Miracle-dz/UniFAR-FTUs huggingface dataset:
One- and Two-Electron Oxidations of β-Amyloid25-35 by Carbonate Radical Anion (CO3•−) and Peroxymonocarbonate (HCO4−): Role of Sulfur in Radical Reactions and Peptide Aggregation

The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer’s disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aβ most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aβ25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4−, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•−). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO3•− causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS•+). The formation of this transient reactive intermediate during Aβ oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.
Importance of epidemiological research of monkeypox: is incidence increasing?

Monkeypox research was mostly of academic interest until the 1980s when with the global waning of smallpox, monkeypox emerged as the most important Orthopoxvirus of public health importance [1,2]. As a result of the knowledge gap inmonkeypox epidemiology and ecology, the Global Commission for the Certification of Smallpox Eradication recommended surveillance and research for monkeypox and other Orthopoxvirus infections [1]. Four decades after this report, there has been a global increase in reported cases of the disease, while the epidemiology and ecology of the disease are still yet to be fully understood. The recent resurgence of monkeypox in a number of African countries, the exportation of the disease to other continents and the possibility of the virus being a potential agent of bioterrorism has placed it on the global public health agenda [3–6]. We reviewed the current monkeypox situation across the African continent and discuss the critical need for more research in tackling this public health challenge.
Experimental Characterization of an Embossed Capacitive Micromachined Ultrasonic Transducer Cell

Capacitive Micromachined Ultrasonic Transducer (CMUT) is a promising ultrasonic transducer in medical diagnosis and therapeutic applications that demand a high output pressure. The concept of a CMUT with an annular embossed pattern on a membrane working in collapse mode is proposed to further improve the output pressure. To evaluate the performance of an embossed CMUT cell, both the embossed and uniform membrane CMUT cells were fabricated in the same die with a customized six-mask sacrificial release process. An annular nickel pattern with the dimension of 3 μm × 2 μm (width × height) was formed on a full top electrode CMUT to realize an embossed CMUT cell. Experimental characterization was carried out with optical, electrical, and acoustic instruments on the embossed and uniform CMUT cells. The embossed CMUT cell achieved 27.1% improvement of output pressure in comparison to the uniform CMUT cell biased at 170 V voltage. The fractional bandwidths of the embossed and uniform CMUT cells were 52.5% and 41.8%, respectively. It substantiated that the embossed pattern should be placed at the vibrating center of the membrane for achieving a higher output pressure. The experimental characterization indicated that the embossed CMUT cell has better operational performance than the uniform CMUT cell in collapse region.
P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer

The GTPase Rac1 is a well-established master regulator of cell motility and invasiveness contributing to cancer metastasis. Dysregulation of the Rac1 signaling pathway, resulting in elevated motile and invasive potential, has been reported in multiple cancers. However, there are limited studies on the regulation of Rac1 in prostate cancer. Here, we demonstrate that aggressive androgen-independent prostate cancer cells display marked hyperactivation of Rac1. This hyperactivation is independent of P-Rex1 activity or its direct activators, the PI3K product PIP3 and Gβγ subunits. Furthermore, we demonstrate that the motility and invasiveness of PC3 prostate cancer cells is independent of P-Rex1, supporting the analysis of publicly available datasets indicating no correlation between high P-Rex1 expression and cancer progression in patients. Rac1 hyperactivation was not related to the presence of activating Rac1 mutations and was insensitive to overexpression of a Rac-GAP or the silencing of specific Rac-GEFs expressed in prostate cancer cells. Interestingly, active Rac1 levels in these cells were markedly reduced by elevations in intracellular calcium or by serum stimulation, suggesting the presence of an alternative means of Rac1 regulation in prostate cancer that does not involve previously established paradigms.
Phenotype and Genotype Characteristics of Staphylococcus aureus Resistant to Methicillin/Oxacillin Carrying Gene mecC in the Czech Republic from 2002 to 2017.

The aim of this study was to detect and characterize isolates of methicillin-/oxacillin-resistant Staphylococcus aureus (MRSA) carrying gene mecC (MRSA/mecC) and occurring in the Czech Republic within the period from 2002 to 2017. Altogether, 18 from 3,472 isolates of MRSA were mecC positive (0.52%). The first detection of MRSA/mecC in the Czech Republic is dated to 2004. MRSA/mecC isolates were susceptible to almost all tested antibiotics with few exceptions. Resistances to erythromycin (n = 2), clindamycin (n = 1), trimethoprim-sulfamethoxazole (n = 1), and rifampicin (n = 1) were found in the collection. Multilocus sequence typing and spa typing revealed a genetic heterogeneity of MRSA/mecC strains: three CCs (130, 425, and 2361), five STs (1245, 130, 2361, 425, and a new ST5480), and eight spa types (t843, t978, t1048, t1535, t1736, t6104, t8842, and t17153), which were detected in the study, with the highest prevalence of CC130/t843 lineage (n = 8, 44%). Except for two strains, none from 18 examined isolates harbored genes encoding any of S. aureus toxins: enterotoxins a-u, exfoliative toxins A, B, and D, toxic shock syndrome toxin-1, and the Panton-Valentine leukocidin.
Electrophysiological Differentiation of the Effects of Stress and Accent on Lexical Integration in Highly Fluent Bilinguals

