Field Detection of Uranyl in Coastal Water of China Using a Portable Device via DNA Photocleavage.

The urgent need for field detection of uranium in seawater is 2-fold: to provide prompt guidance for uranium extraction and to prevent human exposure to nuclear radiation. However, current methods for this purpose are largely hindered by bulky instrumentation, high costs of developed materials, and severe matrix interferences, which limit their further application in the field. Herein, we demonstrated a portable and label-free strategy for the field detection of uranyl in seawater based on the efficient photocleavage of DNA. Further experiments confirmed the generation of ultraviolet (UV) light-induced reactive oxygen species (ROS), such as O2•- and •OH, which fragmented oligomeric DNA in the presence of uranyl and UV light. Detailed studies showed that DNA significantly enhances uranyl absorption in the UV-visible region, leading to the generation of more ROS. A fluorescence system for the selective detection of uranyl in seawater was established by immobilizing two complementary oligonucleotides with the fluorescent dye SYBR Green I. The strategy of UV-induced photocleavage offers high selectivity, excellent interference immunity, and high sensitivity for uranyl, with a detection limit of 6.8 nM. Additionally, the fluorescence can be visually detected using a 3D-printed miniaturized device integrated with a smartphone. This method has been successfully applied to the on-site detection of uranyl in seawater in 18 Chinese coastal cities and along the coast of Hainan Island within 3 min for a single sample. The sample testing and field analysis results indicate that this strategy has promising potential for real-time monitoring of trace uranyl in China's coastal waters. It is expected to be utilized for the rapid assessment of nuclear contamination and nuclear engineering construction.

Iadademstat in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (ALICE): an open-label, phase 2a dose-finding study.

BACKGROUND: Iadademstat is a potent, selective, oral inhibitor of both the enzymatic and scaffolding activities of the transcriptional repressor lysine-specific demethylase 1 (LSD1; also known as KDM1A) that showed promising early activity and safety in a phase 1 trial and strong preclinical synergy with azacitidine in acute myeloid leukaemia cell lines. Therefore, we aimed to investigate the combination of iadademstat and azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukaemia. METHODS: The open-label, phase 2a, dose-finding ALICE study was conducted at six hospitals in Spain and enrolled patients aged 18 years or older with newly diagnosed acute myeloid leukaemia not eligible for intensive chemotherapy and an ECOG performance status of 0-2. In the dose escalation portion of the trial, patients received a starting dose of iadademstat at 90 µg/m2 per day (with de-escalation to 60 µg/m2 per day and escalation up to 140 µg/m2 per day) orally, for 5 days on, 2 days off weekly, with azacitidine 75 mg/m2 subcutaneously, for seven of 28 days. The primary objectives were safety (analysed in the safety analysis set; all patients who received at least one dose of study treatment) and establishing the recommended phase 2 dose; secondary objectives included response rates in the efficacy analysis set (all patients who had at least one efficacy assessment). This study is registered on EudraCT (EudraCT 2018-000482-36) and has been completed. FINDINGS: Between Nov 12, 2018, and Sept 30, 2021, 36 patients with newly diagnosed acute myeloid leukaemia were enrolled; the median age was 76 (IQR 74-79) years, all patients were White, 18 (50%) were male, and 18 (50%) were female, and all had intermediate-risk or adverse-risk acute myeloid leukaemia. The median follow-up was 22 (IQR 16-31) months. The most frequent (≥10%) adverse events considered to be related to treatment were decreases in platelet (25 [69%]) and neutrophil (22 [61%]) counts (all grade 3-4) and anaemia (15 [42%]; of which ten [28%] were grade 3-4). Three patients had treatment-related serious adverse events (one fatal grade 5 intracranial haemorrhage, one grade 3 differentiation syndrome, and one grade 3 febrile neutropenia). Based on safety, pharmacokinetic and pharmacodynamic data, and efficacy, the recommended phase 2 dose of iadademstat was 90 µg/m2 per day with azacitidine. 22 (82%; 95% CI 62-94) of 27 patients in the efficacy analysis set had an objective response. 14 (52%) of 27 patients had complete remission or complete remission with incomplete haematological recovery; of these, ten of 11 evaluable for measurable residual disease achieved negativity. In the safety analysis set, 22 (61%) of 36 patients had an objective response. INTERPRETATION: The combination of iadademstat and azacitidine has a manageable safety profile and shows promising responses in patients with newly diagnosed acute myeloid leukaemia, including those with high-risk prognostic factors. FUNDING: Oryzon Genomics and Spain's Ministerio de Ciencia, Innovacion y Universidades (MICIU)-Agencia Estatal de Investigacion (AEI).

