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Objective: Rare disease Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for severe aplastic anemia (SAA). It is known that SAA can evolve into malignant clonal diseases, such as acute myeloblastic leukemia (AML) or myelodysplastic syndrome. However, the transformation of SAA into AML after allo-HSCT is a rare phenomenon. Here, we report a case of SAA transformed into AML after patient received human leucocyte antigen (HLA)-matched sibling peripheral blood stem cell transplantation. Case Report: A 51-year-old female patient presented with petechiae and fatigue and received a diagnosis of idiopathic SAA. The immunosuppressive therapy combined with umbilical cord blood transplantation failed for this patient. Then, she received HLA-matched sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). However, 445 days after allo-PBSCT, the patient had a diagnosis of AML by bone marrow puncture. Donor-recipient chi-merism monitoring and cytogenetic analysis confirmed that the leukemia was donor cell origin. Notably, a new HOXA11 mutation was detected in the peripheral blood of the patient after transplantation by whole-exome sequencing, which was the same gene mutation detected in the donor. The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission. However, the leukemia relapsed after 2 cycles of consolidation chemotherapy. Unfortunately, the patient died of leukemia progression 575 days after allo-HSCT. Conclusions: The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of regulated cell death caused by iron‐dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine‐glutathione‐glutathione peroxidase 4 system (cyst(e)ine‐GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH4) system (GCH1/BH4 system), ferroptosis suppressor protein 1/coenzyme Q10 system (FSP1/CoQ10 system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q10 (CoQ10), BH4, hydropersulfides, vitamin K, vitamin E, 7‐dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors. [ABSTRACT FROM AUTHOR]

In this study, a stochastic tropical cyclone (TC) intensity model based on a deterministic fast physics-based TC intensity model is developed for potential applications in the TC hazard assessment. To account for the effect of randomness, an error term is introduced to the ordinary differential equation for the TC intensity. The error term is assumed to be the summation of a mean part and a white noise. The geographically weighted summary statistics method is adopted to estimate the geographically varying mean and white noise intensity of the error term using the 1,010 historical tropical cyclone records from the western North Pacific. The effects of the mean and random parts of the error term on the model's performance are investigated in terms of the individual samples and the probabilistic characteristics of TC intensity evolution. The results show that, by introducing the error term, the difference of the 25-, 50-, and 100-year recurrence interval values between the model and observation can be largely reduced from the level of 10% to less than 4%, validating the adequacy of the proposed model in the TC hazard assessment. [ABSTRACT FROM AUTHOR]

Cu-Co/X-MMT (X = Na, SiO2) catalysts were prepared via impregnation method using Na-MMT and SiO2-MMT (montmorillonite pillared by SiO2) as the support and copper nitrate and cobalt nitrate as precursors. In addition, the citric acid was introduced during the preparation of Cu-Co/SiO2-MMT to obtain Cu-Co/SiO2-MMT-Ac catalyst. The catalysts were characterized by XRD, TEM, H2-TPR, XPS and N2 adsorption–desorption at low temperature. The results showed that the acidity and specific surface area of SiO2-MMT were larger than those of Na-MMT, thus resulting in dimethyl ether (DME) conversion and H2 yield of Cu-Co/SiO2-MMT higher than those of Cu-Co/Na-MMT during steam reforming of DME (SRD). However, for Cu-Co/SiO2-MMT, there was a large amount of methanol in the carbon-containing product due to the large particle size of Cu. The Cu particle size of Cu-Co/SiO2-MMT-Ac was decreased significantly due to the introduction of citric acid, thus accelerating the steam reforming of methanol reaction and enabling the timely conversion of the intermediate product methanol of SRD, resulting in the increasing DME conversion and H2 yield. Therefore, Cu-Co/SiO2-MMT-Ac was expected to be a potential catalyst for SRD. [ABSTRACT FROM AUTHOR]

