Gilteritinib-based combination therapy in adult relapsed/refractory FLT3-mutated acute myeloid leukaemia.

Gilteritinib, a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib-based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3-mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3-mutated AML, and it may be considered an effective therapy bridge to transplantation.

Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

Concentration levels and ecological risk assessment of typical organophosphate esters in representative surface waters of a megacity.

Organophosphate esters (OPEs) have been widely used as flame retardants and plasticizers in consumer and industrial products. They have been found to have numerous exposure hazards. Recently, several OPEs have been detected in surface waters around the world, which may pose potential ecological risks to freshwater organisms. In this study, the concentration, spatial variation, and ecological risk of 15 OPEs in the Beiyun and Yongding rivers were unprecedentedly investigated by the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and risk quotient (RQ) method. The result showed that triethyl phosphate (TEP), tri (2-chloroisopropyl) phosphate (TCPP) were the most abundant OPEs with average concentrations of 55.53 ng/L and 42.29 ng/L, respectively. The concentrations of OPEs in the Beiyun River are higher than in the Yongding River, and their levels were higher in densely populated and industrial areas. The risk assessment showed that there was insignificant from OPEs to freshwater organisms in these rivers (RQs <0.1). The risk was higher downstream than upstream, which was related to human-intensive industrial activities downstream in the Yongding River. The ecological risk of OPEs in surface waters worldwide was estimated by joint probability curves (JPCs), and the result showed that there was a moderate risk for tri (2-chloroethyl) phosphate (TCEP), a low risk for trimethyl phosphate (TMP), and insignificant for other OPEs. In addition, the QSAR-ICE-SSD model was used to calculate the hazardous concentration for 5% (HC5). This result validated the feasibility and accuracy of this model in predicting acute data of OPEs and reducing biological experiments on the toxicity of OPEs. These results revealed the ecological risk of OPEs and provided the scientific basis for environmental managers.

Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial.

To reducing chemotherapy-related toxicity, the chemo-free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty-one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow-up of 15.4 months, 2-year disease-free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2-year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2-year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo-free induction and early consolidation regimen was efficacious and well-tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo-free induction.

Gene Mutations and Targeted Therapies of Myeloid Sarcoma.

OPINION STATEMENT: Myeloid sarcoma, a rare malignant tumor characterized by the invasion of extramedullary tissue by immature myeloid cells, commonly occurs concomitantly with acute myeloid leukemia, myelodysplastic syndromes, or myeloproliferative neoplasms. The rarity of myeloid sarcoma poses challenges for diagnosis and treatment. Currently, treatments for myeloid sarcoma remain controversial and primarily follow protocols for acute myeloid leukemia, such as chemotherapy utilizing multi-agent regimens, in addition to radiation therapy and/or surgery. The advancements in next-generation sequencing technology have led to significant progress in the field of molecular genetics, resulting in the identification of both diagnostic and therapeutic targets. The application of targeted therapeutics, such as FMS-like tyrosine kinase 3(FLT3) inhibitors, isocitrate dehydrogenases(IDH) inhibitors, and the B cell lymphoma 2(BCL2) inhibitors, has facilitated the gradual transformation of traditional chemotherapy into targeted precision therapy for acute myeloid leukemia. However, the field of targeted therapy for myeloid sarcoma is relatively under-investigated and not well-described. In this review, we comprehensively summarize the molecular genetic characteristics of myeloid sarcoma and the current application of targeted therapeutics.

Effect and environmental behaviour of microplastics in soil.

Soil microplastic pollution is currently a worldwide concern. Microplastics are organic pollutants that are abundant in the natural environment, are persistent and difficult to degrade and may endanger human health while harming the environment. This article offers a bibliometric analysis of the environmental behaviour of microplastics in soils, as well as a thorough statistical analysis of research goals and trends in this field. We conducted a thorough search of all relevant literature from 2012 to 2022 in the Web of Science core database. The data analysis shows that, starting in 2012, there has been an upward trend in the number of articles about soil microplastic pollution. It can also be seen that China is relatively ahead of the curve in this area of research, followed by the United Kingdom and the United States. This article also systematically describes the research hotspots in this field. The results show that the current research on soil microplastics is mainly focused on their identification, enrichment and toxicity, whereas studies on the migration and transformation of soil microplastics and the mechanism of interaction with other pollutants are still lacking. Our results provide ideas and prospects for future research in this field.

Effects of water quality and bacterial community composition on dissolved organic matter structure in Daihai lake and the mechanisms.