A facile electrochemical aptasensor for chloramphenicol detection based on synergistically photosensitization enhanced by SYBR Green I and MoS2.

This study reports the development of a photocatalytic electrochemical aptasensor for the purpose of detecting chloramphenicol (CAP) antibiotic residues in water by utilizing SYBR Green I (SG) and chemically exfoliated MoS2 (ce-MoS2) as synergistically signal-amplification platforms. The Au nanoparticles (AuNPs) were electrodeposited onto the surface of an indium tin oxide (ITO) electrode. After that, the thiolate-modified cDNA, also known as capture DNA, was combined with the aptamer. Subsequently, photosensitized SG molecules and ce-MoS2 nanomaterial were inserted into the groove of the resultant double-stranded DNA (dsDNA). The activation of the photocatalytic process upon exposure to light resulted in the generation of singlet oxygen. The singlet oxygen effectively split the dsDNA, resulting in significant enhancement in the current of [Fe(CN)6]3-/4-. When the CAP was present, both SG molecules and ce-MoS2 broke away from the dsDNA, which turned off the photosensitization response, leading to significant reduction in the current of [Fe(CN)6]3-/4-. Under the optimal conditions, the aptasensor exhibited a linear relationship between the current of [Fe(CN)6]3-/4- with logarithmic concentrations of CAP from 20 to 1000 nM, with a detection of limit (3σ) of 3.391 nM. The aptasensor also demonstrated good selectivity towards CAP in the presence of interfering antibiotics, such as tetracycline, streptomycin, levofloxacin, ciprofloxacin, and sulfadimethoxine. Additionally, the results obtained from the analysis of natural water samples using the proposed aptasensor were consistent with the findings acquired through the use of a liquid chromatograph-mass spectrometer. Therefore, with its simplicity and high selectivity, this aptasensor can potentially detect alternative antibiotics in environmental water samples by replacing the aptamers based on photosensitization.

One-Pot Biocatalytic Route from Alkanes to α,ω-Diamines by Whole-Cell Consortia of Engineered Yarrowia lipolytica and Escherichia coli.

Metabolically engineered microbial consortia can contribute as a promising production platform for the supply of polyamide monomers. To date, the biosynthesis of long-chain α,ω-diamines from n-alkanes is challenging because of the inert nature of n-alkanes and the complexity of the overall synthesis pathway. We combined an engineered Yarrowia lipolytica module with Escherichia coli modules to obtain a mixed strain microbial consortium that could catalyze an efficient biotransformation of n-alkanes into corresponding α,ω-diamines. The engineered Y. lipolytica strain was constructed (YALI10) wherein the two genes responsible for ß-oxidation and the five genes responsible for the overoxidation of fatty aldehydes were deleted. This newly constructed YALI10 strain expressing transaminase (TA) could produce 0.2 mM 1,12-dodecanediamine (40.1 mg/L) from 10 mM n-dodecane. The microbial consortia comprising engineered Y. lipolytica strains for the oxidation of n-alkanes (OM) and an E. coli amination module (AM) expressing an aldehyde reductase (AHR) and transaminase (TA) improved the production of 1,12-diamine up to 1.95 mM (391 mg/L) from 10 mM n-dodecane. Finally, combining the E. coli reduction module (RM) expressing a carboxylic acid reductase (CAR) and an sfp phosphopantetheinyl transferase with OM and AM further improved the production of 1,12-diamine by catalyzing the reduction of undesired 1,12-diacids into 1,12-diols, which further undergo amination to give 1,12-diamine as the target product. This newly constructed mixed strain consortium comprising three modules in one pot gave 4.1 mM (41%; 816 mg/L) 1,12-diaminododecane from 10 mM n-dodecane. The whole-cell consortia reported herein present an elegant "greener" alternative for the biosynthesis of various α,ω-diamines (C8, C10, C12, and C14) from corresponding n-alkanes.

