Animal genomes are organized into topologically associated domains (TADs). TADs are thought to contribute to gene regulation by facilitating enhancer-promoter (E-P) contacts within a TAD and ...preventing these contacts across TAD borders. However, the absolute difference in contact frequency across TAD boundaries is usually less than 2-fold, even though disruptions of TAD borders can change gene expression by 10-fold. Existing models fail to explain this hypersensitive response. Here, we propose a futile cycle model of enhancer-mediated regulation that can exhibit hypersensitivity through bistability and hysteresis. Consistent with recent experiments, this regulation does not exhibit strong correlation between E-P contact and promoter activity, even though regulation occurs through contact. Through mathematical analysis and stochastic simulation, we show that this system can create an illusion of E-P biochemical specificity and explain the importance of weak TAD boundaries. It also offers a mechanism to reconcile apparently contradictory results from recent global TAD disruption with local TAD boundary deletion experiments. Together, these analyses advance our understanding of cis-regulatory contacts in controlling gene expression and suggest new experimental directions.
How do humans choose one arm or the other to reach single targets in front of the body? Current theories of reward-driven decisionmaking predict that choice results from a comparison of "action ...values," which are the expected rewards for possible actions in a given state. In addition, current theories of motor control predict that in planning arm movements, humans minimize an expected motor cost that balances motor effort and endpoint accuracy. Here, we test the hypotheses that arm choice is determined by comparison of action values comprising expected effort and expected task success for each arm, as well as a handedness bias. Right-handed subjects, in either a large or small target condition, were first instructed to use each hand in turn to shoot through an array of targets and then to choose either hand to shoot through the same targets. Effort was estimated via inverse kinematics and dynamics. A mixed-effects logistic-regression analysis showed that, as predicted, both expected effort and expected success predicted choice, as did arm use in the preceding trial. Finally, individual parameter estimation showed that the handedness bias correlated with mean difference between right- and left-arm success, leading to overall lower use of the left arm. We discuss our results in light of arm nonuse in individuals' poststroke.
Background:
Escherichia coli
is the most common pathogens in patients with community-onset blood stream infections (COBSI). Knowledge of the epidemiology of this disease is crucial to improve ...allocation of health resources, formulate isolation strategies that prevent transmission, and guide empirical antibiotic therapy.
Methods:
This retrospective observational study examined patients with
E. coli
COBSI (EC-COBSI) at a non-tertiary hospital in China. Whole-genome sequencing and analysis of the isolates was performed. The relationships of clinical variables with antimicrobial resistance and the genetic background of the isolates were examined.
Results:
There were 148 isolates in patients with EC-COBSI. All isolates were susceptible to ceftazidime/avibactam, carbapenems, and tigecycline; 35.1% were positive for extended spectrum β-lactamase (ESBL+); and
bla
CTX
–
M
–
14
was the most common ESBL gene. Patients with ESBL- isolates were more likely to receive appropriate empiric treatment than those with ESBL+ isolates (61.5% vs. 91.4%,
p
< 0.001), but these two groups had similar mortality rates. The overall 30-day mortality rate was 9.5%. Phylogenetic analysis showed that the isolates were diverse, and that the main sequence types (STs) were ST95, ST131, and ST69. Intra-abdominal infection was the primary source of disease, and isolates from these patients had lower frequencies of virulence genes.
Conclusion:
The mortality rate of patients with EC-COBSI was unrelated to ESBL status of the isolates. Most isolates had low resistance to most of the tested antimicrobial agents. The isolates were diverse, and multiple strains were related. Prevention and control of EC-COBSI should target prevention of patient colonization and the living environment.
Alzheimer's disease is one common type of dementia. Numerous studies have suggested a correlation between Alzheimer's disease and inflammation. Microglia mainly participate in the inflammatory ...response in the brain. Currently, ample evidence has shown that microglia are closely related to the occurrence and development of Alzheimer's disease.
We opted for bibliometric analysis to comprehensively summarize the advancements in the study of microglia in Alzheimer's disease, aiming to provide researchers with current trends and future research directions.
All articles and reviews pertaining to microglia in Alzheimer's disease from 2000 to 2022 were downloaded through Web of Science Core Collection. The results were subjected to bibliometric analysis using VOSviewer 1.6.18 and CiteSpace 6.1 R2.
