Advancing Albumin Isolation from Human Serum with Graphene Oxide and Derivatives: A Novel Approach for Clinical Applications.

This study introduces a novel, environmentally friendly albumin isolation method using graphene oxide (GO). GO selectively extracts albumin from serum samples, leveraging the unique interactions between GO's oxygen-containing functional groups and serum proteins. This method achieves high purification efficiency without the need for hazardous chemicals. Comprehensive characterization of GO and reduced graphene oxide (rGO) through techniques such as X-ray diffraction (XRD) analysis, Raman spectroscopy, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) confirmed the structural and functional group transformations crucial for protein binding. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry analyses demonstrated over 95% purity of isolated albumin, with minimal contamination from other serum proteins. The developed method, optimized for pH and incubation conditions, showcases a green, cost-effective, and simple alternative for albumin purification, promising broad applicability in biomedical research and clinical applications.

Quinoline-based compounds can inhibit diverse enzymes that act on DNA.

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a key epigenetic process. Developing non-nucleoside inhibitors to cause DNA hypomethylation is crucial for treating various conditions without the toxicities associated with existing cytidine-based hypomethylating agents. This study characterized fifteen quinoline-based analogs, particularly compounds with additions like a methylamine (9) or methylpiperazine (11), which demonstrate similar low micromolar inhibitory potency against human DNMT1 and Clostridioides difficile CamA. These compounds (9 and 11) intercalate into CamA-bound DNA via the minor groove, causing a conformational shift that moves the catalytic domain away from the DNA. This study adds to the limited examples of DNA methyltransferases being inhibited by non-nucleotide compounds through DNA intercalation. Additionally, some quinoline-based analogs inhibit other DNA-interacting enzymes, such as polymerases and base excision repair glycosylases. Finally, compound 11 elicits DNA damage response via p53 activation in cancer cells.

Realizing Long Magnon Diffusion in Organic-Inorganic Hybrid Perovskite Film by the Universal Isotope Effect.

Organic-inorganic halide perovskite (OIHP) spintronics has become a promising research field, as it provides a new precisely manipulable degree of freedom. Recently, by utilizing the spin Seebeck effect and inverse spin-Hall effect measurements, we have discovered substantial magnon injection and transport in Pt/OIHP/Y3Fe5O12 nonlocalized structure. In theory, hyperfine interaction (HFI) is considered to have an important role in the magnon transport of OIHP, but there is no clear experimental evidence reported so far. We report increased spin Seebeck coefficient and lengthened magnon diffusion length in deuterated- (D-) OIHP films that have weaker HFI strength compared with protonated- (H-) OIHP. Consequently, D-MAPbBr3 film, as a non-ferromagnetic spacer, achieves long magnon diffusion length at room temperature (close to 120.3 nm). Our finding provides valuable insights into understanding magnon transport in OIHP films and paves the way for the use of OIHPs in multifunctional applications.

The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA.

CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation.

Genomic characterisation of a multidrug-resistant Klebsiella pneumoniae co-harbouring blaNDM-1, blaKPC-2, and tet(A) isolated from the bloodstream infections of patients.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP), a superbug that can be difficult or impossible to treat, has become a worldwide problem. This study presents the first report of a CRKP strain carrying a plasmid co-harbouring blaNDM-1, blaKPC-2, and tet(A) and the subsequent analysis of its genomic features. METHODS: Isolation and identification of bacteria, antimicrobial susceptibility test, whole genome sequencing, and conjugation experiments assay were conducted in clinical epidemiological investigations and plasmid genetic characterisation analysis. RESULTS: A total of 116 strains of bacteria were isolated from patients with bloodstream infections (BSI) between 2018 and 2023. A total of 89.66% of the isolates were carbapenem-resistant Enterobacteriaceae (CRE), with the majority (75/116) being CRKP. Among these, a novel plasmid co-harbouring blaNDM-1, blaKPC-2, and tet(A) simultaneously was found in CRKP46, and the three genes mediated conjugation by IS26, ISAba125, and IS26, respectively. This plasmid conferred carbapenem resistance to E. coli J53 after conjugative transfer, which was 2 times greater than that of CRKP46. CONCLUSION: The present study identified the occurrence of a rare plasmid co-harbouring blaNDM-1, blaKPC-2, and tet(A), and the spread of these genes was mediated by the corresponding mobile elements. The increased carbapenem resistance created by this novel plasmid challenges public health security and poses a potential threat to human health; therefore, it deserves attention.

