TLS/FUS-ERG fusion gene in acute leukemia and myelodysplastic syndrome evolved to acute leukemia: report of six cases and a literature review.

To investigate the pathogenesis and the refractory/relapse mechanisms in patients with t(16;21)(p11;q22), we retrospectively analyzed the clinical data of six cases in our hospital and sixty-two cases reported in the literature. Among the patients in our hospital, five cases were diagnosed as acute leukemia, and one was myelodysplastic syndrome evolved to acute myeloid leukemia, harboring TLS/FUS-ERG fusion gene; all the cases were detected t(16;21)(p11;q22) translocation, and five cases showed additional chromosomal abnormalities. We firstly report a novel three-way translocation t(11;16;21)(q13;p11;q22), which may affect the prognosis of leukemia with TLS-ERG fusion gene because this patient shows a more satisfactory treatment effect and deeper remission. And we found patients with TLS-ERG are more likely to have bone and arthrosis pain. Besides, CD56 and CD123 were positive in these cases, which are related to poor prognosis and the character of refractory. Moreover, some gene mutations are involved, and GATA2 and SMAD4 mutations were identified when the disease progressed from myelodysplastic syndrome to leukemia. Among sixty-two patients reported in the literature, valid positive percent of CD56 and CD123 were 81% and 14.3%, respectively. Mutation of the RUNX1 gene was detected in four cases, and one patient had multiple mutations, including BCOR, PLCG1, DIS3, BRAF, JAK2, and JAK3. The prominent feature of leukemia carrying the TLS/FUS-ERG gene is its poor prognosis. The relevant mechanism includes new mutation, jumping translocation, different transcripts, and so on. The mechanism still acquaints scarcely, which requires further study.

The impact of infectious disease experience on household consumption: evidence from rural China.

Objective: The issue of low consumption among rural households in China has a longstanding history, and the experience of infectious diseases may exacerbate the existing challenges in fostering consumption growth. However, studies that characterize the impact of infectious diseases on household consumption are limited in China. This study aims to explore rural household consumption responses to infectious diseases post-assessment, and identify the underlying mechanisms. Methods: A total of 1,539 rural households from China Family Panel Studies (CFPS) datasets of 2014, 2016, 2018, and 2020 were recruited as the study sample. The presence of infectious disease experience was employed as the independent variable and household consumption as the dependent variable. A panel fixed effects (FE) regression model was initially employed to identify the influence of infectious disease experiences on rural household consumption. The instrumental variable (IV) method was used to address potential endogeneity between independent and dependent variables. Robustness checks such as Propensity Score Matching (PSM) test were employed to ensure the reliability of the findings. Results: The results reveal a statistically significant negative impact of infectious disease experiences on consumption over time, becoming no more significant at around 7-9 years post-disaster. This effect leads to more pronounced consumption deprivation for households with limited health insurance coverage and heightened healthcare resource constraints. The mechanism test indicates that infectious disease experiences affect the consumption levels of rural households through channels that include income constraints, the crowding-out of healthcare expenditure, and risk perception, with the precautionary savings motive acting as a moderator. Furthermore, the diminishing effect of infectious diseases on individual consumption surpasses that of natural disasters. Temporal discrepancy is observed in the impacts of infectious and chronic disease shocks on household consumption. The accumulation of liquid assets emerges as an effective strategy for households to mitigate the impact of infectious disease shocks. Conclusion: The findings underscore the importance of integrating short- and long-term policies to bolster consumption capacity, strategically allocate inter-regional medical resources, and fortify the resilience of rural households against economic risks.

Changes in the Quality and Microbial Communities of Precooked Seasoned Crayfish Tail Treated with Microwave and Biological Preservatives during Room Temperature Storage.