Overall, 7449 publications were included. The number of publications was increasing yearly. The United States has published the most publications. Harvard Medical School has published the most papers of all institutions. Journal of Alzheimer's Disease and Journal of Neuroscience were the journals with the most studies and the most commonly cited, respectively. Mt Heneka is the author with the highest productivity and co-citation. After analysis, the most common keywords are neuroinflammation, amyloid-beta, inflammation, neurodegeneration. Gut microbiota, extracellular vesicle, dysfunction and meta-analysis are the hotspots of research at the present stage and are likely to continue.
NLRP3 inflammasome, TREM2, gut microbiota, mitochondrial dysfunction, exosomes are research hotspots. The relationship between microglia-mediated neuroinflammation and Alzheimer's disease have been the focus of current research and the development trend of future research.
Single-cell sequencing (SCS) is a technique used to analyze the genome, transcriptome, epigenome, and other genetic data at the level of a single cell. The procedure is commonly utilized in multiple ...fields, including neurobiology, immunology, and microbiology, and has emerged as a key focus of life science research. However, a thorough and impartial analysis of the existing state and trends of SCS-related research is lacking. The current study aimed to map the development trends of studies on SCS during the years 2010-2022 through bibliometric software.
Pertinent papers on SCS from 2010 to 2022 were obtained using the Web of Science Core Collection. Research categories, nations/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords were analyzed using VOSviewer, the R package "bibliometric", and CiteSpace.
The bibliometric analysis included 9,929 papers published between 2010 and 2022, and showed a consistent increase in the quantity of papers each year. The United States was the source of the highest quantity of articles and citations in this field. The majority of articles were published in the periodical
Butler A was the most frequently quoted author on this topic, and his article "
" has received numerous citations to date. The literature and keyword analysis showed that studies involving single-cell RNA sequencing (scRNA-seq) were prominent in this discipline during the study period.
This study utilized bibliometric techniques to visualize research in SCS-related domains, which facilitated the identification of emerging patterns and future directions in the field. Current hot topics in SCS research include COVID-19, tumor microenvironment, scRNA-seq, and neuroscience. Our results are significant for scholars seeking to identify key issues and generate new research ideas.
Solar-driven steam generation as a potential green technology has attracted extensive attention to solve the freshwater scarcity crisis. Photothermal materials as the key section of solar steam ...generation have been widely reported. However, there is still a challenge in developing easily prepared, environmental-friendly, and low-cost materials. Herein, the simple, scalable, and porous carbonized cotton was prepared as an evaporator to enhance solar-based evaporation, which has excellent light absorption ability in the range of the full spectrum (300–2,500 nm). Benefiting from 95% solar absorption and the pores between the cellulose tubes, the carbonized cotton heated by plate carbonization reaches a steam generation rate of 0.8 kg m
−2
h
−1
, which is about 5 times that of untreated cotton. Compared with tube furnace carbonization, flat plate heating carbonization of cotton requires lower equipment requirements and does not need nitrogen protection and cleaning tar, and the photothermal conversion efficiencies of both are similar. In addition, carbonized cotton as an evaporator was heated up rapidly under 1 sun irradiation and reached a stable temperature in 20 s, greatly improving the photothermal conversion rate. Therefore, plate heating carbonized cotton provides a good idea for preparing solar photothermal conversion materials and a novel strategy for simplifying the production of biomass thermal evaporators.
Calcium ion is vital for the regulation of many cellular functions and serves as a second messenger in the signal transduction pathways. Once the intracellular Ca2+ level exceeds the tolerance of ...cells (called Ca2+ overload), oxidative stress, mitochondrial damage, and cell/mitochondria apoptosis happen. Therefore, Ca2+ overload has started to be deeply exploited as a new strategy for cancer therapy due to its high efficiency and satisfactory safety. This review aims to highlight the recent development of Ca2+‐based nanomaterials (such as Ca3(PO4)2, CaCO3, CaO2, CaH2, CaS, and others) able to trigger intracellular Ca2+ overload and apoptosis in cancer therapy. The intracellular mechanisms of varied Ca2+‐based nanomaterials and the different types of strategies to enhance Ca2+ overload are discussed in detail. Moreover, the design of more efficient Ca2+ overload‐mediated cancer therapies is prospected mainly based on 1) the enhanced cellular uptake by surface modification and morphology optimization of nanomaterials, 2) the accelerated Ca2+ release from nanomaterials by increasing the intracellular H+ level and by photothermal effect, and 3) the overload maintenance by Ca2+ efflux inhibition, Ca2+ influx promotion, or promoting Ca2+ release from the endoplasmic reticulum.