Individuals who acquire a second language (L2) after infancy often retain features of their native language (L1) accent. Cross-language priming studies have shown negative effects of L1 accent on L2 comprehension, but the role of specific speech features, such as lexical stress, is mostly unknown. Here, we investigate whether lexical stress and accent differently modulate semantic processing and cross-language lexical activation in Welsh–English bilinguals, given that English and Welsh differ substantially in terms of stress realisation. In an L2 cross-modal priming paradigm, we manipulated the stress pattern and accent of spoken primes, whilst participants made semantic relatedness judgments on visual word targets. Event-related brain potentials revealed a main effect of stress on target integration, such that stimuli with stress patterns compatible with either the L1 or L2 required less processing effort than stimuli with stress incompatible with both Welsh and English. An independent cross-language phonological overlap manipulation revealed an interaction between accent and L1 access. Interestingly, although it increased processing effort, incorrect stress did not significantly modulate semantic priming effects or covert access to L1 phonological representations. Our results are consistent with the concept of language-specific stress templates, and suggest that accent and lexical stress affect speech comprehension mechanisms differentially.
Pancreatic β cell microRNA-26a alleviates type 2 diabetes by improving peripheral insulin sensitivity and preserving β cell function

Type 2 diabetes (T2D) is characterized by insulin resistance along with pancreatic β cell failure. β cell factors are traditionally thought to control glucose homeostasis by modulating insulin levels, not insulin sensitivity. Exosomes are emerging as new regulators of intercellular communication. However, the role of β-cell–derived exosomes in metabolic homeostasis is poorly understood. Here, we report that microRNA-26a (miR-26a) in β cells not only modulates insulin secretion and β cell replication in an autocrine manner but also regulates peripheral insulin sensitivity in a paracrine manner through circulating exosomes. MiR-26a is reduced in serum exosomes of overweight humans and is inversely correlated with clinical features of T2D. Moreover, miR-26a is down-regulated in serum exosomes and islets of obese mice. Using miR-26a knockin and knockout mouse models, we showed that miR-26a in β cells alleviates obesity-induced insulin resistance and hyperinsulinemia. Mechanistically, miR-26a in β cells enhances peripheral insulin sensitivity via exosomes. Meanwhile, miR-26a prevents hyperinsulinemia through targeting several critical regulators of insulin secretion and β cell proliferation. These findings provide a new paradigm for the far-reaching systemic functions of β cells and offer opportunities for the treatment of T2D.
Amyloidogenic Peptides in Human Neuro-Degenerative Diseases and in Microorganisms: A Sorrow Shared Is a Sorrow Halved?

The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that microbes also possess amyloidogenic peptides is intriguing. Transmission of amyloids by iatrogenic means or by consumption of contaminated meat from diseased animals is a well-known fact. What if also our microbial commensals might drive human amyloidosis or suffer from our aggregated amyloids? Moreover, as the microbial amyloids are evolutionarily older, we might learn from these organisms how to cope with the sword of Damocles forged of endogenous, potentially toxic peptides. This review summarizes knowledge about the interplay between human amyloids involved in neurodegenerative diseases and microbial amyloids.
The role of gut microbiota in mediating obesity and diabetes mellitus.

OBJECTIVE This review inspects the relations between the microbiota and the intestinal immune system in the advancement of metabolic illnesses, such as obesity and diabetes mellitus. The role of the microbiota in intestinal immune defense and the control of metabolism are subject to examination. MATERIALS AND METHODS In type 1 diabetes, the adhesion proteins prompt inside the intestinal epithelium prompt a more significant immune response that may result in the destruction of pancreatic β cells by CD8+ T-lymphocytes, as well as increased articulation of interleukin-17, which is associated with autoimmunity. Studies suggest that the beginning of metabolic ailments and certain co-morbidities can be viewed in light of the protection between the gut microbiota and the intestinal immune system. The gut microbiota is analyzed as a key regulator of metabolic ailments. Research demonstrates that obese patients with type 2 diabetes have a certain gut microbiota and that the microbiota is translocated from the gut to the tissues in conjunction with the illness, which instigates inflammation. RESULTS Research in animals and people suggests that a probiotic supplement may regulate the gut microbiota, thereby improving the prognosis for diabetes. CONCLUSIONS The mechanism underlying this phenomenon relates to a decrease in the inflammatory reaction and oxidative stress, as well as a decrease in leaky gut. Such reactions increase insulin sensitivity and reduce autoimmune responses.
Distributed Multi-Antenna Positioning for Automatic-Guided Vehicle