[Determination of 11 nutrients in liquid milk by ultra-performance liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.

Influence of environmental filtering and spatial processes on macroinvertebrate community in urban lakes in the Taihu Lake Basin, China.

Studies identifying the relative importance of multiple ecological processes in macroinvertebrate communities in urban lakes at a basin scale are rare. In this study, 14 urban lakes in the Taihu Lake Basin were selected to explore the relative importance of environmental filtering and spatial processes in the assembly of macroinvertebrate communities. Our findings revealed significant spatiotemporal variations in macroinvertebrate communities, both between lakes and across seasons. We found that environmental filtering exerted a greater influence on taxonomic total beta diversity and its individual components (species turnover and nestedness) compared to spatial processes. Key environmental variables such as water depth, water temperature, total dissolved solids, chlorophyll a, and lake surface area were found to be crucial in shaping macroinvertebrate communities within these urban lakes. The observed high spatial heterogeneity in environmental conditions, along with intermediate basin areas, good connectivity and short distances between lakes, and the high dispersal ability of dominant taxa, likely contributed to the dominance of environmental filtering in macroinvertebrate community assembly. Our study contributes to a better understanding of the underlying mechanisms governing macroinvertebrate community assembly in urban lakes, thereby providing valuable insights for studies on community ecology and water environmental protection in urban lakes.

Quinoline-based compounds can inhibit diverse enzymes that act on DNA.

DNA methylation, as exemplified by cytosine-C5 methylation in mammals and adenine-N6 methylation in bacteria, is a crucial epigenetic mechanism driving numerous vital biological processes. Developing non-nucleoside inhibitors to cause DNA hypomethylation is a high priority, in order to treat a variety of significant medical conditions without the toxicities associated with existing cytidine-based hypomethylating agents. In this study, we have characterized fifteen quinoline-based analogs. Notably, compounds with additions like a methylamine ( 9 ) or methylpiperazine ( 11 ) demonstrate similar low micromolar inhibitory potency against both human DNMT1 (which generates C5-methylcytosine) and Clostridioides difficile CamA (which generates N6-methyladenine). Structurally, compounds 9 and 11 specifically intercalate into CamA-bound DNA via the minor groove, adjacent to the target adenine, leading to a substantial conformational shift that moves the catalytic domain away from the DNA. This study adds to the limited examples of DNA methyltransferases being inhibited by non-nucleotide compounds through DNA intercalation, following the discovery of dicyanopyridine-based inhibitors for DNMT1. Furthermore, our study shows that some of these quinoline-based analogs inhibit other enzymes that act on DNA, such as polymerases and base excision repair glycosylases. Finally, in cancer cells compound 11 elicits DNA damage response via p53 activation. Highlights: Six of fifteen quinoline-based derivatives demonstrated comparable low micromolar inhibitory effects on human cytosine methyltransferase DNMT1, and the bacterial adenine methyltransferases Clostridioides difficile CamA and Caulobacter crescentus CcrM. Compounds 9 and 11 were found to intercalate into a DNA substrate bound by CamA. These quinoline-based derivatives also showed inhibitory activity against various base excision repair DNA glycosylases, and DNA and RNA polymerases. Compound 11 provokes DNA damage response via p53 activation in cancer cells.

Rewiring cis-2-butene-1,4-dial mediated urinary metabolomics fingerprints of short-term exposure to furan.