The qualities of precooked foods can be significantly changed by the microorganisms produced during room temperature storage. This work assessed the effects of different antibacterial treatments (CK, without any treatment; microwave treatment, MS; microwave treatment and biological preservatives, MSBP) on the physicochemical properties and microbial communities of precooked crayfish tails during room temperature storage. Only the combination of microwave sterilization and biological preservatives significantly inhibited spoilage, as evidenced by the total viable count (4.15 log CFU/g) after 3 days of room temperature storage, which satisfied the transit time of most logistics companies in China. Changes in pH and TVB-N were also significantly inhibited in the MSBP group compared with those in the CK and MS groups. More than 30 new volatile compounds were produced in the CK groups during room temperature storage. However, in the MSBP groups, the volatile compounds were almost unchanged. The correlations between the microbial composition and volatile compounds suggested that specific bacterial species with metabolic activities related to amino acid, energy, cofactor, and vitamin metabolism, as well as xenobiotics biodegradation and metabolism, were responsible for the changes in volatile compounds. These bacteria included Psychrobacter, Arthrobacter, Facklamia, Leucobacter, Corynebacterium, Erysipelothrix, Devosia, Dietzia, and Acidovorax. Overall, our findings provide a foundation for the development of strategies to inhibit spoilage in precooked crayfish tails stored at room temperature.

Can financial technology development reduce household energy consumption? Evidence from China.

This paper examines whether financial technology (FinTech) development affect household energy consumption. The proposed point that FinTech can reduce household energy consumption is theoretically discussed and empirically tested using data from the 2017 Digital Financial Inclusion Index, the 2018 China Family Panel Studies (CFPS), the 2018 China Environmental Statistical Yearbook and the 2018 China Science and Technology Statistical Yearbook. The results show that FinTech contributes to reducing household energy consumption. Several retests, including the instrumental variable, replacement sample and propensity score matching methods, prove its robustness. Mechanism tests show that investment in environmental governance and technological innovation promotion are the two main transmission channels. We also find that the reducing effect is more significant in the following groups: the low-middle income level classes, the eastern regional residents, those with bachelor's degrees and above, the those aged over 60 and rural residents. The outcomes of this paper call for government departments to positively guide FinTech development to reduce household energy consumption. From another perspective, the conclusions drawn from our analysis make a great reference value for countries and provide new ideas for Chinese carbon peaking and carbon neutralisation goals.

Sequential administration of pemetrexed and cisplatin reprograms tumor immune microenvironment and potentiates PD-1/PD-L1 treatment in a lung cancer model.

This article aimed to investigate the effects of the administration method of pemetrexed and cisplatin on the efficacy and safety of treating non-small cell lung cancer (NSCLC) and the intrinsic molecular mechanism. Subcutaneous injection of A549 cells into BALB/C nude mice was used to explore the efficacy of different administration methods of pemetrexed and cisplatin in vivo. Immunogenic cell death (ICD) was evaluated by ATP secretion, ecto-CALR expression, and high mobility group protein 1 release. Western blot, qRT-PCR, and immunohistochemical staining were applied to detect the expression of apoptosis, cell cycle, and stimulator of interferon genes (STING) pathway-related markers. Immune microenvironment was evaluated by secretion of cytokines, infiltration of CD8+ T cells, and expression of programmed death molecular ligand-1 (PD-L1). Sequential treatment with pemetrexed and cisplatin inhibited A549 cell-driven tumor formation in nude mice and regulated the expression of apoptosis and cell cycle-related genes. STING pathway and ICD were further activated by sequential treatment with pemetrexed and cisplatin. This sequential administration method increased the levels of interferon ß, tumor necrosis factor α, interleukin 12, and C-X-C motif chemokine ligand 10, enhanced the infiltration of CD8+ T cells, and upregulated the expression of PD-L1. Sequential administration of pemetrexed and cisplatin in the treatment of mouse NSCLC model may have a better effect than combination of drugs, providing theoretical basis and potential guidance for clinical medication.

Reactive Langerhans Cell Proliferation Mimicking Langerhans Cell Histiocytosis in Association with Sézary Syndrome: A Case Report and Literature Review.

Sézary syndrome (SS) is a rare type of cutaneous T-cell lymphoma (CTCL) that is characterized by erythroderma, lymphadenopathy and circulating clonal T-cells (Sézary cells). However, to our knowledge, reactive Langerhans cell (LC) proliferation mimicking Langerhans cell histiocytosis (LCH) associated with SS has not been reported. In this report, we describe an unusual case of reactive LC proliferation mimicking LCH associated with SS in a 57-year-old female patient. With complaints of recurrent skin symptoms and enlarged lymph nodes (LNs), she was admitted to our center with a presumptive diagnosis of LCH as demonstrated by LN biopsy pathology. However, other than adenopathy, no lesions were noted in any organ system commonly involved in LCH. Typical Sézary cells were identified through morphology and further confirmed by flow cytometric immunophenotyping in peripheral blood (PB) and bone marrow (BM). In addition, T-cell receptor gene rearrangement was positive, whereas the BRAF V600E gene mutation was negative in skin, LN, PB and BM. The patient was ultimately diagnosed with SS with reactive LC proliferation. This case should remind clinicians to be wary of diagnosing LCH if LCH-like pathology occurs exclusively in LNs. Moreover, morphologic, immunologic, cytogenetic and molecular biologic studies should be performed to avoid misdiagnosis.