Ultrasensitive Fluorescent Microsensors Based on Aptamers Modified with SYBR Green I for Visual Quantitative Detection of Organophosphate Pesticides.

Organophosphate pesticides (OPs) are widely utilized in agricultural production, and the residues threaten public health and environmental safety due to their toxicity. Herein, a novel and simple DNA aptamer-based sensor has been fabricated for the rapid, visual, and quantitative detection of profenofos and isocarbophos. The proposed DNA aptamers with a G-quadruplex spatial structure could be recognized by SYBR Green I (SG-I), resulting in strong green fluorescence emitted by SG-I. The DNA aptamers exhibit a higher specific binding ability to target OP molecules through aromatic ring stacking, disrupting the interaction between SG-I and DNA aptamers to induce green fluorescence quenching. Meanwhile, the fluorescence wavelength of G-quadruplex fluorescence emission peaks changes, accompanied by an obvious fluorescence variation from green to blue. SG-I-modified aptasensor without any additive reference fluorescence units for use in multicolor fluorescence assay for selective monitoring of OPs was first developed. The developed aptasensor provides a favorable linear range from 0 to 200 nM, with a low detection limit of 2.48 and 3.01 nM for profenofos and isocarbophos, respectively. Moreover, it offers high selectivity and stability in real sample detection with high recoveries. Then, a self-designed portable smartphone sensing platform was successfully used for quantitative result outputs, demonstrating experience in designing a neotype sensing strategy for point-of-care pesticide monitoring.

Real-time PCR detection of PI*S and PI*Z alleles of SERPINA1 gene using SYBR green.

BACKGROUND: Alpha-1 antitrypsin deficiency is an underdiagnosed genetic condition that predisposes to pulmonary complications and is mainly caused by rs28929474 (PI*Z allele) and rs17580 (PI*S allele) mutations in the SERPINA1 gene. OBJECTIVE: Development of a homogeneous genotyping test for detection of PI*S and PI*Z alleles based on the principles of allele-specific PCR and amplicon melting analysis with a fluorescent dye. METHODS: Sixty individuals, which included all possible genotypes that result from combinations of rs28929474 and rs17580 single nucleotide variants, were assayed with tailed allele-specific primers and SYBR Green dye in a real-time PCR machine. RESULTS: A clear discrimination of mutant and wild-type variants was achieved in the genetic loci that define PI*S and PI*Z alleles. Specific amplicons showed a difference of 2.0 °C in melting temperature for non-S and S variants and of 2.9 °C for non-Z and Z variants. CONCLUSIONS: The developed genotyping method is robust, fast, and easily scalable on a standard real-time PCR platform. While it overcomes the handicaps of non-homogeneous approaches, it greatly reduces genotyping costs compared with other homogeneous approaches.

Synergistic interfacial polymerization between hydramine/diamine and trimesoyl chloride: A novel reaction for NF membrane preparation.

