Asymptomatic multicentric Castleman disease: A potential early stage of idiopathic MCD.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

Microplastic accumulation and oxidative stress in sweet pepper (Capsicum annuum Linn.): Role of the size effect.

Microplastics (MPs), which are widely dispersed in terrestrial environments, threaten crop growth and human food security. However, plant accumulation and phytotoxicity related to the size effects of MPs remain insufficiently explored. This study investigated the accumulation and toxicity of two sizes of MPs on Capsicum annuum Linn. (C. annuum) through fluorescence tracing and antioxidant defense system assessment. The results revealed that the size of MPs significantly impacts their accumulation characteristics in C. annuum roots, leading to variations in toxic mechanisms, including oxidative stress and damage. Smaller MPs and higher exposure concentrations result in more pronounced growth inhibition. C. annuum roots have a critical size threshold for the absorption of MPs of approximately 1.2 µm. MPs that enter the root tissue exhibit an aggregated form, with smaller-sized MPs displaying a greater degree of aggregation. MP exposure induces oxidative stress in root tissues, with high concentrations of smaller MPs causing lipid peroxidation. Analysis of the IBR values revealed that C. annuum roots utilize ascorbic acid (ASA) to prevent oxidative damage caused by larger MPs. Conversely, smaller MPs primarily induce superoxide dismutase (SOD) and glutathione (GSH). These results emphasize the significant impact of MP size on plant antioxidant defense response mechanisms, laying the foundation for further investigating the implications for human health.

Concept for power scaling by harmonic beam coaxial combination in an intra-cavity frequency doubling laser.

A new method of harmonic beam coaxial combination (HBCC) from two intra-cavity frequency doubling branches was demonstrated. Firstly, two identical nanosecond (ns) 532 nm green lasers with high power and good beam quality were created. Each green laser was constructed of an intra-cavity frequency doubling branch based on a laser diode (LD) end-pumped acousto-optical (AO) Q-switched 1064 nm Nd:YVO4 laser in a LiB3O5 (LBO) nonlinear crystal. Each branch generated about 45 W green output at a 50 kHz pulse repetition rate (PRR) with diffraction limited beam quality. The first green beam was injected into the LBO crystal in the second branch, and the pulses from the two branches did not exist simultaneously. Then, the HBCC was performed. Consequently, an 83 W combined green output power at 532 nm was obtained with a combination efficiency of 92.2%. The PRR of the HBCC pulse was doubled to be 100 kHz, with a pulse width of about 22 ns, corresponding to a single pulse energy of 0.83 mJ and a peak power of 37.73 kW. The combined beam quality factor was measured to be M x2 = 1.80 in the x direction and M y2 = 1.71 in the y direction, respectively. Moreover, many more beams could also be combined with this method for further scaling the green power.

Co-hydrothermal carbonization of municipal sludge and agricultural waste to reduce plant growth inhibition by aqueous phase products: Molecular level analysis of organic matter.

The organic matter molecular mechanism by which combined hydrothermal carbonization (co-HTC) of municipal sludge (MS) and agricultural wastes (rice husk, spent mushroom substrate, and wheat straw) reduces the inhibitory effects of aqueous phase (AP) products on pak choi (Brassica campestris L.) growth compared to HTC of MS alone is not clear. Fourier-transform ion cyclotron resonance mass spectrometry was used to characterize the differences in organic matter at the molecular level between AP from MS HTC alone (AP-MS) and AP from co-HTC of MS and agricultural waste (co-Aps). The results showed that N-bearing molecules of AP-MS and co-Aps account for 70.6 % and 54.2 %-64.1 % of all molecules, respectively. Lignins were present in the highest proportion (56.3 %-78.5 %) in all APs, followed by proteins and lipids. The dry weight of co-APs hydroponically grown pak choi was 31.6 %-47.6 % higher than that of the AP-MS. Molecules that were poorly saturated and with low aromaticity were preferentially consumed during hydroponic treatment. Molecules present before and after hydroponics were defined as resistant molecules; molecules present before hydroponics but absent after hydroponics were defined as removed molecules; and molecules absent before hydroponics but present after hydroponics were defined as produced molecules. Large lignin molecules were broken down into more unsaturated molecules, but lignins were the most commonly resistant, removed, and produced molecules. Correlation analysis revealed that N- or S-bearing molecules were phytotoxic in the AP. Tannins positively influenced the growth of pak choi. These results provide new insights into potential implementation strategies for liquid fertilizers produced from AP arising from HTC of MS and agricultural wastes.

Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

[Yes-associated protein (YAP) promotes invasion and migration of cutaneous squamous cell carcinoma cells by activating the PI3K/AKT pathway].

Objective To investigate the expression of Yes-associated protein (YAP) in cutaneous squamous cell carcinoma (cSCC) and its effects on invasion and migration. Methods Immunohistochemical staining was used to detect the expression of YAP in cSCC, Bowen disease (BD), and adjacent normal tissues, and analyzed the correlation between YAP expression and clinicopathological characteristics of cSCC. A stable cell line in A431 cells with YAP gene silencing was established through lentiviral infection. Tetramethylrhodamine isothiocyanate (TRITC)-phalloidin staining was performed to analyze the distribution and number of microfilaments in A431 cells. TranswellTM chamber assay was performed to detect the invasion ability of cells, and scratch healing assay was used to determine the migration ability. Immunofluorescence cytochemistry was used to detected the expression of EMT-related markers, including epithelial-cadherin (E-cadherin), zinc-finger transcription factors Snail in A431 cells with YAP silencing. Western blot analysis was employed to detect the expression of E-cadherin, snail, ß-catenin, phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylaedAKT (p-AKT), ribosomal proteinS6(S6), phosphorylatedS6 (p-S6), 4E-binding protein 1 (4EBP1), and phosphorylated 4EBP1 (p-4EBP1). ResultsThe expression of YAP was significantly higher in BD and cSCC tissues compared to adjacent tissues. The strong positive rate of YAP in cSCC tissues was associated with tumor size, differentiation and the level of invasion. However, there was no correlation between YAP expression and gender, age, tumor location, morphological type, or nerve and vascular invasion. After silencing the expression of YAP in A431 cells, the migration and invasion ability of tumor cells were significantly reduced, and cell microfilaments became thinner with reduced pseudopodia. The expression of E-cadherin was increased, while the expression of snail, ß-catenin, p-AKT, p-S6 and p-4EBP1were decreased. Conclusion YAP is highly expressed in cSCC tissues, and promotes the cell migration and invasion of cSCC cells by activating the PI3K/AKT signaling pathway and EMT.

Farmland Microhabitat Mediated by a Residual Microplastic Film: Microbial Communities and Function.

How the plastisphere mediated by the residual microplastic film in farmlands affects microhabitat systems is unclear. Here, microbial structure, assembly, and biogeochemical cycling in the plastisphere and soil in 33 typical farmland sites were analyzed by amplicon sequencing of 16S rRNA genes and ITS and metagenome analysis. The results indicated that residual microplastic film was colonized by microbes, forming a unique niche called the plastisphere. Notable differences in the microbial community structure and function were observed between soil and plastisphere. Residual microplastic film altered the microbial symbiosis and assembly processes. Stochastic processes significantly dominated the assembly of the bacterial community in the plastisphere and soil but only in the plastisphere for the fungal community. Deterministic processes significantly dominated the assembly of fungal communities only in soil. Moreover, the plastisphere mediated by the residual microplastic film acted as a preferred vector for pathogens and microorganisms associated with plastic degradation and the nitrogen and sulfur cycle. The abundance of genes associated with denitrification and sulfate reduction activity in the plastisphere was pronouncedly higher than that of soil, which increase the potential risk of nitrogen and sulfur loss. The results will offer a scientific understanding of the harm caused by the residual microplastic film in farmlands.

Ixazomib-based frontline therapy followed by ixazomib maintenance in frail elderly newly diagnosed with multiple myeloma: a prospective multicenter study.

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

Predicting leukemic transformation in myelodysplastic syndrome using a transcriptomic signature.