The lncKLF6/KLF6 feedback loop regulates the growth of non-small cell lung cancer.

Non-small lung cancer (NSCLC) is one of the most common causes of cancer-associated death worldwide. Long noncoding RNAs (lncRNAs) regulate cancer initiation and progression through different mechanisms. In the present study, we characterized a novel lncRNA named lncKLF6, which was upregulated in NSCLC and associated with poor clinical outcomes. lncKLF6 inhibited Kruppel-like factor 6 (KLF6) transcription and then facilitated NSCLC growth. lncKLF6 is associated with the epigenetic repressor BMI1 and regulates its stability via recruiting deubiquitinase USP22. Moreover, it was revealed that lncKLF6 was a KLF6-responsive lncRNA, as KLF6 could occupy the lncKLF6 promoter to facilitate its transcription. The negative feedback loop of lncKLF6 and KLF6 continuously enhanced the oncogenic effects. Thus, our study elucidates the mechanism of lncKLF6-mediated growth via suppression of KLF6, which provides the promising target for developing new therapeutic strategy in NSCLC.

[Levels of P27Kip1 expression and apoptosis in HL-60 cells after treatment with TGF-ß1 and/or arsenic trioxide].

This study was purposed to investigate the effects of TGF-beta1 and arsenic trioxide (As2O3) on cell apoptosis, cell cycle and changes of P27(Kip1), endogenous TGF-ß1, cyclin E and BCL-2 in HL-60 cells, and to explore the relationship between expression of P27(Kip1) and apoptosis induced by As2O3 and/or TGFß1. Cell apoptosis and cell cycle changes of HL-60 cells treated with As2O3 and/or TGFß1 were detected by cytomorphologic observation and flow cytometry, the protein expressions of P27(Kip1), TGF-ß1, cyclin E and BCL-2 were measured by immunohistochemistry. The results showed the effect of 5 µmol/L of As2O3 was the most strong among the different concentration of As2O3 ,and the effect on apoptosis at 48 hour was more strong than that at 24 hours (p < 0.05). The TGF-beta1 (5 ng/ml) induced arrest of cells in G1 phase (p < 0.05) compared with As2O3 alone and As2O3 combined with TGF-ß1, while there was no difference with control. P27(Kip1) expression was up regulated (p < 0.05), cyclin E and BCL-2 expression was down-regulated (p < 0.05) in TGFß1-treated group. BCl-2 expression was down regulated, endogenesis TGFß1 expression was up regulated (p < 0.05), and the level of P27(kip1) and cyclin E were not changed in As2O3-treated group (p > 0.05). The down-regulating effect of TGF-ß1 combined with As2O3 on BCL-2 protein was more strong than that in single factor treated group (p < 0.05). It is concluded that TGFß1 induces cell cycle arrest and apoptosis in HL-60 cells, while the P27(kip1) expression is up regulated. P27 protein is the key effector of TGFß-induced cell cycle arrest. The effect of TGF-ß1 combined with As2O3 on apoptosis as well as the down-regulation of BCL-2 protein in HL-60 cells is more strong than that in single factor-treated groups, that indicates the passages linking up each other.

Synergistic effects of surfactants and sugars on lipoplex stability during freeze-drying and rehydration.

