Decreasing circ_0014614 promotes the differentiation of bone marrow flineage cells into megakaryocytes in essential thrombocythemia via activiation of miR-138-5p/caspase3 axis.

BACKGROUND: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes. METHODS: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614，miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay. RESULTS: FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation. CONCLUSION: Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

[An emerging discipline: brain-computer interfaces medicine].

With the development of brain-computer interface (BCI) technology and its translational application in clinical medicine, BCI medicine has emerged, ushering in profound changes to the practice of medicine, while also bringing forth a series of ethical issues related to BCI medicine. BCI medicine is progressively emerging as a new disciplinary focus, yet to date, there has been limited literature discussing it. Therefore, this paper focuses on BCI medicine, firstly providing an overview of the main potential medical applications of BCI technology. It then defines the discipline, outlines its objectives, methodologies, potential efficacy, and associated translational medical research. Additionally, it discusses the ethics associated with BCI medicine, and introduces the standardized operational procedures for BCI medical applications and the methods for evaluating the efficacy of BCI medical applications. Finally, it anticipates the challenges and future directions of BCI medicine. In the future, BCI medicine may become a new academic discipline or major in higher education. In summary, this article is hoped to provide thoughts and references for the development of the discipline of BCI medicine.

[Ethical considerations for medical applications of implantable brain-computer interfaces].

Implantable brain-computer interfaces (BCIs) have potentially important clinical applications due to the high spatial resolution and signal-to-noise ratio of electrodes that are closer to or implanted in the cerebral cortex. However, the surgery and electrodes of implantable BCIs carry safety risks of brain tissue damage, and their medical applications face ethical challenges, with little literature to date systematically considering ethical norms for the medical applications of implantable BCIs. In order to promote the clinical translation of this type of BCI, we considered the ethics of practice for the medical application of implantable BCIs, including: reducing the risk of brain tissue damage from implantable BCI surgery and electrodes, providing patients with customized and personalized implantable BCI treatments, ensuring multidisciplinary collaboration in the clinical application of implantable BCIs, and the responsible use of implantable BCIs, among others. It is expected that this article will provide thoughts and references for the research and development of ethics of the medical application of implantable BCI.

GO-CoNiP New Composite Material Modified Separator for Long Cycle Lithium-Sulfur Batteries.

Lithium-sulfur batteries with high capacity are considered the most promising candidates for next-generation energy storage systems. Mitigating the shuttle reaction and promoting catalytic conversion within the battery are major challenges in the development of high-performance lithium-sulfur batteries. To solve these problems, a novel composite material GO-CoNiP is synthesized in this study. The material has excellent conductivity and abundant active sites to adsorb polysulfides and improve reaction kinetics within the battery. The initial capacity of the GO-CoNiP separator battery at 1 C is 889.4 mAh g-1 , and the single-cycle decay is 0.063% after 1000 cycles. In the 4 C high-rate test, the single-cycle decay is only 0.068% after 400 cycles. The initial capacity is as high as 828.2 mAh g-1 under high sulfur loading (7.3 mg cm-2 ). In addition, high and low-temperature performance tests are performed on the GO-CoNiP separator battery. The first cycle discharge reaches 810.9 mAh g-1 at a low temperature of 0 °C, and the first cycle discharge reaches 1064.8 mAh g-1 at a high temperature of 60 °C, and both can run stably for 120 cycles. In addition, in situ Raman tests are conducted to explain the adsorption of polysulfides by GO-CoNiP from a deeper level.

A novel insight on the intensification mechanism of sludge dewaterability by ionic liquids.