Polyester-amide (PEA) thin film composite (TFC) NF membranes have rapidly evolved towards a competitive performance, benefiting from their remarkable antifouling capability and superior chlorine resistance. In this report, a new concept of synergistic interfacial polymerization is explored, which promptly triggers the reaction between hydramines and trimesoyl chloride (TMC) in the presence of a trace amount of diamines. This rapid-start mode enables the formation of defect-free PEA films without the requirement of catalysis. A comprehensive characterization of physicochemical properties using high-resolution mass spectrometer (HRMS) reveals that the recombination and formation of a "hydramine-diamine" coupling unit plays a decisive role in activating the synergistic interfacial polymerization reaction with TMC molecules. Taking the pair of serinol and piperazine (PIP) as an example, the PEA-NF membrane fabricated with 0.1 w/v% serinol mixed with 0.04 w/v% PIP as water-soluble monomer and 0.1 w/v% TMC as oil phase monomer was found to have a pure water permeability (PWP) of 18.5 L·m-2·h-1·bar-1 and a MgSO4 rejection of 95.5 %, which surpasses almost all the reported PEA NF membranes. Findings of the current research provide more possibilities for the low-cost and rapid synthesis of high-performance PEA membranes aiming for water purification.

Toothpaste containing TiF4 and chitosan against erosive tooth wear in situ.

OBJECTIVE: This study compared the protective effect of an experimental TiF4/Chitosan toothpaste with a commercial toothpaste on the prevention of erosive tooth wear (ETW) in situ. METHODS: Fifteen subjects took part in this crossover and double-blind study, in which they wore a palatal appliance containing 4 bovine enamel and 4 dentin in 3 phases (5 days each). Half of the samples were subjected to erosive challenges (90 s in 0.1 % citric acid, pH 2.5, 4 times/day), and the other half to erosive plus abrasive challenges (15 s plus 45 s of contact, 2 times/day). The phases corresponded to the application of the different toothpastes: 1) TiF4 (1400 ppm F-) plus Chitosan, 2) Elmex®, Erosion Protection (1400 ppm F-, Chitosan), and 3) Placebo (negative control). Tooth wear was measured using contact profilometry (µm) and submitted to two-way RM ANOVA/Tukey test (p < 0.05). RESULTS: No significant differences were detected between the experimental and commercial toothpastes, regardless of the challenge on both tissues. Both significantly reduce ETW compared to negative control (p < 0.0006). Tooth wear was increased by brushing only on eroded enamel (p < 0.01), but not on dentin (p = 0.6085). TiF4/Chitosan [erosion 2.98 ± 1.12 µm vs. erosion and abrasion 3.12 ± 1.33 µm] and Elmex® toothpastes [erosion 2.35 ± 0.93 µm vs. erosion and abrasion 2.98 ± 1.0 µm] minimized the impact of brushing compared to placebo on enamel [erosion 4.62 ± 1.48 µm vs. erosion and abrasion 5.15 ± 1.50 µm]. CONCLUSIONS: TiF4 plus chitosan toothpastes showed to be effective in minimizing the ETW as the commercial toothpaste is in situ. CLINICAL RELEVANCE: The experimental toothpaste has similar effect against ETW compared to the commercial toothpaste. Considering the increased ETW prevalence worldwide, this result supports clinical trials and a possible application of this experimental anti-erosive toothpaste in the future.

Bacteriological evaluation and advanced SYBR-green multiplex real-time PCR assay for detection of minced meat adulteration.

Background: Minced meat is a valuable source of nutrients, but it is vulnerable to contamination by microorganisms commonly present in the environment. In addition, there is a risk of adulteration with cheaper meat sources, which can be harmful to consumers. Aim: It is crucial to identify meat adulteration with distinct microbiological analysis for legal, economic, religious, and public health purposes. Methods: A total of 100 minced meat samples were collected from several markets in Sharkia Governorate, Egypt. These samples were then subjected to bacteriological testing and an advanced multiplex PCR method. This method enables the detection of bovine, equine, porcine, and dog species in meat samples with just one step. Results: The adulterated samples had a higher total bacterial count and pH values compared to pure bovine meat. These differences in bacterial count and pH values were statistically significant, with p-values of 0.843 (log10) and 0.233, respectively. The frequency of Escherichia coli occurrence was 13%, and the O111 serotype was predominant in the adulterated samples. Listeria monocytogenes and Staphylococcus aureus were isolated with prevalence rates of 3% and 29%, respectively. Besides, the SYBR-green multiplex real-time PCR assay used in this study detected adulteration with dog, equine, and porcine meats in the examined samples at rates of 9%, 5%, and 4%, respectively. Conclusion: This method provides a sensitive and specific approach to detect issues related to well-being and safety.