The stability of nonviral vectors during freeze-drying has been well-studied, and it has been established that sugars can protect lipoplexes during freeze-drying. However low levels of damage are often observed after freeze-drying, and this damage is more evident in dilute lipoplex preparations. By investigating the stability of lipoplexes after each step in the freeze-drying cycle (i.e., freezing, primary drying, and secondary drying), we strive to understand the mechanisms responsible for damage and identify improved stabilization strategies. N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP)-cholesterol/plasmid DNA lipoplexes were prepared at an equimolar DOTAP-cholesterol ratio, and a 3:1 DOTAP(+)-DNA(-) charge ratio. Our experiments indicate that despite sufficient levels of "stabilizing" sugars, significant damage is still evident when dilute lipoplex preparations are subjected to freeze-drying. Analysis of the different stages of freeze-drying suggests that significant damage occurs during freezing, and that sugars have a limited capacity to protect against this freezing-induced damage. Similar effects have been observed in studies with proteins, and surfactants have been employed in protein formulations to protect against surface-induced damage, for example, at the ice crystal, solid, air, or sugar glass surfaces. However, the use of surfactants in a lipid-based formulation is inherently risky due to the potential for altering/solubilizing the lipid delivery vehicle. Our data indicate that judicious use of surfactants can reduce surface-induced damage and result in better preservation of lipoplex size and transfection activity after freeze-drying.

Effects of moisture content on the storage stability of dried lipoplex formulations.

The purpose of this study is to investigate the effects of moisture content on the storage stability of freeze-dried lipoplex formulations. DC-Cholesterol: DOPE (dioleoyl phosphatidylethanolamine)/plasmid DNA lipoplexes were prepared at a 3-to-2 DC-Cholesterol(+) to DNA(-) molar ratio and lyophilized prior to storing at room temperature, 40, and 60 degrees C for 3 months. Different residual moistures (1.93%, 1.10%, 1.06%, and 0.36%) were obtained by altering the secondary drying temperatures. In addition to moisture content, lipoplex formulations were evaluated after freeze-drying and/ or storage for particle size, transfection efficiency, accumulation of thiobarbituric acid reactive substances (TBARS), glass transition temperature, DNA supercoil content, and surface area. Lipoplex formulations stored at room temperature for 3 months maintain TBARS concentrations and supercoil contents. At higher storage temperatures, formulations possessing the highest moisture content (1.93%) maintained significantly lower TBARS concentrations and higher supercoil content than those with the lowest (0.36%) moisture content. Curiously, the intermediate moisture contents exhibited marked differences in stability despite virtually identical moisture contents. Subsequent measurements of surface area indicated that the lower stability corresponded to higher surface area in the dried cake, suggesting that there may be an interplay between water content and surface area that contributes to storage stability.

Phase separation at the surface of poly(ethylene oxide)-containing biodegradable poly(L-lactic acid) blends.

The surface chemistry and in-depth distribution of the composition of a poly(ethylene oxide) (PEO)-containing biodegradable poly(L-lactic acid) (PLLA) blend matrix system have been investigated using X-ray photoelectron spectroscopy (XPS). This study reports detailed quantitative compositional information using a novel numerical method for determining depth profiles. The PEO system studied is an amphiphilic Pluronic P104 surfactant, PEO-b-poly(propylene oxide) (PPO)-b-PEO. The extent of phase separation is analyzed by determining the surface enrichment of the PEO component via measurement of chemical composition at the polymer-air interface. For this blend system, the combination of the PPO component in the Pluronic surfactants drives the formation of a surface excess of Pluronic in the blends with PLLA. The surface excess profile shows a rapid increase in Pluronic surface composition versus bulk Pluronic mass fractions of 1-5%, but the profile levels off above bulk Pluronic mass fractions of 5%.

Depth profiling of poly(L-lactic acid)/triblock copolymer blends with time-of-flight secondary ion mass spectrometry.

Time-of-flight secondary ion mass spectrometry employing an SF5+ polyatomic primary ion source was utilized to obtain a series of in-depth profiles from PLLA/Pluronic-P104 (poly(ethylene oxide-co-propylene oxide) triblock copolymer) blends in attempts to quantify the in-depth surface segregated Pluronic region. The resultant in-depth profiles were consistent with theoretical models describing the surface segregated region in polymeric blends and copolymer systems, with a surface enriched Pluronic-P104 region, followed by a P104 depletion layer, and finally a constant composition bulk region. These results were consistent over a range of concentrations (1-25%). The depth profiles obtained using cluster SIMS were compared to information obtained using X-ray photoelectron spectroscopy. The results demonstrate that, with cluster primary ion bombardment, we are for the first time able to quantify the polymeric composition as a function of depth within certain multicomponent polymer blends. This success can be attributed to the sputter characteristics of polyatomic primary ion bombardment (SF5+) as compared to monatomic primary ion beams.