The huge output of sewage sludge has caused a remarkable environmental burden. Sludge dewatering is considered as an important way to reduce the sludge volume. Five imidazole-based ionic liquids were used to improve the dewaterability of sewage sludge. 1-ethyl-3-methylimidazolium dihydrogen phosphate ([Emim][H2PO4]) was screened out as a potential conditioner of sludge due to its excellent dewatering performance and reusability. The solid content of sludge filter cake after treatment with [Emim][H2PO4] was about 10% higher than that of sludge treated by cationic polyacrylamides (CPAM). The intensification mechanism of ionic liquids to the improvement of sludge dewatering performance was studied. The presence of acidic ionic liquids [Emim][H2PO4] resulted the increase of zeta potential from -14.57 ± 0.81 mV to -5.60 ± 0.30 mV and led to the protonation of biopolymers. Acidic ionic liquids [Emim][H2PO4] inactivated the microorganism and led to a porous and unconsolidated structure of the solid sludge particles. All these effects were conducive to destroy the microstructure of sludge and release water. However, [Emim]Cl, [Bmim][OTf] and [Hmim][OTf] showed little effect on the protonation of ionizable functional groups at near-neutral environment. The dissolution of biopolymer decreased the zeta potential and strengthened the electrostatic repulsion. So, they showed weaker intensification effects than CPAM.

MoO2@C modified separator as an interlayer for high performance lithium-sulfur batteries.

Lithium-sulfur batteries have attracted much attention as a promising next-generation energy storage system due to their high theoretical specific capacity and energy density. However, lithium-sulfur batteries are still facing some problems that hinder their large-scale commercial application. High conductivity molybdenum dioxide coated with carbon composite (MoO2@C) were introduced to coat the separator to study its application in lithium sulfur batteries. Molybdenum dioxide coated with carbon composite nanoparticles were synthesized by hydrothermal method and high-temperature calcination and then was coated on the separator with acetylene black. The coating layer can take advantage of the synergetic effect of physical barrier and chemical adsorption to reduce the loss of active substances. The electrochemical performance of the battery has been improved by applying MoO2@C in lithium-sulfur separator. The first discharge specific capacity is 917 mA h g-1 under the current density of 1.0 A g-1, after 300 cycles, the capacity is 618 mA h g-1; after 200 cycles under the current density of 2.0 A g-1, the reversible specific capacity can still maintain 551 mA h g-1.

Considerations and discussions on the clear definition and definite scope of brain-computer interfaces.

Brain-computer interface (BCI) is a revolutionizing human-computer interaction with potential applications in both medical and non-medical fields, emerging as a cutting-edge and trending research direction. Increasing numbers of groups are engaging in BCI research and development. However, in recent years, there has been some confusion regarding BCI, including misleading and hyped propaganda about BCI, and even non-BCI technologies being labeled as BCI. Therefore, a clear definition and a definite scope for BCI are thoroughly considered and discussed in the paper, based on the existing definitions of BCI, including the six key or essential components of BCI. In the review, different from previous definitions of BCI, BCI paradigms and neural coding are explicitly included in the clear definition of BCI provided, and the BCI user (the brain) is clearly identified as a key component of the BCI system. Different people may have different viewpoints on the definition and scope of BCI, as well as some related issues, which are discussed in the article. This review argues that a clear definition and definite scope of BCI will benefit future research and commercial applications. It is hoped that this review will reduce some of the confusion surrounding BCI and promote sustainable development in this field.

Several inaccurate or erroneous conceptions and misleading propaganda about brain-computer interfaces.

Brain-computer interface (BCI) is a revolutionizing human-computer interaction, which has potential applications for specific individuals or groups in specific scenarios. Extensive research has been conducted on the principles and implementation methods of BCI, and efforts are currently being made to bridge the gap from research to real-world applications. However, there are inaccurate or erroneous conceptions about BCI among some members of the public, and certain media outlets, as well as some BCI researchers, developers, manufacturers, and regulators, propagate misleading or overhyped claims about BCI technology. Therefore, this article summarizes the several misconceptions and misleading propaganda about BCI, including BCI being capable of "mind-controlled," "controlling brain," "mind reading," and the ability to "download" or "upload" information from or to the brain using BCI, among others. Finally, the limitations (shortcomings) and limits (boundaries) of BCI, as well as the necessity of conducting research aimed at countering BCI systems are discussed, and several suggestions are offered to reduce misconceptions and misleading claims about BCI.