Background: For prediction on leukemic transformation of MDS patients, emerging model based on transcriptomic datasets, exhibited superior predictive power to traditional prognostic systems. While these models were lack of external validation by independent cohorts, and the cell origin (CD34+ sorted cells) limited their feasibility in clinical practice. Methods: Transformation associated co-expressed gene cluster was derived based on GSE58831 ('WGCNA' package, R software). Accordingly, the least absolute shrinkage and selection operator algorithm was implemented to establish a scoring system (i.e., MDS15 score), using training set (GSE58831 originated from CD34+ cells) and testing set (GSE15061 originated from unsorted cells). Results: A total of 68 gene co-expression modules were derived, and the 'brown' module was recognized to be transformation-specific (R2 = 0.23, p = 0.005, enriched in transcription regulating pathways). After 50,000-times LASSO iteration, MDS15 score was established, including the 15-gene expression signature. The predictive power (AUC and Harrison's C index) of MDS15 model was superior to that of IPSS/WPSS in both training set (AUC/C index 0.749/0.777) and testing set (AUC/C index 0.933/0.86). Conclusion: By gene co-expression analysis, the crucial gene module was discovered, and a novel prognostic system (MDS15) was established, which was validated not only by another independent cohort, but by a different cell origin.

Synergistic effect of docetaxel combined with a novel multi-target inhibitor CUDC-101 on inhibiting human prostate cancer.

Histone deacetylases (HDACs) are commonly overexpressed in several types of human cancers, including prostate cancer (PCa). Histone deacetylase inhibitors (HDACis) are emerging as promising tools for cancer therapy. However, there is still a need to understand their anti-tumor effects and the mechanisms underlying their action. In our study, we investigated the effects of co-treatment with CUDC-101 and docetaxel (DTX) on cell growth, clonogenicity, invasion and migration of PCa cells both in vitro, and in a xenograft mouse model. We found that the combination of CUDC-101 and DTX significantly reduced tumor growth, as evidenced by lower tumor weight and volumes. Moreover, apoptotic cell death was increased in the combination group compared to either drug alone or control. Mechanistically, we observed that the combined treatment of CUDC-101 with DTX suppressed the progression of PCa cell lines through the AKT and ERK1/2 signaling pathways. Additionally, this combination treatment reversed EMT by modulating the expression of key markers such as E-cadherin, vimentin, Snail and MMP-9. To conclude, these results demonstrated that the combination of CUDC-101 with DTX had a synergistic and significantly improved anti-carcinogenic effect. This combination may serve as a potential strategy for clinical treatment and prognosis improvement in PCa.

Effects of high manganese-cultivated seedlings on cadmium uptake by various rice (Oryza sativa L.) genotypes.

Cadmium (Cd) contamination in paddy soil threatens rice growth and food safety, enriching manganese (Mn) in rice seedlings is expected to reduce Cd uptake by rice. The effects of 250 µM Mn-treated seedlings on reducing Cd uptake of four rice genotypes (WYJ21, ZJY1578, HHZ, and HLYSM) planted in 0.61 mg kg-1 Cd-contaminated soil, were studied through the hydroponic and pot experiments. The results showed that the ZJY1578 seedling had the highest Mn level (459 µg plant-1), followed by WYJ21 (309 µg plant-1), and less Mn accumulated in the other genotypes. The relative expression of OsNramp5 (natural resistance-associated macrophage protein) was reduced by 42.7 % in ZJY1578 but increased by 23.3 % in HLYSM. The expressions of OsIRT1 (iron-regulated transporter-like protein) were reduced by 24.0-56.0 % in the four genotypes, with the highest reduction in ZJY1578. Consequently, a greater reduction of Cd occurred in ZJY1578 than that in the other genotypes, i.e., the root and shoot Cd at the tillering were reduced by 27.8 % and 48.5 %, respectively. At the mature stage, total Cd amount and distribution in the shoot and brown rice were also greatly reduced in ZJY1578, but the inhibitory effects were weakened compared to the tillering stage. This study found various responses of Cd uptake and transporters to Mn-treated seedlings among rice genotypes, thus resulting in various Cd reductions. In the future, the microscopic transport processes of Cd within rice should be explored to deeply explain the genotypic variation.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

Identification of factors influencing the microplastic distribution in agricultural soil on Hainan Island.