Furan represents one of the dietary-sourced persistent organic pollutants and thermal processing contaminants. Given its widespread occurrence in food and various toxicological effects, accurately assessing furan exposure is essential for informing public health risks. Furan is metabolized to a reactive primary product, cis-2-butene-1,4-dial (BDA) upon absorption. Some of the resulting BDA-derived metabolites have been proposed as potential exposure biomarkers of furan. However, the lack of quantification for recognized and feasible furan biomarkers has hampered the development of internal exposure risk assessment of furan. In this study, we employed reliable non-targeted metabolomics techniques to uncover urinary furan metabolites and elucidate their chemical structures. We characterized 8 reported and 11 new furan metabolites derived from the binding of BDA with glutathione (GSH), biogenic amines, and/or amino acids in the urine of male rats subjected to varying doses of furan. Notably, a mono-GSH-BDA adduct named cyclic GSH-BDA emerged as a highly prospective specific biomarker of furan exposure, as determined by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Cyclic GSH-BDA demonstrated a robust mass spectrometry ion response intensity and exhibited evident time- and dose response. Additionally, we conducted a comprehensive profiling of the kinetics of potential furan biomarkers over time to capture the metabolic dynamics of furan in vivo. Most urinary furan metabolites reached peak concentrations at either the first (3 h) or second (6 h) sampling time point and were largely eliminated within 36 h following furan treatment. The present study provides novel insights into furan metabolism and sheds light on the biomonitoring of furan exposure.

Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook.

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

Estimating the prevalence of dyslipidemia by measuring fenofibrate in 33 cities in China.

Dyslipidemia, recognized as a predominant risk factor for atherosclerotic cardiovascular disease (CVD), remains a pressing health concern worldwide, particularly in China with nearly 40 % of the population adversely suffering. Fenofibrate, as one of the most commonly used drugs for dyslipidemia therapy, excreted as the format of fenofibrate-acid, which showed considerable stability in sewage samples and could be detected as WBE-biomarkers to monitor the prevalence of dyslipidemia. In this work, we reported the first research on estimating the prevalence of dyslipidemia by WBE approach. 527 sewage samples from 33 cities in China were extracted by solid phase and analyzed by LC-MS/MS. The detected concentration of fenofibrate acid in sewage was on an average of 120.5 ± 59.9 ng/L, and the reverse-calculated consumption of fenofibrate based on fenofibrate acid was 77.8 ± 25.0 mg/day/1000inh. Detailed analysis unveiled an average prevalence of fenofibrate at 0.056 % ± 0.018 %, and the dyslipidemia prevalence among the population aged over 15 was ultimately estimated to be 37.9 % ± 9.3 % and was in accordance with the China Cardiovascular research result of 40.4 %, which proves that WBE is a substitutable approach of traditional epidemiological investigation methods due to its timeliness and cost-effectiveness. This study demonstrated that estimating dyslipidemia prevalence by WBE with metabolite fenofibrate acid as a biomarker is feasible in most Chinese cities.

Selective Single-Molecule Nanopore Detection of mpox A29 Protein Directly in Biofluids.

Single-molecule antigen detection using nanopores offers a promising alternative for accurate virus testing to contain their transmission. However, the selective and efficient identification of small viral proteins directly in human biofluids remains a challenge. Here, we report a nanopore sensing strategy based on a customized DNA molecular probe that combines an aptamer and an antibody to enhance the single-molecule detection of mpox virus (MPXV) A29 protein, a small protein with an M.W. of ca. 14 kDa. The formation of the aptamer-target-antibody sandwich structures enables efficient identification of targets when translocating through the nanopore. This technique can accurately detect A29 protein with a limit of detection of ∼11 fM and can distinguish the MPXV A29 from vaccinia virus A27 protein (a difference of only four amino acids) and Varicella Zoster Virus (VZV) protein directly in biofluids. The simplicity, high selectivity, and sensitivity of this approach have the potential to contribute to the diagnosis of viruses in point-of-care settings.

Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes.