In nuclear radiation detection, some measured radiation counts are lost due to dead time. Estimation of dead time is necessary to restore the counting information in quantitative analysis. This study aims to propose a method for estimating dead time at high counting rate. First of all, a measurement system of pulse interval distribution was used to estimate the true input counting rate of the detection system and implemented in FPGA. Then, a digital pole-zero cancellation technique was introduced in the measurement system to decrease the decay time constant of pulse. This was aimed at mitigating the impact of pile-up on the pulse interval distribution spectrum, especially at high counting rate. The feasibility of this measurement system at high counting rate was verified by the experimental platform of EDXRF. The dead time was calculated using the measured counting rate and the estimated true input counting rate. The accuracy of the dead time relies on the precision of the estimated true count rate. When the counting rate reaches 600 kCPS, the relative error between the theoretical counting rate and the estimated true input counting rate is less than 5%. • An EDXRF was used to verify the validity of pulse interval distribution measurement system to estimate the dead time. • Estimation of the true input counting rate accurately in the high counting rate scenario. • The measured counting rate will enter the nonlinear region when the dead time exceeds 20%. [ABSTRACT FROM AUTHOR]

Opportunistic spectrum access (OSA), a promising technology to resolve radio spectrum scarcity, is still faced with some challenges, of which one is potentially frequent channel handoff (CH) even handoff blocking (HB) for secondary user (SU) to avoid primary user (PU). Reaccess is a direct way to resolve HB. However, multiple handoff blocking‐then‐reaccess (H‐BTR) are time consuming. Whether it is worthwhile to make multiple H‐BTR, is an interesting but hardly mentioned issue. To this end, the multiple H‐BTR‐based OSA are focused on here. Three key indices, the average transmission probability, handoff delay, and average reaccess times of SU in the H‐BTR‐based OSA, are deduced as close form first. Then, the effects of H‐BTR frequency and service traffic rate of SU on OSA are discussed. Finally, the H‐BTR‐based OSA is compared to two other schemes, the handoff without BTR (HWBTR)‐based OSA and the stop‐and‐waiting (SW)‐based OSA. Theoretical and simulated results show that the H‐BTR‐based OSA performs best among three schemes. Making H‐BTR in moderate frequency according to service traffic rate can increase transmission opportunity while additional delay of SU is tolerable, thus the performance of OSA can be well improved. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ligustilide improved lipid accumulation and inflammation in alcoholic steatosis based on RXFP1. • Ligustilide inhibited the RXFP1-NLRP3 axis to reduce the release of inflammatory factors. • Ligustilide reduced the infiltration of immune cells via inhibiting the formation of NETs. Ligustilide (Lig) is the main active ingredient of Umbelliferae Angelicae Sinensis Radix (Chinese Angelica) and Chuanxiong Rhizoma (Sichuan lovase rhizome). Lig possesses various pharmacological properties and could treat obesity by regulating energy metabolism. However, the impact and regulatory mechanism of Lig on alcoholic hepatic steatosis remains unclear. This study aimed to explore the therapeutic effect of Lig on alcoholic hepatic steatosis and its related pharmacological mechanism. With chronic and binge ethanol feeding, liver tissue damage and lipid accumulation in mice suffering alcoholic hepatic steatosis were significantly improved after Lig treatment. Lig effectively regulated the expression levels of lipid metabolism-related proteins in alcoholic hepatic steatosis. In addition, Lig reduced RXFP1 expression, inhibited the activation of NLRP3 inflammasome, and blocked NET formation. Lig reduced the infiltration of immune cells to the liver and the further prevented the occurrence of alcohol-stimulated inflammatory response in liver. Lig significantly regulated lipid accumulation in alcohol exposed AML12 cells via modulating PPARα and SREBP1. In MPMs, Lig decreased the expression of RXFP1, inhibited the activation of NLRP3 in macrophages stimulated by LPS/ATP, and slowed down the occurrence of inflammatory response. Lig sustained lipid metabolism homeostasis in alcoholic hepatic steatosis, through inhibiting the activation of NLRP3 inflammasomes and the formation of NETs, especially targeting RXFP1 in macrophages. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON), namely vomitoxin, is one of the most prevalent fungal toxins in cereal crops worldwide. However, the underlying toxic mechanisms of DON remain largely unknown. DON exposure-caused changes in the murine plasma metabolome and gut microbiome were investigated by an LC-MS/MS-based nontargeted metabolomics approach and sequencing of 16S rRNA in fecal samples, respectively. Cellular models were then used to validate the findings from the metabolomics study. DON exposure increased intestinal barrier permeability evidenced by its-mediated decrease in colonic Claudin 5 and E-cadherin, as well as increases in colonic Ifn-γ , Cxcl9 , Cxcl10 , and Cxcr3. Furthermore, DON exposure resulted in a significant increase in murine plasma levels of deoxycholic acid (DCA). Also, DON exposure led to gut microbiota dysbiosis, which was associated with DON exposure-caused increase in plasma DCA. In addition, we found not only DON but also DCA dose-dependently caused a significant increase in the levels of IFN-γ , CXCL9 , CXCL10 , and/or CXCR3 , as well as a significant decrease in the expression levels of Claudin 5 and/or E-cadherin in the human colonic epithelial cells (NCM460). DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity. [Display omitted] • This study first demonstrated increased Deoxycholic acid (DCA) from Deoxynivalenol (DON) exposure using metabolomics. • DCA stimulates the expression of IFN-γ, related chemokines, and increase intestinal epithelial barrier permeability. • DCA contributes to DON-mediated gut barrier dysfunction. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a prevalent malignancy, with advanced and metastatic forms exhibiting poor treatment outcomes and high relapse rates. To enhance patient outcomes, a comprehensive understanding of the pathophysiological processes and the development of targeted therapies are imperative. The high heterogeneity of colorectal cancer demands precise and personalized treatment strategies. Colorectal cancer organoids, a three-dimensional in vitro model, have emerged as a valuable tool for replicating tumor biology and exhibit promise in scientific research, disease modeling, drug screening, and personalized medicine. In this review, we present an overview of colorectal cancer organoids and explore their applications in research and personalized medicine, while also discussing potential future developments in this field. [ABSTRACT FROM AUTHOR]