Microplastics (MPs) are ubiquitous in agricultural soils, but to what extent and how environmental factors determine the source and fate of MPs in agricultural soils is not clear. In this study, Hainan Island, which has different climatic conditions, altitudes, and land uses across the island, was selected to investigate the MPs abundance and the shape, size, color, and polymer type of the MPs in agricultural soils. The main focus was on the role of land use type and the identification of environmental influencing factors. The results showed that MPs were detected in all the soil samples across the island, with an abundance range of 20 to 6790 items kg-1 and an average of 417 items kg-1. Fragments (46.8 %), MPs smaller than 0.5 mm (37.8 %), black MPs (48.3 %), and polypropylene MPs (56.8 %) were observed as the dominant MPs species. Significantly higher MPs abundance was found in mulched arable land, and higher contents of fibers and fragments were observed in woodland and paddy lands, respectively. With correlation and redundancy analyses, soil pH, soil organic matter content, and average annual temperature were found to be the main factors influencing the biotic/abiotic fragmentation of MPs. The regional population density, including tourism represented by the night light index, affects the input process of MPs. MPs transport and deposition were found to be affected by altitude, annual precipitation, and soil moisture content. This study represents the first large-scale study of MPs contamination in island agricultural soils and provides important data on the distribution, transport, and fate of MPs.

Effects of electrostatic neutralization of Keggin Fe13 on the removal of micro and nano plastic.

The successful preparation and identification of Keggin-structure Fe13 clusters in recent years further enriched the potential application scenarios of ferric coagulants. Comparing the coagulation efficiencies and mechanisms of Fe13 in the removal of nano/microplastics with conventional polymeric Al13 and monomeric Al/Fe, this work aimed to elucidate the coagulation behaviour of Fe13 compared with the traditional mono ferric coagulant, which has the coagulation applied bottleneck of quick and violet hydrolysis. The results showed that Fe13 has a similar electrostatic neutralization potential to Al13, which could keep a positively charged species, especially in acid conditions. The Fe13 species has a selective removal potential toward the microplastics with a polar functional group like ester. Moreover, Fe13 could hydrolyze to form active sol-gel hydroxides in neutral and alkalinity conditions, which is like the behaviour of traditional monomeric Fe coagulants but seldom restabilization. The electrostatic neutralization of Fe13 could enhance the removal of nano plastic from - 25-75% compared with monomeric Fe at pH 4. The higher floc density as a monomeric Fe coagulant and better electrostatic neutralization potential of Keggin Fe13 posed a good prospect for Fe13 to replace the monomeric Fe coagulants in conventional coagulation.

A review of freshwater benthic clams (Corbicula fluminea): Accumulation capacity, underlying physiological mechanisms and environmental applications.

Asian clams (Corbicula fluminea) have been extensively applied in biomonitoring and other environmental fields based on their high enrichment capacity and rapid response to pollutants. This review first summarizes the kinetic process of metals and organic pollutants enriched by C. fluminea and discusses the environmental behavior and application. The accumulation ability of Cu, Zn, and Mn were significantly higher than that of other metals, which were attributed to their high uptake rate constant and low elimination rate constant. The visceral mass was found to be the major burden tissue. However, large knowledge gaps existed regarding the accumulation capacity of C. fluminea for organic pollutants and nanoparticles. Moreover, physiological mechanisms underlying the accumulation of environmental pollutants were proposed. C. fluminea can improve the niche of benthic algae by ingesting pelagic algae, mitigating water eutrophication. It can also remove pathogens and parasites based on the biological assimilation of nonspecific immunity, interrupting disease transmission. The novel insight into the application of C. fluminea in wastewater treatment further broadens the range of pest management strategies and offers the feasibility of blocking the spread of invasive bivalves.

Whole-genome sequencing as an alternative to analyze copy number abnormalities in acute myeloid leukemia and myelodysplastic syndrome.

Copy number aberrations (CNA) are the core determinants for diagnosis, risk stratification and prognosis in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, a shallow whole-genome sequencing-based assay, LeukoPrint, was utilized to depict genomic CNA profiles from the bone marrow of 137 newly diagnosed AML/MDS patients. It demonstrated 98.1% concordance of CNA profiles with cytogenetics and/or fluorescence in situ hybridization (FISH). It is advantageous in detecting CNAs of short segments (1 Mb) and from samples with low leukemic cell content, more accurate for describing complex karyotypes and less confounded by subjective bias. LeukoPrint improved the overall diagnostic yield by redefining the risk categories for 16 patients by presenting new information. In summary, LeukoPrint provided an automated, convenient, and cost-effective approach to describe genomic CNA profiles. It brought greater diagnostic yield and risk stratification information by incorporating into the routine cytogenetics based on the CNA-related criteria of standard ELN/IPSS-R guidelines.