We report on single-molecule nanopore sensing combined with position-encoded DNA molecular probes, with chemistry tuned to simultaneously identify various antigen proteins and multiple RNA gene fragments of SARS-CoV-2 with high sensitivity and selectivity. We show that this sensing strategy can directly detect spike (S) and nucleocapsid (N) proteins in unprocessed human saliva. Moreover, our approach enables the identification of RNA fragments from patient samples using nasal/throat swabs, enabling the identification of critical mutations such as D614G, G446S, or Y144del among viral variants. In particular, it can detect and discriminate between SARS-CoV-2 lineages of wild-type B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.539 (Omicron) within a single measurement without the need for nucleic acid sequencing. The sensing strategy of the molecular probes is easily adaptable to other viral targets and diseases and can be expanded depending on the application required.

Effects of calcium-free ageing on ethanol-induced activation and developmental potential of mouse oocytes.

Although ethanol treatment is widely used to activate oocytes, the underlying mechanisms are largely unclear. Roles of intracellular calcium stores and extracellular calcium in ethanol-induced activation (EIA) of oocytes remain to be verified, and whether calcium-sensing receptor (CaSR) is involved in EIA is unknown. This study showed that calcium-free ageing (CFA) in vitro significantly decreased intracellular stored calcium (sCa) and CaSR expression, and impaired EIA, spindle/chromosome morphology and developmental potential of mouse oocytes. Although EIA in oocytes with full sCa after ageing with calcium does not require calcium influx, calcium influx is essential for EIA of oocytes with reduced sCa after CFA. Furthermore, the extremely low EIA rate in oocytes with CFA-downregulated CaSR expression and the fact that inhibiting CaSR significantly decreased the EIA of oocytes with a full complement of CaSR suggest that CaSR played a significant role in the EIA of ageing oocytes. In conclusion, CFA impaired EIA and the developmental potential of mouse oocytes by decreasing sCa and downregulating CaSR expression. Because mouse oocytes routinely treated for activation (18 h post hCG) are equipped with a full sCa complement and CaSR, the present results suggest that, while calcium influx is not essential, CaSR is required for the EIA of oocytes.

Improved performance of InGaAs/AlGaAs quantum well lasers on silicon using InAlAs trapping layers.

InGaAs/AlGaAs multiple quantum well lasers grown on silicon (001) by molecular beam epitaxy have been demonstrated. By inserting InAlAs trapping layers into AlGaAs cladding layers, misfit dislocations easily located in the active region can be effectively transferred out of the active region. For comparison, the same laser structure without the InAlAs trapping layers was also grown. All these as-grown materials were fabricated into Fabry-Perot lasers with the same cavity size of 20 × 1000 µm2. The laser with trapping layers achieved a 2.7-fold reduction in threshold current density under pulsed operation (5 µs-pulsed width, 1%-duty cycle) compared to the counterpart, and further realized a room-temperature continuous-wave lasing with a threshold current of 537 mA which corresponds to a threshold current density of 2.7 kA/cm2. When the injection current reached 1000 mA, the single-facet maximum output power and slope efficiency were 45.3 mW and 0.143 W/A, respectively. This work demonstrates significantly improved performances of InGaAs/AlGaAs quantum well lasers monolithically grown on silicon, providing a feasible solution to optimize the InGaAs quantum well structure.

Nanopore Detection Using Supercharged Polypeptide Molecular Carriers.

The analysis at the single-molecule level of proteins and their interactions can provide critical information for understanding biological processes and diseases, particularly for proteins present in biological samples with low copy numbers. Nanopore sensing is an analytical technique that allows label-free detection of single proteins in solution and is ideally suited to applications, such as studying protein-protein interactions, biomarker screening, drug discovery, and even protein sequencing. However, given the current spatiotemporal limitations in protein nanopore sensing, challenges remain in controlling protein translocation through a nanopore and relating protein structures and functions with nanopore readouts. Here, we demonstrate that supercharged unstructured polypeptides (SUPs) can be genetically fused with proteins of interest and used as molecular carriers to facilitate nanopore detection of proteins. We show that cationic SUPs can substantially slow down the translocation of target proteins due to their electrostatic interactions with the nanopore surface. This approach enables the differentiation of individual proteins with different sizes and shapes via characteristic subpeaks in the nanopore current, thus facilitating a viable route to use polypeptide molecular carriers to control molecular transport and as a potential system to study protein-protein interactions at the single-molecule level.

