Heavy carbon nanodots: a new phosphorescent carbon nanostructure.

Carbon nanodots are nanometer sized fluorescent particles studied for their distinct photoluminescent properties and biocompatibility. Although extensive literature reports the modification and application of carbon nanodot fluorescence, little has been published pertaining to phosphorescence emission from carbon nanodots. The use of phosphors in biological imaging can lead to clearer detection, as the long lifetimes of phosphorescent emission permit off-gated collection that avoids noise from biological autofluorescence. Carbon nanodots present a desirable scaffold for this application, with advantageous qualities ranging from photostability to multi-color emission. This research reports the generation of a novel phosphorescent "heavy carbon" nanodot via halogenation of the carbon nanodot structure. By employing a collection pathway that effectively incorporates bromine into the nanostructure, T1 triplet character is introduced, and subsequently phosphorescence is observed in liquid media at room temperature for the first time in the nanodot literature. Further experiments are reported characterizing the conditions of observed phosphorescence and its pH-dependence. Our approach for producing "heavy carbon nanodots" is a low-cost and relatively simple method for generating the phosphorescent nanodots, which sets the foundation for its potential future use as a phosphorescent probe in application.

The Latest Sensor Detection Methods for per- and Polyfluoroalkyl Substances.

Per- and polyfluoroalkyl substances (PFASs) have emerged as a prominent environmental pollutant in recent years, primarily due to their tendency to accumulate and magnify in both the environment and living organisms. The entry of PFASs into the environment can have detrimental effects on human health. Hence, it is crucial to actively monitor and detect the presence of PFASs. The current standard detection method of PFAS is the combination of chromatography and mass spectrometry. However, this requires expensive instruments, extra sample pretreatment steps, complicated operation and long analysis time. As a result, new methods that do not rely on chromatography and mass spectrometry have been developed and applied. These alternative methods mainly include optical and electrochemical sensor methods, which offer great potential in terms of real-time field detection, instrument miniaturization, shorter analysis time, and reduced detection cost. This review provides a summary of recent advancements in PFAS detection sensors. We categorize and explain the principles and mechanisms of these sensors, and compare their limits of detection and sensitivity. Finally, we discuss the future challenges and improvements needed for PFAS sensors, such as field application, commercialization, and other related issues.

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy.

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe3O4@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe3O4@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe3O4@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T2 magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe3O4@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

Erratum: Author correction to 'Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy' [Acta Pharm Sin B 13 (2023) 1303-1317].

[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].

Multiple Sclerosis in a Patient With Prior West Nile Encephalitis.

Multiple sclerosis is a neurodegenerative disease characterized by an inflammatory demyelination of the central nervous system. The degenerative disease has been linked to numerous viral infections, geographical locations, and genetic predisposition. One link that has not been fully established is the relationship between West Nile virus infection and its role in the initiation of multiple sclerosis. This case study provides further evidence that the proinflammatory neurological processes induced by the West Nile virus may lead to systemic demyelination of neuronal axons, ultimately causing multiple sclerosis.

Aggregation-induced emission luminogens for highly effective microwave dynamic therapy.

Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light. Herein, for the first time, we report AIEgen-mediated microwave dynamic therapy (MWDT) for cancer treatment. We found that two AIEgens (TPEPy-I and TPEPy-PF6) served as a new type of microwave (MW) sensitizers to produce ROS, including singlet oxygen (1O2), resulting in efficient destructions of cancer cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22 µM, respectively. Overall, the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT, but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome, thus reducing the occurrence of side-effects of MW radiation.

Characterization of nanoparticles combining polyamine detection with photodynamic therapy.

Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment. However, the therapeutic efficacy is far from satisfactory, mainly due to a polyamine compensation mechanism from the systemic circulation in the tumor environment. Herein, we explore a new solution for improving polyamine detection as well as a possible consumption therapy based on a new photosensitizer that can efficiently consume polyamines via an irreversible chemical reaction. The new photosensitizer is pyrrolopyrroleaza-BODIPY pyridinium salt (PPAB-PyS) nanoparticles that can react with the over-expressed polyamine in cancer cells and produce two photosensitizers with enhanced phototoxicity on cancer destruction. Meanwhile, PPAB-PyS nanoparticles provide a simultaneous ratiometric fluorescence imaging of intracellular polyamine. This combination polyamine consumption with a chemical reaction provides a new modality to enable polyamine detection along with photodynamic therapy as well as a putative depletion of polyamines for cancer treatment and prevention.

Nano-octahedral bimetallic Fe/Eu-MOF preparation and dual model sensing of serum alkaline phosphatase (ALP) based on its peroxidase-like property and fluorescence.