• The proposed tropical cyclone model is completely driven by a set of environmental variables. • This model reproduces the spatial and temporal characteristics of observed tropical cyclones. • The model achieves remarkable balance between computational complexity and efficiency. • This model will provide decision-makers with valuable information regarding potential wind-induced hazards. • When future climate data are fed into this model, the impact of climate change on tropical cyclones can be evaluated. This paper presents an environment-driven tropical cyclone (TC) model for the Western North Pacific basin, which comprises a revised Poisson regression genesis model, a tailored beta-advection track model, and a fast intensity model. The TC model reproduces the temporal and spatial distributions of genesis events, the motion pattern of tracks, as well as the intensity evolutions along tracks. Risk analyses for Hong Kong and along the southeast coastline of mainland China demonstrate that this model can simulate extreme TC events with high fidelity. And the Gaussian mixture model outperforms the Frank Copula in approximating the joint distributions of the annual maximum wind speeds and the corresponding wind directions. This model is driven by a set of environmental variables including relative vorticity, relative humidity, sea surface temperature, vertical wind shear, potential intensity, sub mixed layer depth stratification, mixture layer depth and so on. This enables the model to not only reproduce historical records, but also make predictions for future TC behaviors under climate change with combination of global climate models. Besides, the computational efficiency of the TC model is comparable to traditional purely statistical models. The proposed model can also be coupled with other natural hazard models to conduct multi-hazard analysis. [ABSTRACT FROM AUTHOR]

The timely degradation of proteins that regulate the cell cycle is essential for oocyte maturation. Oocytes are equipped to degrade proteins via the ubiquitin-proteasome system. In meiosis, anaphase promoting complex/cyclosome (APC/C), an E3 ubiquitin-ligase, is responsible for the degradation of proteins. Ubiquitin-conjugating enzyme E2 S (UBE2S), an E2 ubiquitin-conjugating enzyme, delivers ubiquitin to APC/C. APC/C has been extensively studied, but the functions of UBE2S in oocyte maturation and mouse fertility are not clear. In this study, we used Ube2s knockout mice to explore the role of UBE2S in mouse oocytes. Ube2s-deleted oocytes were characterized by meiosis I arrest with normal spindle assembly and spindle assembly checkpoint dynamics. However, the absence of UBE2S affected the activity of APC/C. Cyclin B1 and securin are two substrates of APC/C, and their levels were consistently high, resulting in the failure of homologous chromosome separation. Unexpectedly, the oocytes arrested in meiosis I could be fertilized and the embryos could become implanted normally, but died before embryonic day 10.5. In conclusion, our findings reveal an indispensable regulatory role of UBE2S in mouse oocyte meiosis and female fertility. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. Materials and methods: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. Results: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). Conclusions: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform. [ABSTRACT FROM AUTHOR]

