shigella or Klebsiella pneumoniae were loaded onto NP(LTIB) and NP(LTIIbB). The animal experimental results indicated that LTIB, as a pentamer module, exhibited excellent protection against lethal infections. This effect was also consistent with that of the reported cholera toxin B subunit (CTB) modular NP in all three models. For the first time, we prepared a novel promising self-assembled NP based on LTIB. In summary, these results indicated that the LTB-based nanocarriers have the potential for broad applications, further expanding the library of self-assembled nanocarriers.

Higher disease burden and lower utilization in Mongolian with breast cancer: a 9-year retrospective cohort study of 18.19 million adults in China.

BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. The authors aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female BC patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34 878 female patients [mean (SD) age, 52.34 (10.93) years] were included among 18.19 million Chinese, and 4315 (12.03%) participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100 000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of BC annually per capita was significantly lower for Mongolian than Han [$1948.43 (590.11-4 776.42) vs. $2227.35 (686.65-5929.59), P <0.001]. Mongolian females showed higher all-cause mortality [30.92 (95% CI: 28.15-33.89) vs. 27.78 (95% CI: 26.77-28.83) per 1000, P =0.036] and BC-specific mortality [18.78 (95% CI: 16.64-21.13) vs. 15.22 (95% CI: 14.47-16.00) per 1000, P =0.002] than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality [HR, 1.21, (95% CI: 1.09-1.34); P <0.001] and BC-specific mortality [HR, 1.31, (95% CI: 1.14-1.49); P <0.001]. CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.