Herein a nano-scale bimetallic Fe/Eu-MOF with a regular octahedral structure was synthesized for the first time. The synthesized Fe/Eu-MOF has both peroxidase-like activity and fluorescence properties. Fe/Eu-MOF can catalyze H2O2 to oxidize the chromogenic substrate TMB to produce blue oxTMB, which has ultraviolet absorption at 652 nm. Unexpectedly, the generated oxTMB can effectively quench the fluorescence of the catalyst Fe/Eu-MOF at 450 nm. The quenching mechanism is mainly the internal filtration effect (IFE), accompanied by static quenching (SQE), Förster resonance energy transfer (FRET) and photoelectron transfer (PET). Fe/Eu-MOF has a high affinity for sodium pyrophosphate (PPi). PPi can be adsorbed to the surface of Fe/Eu-MOF, destroying the structure of Fe/Eu-MOF and inhibiting its catalytic activity, resulting in a decrease in UV absorbance and the decline of fluorescence quenching. In contrast, phosphoric acid (Pi) has almost no effect on the reaction system. Alkaline phosphatase (ALP) can catalyze the hydrolysis of PPi to Pi, thereby reducing the inhibitory effect of PPi. Based on this, we successfully constructed a dual-mode ALP sensor with high selectivity. The linear ranges based on the 652 nm absorption or the fluorescence detection are from 1 to 200 U/L, and the detection limits are 0.6 for the absorption method and 0.9 U/L for the fluorescence method, respectively.

Nitrogen-doped fluorescence carbon dots as multi-mechanism detection for iodide and curcumin in biological and food samples.

Iodine ion is one of the most indispensable anions in living organisms, particularly being an important substance for the synthesis of thyroid hormones. Curcumin is a yellow-orange polyphenol compound derived from the rhizome of Curcuma longa L., which has been commonly used as a spice and natural coloring agent, food additives, cosmetics as well as Chinese medicine. However, excess curcumin may cause DNA inactivation, lead to a decrease in intracellular ATP levels, and trigger the tissue necrosis. Therefore, quantitative detection of iodine and curcumin is of great significance in the fields of food and life sciences. Herein, we develop nitrogen-doped fluorescent carbon dots (NCDs) as a multi-mechanism detection for iodide and curcumin in actual complex biological and food samples, which was prepared by a one-step solid-phase synthesis using tartaric acid and urea as precursors without adding any other reagents. An assembled NCDs-Hg2+ fluorescence-enhanced sensor for the quantitative detection of I- was established based on a fluorescence "turn-off-on" mechanism in a linear range of 0.3-15 µM with a detection limit of 69.4 nM and successfully quantified trace amounts of I- in water samples and urine sample. Meanwhile, the as-synthesized NCDs also can be used as a fluorescent quenched sensor for curcumin detection based on the synergistic internal filtration effect (IFE) and static quenching, achieving a good linear range of 0.1-20 µM with a satisfactory detection limit of 29.8 nM. These results indicate that carbon dots are potential sensing materials for iodine and curcumin detection for the good of our health.

DNA double-strand breaks as a method of radiation measurements for therapeutic beams.

PURPOSE: Many types of dosimeters are used to measure radiation dose and calibrate radiotherapy equipment, but none directly measure the biological effect of this dose. The purpose here is to create a dosimeter that can measure the probability of double-strand breaks (DSB) for DNA, which is directly related to the biological effect of radiation. METHODS: A DNA dosimeter, consisting of magnetic streptavidin beads attached to four kilobase pair DNA strands labeled with biotin and fluorescein amidite (FAM) on opposing ends, was suspended in phosphate-buffered saline (PBS). Fifty microliter samples were placed in plastic tubes inside a water tank setup and irradiated at the dose levels of 25, 50, 100, 150, and 200 Gy. After irradiation, the dosimeters were mechanically separated into beads (intact DNA) and supernatant (broken DNA/FAM) using a magnet. The fluorescence was read and the probability of DSB was calculated. This DNA dosimeter response was benchmarked against a Southern blot analysis technique for the measurement of DSB probability. RESULTS: For the DNA dosimeter, the probabilities of DSB at the dose levels of 25, 50, 100, 150, and 200 Gy were 0.043, 0.081, 0.149, 0.196, and 0.242, respectively, and the standard errors of the mean were 0.002, 0.003, 0.006, 0.005, and 0.011, respectively. For the Southern blot method, the probabilities of DSB at the dose levels of 25, 50, 100, 150, and 200 Gy were 0.053, 0.105, 0.198, 0.235, and 0.264, respectively, and the standard errors of the mean were 0.013, 0.024, 0.040, 0.044, and 0.063, respectively. CONCLUSIONS: A DNA dosimeter can accurately determine the probability of DNA double-strand break (DSB), one of the most toxic effects of radiotherapy, for absorbed radiation doses from 25 to 200 Gy. This is an important step in demonstrating the viability of DNA dosimeters as a measurement technique for radiation.

Inhibition of autophagy potentiates the apoptosis-inducing effects of photodynamic therapy on human colon cancer cells.