Sediments are important in regulating the algae-derived off-flavor (ß-cyclocitral) in eutrophic lakes.

In recent years, due to global warming and water eutrophication, cyanobacterial blooms have occurred frequently worldwide, resulting in a series of water quality problems, among which the odor problem in lakes is one of the focuses of attention. In the late stage of the bloom, a large amount of algae accumulated on the surface sediment, which will be a great hidden danger to cause odor pollution in lakes. ß-Cyclocitral is one of the typical algae-derived odor compounds that cause odor in lakes. In this study, an annual survey of 13 eutrophic lakes in the Taihu Lake basin was investigated to assess the effects of abiotic and biotic factors on ß-cyclocitral in water. Our results showed that high concentrations of ß-cyclocitral in the pore water (pore-ß-cyclocitral) were detected in the sediment and far exceeded that in the water column, with an average of about 100.37 times. Structural equation modeling indicated that algal biomass and pore-ß-cyclocitral can directly regulate the concentrations of ß-cyclocitral in the water column, and total phosphorus (TP) and temperature (Temp) promoted the algal biomass which further enhanced the production of ß-cyclocitral both in the water column and pore water. It was worth noting that when Chla ≥30 µg/L, the effects of algae on pore-ß-cyclocitral were significantly enhanced, and pore-ß-cyclocitral played a major role in the regulation of ß-cyclocitral concentrations in water column. Overall, our study facilitated a comprehensive and systematic understanding of the effects of algae on odorants and the dynamic regulatory processes in complex aquatic ecosystems, and revealed a long-neglected process, that was, the important contribution of sediments to ß-cyclocitral in the water column in eutrophic lakes, which would conduce to a more accurate understanding of the evolution of off flavors in lakes and also useful for the management of odors in lakes in the future.

Assessing human exposure to phthalate esters in drinking water migrated from various pipe materials and water filter elements during water treatments and storage.

Plastic water-supply pipes and filter element are frequently used in municipal water supply systems. Leaching of phthalate esters (PAEs) from these pipes and filter elements to drinking water has become a common concern among the public. In this study, the migrations of 16 phthalate esters (PAEs) in seven different kinds of water-supply product materials were investigated. Di-n-butyl phthalate (DBP) had the highest detection frequency of 54.4% in the water leaching samples of various water supply pipes and water filter elements samples, followed by Diisobutyl phthalate (DIBP, 46/90, 51.1%). The maximum detected concentration level for di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), and DBP in the leaching experiment was below the regulatory limit values of 8 µg/L, 300 µg/L, and 3 µg/L for each compound in China standards for drinking water quality. The increasing of the water temperature, the lower pH of the water, and the increasing of the leaching time will increase the migration of PAEs from plastic pipes into water. The chronic daily intake of children aged < 1-12 years to PAEs through drinking water was higher than the rest of the population groups. Carcinogenic risks (CR) of DEHP via drinking water were neglectable for most groups of people, while for young children with age of 1-2 years old, the CR is an acceptable risk.

Simulation and design of a high-speed and high-power modified uni-traveling carrier photodiode based on the electric field distribution in the depletion region.

A modified uni-traveling carrier photodiode with an electric field control layer is proposed to achieve high-speed and high-power performance at a lower bias voltage. By inserting the 10 nm p-type InGaAs electric field control layer between the intrinsic absorption layer and space layer, the electric field distribution in the depleted absorption layer and depleted non-absorption layer can be changed. It is beneficial for reducing power consumption and heat generation, meanwhile suppressing the space-charge effect. Compared with the original structure without the electric field control layer, the 3 dB bandwidth of the 20 µm diameter novel structure, to the best of our knowledge, is improved by 27.1% to 37.5 GHz with a reverse bias of 2 V, and the RF output power reaches 23.9 dBm at 30 GHz. In addition, under 8 V bias voltage, the bandwidth reaches 47.3 GHz.