Acid tolerance response of Salmonella during the squid storage and its amine production capacity analysis.

Salmonella exhibits a strong inducible acid tolerance response (ATR) under weak acid conditions, and can also induce high-risk strains that are highly toxic, acid resistant, and osmotic pressure resistant to aquatic products. However, the induction mechanism is not yet clear. Therefore, this study aims to simulate the slightly acidic, low-temperature, and high-protein environment during squid processing and storage. Through λRed gene knockout, exploring the effects of low-acid induction, long-term low-temperature storage, and two-component regulation on Salmonella ATR. In this study, we found the two-component system, PhoP/PhoQ and PmrA/PmrB in Salmonella regulates the amino acid metabolism system and improves bacterial acid tolerance by controlling arginine and lysine. Compared with the two indicators of total biogenic amine and diamine content, biogenic amine index and quality index were more suitable for evaluating the quality of aquatic products. The result showed that low-temperature treatment could inhibit Salmonella-induced ATR, which further explained the ATR mechanism from the amino acid metabolism.

Cyy-287, a novel pyrimidine-2,4-diamine derivative, efficiently mitigates inflammatory responses, fibrosis, and lipid synthesis in obesity-induced cardiac and hepatic dysfunction.

Background: Inflammation and metabolic disorders are important factors in the occurrence and development of obesity complications. In this study, we investigated the protective effect and underlying mechanism of a novel pyrimidine-2,4-diamine derivative, Cyy-287, on mice fed a high-fat diet (HFD). Methods: The mice were randomly separated into four groups (n ≥ 7): control (regular diet), HFD, HFD with Cyy-287 (5 mg/kg), and HFD with Cyy-287 (20 mg/kg) following HFD feeding for 10 weeks. After a 10-week administration, ALT and AST enzymes, echocardiography, immunohistochemical (IHC), Western blot (WB), Masson and Sirius Red staining were used to evaluate functional and morphological changes to the heart and liver. Microsomes from the mouse liver were extracted to quantify the total amount of CYP450 enzymes after drug treatment. Results: Cyy-287 decreased the levels of serum glucose, LDL, TC, ALT, and AST activities in HFD-treated mice. However, Cyy-287 administration increased ejection fraction (EF) and fractional shortening (FS) index of the heart. Cyy-287 inhibited histopathological changes in the heart and liver; decreased inflammatory activity; significantly diminished p38 mitogen-activated protein kinase (MAPK), the nuclear factor-kappa B (NF-κB) axis, and sterol regulatory element-binding protein-1c (SREBP-1c); and upregulated the AMP-activated protein kinase (AMPK) pathway in HFD-treated mice. Cyy-287 restored the content of hepatic CYP450 enzymes. Conclusion: These findings demonstrated that Cyy-287 protected heart and liver cells from obesity-induced damage by inhibiting inflammation, fibrosis, and lipid synthesis.

Measurement constrained emission estimates of alkylated polycyclic aromatic hydrocarbons in the Canadian Athabasca oil sands region.