The migration of organic matter in salinized lakes was critical in maintaining ecological balance and material circulation process of inland shallow lakes. To clarify the ecological and microbial mechanism of material transport and transformation, the microbial community structure and the characteristics of dissolved organic matter (DOM) in the sediment of Daihai Lake, a typical saline lake at the Yellow River Basin, were explored with three-dimensional excitation and emission matrix fluorescence (3DEEM), parallel factor analysis (PARAFAC) and 16 S rRNA techniques. The correlation between environmental factors, DOM composition and the bacterial community structure were also studied for identifying the key factors of community formation. DOM in the lake demonstrated both terrigenous and endogenous characteristics. Protein-like materials accounted for 74% of the total fluorescence intensity in the sediment, where 1127 species, 671 genera, 468 families, 157 classes, 317 orders, 59 phyla of microorganisms were detected. Among the top 10 abundant taxa of each level, Firmicutes, Actinobacterota, Acidimicrobiia and Alphaproteobacteria had the greatest influence on the composition and structure of DOM (|R| > 0.7, p < 0.01). Microbial metabolism was a key process of transforming sediment organic matter from terrestrial humic-like to protein-like matter, accounting for 81% of total fluorescence signal in saline lake samples, while salinity, temperature, dissolved oxygen and electrical conductivity also had significant impacts during the process (|R|>0.7, p < 0.05). The research provides fundamental data and enlightenment for the improvement of the saline inland lake environment.

A meta-analysis of neonatal outcomes in pregnant women with immune thrombocytopenic purpura.

AIM: Thrombocytopenia is an autoimmune disorder characterized by reduced platelet counts. Neonatal thrombocytopenia incidence has been linked with immune thrombocytopenic purpura in mothers during pregnancy, possibly because antiplatelet antibodies can cross the placental barrier. To date, no study has attempted to evaluate the actual prevalence of neonatal thrombocytopenia in infants born to mothers with immune thrombocytopenic purpura. In this meta-analysis of the available literature, we attempt to fill this gap. We want to evaluate the overall prevalence of neonatal thrombocytopenia, its severity, and the incidence of hemorrhage in infants with thrombocytopenia born from mothers with immune thrombocytopenic purpura. METHODS: Adhering to PRISMA guidelines, we systematically scanned four academic databases including EMBASE, CENTRAL, Scopus, and MEDLINE to identify relevant literature. We performed a meta-analysis to summarize thrombocytopenia incidence rate and severity in newborn infants of mothers with immune thrombocytopenic purpura. RESULTS: We identified 21 eligible studies involving 1951 mothers and 1844 neonates. Meta-analysis showed high prevalence for neonatal thrombocytopenia (24%). Within these, severe cases were the most prevalent (41.2%), followed by moderate (37.7%) and mild (17.6%) cases. Hemorrhage was only reported in 4.1% of the observed neonatal thrombocytopenia cases. CONCLUSION: This review provides preliminary evidence that neonatal thrombocytopenia incidence is high in infants born to mothers with immune thrombocytopenic purpura. This study further reports that the largest proportion of these cases are severe.

Effect mechanism of biochar application on soil structure and organic matter in semi-arid areas.

There are global concerns regarding soil remediation and water conservation in arid and semi-arid areas. Studying the mechanism and factors influencing soil structure and organic matter content is very important for soil remediation and the rational utilization of water resources. We tracked the changes in soil aggregates and organic matter content during the growth period of maize using different application rates of straw biochar (10, 20, 30, and 50 t/ha) to investigate the effects of biochar on the structure of weakly alkaline soil. The results were as follows: 1) Biochar significantly increased the content of water-stable soil aggregates. The content of water-stable macroaggregates (≥0.25 mm) increased by 8.3-35.0%, and the increase was the highest (35%) when biochar was applied at a rate of 30 t/ha 2) After applying biochar, the content of air-dried aggregates on the surface layer increased by 112.6-168.5%. 3). Biochar increased the organic matter content to varying degrees from the spatiotemporal aspect. In terms of soil depth, organic matter content increased by 2.15-5.88 g/kg. The jointing stage, which the time demand for organic matter is the highest, organic matter content increased by 35.4% when biochar was applied at 50 t/ha 4) We established a three-dimensional surface correlation equation based on the synergistic relationships among biochar, water-stable aggregates, and organic matter content. The particle size of soil aggregates was the highest when the biochar application rate was 29.38 t/ha and the organic matter content increased by 25.7%. It provided evidence that applies to biochar has good potential for water-saving irrigation and soil remediation.

Effects of straw biochar application on soil temperature, available nitrogen and growth of corn.