Association of Fine Particulate Matter and Residential Greenness With Risk of Pulmonary Tuberculosis Retreatment: Population-Based Retrospective Study.

Background: The evidence on the association of fine particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) with pulmonary tuberculosis (PTB) retreatment is limited. There are no data on whether greenness exposure protects air pollution-related PTB retreatment in patients with prior PTB. Objective: In a population-based retrospective study, we aimed to investigate the influence of PM2.5 and residential greenness on the risk of PTB retreatment. Methods: A total of 26,482 patients with incident PTB, registered in a mandatory web-based reporting system between 2012 and 2019 in Zhengzhou, China, were included in the analysis. The exposure to PM2.5 was assessed based on the China High Air Pollutants dataset, and the level of greenness was estimated using the Normalized Difference Vegetation Index (NDVI) values. The associations of PTB retreatment with exposure to PM2.5 and greenness were evaluated, respectively, considering the local socioeconomic level indicated by the nighttime light index. Results: Among the 26,482 patients (mean age 46.86, SD 19.52 years) with a median follow-up time of 1523 days per patient, 1542 (5.82%) PTB retreatments were observed between 2012 and 2019. Exposure to PM2.5 was observed to be significantly associated with the increased risk of PTB retreatment in fully adjusted models with a hazard ratio of 1.97 (95% CI 1.34-2.83) per 10 µg/m3 increase in PM2.5. Patients living in the regions with relatively high quartiles of NDVI values had a 45% lower risk of PTB retreatment than those living in the regions with the lowest quartile for the 500 m buffers (hazard ratio 0.55, 95% CI 0.40-0.77). Such a protective effect of residential greenness was more pronounced among patients living in lower nighttime light areas. The strength of the association between PM2.5 exposure and the risk of PTB retreatment was attenuated by greenness. No significant association was observed between NDVI and the incidence of drug resistance. Conclusions: Long-term exposure to PM2.5 might be a risk factor for PTB retreatment, while an increased level of residential greenness was found to be associated with reduced risks of PTB retreatment. Our results suggest strengthening the control of ambient air pollution and improving residential greenness may contribute to the reduction of PTB retreatment.

Impact of fine particulate matter on latent tuberculosis infection and active tuberculosis in older adults: a population-based multicentre cohort study.

Evidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 µg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

Identifying prognostic biomarker related to immune infiltration in acute myeloid leukemia.

The immune cells of tumor microenvironment (TME) constitute a vital element of the tumor tissue. There is increasing evidence for their clinical significance in predicting prognosis and therapeutic outcomes. However, the TME immune cell infiltrating pattern of the bone marrow in acute myeloid leukemia (AML) patients remains unclear. Here, RNA-sequencing results of AML patients from TCGA database were used to quantify the abundance of 28 types of immune cells in the TME using the single-sample gene set enrichment analysis algorithm. We comprehensively evaluated the immune infiltration status in the TCGA-LAML cohort and defined two immunophenotypes: the immune hot and immune cold subtypes. Additionally, we constructed a TME score reflecting the immune infiltrating pattern of the patients using Cox regression algorithm. Subtypes with high TME score were characterized by over-activation of immune inflammation-related pathways, release of inflammatory factors, T-cell dysfunction, and poor prognosis. Subtypes with a low TME score were characterized by relatively low immune infiltration and immune exclusion. Our analysis indicated that patients in the low TME score group were more sensitive to chemotherapeutic drugs, and those in high TME score were more likely to respond to immunotherapy. Our study provides a new direction to evaluate anti-tumor therapy from immune infiltration of the TME, and the individualized scoring system in this study has important clinical significance in identifying patients who respond to immunotherapy.