Alkylated polycyclic aromatic hydrocarbons (APAH) are important contaminants of crude oil production and exhibit similar toxicity to their parent compounds. This study developed an emission inventory of APAH in a major oil sands development region of Alberta, Canada, and validated the inventory with ambient concentration measurements through dispersion modeling. The initial estimate of regional total annual emissions of 21 APAH species was 362 tonnes/year in the last decade, of which 309 and 53 tonnes/year were in particle-bound and gas-phase APAH, respectively. Fugitive dust from oil sands mining activities is the primary source of particle-bound APAH, emitting 274 tonnes/year. Other major sources of APAH include point sources (31), tailings ponds (21), anthropogenic fuel consumption from mine fleet (17), and local transportation (13). The group of species with highest emissions was C1-C4 alkylnaphthalenes (53%), followed by C1-C4 alkylphenanthrenes/anthracenes (19%), C1-C4 fluorenes (13%), and C1-C4 fluoranthenes/pyrenes and C1-C4 benz[a]anthracenes/chrysene/triphenylenes (7% each). CALPUFF dispersion modeling was performed using the APAH emissions as model input. The model-predicted annual average ambient APAH concentrations at 17 monitoring sites were 1%-52% (19% on average) lower than the measurements. Inverse dispersion modeling was then applied to adjust APAH emissions higher by 19% for each of the 21 APAH species, which resulted in a revised estimate of APAH emissions to 431 tonnes/year. With the revised emissions as model input, model bias in the predicted ambient concentration was reduced from -19% to -8%. The model results showed the highest concentrations of APAH were near tailings ponds and open mining faces and downwind areas, with total APAH concentrations being higher than 50 ng/m3.

Design, synthesis and biological evaluation of CDC20 inhibitors for treatment of triple-negative breast cancer.

The involvement of CDC20 in promoting tumor growth in different types of human cancers and it disturbs the process of cell division and impedes tumor proliferation. In this work, a novel of Apcin derivatives targeting CDC20 were designed and synthesized to evaluate for their biological activities. The inhibitory effect on the proliferation of four human tumor cell lines (MCF-7, MDA-MB-231, MDA-MB-468 and A549) was observed. Among them, compound E1 exhibited the strongest inhibitory effect on the proliferation of MDA-MB-231 cells with an IC50 value of 1.43 µM, which was significantly superior to that of Apcin. Further biological studies demonstrated that compound E1 inhibited cancer cell migration and colony formation. Furthermore, compound E1 specifically targeted CDC20 and exhibited a higher binding affinity to CDC20 compared to that of Apcin, thereby inducing cell cycle arrest in the G2/M phase of cancer cells. Moreover, it has been observed that compound E1 induces autophagy in cancer cells. In 4T1 Xenograft Models compound E1 exhibited the potential antitumor activity without obvious toxicity. These findings suggest that E1 could be regarded as a CDC20 inhibitor deserved further investigation.

An ATMND/SGI based three-way junction ratiometric fluorescent probe for rapid and sensitive detection of bleomycin.

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket. The unique "Y" structure not only could entrap ATMND in the mismatch pocket with high affinity, leading to FL quenching at 408 nm, but also embed SGI in the grooves of the double-stranded portion, resulting in FL enhancement at 530 nm. In the presence of BLM-Fe(II), the "Y" structure of D6 was destroyed due to the specific cleavage of the BLM recognition site, the 5'-GT-3' site in D6. This caused the release of ATMND and SGI and thus the ratiometric signal change of FL enhancement by ATMND and FL quenching by SGI. Under optimal conditions, the ratiometric probe exhibited a linear correlation between the intensity ratio of F408/F530 and the concentration of BLM in the range of 0.5-1000 nM, with a detection limit of 0.2 nM. In addition, the probe was applied to detect BLM in human serum samples with satisfactory results, indicating its good clinical application potential.

Development of a Thermodynamically Favorable Multi-enzyme Cascade Reaction for Efficient Sustainable Production of ω-Amino Fatty Acids and α,ω-Diamines.

Invited for this issue's cover is the group of Huilei Yu at the East China University of Science and Technology. The image shows a sustainable biosynthesis route to nylon monomers from bio-based substrate α, ω-dicarboxylic acids. The Research Article itself is available at 10.1002/cssc.202301477.

Enhancing CO2 capture of an aminoethylethanolamine-based non-aqueous absorbent by using tertiary amine as a proton-transfer mediator: From performance to mechanism.