Straw biochar could improve the water holding capacity effectivity of salinized soil, increase soil fertili, enhance crop yield, reduce greenhouse gas emission, and mitigate climate change. The mechanism of using straw biochar for soil improvement is different under various climate and soil texture conditions. To explore the mechanism of using straw biochar to improve soil and its influence on crop yield in the typical arid and semi-arid, a large temperature difference between day and night, soil temperature at different depths, and physiological changes and crop yield of maize at different growth stages were studied. It is assumed that straw biochar can improve the properties of salinized soil including physicochemical indexes, and crop physiological index, stimulates the positive circulation between soil, vegetation, and microorganisms, and plays a role in improving soil quality. The results showed that biochar application increased the average soil temperature (T) by 2 °C and reduced day-night T differences. Application of 30 t/ha biochar increased the average maize leaf T by 2.2 °C and photosynthetic rate by 16.5%. Furthermore, the average transpiration rate doubled compared to control, and the chlorophyll value increased by 21%. The application of biochar improved the utilization rate of nitrogen fertilizer by enhancing ammonification. Biochar application caused a maximum overall yield increase of 11.9% compared to control treatment (CK). Therefore, these results provide a practical basis for improving weakly alkaline farmland soils in arid and semi-arid areas, and provide an effective method to potentially mitigate the environmental crisis and promote sustainable development in agriculture.

Specific biotests to assess eco-toxicity of biodegradable polymer materials in soil.

Eco-toxicity investigation of polymer materials was considered extremely necessary for their potential menace, which was widely use as mulching materials in agricultural. In this study, polyethylene (PE), polystyrene (PS) and synthetic biomaterials-Ecoflex and cellulose were applying into soil cultivated with two potential indicator plants species: oat (Avena sativa) and red radish (Raphanus sativum). Variety of chemical, biochemical parameters and enzyme activity in soil were proved as effective approach to evaluate polymers phytotoxicity in plant-soil mesocosm. The F-value of biomass, pH, heavy metal and electoral conductivity of Raphanus behaved significant different from T0. Significant analysis results indicated biodegradation was fast in PE than PS, besides, heavy metals were dramatically decrease in the end implied the plant absorption may help decrease heavy metal toxicity. The increase value at T2 of Dehydrogenase activity (0.84 higher than average value for Avena & 0.91 higher for Raphanus), Metabolic Index (3.12 higher than average value for Avena & 3.81 higher for Raphanus) means during soil enzyme activity was promoted by biodegradation for its heterotrophic organisms' energy transportation was stimulated. Statistics analysis was carried on Biplot PC1 (24.2% of the total variance), PC2 (23.2% of the total variance), versus PC3 (22.8% of the total variance), which indicated phosphatase activity and metabolic index was significant correlated, and high correlation of ammonium and protease activity. Furthermore, the effects were more evident in Raphanus treatments than in Avena, suggesting the higher sensitivity of Raphanus to polymers treatment, which indicate biodegradation of polymers in Raphanus treatment has produced intermediate phytotoxic compounds.

Role of Th 1- and Th 2- Chemokine Receptor in the Diagnosis and Prognosis of Primary Immune Thrombocytopenia.

BACKGROUND: The diagnostic and prognostic role of Th-1 chemokine receptor and Th-2 chemokine receptor in patients with primary immune thrombocytopenia has not been investigated extensively so far. In this study, our goal is to explore the diagnostic and prognostic role of C-C chemokine receptor 3 (CCR3) and C-C chemokine receptor 5 (CCR5) in patients with primary immune thrombocytopenia. METHODS: The expression levels of CCR3 and CCR5 were measured in peripheral blood mononuclear cells of pa-tients with primary immune thrombocytopenia and healthy subjects. The relationship between the expression levels of CCR3 and CCR5 and clinicopathological characteristics was analyzed. The diagnostic accuracy of CCR3 and CCR5 as biomarkers to discriminate primary immune thrombocytopenia patients from healthy subjects was determined. Univariate and multivariate Cox regression analysis were performed to determine the prognosis value of CCR3 and CCR5 in primary immune thrombocytopenia. The outcome of primary immune thrombocytopenia patients was also evaluated. RESULTS: Compared to healthy subjects, the expression level of CCR3 was significantly downregulated and CCR5 was significantly upregulated (p < 0.05). The expression levels of CCR3 and CCR5 were significantly correlated with bleeding times and platelet counts at diagnosis (p < 0.05). CCR3 and CCR5 could act as a suitable biomarker for differentiating the primary immune thrombocytopenia patients from healthy subjects. CCR3 and CCR5 were independent prognostic factors. Overexpression of CCR5 and low expression of CCR3 lead to poor clinical benefits and indicated poor prognosis of primary immune thrombocytopenia. CONCLUSIONS: To summarize, our results suggested that CCR3 and CCR5 could act as suitable biomarkers and indicated poor prognosis of primary immune thrombocytopenia.