Radio-based positioning systems are typically utilized to provide high-precision position information for automatic-guided vehicles (AGVs). However, the presence of obstacles in harsh environments, as well as carried cargoes on the AGV, will degrade the localization performance, since they block the propagation of radio signals. In this paper, a distributed multi-antenna positioning system is proposed, where multiple synchronous antennas are equipped on corners of an AGV to improve the availability and accuracy of positioning. An estimator based on the Levenberg–Marquardt algorithm is introduced to solve the nonlinear pseudo-range equations. To obtain the global optimal solutions, we propose a coarse estimator that utilizes the displacement knowledge of the antennas to provide a rough initial guess. Simulation results show a better availability of our system compared with the single antenna positioning system. Decimeter accuracy can be obtained under a Gaussian measurement noise with a standard deviation of 0.2 m. The results also demonstrate that the proposed algorithm can achieve positioning accuracy close to the theoretical Cramer–Rao lower bound. Furthermore, given prior information of the yaw angle, the same level of accuracy can be obtained by the proposed algorithm without the coarse estimation step.
Acute Kidney Injury Biomarker Responses to Short-Term Heat Acclimation

The combination of hyperthermia, dehydration, and strenuous exercise can result in severe reductions in kidney function, potentially leading to acute kidney injury (AKI). We sought to determine whether six days of heat acclimation (HA) mitigates the rise in clinical biomarkers of AKI during strenuous exercise in the heat. Twenty men completed two consecutive 2 h bouts of high-intensity exercise in either hot (n = 12, 40 °C, 40% relative humidity) or mild (n = 8, 24 °C, 21% relative humidity) environments before (PreHA) and after (PostHA) 4 days of 90–120 min of exercise per day in a hot or mild environment. Increased clinical biomarkers of AKI (CLINICAL) was defined as a serum creatinine increase ≥0.3 mg·dL−1 or estimated glomerular filtration rate (eGFR) reduction >25%. Creatinine similarly increased in the hot environment PreHA (0.35 ± 0.23 mg·dL−1) and PostHA (0.39 ± 0.20 mg·dL−1), with greater increases than the mild environment at both time points (0.11 ± 0.07 mg·dL−1, 0.08 ± 0.06 mg·dL−1, p ≤ 0.001), respectively. CLINICAL occurred in the hot environment PreHA (n = 9, 75%), with fewer participants with CLINICAL PostHA (n = 7, 58%, p = 0.007), and no participants in the mild environment with CLINICAL at either time point. Percent change in plasma volume was predictive of changes in serum creatinine PostHA and percent changes in eGFR both PreHA and PostHA. HA did not mitigate reductions in eGFR nor increases in serum creatinine during high-intensity exercise in the heat, although the number of participants with CLINICAL was reduced PostHA.
Comparative risk factor analyses on bi-level injury severity of taxi and private car crashes in Seoul, South Korea

Abstract Objectives: Taxis, one of the main transportation modes that occupy the roadways in Seoul, are semipublic transportation modes for transporting passengers safely and promptly. Considering that one fifth of passenger vehicles on the roads in Seoul are taxis and the crash rate of taxis is double the exposure to traffic, it is important to identify risk factors of taxis from that of private cars. In this paper, crash causes and characteristics in both taxi crashes and private car crashes are investigated to identify the risk factors in accordance with the injury severity. Methods: An eight-year light-vehicle crash dataset was utilized, in which injury levels were defined as severe vs. non-severe. Three binary logit models that estimate the severity of crashes, the injury severity for at-fault drivers, and the injury severity for victims were modeled for taxi crashes and private car crashes. Independent variables were extracted and included in the models to evaluate the odds ratio of each predictor variable. Results: The results indicated that violation of traffic signals and signs was the highest contributor among all violation types for taxi crashes and parties involved (at-fault driver and victims), while driving on the wrong side of the road resulted in the highest increase in the odds ratio for private cars. Head-on collision and nighttime driving increased the likelihood of severe injury risk for all models, while age was the most prominent factor for the injury level of victims. Use of seatbelts had a major impact on the at-fault drivers, especially for taxis. Conclusions: This study identified the risk factors that affect the crash- and party-related severity level when casualties involved taxis and private cars. By employing both crash- and party-level models, the study not only identifies the risk factors among taxis and private car crashes but also provides a comprehensive picture of the injury profile of all vehicular occupants, which helps to devise safety measures that enhance the safety and reduce the injury severity for parties involved in crashes.
A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin

Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP). Cells transduced with the SORE6-GFP reporter system were sorted into SORE6+ and SORE6– cell populations, and their biological behavior characterized. SORE6+ cells were enriched for SOX2 and exhibited CSC features, including a greater ability to proliferate and form gastrospheres in non-adherent conditions, a larger in vivo tumor initiating capability, and increased resistance to 5-fluorouracil (5-FU) treatment. The overexpression and knockdown of SOX2 revealed a crucial role of SOX2 in cell proliferation and drug resistance. By combining the reporter system with a high-throughput screening of pharmacologically active small molecules we identified monensin, an ionophore antibiotic, displaying selective toxicity to SORE6+ cells. The ability of SORE6-GFP reporter system to recognize cancer stem-like cells facilitates our understanding of gastric CSC biology and serves as a platform for the identification of powerful therapeutics for targeting gastric CSCs.
Bone marrow mesenchymal stem cells repair brachial plexus injury in rabbits through ERK pathway.

OBJECTIVE To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) on repairing brachial plexus injury in rabbits and their influence on expression of the extracellular signal-regulated kinase (ERK) pathway. MATERIALS AND METHODS With big-ear rabbits as the objects, the BMSCs were first isolated, and the cluster of differentiation (CD)45- and CD90+ BMSCs were sorted out via flow cytometry. BMSCs were transfected with red fluorescent protein (RFP), and the transfection effect was detected. Then, the big-ear rabbits were subjected to brachial plexus root avulsion injury (BPAI) to establish injury Model group and sham-operation group (Sham group). Later, the BMSCs were transfected with RFP to construct RFP-BMSCs. The RFP-BMSCs (5×106, Treat group) and normal saline (Model group) were intraperitoneally injected, and the recovery rate of wet weight of the upper limb muscle was measured by weighing. The injured nerve tissues were embedded for hematoxylin and eosin (HE) staining and observation of pathological changes. The electrophysiological measurement of the compound muscle action potential (CMAP) on the injured side was conducted for the rabbits to be sacrificed immediately using an electromyogram instrument, and the CMAP amplitude and latency were applied to evaluate the recovery of upper limb muscle. Finally, the location of RFP-BMSCs in the nerve tissues was traced by a fluorescence microscope, and the protein expression levels of phosphorylated ERK (p-ERK) and phosphorylated mitogen-activated protein kinase (p-MAPK) in the injured nerve tissues were determined by means of Western blotting. RESULTS Persistently expressed red fluorescence was observed in CD45- and CD90+ BMSCs sorted via flow cytometry under the fluorescence microscope, indicating that the RFP-BMSCs were constructed successfully. Compared with Sham group, Model group had a remarkably decreased recovery rate of wet muscle weight (p<0.05), while Treat group exhibited a notably increased recovery rate of wet muscle weight in comparison with Model group. The CMAP amplitude was reduced markedly (p<0.05), while the CMAP latency was prolonged significantly (p<0.05) in Model group compared with those in Sham group. Moreover, Treat group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than Model group (p<0.05). It was discovered under the fluorescence microscope that RFP-BMSCs were visibly arranged on both sides of nerve fibers in Treat group. The expressions of p-MAPK and p-ERK were raised prominently in Model group in comparison with those in Sham group (p<0.05), and they were lowered apparently in Treat group compared with those in Model group (p<0.05). CONCLUSIONS BMSCs can repair the impaired brachial plexus neurons and restore their physiological functions, and the protective effect of the BMSCs on the neurons is associated with the mediated MAPK/ERK pathway.
Engineering thermophilic Geobacillus thermoglucosidasius for riboflavin production

The potential advantages for fermentation production of chemicals at high temperatures are attractive, such as promoting the rate of biochemical reactions, reducing the risk of contamination and the energy consumption for fermenter cooling. In this work, we de novo engineered the thermophile Geobacillus thermoglucosidasius to produce riboflavin, since this bacterium can ferment diverse carbohydrates at an optimal temperature of 60°C with a high growth rate. We first introduced a heterogeneous riboflavin biosynthetic gene cluster and enabled the strain to produce detectable riboflavin (28.7 mg l−1). Then, with the aid of an improved gene replacement method, we preformed metabolic engineering in this strain, including replacement of ribCGtg with a mutant allele to weaken the consumption of riboflavin, manipulation of purine pathway to enhance precursor supply, deletion of ccpNGtg to tune central carbon catabolism towards riboflavin production and elimination of the lactate dehydrogenase gene to block the dominating product lactic acid. Finally, the engineered strain could produce riboflavin with the titre of 1034.5 mg l−1 after 12‐h fermentation in a mineral salt medium, indicating G. thermoglucosidasius is a promising host to develop high‐temperature cell factory of riboflavin production. This is the first demonstration of riboflavin production in thermophilic bacteria at an elevated temperature.