Non-aqueous absorbents (NAAs) have attracted increasing attention for CO2 capture because of their great energy-saving potential. Primary diamines which can provide high CO2 absorption loading are promising candidates for formulating NAAs but suffer disadvantages in regenerability. In this study, a promising strategy that using tertiary amines (TAs) as proton-transfer mediators was proposed to enhance the regenerability of an aminoethylethanolamine (AEEA, diamine)/dimethyl sulfoxide (DMSO) (A/D) NAA. Surprisingly, some employed TAs such as N,N-diethylaminoethanol (DEEA), N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA), 3-dimethylamino-1-propanol (3DMA1P), and N,N-dimethylethanolamine (DMEA) enhanced not only the regenerability of the A/D NAA but also the CO2 absorption performance. Specifically, the CO2 absorption loading and cyclic loading were increased by about 12.7% and 15.5%-22.7%, respectively. The TA-enhanced CO2 capture mechanism was comprehensively explored via nuclear magnetic resonance technique and quantum chemical calculations. During CO2 absorption, the TA acted as an ultimate proton acceptor for AEEA-zwitterion and enabled more AEEA to form carbamate species (AEEACOO-) to store CO2, thus enhancing CO2 absorption. For CO2 desorption, the TA first provided protons directly to AEEACOO- as a proton donor; moreover, it functioned as a proton carrier and facilitated the low-energy step-wise proton transfer from protonated AEEA to AEEACOO-. Consequently, the presence of TA made it easier for AEEACOO- to obtain protons to decompose, resulting in enhanced CO2 desorption. In a word, introducing the TA as a proton-transfer mediator into the A/D NAA enhanced both the CO2 absorption performance and the regenerability, which was an efficient way to "kill two birds with one stone".

Significantly Improved Cold Preservation of Rat Hind Limb Vascularized Composite Allografts Using the New PrC-210 Free Radical Scavenger.

Vascularized composite allotransplantation (VCA) represents a promising reconstructive solution primarily conducted to improve quality of life. However, tissue damage caused by cold-ischemia (CI) storage prior to transplant represents a major factor limiting widespread application. This study investigates the addition of the novel free radical scavenger PrC-210 to UW Organ Preservation Solution (UW Solution) to suppress CI-induced skeletal muscle injury in a rat hind limb amputation model. Lewis rats received systemic perfusion of UW solution +/- PrC-210 (0 mM control, 10 mM, 20 mM, 30 mM, or 40 mM), followed by bilateral transfemoral amputation. Limbs were stored in 40 mL of the same perfusate at 4 °C for 48 h. Muscle punch biopsies were taken at set times over the 48 h cold-storage period and analyzed for caspase-3,7 activity, cytochrome C levels, and qualitative histology. A single 15 s perfusion of PrC-210-containing UW Solution conferred a dose-dependent reduction in CI-induced muscle cell death over 48 h. In the presence of PrC-210, muscle cell mitochondrial cytochrome C release was equivalent to 0 h controls, with profound reductions in the caspase-3,7 apoptotic marker that correlated with limb histology. PrC-210 conferred complete prevention of ROS-induced mitochondrial lysis in vitro, as measured by cytochrome C release. We conclude that the addition of 30 mM PrC210 to UW Solution conferred the most consistent reduction in CI limb damage, and it warrants further investigation for clinical application in the VCA setting.