Three decades of changes in water environment of a large freshwater Lake and its relationship with socio-economic indicators.

Tai Lake (Ch: Taihu) has attracted international attention forcyanobacteria blooms. However, the drivers of cultural eutrophication, especially long-term socio-economic indicators have been little researched. The results of research demonstrate how socio-economic development affected quality of water and how it has been improved by anthropogenic activities. This study described variability in indicators of water quality in Tai Lakeand investigated thedrivers. Significant relationships existed between concentrations of annual mean total nitrogen (TN), total phosphorous (TP), chemical oxygen demand (COD) and biological oxygen demand (BOD), and population, per capital gross domestic production (GDP) and sewage discharge (p < 0.05). However, mechanisms causing change varied among TN, TP, COD and BOD. Before 2000, the main contributors to increases in concentrations of TN were human population, GDP and volumes of domestic sewage discharges. After 2000, discharges of industrial sewage become the primary contributor. After 1998, the regressions of annual mean TN, TP and COD on per capital GDP, population and domestic sewage discharge were reversed compared to the former period. Since 1999, an apparent inverted U-shaped relationship between environmental pollution and economic development has developed, which indicated that actions taken by governments have markedly improved quality of water in Tai Lake. The statistical relationship between BOD and per capital GDP didn't conform to the Kuznet curve. The U-shaped Kuznet curve may offer hope for the future that with significant environmental investments a high GDP can be reached and maintained without degradation of the environment, especially through appropriate management of industrial sewage discharge.

Fluorescence regional integration and differential fluorescence spectroscopy for analysis of structural characteristics and proton binding properties of fulvic acid sub-fractions.

Structural characteristics and proton binding properties of sub-fractions (FA3-FA13) of fulvic acid (FA), eluted stepwise by pyrophosphate buffer were examined by use of fluorescence titration combined with fluorescence regional integration (FRI) and differential fluorescence spectroscopy (DFS). Humic-like (H-L) and fulvic-like (F-L) materials, which accounted for more than 80% of fluorescence response, were dominant in five sub-fractions of FA. Based on FRI analysis, except the response of F-L materials in FA9 and FA13, maximum changes in percent fluorescence response were less than 10% as pH was increased from 2.5 to 11.5. Contents of carboxylic and phenolic groups were compared for fluorescence peaks of FA sub-fractions based on pH-dependent fluorescence derived from DFS. Static quenching was the dominant mechanism for binding of protons by FA sub-fractions. Dissociation constants (pKa) were calculated by use of results of DFS and the modified Stern-Volmer relationship. The pKa of H-L, F-L, tryptophan-like and tyrosine-like materials of FA sub-fractions exhibited ranges of 3.17-4.06, 3.12-3.97, 4.14-4.45 and 4.25-4.76, respectively, for acidic pHs. At basic pHs, values of pKa for corresponding materials were in ranges of 9.71-10.24, 9.62-10.99, 9.67-10.31 and 9.33-10.28, respectively. At acidic pH, protein-like (P-L) materials had greater affinities for protons than did either H-L or F-L materials. The di-carboxylic and phenolic groups were likely predominant sites of protonation for both H-L and F-L materials at both acidic and basic pHs. Amino acid groups were significant factors during proton binding to protein-like materials of FA sub-fractions at basic pH.

Functions of N6-methyladenosine (m6A) RNA modifications in acute myeloid leukemia.

N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA. m6A participates in RNA splicing, nuclear export, translation, and degradation through regulation by methyltransferases, methylation readers, and demethylases, affecting mRNA stability and translation efficiency. Through the dynamic and reversible regulatory network composed of " Writers-Erasers-Readers", m6A modification plays a unique role in the process of hematopoiesis. Acute myeloid leukemia (AML) is a heterogeneous disease characterized by malignant proliferation of hematopoietic stem cells/progenitor cells. Many studies have shown that m6A-related proteins are abnormally expressed in AML and play an important role in the occurrence and development of AML, acting as carcinogenic or anticancer factors. Here, we describe the mechanisms of action of reversing m6A modification in hematopoiesis and AML occurrence and progression to provide a basis for further research on the role of m6A methylation and its regulatory factors in normal hematopoiesis and AML, to ultimately estimate its potential clinical value.

Molecular-level insights into the temperature-dependent formation dynamics and mechanism of water-soluble dissolved organic carbon derived from biomass pyrolysis smoke.