Treatment of Pneumocystis jirovecii pneumonia in non-human immunodeficiency virus-infected patients using a combination of trimethoprim-sulfamethoxazole and caspofungin.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an infectious disease common in immunocompromised hosts. However, the currently, the clinical characteristics of non-HIV patients with PJP infection have not been fully elucidated. AIM: To explore efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and caspofungin for treatment of non-human immunodeficiency virus (HIV)-infected PJP patients. METHODS: A retrospective study enrolled 22 patients with non-HIV-infected PJP treated with TMP-SMX and caspofungin from 2019 to 2021. Clinical manifestations, treatment and prognosis of the patients were analyzed. RESULTS: Five patients presented with comorbidity of autoimmune diseases, seven with lung cancer, four with lymphoma, two with organ transplantation and four with membranous nephropathy associated with use of immunosuppressive agents. The main clinical manifestations of patients were fever, dry cough, and progressive dyspnea. All patients presented with acute onset and respiratory failure. The most common imaging manifestation was ground glass opacity around the hilar, mainly in the upper lobe. All patients were diagnosed using next-generation sequencing, and were treated with a combination of TMP-SMX and caspofungin. Among them, 17 patients received short-term adjuvant glucocorticoid therapy. All patients recovered well and were discharged from hospital. CONCLUSION: Non-HIV-infected PJP have rapid disease progression, high risk of respiratory failure, and high mortality. Combination of TMP-SMX and caspofungin can effectively treat severe non-HIV-infected PJP patients with respiratory failure.

Novel functional separator with self-assembled MnO2 layer via a simple and fast method in lithium-sulfur battery.

Modifying separator with metal oxides has been considered as a strong strategy to inhibit the shuttling of soluble polysulfide in the lithium-sulfur battery (Li-S battery). Manganesedioxide (MnO2), one kind of transition metal oxide, is widely applied to decorate the PP (Polypropylene) separator. However, the fabrication by physical coating is always multistep and complicated. Here, we design a simple and fast method to chemically decorate separator. Based on the oxidizing property of acidic KMnO4 solution, the PP separator was oxidized and an ultrathin self-assembled MnO2 layer was directly constructed on one side of separator, by immersing in acidic KMnO4 solution for only 1 h. The self-assembled MnO2 layer has the synergistic effect of adsorption and catalytic conversion on polysulfides, which can effectively inhibit the shuttle effect. It can also help battery to maintain excellent electrochemical kinetics in the electrochemical cycle and maintain the effective recycling of active substances. As a result, the shuttling of polysulfide is greatly prohibited by this novel functional separator, and cycling stability is outstandingly improved, with a low-capacity decaying of 0.058% after 500 cycles at 0.5C. The rapid and simple modification method proposed in this study has a certain reference value for the future large-scale application of lithium-sulfur battery.

A polyethylene oxide/metal-organic framework composite solid electrolyte with uniform Li deposition and stability for lithium anode by immobilizing anions.

All solid-state batteries (ASSBs) are regarded as promising energy storage batteries with high energy density and high safety. The polyethylene oxide (PEO)-based electrolyte with succinonitrile (SN) has attracted critical attention for its high ionic conductivity at room temperature. However, SN can react with Li metal to result in an unstable interface between electrolyte and electrode, which deteriorates the electrochemical performance. In this work, zeolitic imidazolate framework-67 (ZIF-67) is used as a filler to construct composite electrolytes and solve the aforementioned instability issue. The composite electrolyte shows nonflammability, high processability, and a competitive ionic conductivity of 2.78 * 10-5 S/cm at room temperature. Due to the regular dodecahedron structure and abundant Lewis acid sites, the composite electrolyte film exhibits a high Li-ion transference number of 0.654 and a wide electrochemical window of more than 5 V. Moreover, the ZIF-67 helps to construct a uniform and fast ion transport channel and can promote the generation of LiF to prevent SN from contacting Li anode, which contributes to the excellent stability of the Li symmetric batteries cycling for over 1000 h at a current density of 1 mA cm-2. And the assembled LiFePO4||Li batteries based on the composite electrolyte display high discharge specific capacities of 158.6 and 70 mAh g-1 at 60 °C and room temperature, respectively.