Gamma-Secretase Inhibitors Downregulate the Profibrotic NOTCH Signaling Pathway in Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin fragility disorder caused by mutations in COL7A1. RDEB is hallmarked by trauma-induced unremitting blistering, chronic wounds with inflammation, and progressive fibrosis, leading to severe disease complications. There is currently no cure for RDEB-associated fibrosis. Our previous studies and increasing evidence highlighted the profibrotic role of NOTCH pathway in different skin disorders, including RDEB. In this study, we further investigated the role of NOTCH signaling in RDEB pathogenesis and explored the effects of its inhibition by γ-secretase inhibitors DAPT and PF-03084014 (nirogacestat). Our analyses demonstrated that JAG1 and cleaved NOTCH1 are upregulated in primary RDEB fibroblasts (ie, RDEB-derived fibroblasts) compared with controls, and their protein levels are further increased by TGF-ß1 stimulation. Functional assays unveiled the involvement of JAG1/NOTCH1 axis in RDEB fibrosis and demonstrated that its blockade counteracts a variety of fibrotic traits. In particular, RDEB-derived fibroblasts treated with PF-03084014 showed (i) a significant reduction of contractility, (ii) a diminished secretion of TGF-ß1 and collagens, and (iii) the downregulation of several fibrotic proteins. Although less marked than PF-03084014-treated cells, RDEB-derived fibroblasts exhibited a reduction of fibrotic traits also upon DAPT treatment. This study provides potential therapeutic strategies to antagonize RDEB fibrosis onset and progression.

The Significance and Importance of dPCR, qPCR, and SYBR Green PCR Kit in the Detection of Numerous Diseases.

Digital PCR (dPCR) is the latest technique that has become commercially accessible for various types of research. This method uses Taq polymerase in a standard polymerase chain reaction (PCR) to amplify a target DNA fragment from a complex sample, like quantitative PCR (qPCR) and droplet digital PCR (dd- PCR). ddPCR may facilitate microRNA (miRNA) measurement, particularly in liquid biopsy, because it has been proven to be more effective and sensitive, and in this method, ddPCR can provide an unprecedented chance for deoxyribonucleic acid (DNA) methylation research because of its capability to increase sensitivity and precision over conventional PCR-based methods. qPCR has also been found to be a valuable standard technique to measure both copy DNA (cDNA) and genomic DNA (gDNA) levels, although the finding data can be significantly variable and non-reproducible without relevant validation and verification of both primers and samples. The SYBR green quantitative real-time PCR (qPCR) method has been reported as an appropriate technique for quantitative detection and species discrimination, and has been applied profitably in different experiments to determine, quantify, and discriminate species. Although both TaqMan qRT-PCR and SYBR green qRT-PCR are sensitive and rapid, the SYBR green qRT-PCR assay is easy and the TaqMan qRT-PCR assay is specific but expensive due to the probe required. This review aimed to introduce dPCR, qPCR, SYBR green PCR kit, and digital PCR, compare them, and also introduce their advantages in the detection of different diseases.

Preparation of multifunctional cellulose macromolecule blended fabrics through internal and external synergy by N1, N6-bis (ethylene oxide-2-ylmethyl) hexane-1,6-diamine.

With the diversification of people's demand for textile functions, the preparation of multifunctional fabrics is still a current research hotspot. In this study, the water-soluble epoxy compound N1, N6-bis(oxiran-2-ylmethyl) hexane-1,6-diamine (EH) was introduced into cellulose macromolecule blended fabrics (cotton/modal) by two-phase vaporization technique, resulting in excellent wrinkle, hydrophobicity, and certain UV protection effects. It could be observed by electron microscopy that EH formed a polymer film on the fiber surface. In addition, the results of EDS scans and fiber swelling rate tests showed that EH was uniformly distributed and formed a cross-linked structure in the amorphous zones inside the fibers. Compared with the control fabrics, the wrinkle recovery angle of the EH-treated fabric was increased by 39.7 %. The fabrics could reach a contact angle of 136.9°, providing excellent hydrophobic effect. In addition, the fabrics achieved certain UV protection effects (UPF of 50+). The EH-treated fabrics were less stabilized in strong acid and alkali conditions, but exhibited greater durability in other environments. In summary, the internal and external synergistic effects of EH in forming polymer films on the fibers surface and internal cross-linking structures provided a cleaner, simple, and feasible method for the preparation of multifunctional cellulose macromolecule fibers textiles.