Water soluble organic carbon (WSOC) derived from biomass pyrolytic smoke is deposited through atmospheric aerosols, negatively affecting aquatic ecological quality and safety. However, the temperature-dependent molecular diversity and dynamic formation of smoke-derived WSOC remain poorly understood in water. Herein, we explored the molecular-level formation mechanism of pyrolytic smoke-derived WSOC in water to explain the evolution, heterogeneous correlations, and sequential responses of molecules and functional groups to increasing pyrolysis temperature. Two-dimensional correlation spectroscopy was used to innovatively establish the characteristic correlations between spectroscopy and Fourier transform-ion cyclotron resonance mass spectrometry. Temperature-dependent formation of WSOC exhibited diversity in absorbance/fluorescent components, unique/common molecules, and their chemical parameters, showing the simultaneous formation and degradation reactions. The common WSOC molecules with lower and higher degrees of oxidation showed significant positive and negative correlations with the fluorescent components, respectively. The primary sequential response of WSOC molecules to increasing pyrolysis temperature (lignin-like molecules â†’ unsaturated hydrocarbons, condensed aromatic molecules â†’ lipid-like/aliphatic-/peptide-like molecules) corresponded to the temperature response of functional groups (carboxylic/alcoholic â†’ polysaccharides â†’ aromatics/amides/phenolic/aliphatic groups), demonstrating well synergistic relationships between them. These novel findings will contribute to the comprehensive understanding and assessments of potential environmental behavior or risks of WSOC in aquatic ecosystems.

Underlying mechanisms governing on distribution and stratification of DOM during seasonal freeze-thaw cycles.

During the freeze-thaw cycles of ice-covered lakes, DOM undergoes a series of transformations including enrichment, dispersion, and filtration. However, the mechanisms and influence factors on lake pollution processes remain unclear. Therefore, this study investigates the distribution of DOM components and elucidate the role of ice-layer sieving its mechanisms within ice-water-sediments. Study identifies significant variations in the characteristics of DOM, protein-like substances tend to migrate towards the ice layer, while humic-like substances predominantly remain in water. This selective distribution is primarily influenced by the physical and chemical properties of DOM during the freezing process. The ice layer acts as a sieve, allowing smaller molecules such as protein-like substances to pass through more easily, while larger molecules like humic-like substances are retained in the water. Additionally, Temperature plays a pivotal role in affecting the contents of DOM. As the temperature decreases, the solubility of DOM decreases, leading to its precipitation and enrichment in sediments. Conversely, an increase in temperature can facilitate the release of DOM from sediments into the water. Furthermore, high content of total dissolved solids can affect the solubility and stability of DOM, potentially leading to changes in its composition and distribution. These insights provide a deeper understanding of the complex interplay between thermal processes and chemical dynamics within ice-covered aquatic environments. They offered valuable insights into the behavior of organic pollutants in frozen lake systems. The findings have potential implications for environmental management strategies aimed at mitigating the effects of climate.

Shared genetic factors and causal association between chronic hepatitis C infection and diffuse large B cell lymphoma.

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

Characteristics of the presence and migration patterns of DOM between ice and water in the cold and arid Daihai Lake.

Seasonal ice cover plays a crucial role in shaping the physical characteristics of lakes in cold and arid regions. Moreover, the ice significantly affects the level and quality of dissolved organic matter (DOM) in the water column. We utilized spectroscopy and mass spectrometry to analyze the molecular composition and distribution of DOM in ice cores and under-ice water in Daihai Lake. We identified the main environmental factors affecting DOM migration through structural equation modelling (SEM). The freezing process created a repulsive effect on DOM, with water samples demonstrating a greater DOM content than ice. The dominant part of the DOM in the ice cores was mainly comprised of protein-like materials (71.45 %), whereas water consisted of humus-like materials (54.81 %). The average molecular weight of the ice cover DOM (m/z = 396.77) was smaller than in the under-ice water (m/z = 405.42). While low-molecular and low-aromatic protein-like material tended to be trapped in the ice layer during ice formation, large-molecular and highly aromatic humic substances were more easily expelled into the water. Interestingly, condensed aromatic hydrocarbons were found to occur less frequently in the ice phase (11 %) compared to the aqueous phase (13 %). Both the lipid and protein/aliphatic compound structures exhibited slightly higher ratios in the ice (6 % and 8 %, respectively) than in water (1 % and 5 %, respectively). SEM between the ice cover environment and DOM indicated that the ice can influence the distribution pattern of DOM through the regulation of internal solute factors and other chemicals. The nature of the DOM and the rate of ice growth also play critical roles in determining the distribution mechanism of DOM for ice and water. The pollutant distribution characteristics and migration patterns between ice and water are essential for comprehending environmental water pollution and promoting pollution management and protection measures in cold region lakes.