The Motor tic, Obsessions and Compulsions, Vocal tic Evaluation Survey (MOVES) is a widely used screening tool for Tourette syndrome (TS) and associated comorbidities. This study evaluated its applicability for children in China using 7,125 participants from the National Center for Children’s Health (Beijing). Psychometric evaluations included exploratory and confirmatory factor analysis, yielding a 16-item, four-factor model that explained 55.11% of the variance and demonstrated good internal consistency (Cronbach’s alpha = 0.88) and test-retest reliability (ICC = 0.86). The scale showed strong convergent, discriminant, and criterion-related validity and was significantly correlated with other established TS scales. The results affirm the reliability and validity of the MOVES for screening TS in Asian contexts, addressing a crucial gap in the region’s TS assessment tools. [ABSTRACT FROM AUTHOR]

Temozolomide (TMZ) offers substantial therapeutic benefits for glioblastoma (GB), yet its efficacy is hindered the development of chemoresistance. The role of long non-coding RNAs (lncRNAs) in tumorigenesis and chemoresistance has garnered great attention in studies on TMZ resistance. This study aimed to reveal the role of LINC00473 in TMZ chemoresistance and the underlying mechanism in GB. The expression of LINC00473 in TMZ-resistant and TMZ-sensitive GB cells was investigated using qPCR analysis. The role of LINC00473 in regulating TMZ resistance in GB cells was analyzed using the CCK-8 assay, colony formation assay, and flow cytometry. The next steps included assessing if LINC00473 is regulated by CREB and whether LINC00473 promotes chemoresistance through MGMT regulation via CEBPα. Further, chemoresistance delivery between cells via exosomal LINC00473 was validated in vitro and in vivo. Results showed that LINC00473 levels were elevated in TMZ-resistant cells upon CREB activation, and the lncRNA promoted the chemoresistance of GB cells through the upregulation of MGMT expression. Mechanistically, LINC00473 regulated the MGMT expression by binding to CEBPα. The highly-expressed LINC00473 packaged in exosomes transferred chemoresistance to the adjacent TMZ-sensitive GB cells. In conclusion, a novel CREB/LINC00473/CEBPα/MGMT pathway was revealed in the GB TMZ-resistance formation. In addition, an exosome-based mechanism of chemoresistance transmission was revealed, suggesting that LINC00473 could be used as a novel therapeutic target for GB. [Display omitted] • LINC00473 is elevated in TMZ resistant GB and is associated poor survival. • LINC00473 is activated by CREB activation in GB cells. • LINC00473 upregulates MGMT by recruiting CEBPα to MGMT promoter. • LINC00473 has potential as a therapeutic target for GB. [ABSTRACT FROM AUTHOR]

Huaier (Trametes robiniophila Murr), a traditional Chinese medicinal fungus, possesses potent anticancer efficacy and has been used as an adjuvant medication for liver, breast, gastric, intestinal, and non-small cell lung cancer (NSCLC). However, the potential regulatory functions and underlying molecular mechanisms of Huaier in cisplatin resistance of NSCLC remain unknown. To evaluate the potential regulatory functions and underlying molecular mechanisms of Huaier in cisplatin resistance of NSCLC. In vitro and in vivo experiments were employed to evaluate the regulatory functions of Huaier in cisplatin-resistant NSCLC cells. Transcriptome sequencing and validation analyses was undertaken to identify the downstream targets of Huaier. Network pharmacology, ultra-performance liquid chromatography-mass spectroscopy, and in vitro and in vivo experiments were performed to identify key small molecule drug candidates in Huaier and the regulatory mechanisms these employ to suppress cisplatin resistance in NSCLC. Huaier suppressed cisplatin resistance and cancer cell stemness in cisplatin-resistant NSCLC cells, both in vitro and in vivo. Mechanistically, Huaier could suppress expression of interleuken-8 (IL-8) through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein-1 (AP-1), two key transcription factors responsible for the activation of IL-8 transcription. Kaempferol was identified as one of the key small molecule compounds in Huaier that could suppress cisplatin resistance by inhibiting the phosphorylation and nuclear translocation of proto-oncogene c-Jun (JUN) by binding and inhibiting the kinase activity of c-Jun N-terminal protein kinase (JNK). Huaier suppressed cisplatin resistance of NSCLC cells by inhibiting the JNK/JUN/IL-8 signaling pathway. [Display omitted] • Huaier suppresses cisplatin resistance of NSCLC cells. • AP-1/IL-8 signing pathway is main downstream targets of Huaier. • Kaempferol is one of the key small molecule compounds Huaier. • Kaempferol bind JNK to inhibit phosphorylation and nuclear translocation of c-Jun. • Supplementation of IL-8 could rescue inhibitory effect of Huaier. [ABSTRACT FROM AUTHOR]