Microplastic bioaccumulation in estuary-caught fishery resource.

The environmental behavior of microplastics (MPs) in estuaries with saline and freshwater intersections is extremely complex. This increases the chance of MP ingestion by fishery resources, posing potentially tremendous health risks for humans. Herein, a total of 105 fishes from 14 different species, and 86 crustaceans (including shrimps and crabs) from five different species were sampled in the Yangtze River estuary and offshore, and MP bioaccumulation, accumulative organ, and the influencing factors were comprehensively studied. The results elucidated that MP accumulation in benthos was significantly higher than that in pelagic animals due to the lower acceptance threshold, assimilation efficiency and egestion rate for benthos. The MP content in crustaceans with the burrowing favoring the MP retention was significantly higher than that in fishes. MPs ingested by fish can accumulate in skin, gills and viscera rather than muscles. Most MPs accumulated in fishery resources were cellulose and polyethylene terephthalate characterized by black and gray fibrous and lengths ranging from 0.1 mm to 1 mm. The gill retention capacity of pelagic fish to smaller-size (<0.1 mm) MPs was pronouncedly stronger than that of benthic fish. It was more accurate to assess the ecological risk of MPs in terms of the maximum size of MPs accumulated in organisms. Compared with the offshore area, the incidence of MP uptake was higher in the estuary owing to anthropogenic impacts. This study helps understand the transfer of MPs in aquatic food webs and offers a foundation for assessing the risk of human exposure to MPs.

MAPK14 over-expression is a transcriptomic feature of polycythemia vera and correlates with adverse clinical outcomes.

BACKGROUND: The transcriptomic signature has not been fully elucidated in PV, as well as mRNA markers for clinical variables (thrombosis, leukemic transformation, survival, etc.). We attempted to reveal and validate crucial co-expression modules and marker mRNAs correlating with polycythemia vera (PV) by weighted gene co-expression network analysis (WGCNA). MATERIAL AND METHODS: The GSE57793/26014/61629 datasets were downloaded from Gene Expression Omnibus (GEO) database and integrated into one fused dataset. By R software and 'WGCNA' package, the PV-specific co-expression module was identified, the pathway enrichment profile of which was obtained by over-representation analysis (ORA). Protein-protein interaction (PPI) network and hub gene analysis identified MAPK14 as our target gene. Then the distribution of MAPK14 expression in different disease/mutation types, were depicted based on external independent datasets. Genome-scale correlation analysis revealed the association of MAPK14 and JAK/STAT family genes. Then gene set enrichment analysis (GSEA) was performed to detect the activated and suppressed pathways associating with MAPK14 expression. Moreover, GSE47018 dataset was utilized to compare clinical variables (thrombosis, leukemic transformation, survival, etc.) between MAPK14-high and MAPK14-low groups. RESULTS: An integrated dataset including 177 samples (83 PV, 35 ET, 17 PMF and 42 normal donors) were inputted into WGCNA. The 'tan' module was identified as the PV-specific module (R2 = 0.56, p = 8e-16), the genes of which were dominantly enriched in pro-inflammatory pathways (Toll-like receptor (TLR)/TNF signaling, etc.). MAPK14 is identified as the top hub gene in PV-related PPI network with the highest betweenness. External datasets validated that the MAPK14 expression was significantly higher in PV than that of essential thrombocytosis (ET)/primary myelofibrosis (PMF) patients and normal donors. JAK2 homozygous mutation carriers have higher level of MAPK14 than that of other mutation types. The expression of JAK/STAT family genes significantly correlated with MAPK14, which also contributed to the activation of oxidated phosphorylation, interferon-alpha (IFNα) response and PI3K-Akt-mTOR signaling, etc. Moreover, MAPK14-high group have more adverse clinical outcomes (splenectomy, thrombosis, disease aggressiveness) and inferior survival than MAPK14-low group. CONCLUSION: MAPK14 over-expression was identified as a transcriptomic feature of PV, which was also related to inferior clinical outcomes. The results provided novel insights for biomarkers and therapeutic targets for PV.