Destroying the structure of extracellular polymeric substance to improve the dewatering performance of waste activated sludge by ionic liquid.

The disposal and resource utilization of waste activated sludge (WAS) is a big challenge for its high moisture content. Ionic liquid (IL), 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIM][OTf]), was innovatively used as a conditioner to improve the dewatering performance of WAS. The WAS was characterized by flocs size, three-dimensional excitation-emission matrix (3D-EEM), zeta potential, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM) for the investigation of intensification mechanism. The results showed that the dewatering performance of WAS conditioned by [EMIM][OTf] was significantly improved. The moisture content was successfully decreased to 64.99±0.92 %, and the intensification mechanism was investigated. The results showed that the structures of extracellular polymeric substance (EPS) were destroyed by [EMIM][OTf]. It brought a sharp decrease of the contents of polysaccharides (PS), proteins (PN), humic acid (HA) and fulvic acid (FA) in tightly bound extracellular polymeric substance (TB-EPS) structure. The inactivation of microbial cells promoted the disintegration of flocs. Large flocs were converted into unstable small particles and biopolymers. In addition, the negative charges of WAS were also neutralized for dissolution of biopolymers in [EMIM][OTf], and the electrostatic repulsion between flocs was weakened. [EMIM][OTf] was easily recycled five times. The research results indicate that specific IL, such as [EMIM][OTf], is a potential conditioner to improve the dewatering performance of WAS.

N, O co-doped chlorella-based biomass carbon modified separator for lithium-sulfur battery with high capacity and long cycle performance.

As a lithium-ion secondary battery with high energy density, lithium-sulfur batteries have very bright development prospects. But the shuttle effect is still a thorny issue in the development process. The N, O co-doped chlorella-based biomass carbon (CBBC) synthesized by chemical activation method possesses a microporous and mesoporous composite structure, large specific surface area, and good electrical conductivity. The CBBC interlayer can improve the wettability between the separator and the electrolyte, and accelerate the transmission of Li+. N, O heteroatoms have a strong chemical adsorption operation for LiPs. The modified separator restrains lithium polysulfide through physical barriers and chemical adsorption, and improves the capacity and cycle performance of lithium-sulfur batteries. The batteries with CBBC exhibit excellent cycling stability (0.067% per cycle at 0.5C) and better rate performance (918 mAh g-1 at 2C). The first discharge capacity at 0.05C was 1540 mAh g-1. Even after 600 cycles the discharge capacity retains 656 mAh g-1 at 0.5C. The low price and simple preparation of CBBC interlayer is an attractive choice for improving lithium-sulfur batteries.

Inhibition of the shuttle effect of lithium-sulfur batteries via a tannic acid-metal one-step in situ chemical film-forming modified separator.

The dissolution of polysulfides in an electrolyte is a thermodynamically favorable process, which in theory means that the shuttle effect in lithium-sulfur batteries (LSBs) cannot be completely suppressed. So, it is very important to modify the separator to prevent the migration of polysulfides to the lithium anode. The traditional coating modification process of the separator is cumbersome and uses a solvent that is harmful to the environment, and too many inactive components affect the overall energy density of the battery. It is thus imperative to find a simple and environmentally friendly modification process of the separator. In this study, a fast chemical film-forming method is proposed to modify the separator of a lithium-sulfur battery using tannic acid (TA) and cobalt ions (Co2+). This method requires only simple steps and environmentally friendly raw materials to obtain a thin coating (only 5.83 nm) that can effectively inhibit the shuttle effect. The lithium-sulfur battery with the TA-Co separator shows superior long cycle performance. After 500 cycles at 0.5 C, the capacity decay rate of each cycle is only 0.065%. On the other hand, the TA-Co separator can inhibit the growth of lithium dendrites and help to build a stable lithium anode, which can exhibit minimal polarization (56 mV) in a lithium-lithium symmetrical battery at the current density of 2 mA cm-2. The rapid and simple modification method proposed in this study has a certain reference value for the future large-scale application of lithium sulfur batteries.