This review aims to highlight the recent development of Ca2+‐based nanomaterials able to trigger intracellular Ca2+ overload and apoptosis in cancer therapy. The intracellular mechanisms of varied Ca2+‐based nanomaterials and the different types of strategies to enhance Ca2+ overload are discussed in detail. Moreover, the design of more efficient Ca2+ overload‐mediated cancer therapies is prospected.
Algal cultivation is a potential candidate for CO₂ mitigation. CO₂ plays important roles in mass cultivation of algae, including supplying carbon source and adjusting medium pH. To assess the ...possibility of using edible cyanobacterium Nostoc flagelliforme as carbon storage device, the growth characteristics of N. flagelliforme batch cultured under elevated CO₂ concentrations (0, 2.5, 5, 20, and 40%) were investigated in this study. Results showed that the net photosynthetic rate, efficiency and carbon sequestration rate at 20% CO₂ were increased at a maximum of 121 μmol O₂ (mg chla)⁻¹ h⁻¹ 8.40% and 0.17 g CO₂ L⁻¹ day⁻¹, and increased by 0.42, 1.03 and 1.13 folds compared with that of the control, respectively. Higher CO₂ concentration resulted in the declines in photosynthetic rate, efficiency and carbon sequestration rate because of medium pH reduction. Accordingly, the dry cell weight, amount of exopolysaccharides and protein content of N. flagelliforme cells at 20% CO₂ were obtained at a maximum of 1.45 g L⁻¹, 54.98 mg L⁻¹ and 57.75%, increased by 0.93, 0.29 and 0.8 folds compared with that of the control, respectively. These results provided important information for CO₂ mitigation by N. flagelliforme and would shed more light on elucidating the mechanisms of CO₂ tolerance in cyanobacterium.
We prepared M/CeO2 (M = Fe, Co or Ni) by coprecipitation method, and then fabricated M@CNT/CeO2 electrocatalysts through ethanol decomposition on M/CeO2. Experimental results showed that the activity ...of Co@CNT/CeO2 for hydrogen evolution reaction (HER) was much higher than that of Fe@CNT/CeO2 and Ni@CNT/CeO2, these experimental results were consistent with the density functional theory (DFT) calculation results. The electrocatalysts from ethanol decomposition on Co/CeO2 at 800 °C with different time were obtained, and their electrocatalytic activities for HER were discussed. Co@CNT-90 showed higher activity than others, when the reaction time exceeded 90 min, their HER activities declined gradually, because long-term ethanol decomposition caused decreased dispersion and thicker layers of carbon nanotube (CNT). To obtain a current density of 10 mA cm−2, overpotential of 181 mV was required for Co@CNT-90, and its polarization curve after 8000 cycles retained a similar performance to the initial polarization curve. The high activity and durability of Co@CNT-90 could be explained from the carbon-encapsulated-metal structure, thus metal was protected by carbon layers and prevented metal from contacting with electrolyte directly. XRD patterns, TEM images and experimental results proved that Co was well encapsulated by CNT.
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•The electrocatalytic activity of Co@CNT/CeO2 for HER was related to the time of ethanol decomposition.•The overpotential of Co@CNT-90 reached 181 mV, and exhibited a good stability.•High activity of Co@CNT-90 was attributed to the excellent dispersity.
The voltage and capacity degradation of high-capacity Li-rich Mn-based (LRM) batteries during cycling have been a formidable barrier to their commercial application. In this study, a modified ...material coated with 15 nm-thick hydroxy-rich carbon layer (C-LRM) is synthesized by hydrothermal method, and C-LRM-PAA electrode is assembled by combining C-LRM with LiPAA binder. The strong hydrogen bond formed by the rich carboxyl group in LiPAA and the hydroxyl group in C-LRM makes the components of the C-LRM-PAA electrode closely connected to avoid electrode cracking, and the coating of the carbon layer avoids the cracking of the cathode particles. Consequently, this unique combination successfully inhibits transition metal dissolution, diminishes charge transfer impedance, and augments the lithium-ion diffusion coefficient, all of which contribute to suppressing the capacity and voltage attenuation. The electrochemical performance shows that after 200 cycles at 1C, the capacity retention rate increases from 40.8 % to 75.5 %, and the voltage decay rate decreases from 2.925 mV per cycle to 2.135 mV per cycle. This provides a new perspective for the electrode design of high energy density LRM batteries.
The cathode synergistic strategy of carbon coating and hydroxyl groups dramatically curtails the cracking of the cathode particles as well as the electrode sheet during the cycling process. Display omitted
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