BACKGROUND: Photodynamic therapy (PDT) has been reported to be a promising therapy for colon cancer because of its substantial safety features and its ability to induce a systematic reaction rather than local effects on the focal lesion in the intestine. Autophagy and apoptosis play important roles in the response to PDT. However, the role of autophagy after PDT treatment has not yet been clarified. METHODS: In this study, we investigated the relationship between apoptosis and autophagy in porphyrin IX (PpIX)-mediated PDT (PpIX-PDT) in HCT116 colon cancer cells. PpIX-PDT decreased cell viability in a concentration- and light dose-dependent manner. RESULTS: PpIX-PDT results in nuclear condensation, increased the expression of Caspase-3, Bax, and PARP, and decreased expression of Bcl-2. PpIX-PDT also induces the double membrane autophagosome, up-regulates LC3B, Atg7, Beclin-1, and Bcl-2 expression and down-regulates P62 expression. Inhibition of autophagy using chloroquine (CQ) or Atg7 knockdown with a shRNA enhances apoptotic cell death. Based on these findings, autophagy plays a self-protective role in HCT116 cells in response to PpIX-PDT treatment. DISCUSSION: Both autophagy and apoptosis were induced by PpIX-PDT in HCT116 cells, and the inhibition of autophagy strengthened the proapoptotic effect of PpIX-PDT. Thus, the appropriate modulation of autophagy may be as a potential therapeutic target for colon cancer cells treated with PpIX-PDT.

Robust single-cell DNA methylome profiling with snmC-seq2.

Single-cell DNA methylome profiling has enabled the study of epigenomic heterogeneity in complex tissues and during cellular reprogramming. However, broader applications of the method have been impeded by the modest quality of sequencing libraries. Here we report snmC-seq2, which provides improved read mapping, reduced artifactual reads, enhanced throughput, as well as increased library complexity and coverage uniformity compared to snmC-seq. snmC-seq2 is an efficient strategy suited for large-scale single-cell epigenomic studies.

A Psychiatric Formulary for Long-Duration Spaceflight.

INTRODUCTION: Behavioral health is essential for the safety, well-being, and performance of crewmembers in both human spaceflight and Antarctic exploration. Over the past five decades, psychiatric issues have been documented in orbital spaceflight. In Antarctica, literature suggests up to 5% of wintering crewmembers could meet criteria for a psychiatric illness, including mood disorders, stressor-related disorders, sleep-wake disorders, and substance-related disorders. Experience from these settings indicates that psychiatric disorders on deep space missions must be anticipated. An important part of planning for the psychological health of crewmembers is the onboard provision of psychotropic drugs. These medications have been available on orbital missions. A greater variety and supply of these drugs exist at Antarctic facilities. The size and diversity of a deep space psychiatric formulary will be greater than that provided on orbital missions. Drugs to be provisioned include anxiolytics, antidepressants, mood stabilizers, antipsychotics, and hypnotics. Each drug category should include different medications, providing diverse pharmacokinetic, pharmacodynamic, and side effect profiles. The formulary itself should be rigorously controlled, given the abuse potential of some medications. In-flight treatment strategies could include psychological monitoring of well-being and early intervention for significant symptoms. Psychiatric emergencies would be treated aggressively with behavioral and pharmacological interventions to de-escalate potentially hazardous situations. On long-duration space missions, a robust psychiatric formulary could provide crewmembers autonomy and flexibility in treating a range of behavioral issues from depression to acute psychosis. This will contribute to the safety, health, and performance of crewmembers, and to mission success.Friedman E, Bui B. A psychiatric formulary for long-duration spaceflight. Aerosp Med Hum Perform. 2017; 88(11):1024-1033.

Single-cell methylomes identify neuronal subtypes and regulatory elements in mammalian cortex.

The mammalian brain contains diverse neuronal types, yet we lack single-cell epigenomic assays that are able to identify and characterize them. DNA methylation is a stable epigenetic mark that distinguishes cell types and marks regulatory elements. We generated >6000 methylomes from single neuronal nuclei and used them to identify 16 mouse and 21 human neuronal subpopulations in the frontal cortex. CG and non-CG methylation exhibited cell type-specific distributions, and we identified regulatory elements with differential methylation across neuron types. Methylation signatures identified a layer 6 excitatory neuron subtype and a unique human parvalbumin-expressing inhibitory neuron subtype. We observed stronger cross-species conservation of regulatory elements in inhibitory neurons than in excitatory neurons. Single-nucleus methylomes expand the atlas of brain cell types and identify regulatory elements that drive conserved brain cell diversity.

Latex carrier for improving protoporphyrin IX for photodynamic therapy.

Attachment of Protoporphyrin IX (PPIX) to poly (styrene-co-4-vinylpyridine) (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions. After using an oil-in-water heated emulsion polymerization technique to synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing self-reactions between the carboxyl groups and the porphyrin core. Refraining the two parts from interacting while attached to the nanobeads prevented PPIX from aggregating, which then increased water solubility, enhanced luminescence and singlet oxygen production. Attachment also improved cell uptake and cell destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve aspects of photodynamic therapy for the treatment of cancer.

Synthesis and conjugation of Sr2MgSi2O7:Eu2+, Dy3+ water soluble afterglow nanoparticles for photodynamic activation.

The applications of afterglow particles for photodynamic activation and biological imaging have become a topical research area. For these applications, it is critical to have water soluble nanoparticles. However, the synthesis of water soluble afterglow nanoparticles like Sr2MgSi2O7:Eu2+, Dy3+ is a challenging issue because most afterglow materials are very complicated in composition that cannot be synthesized by simple chemical routes. Here, for the first time, Sr2MgSi2O7:Eu2+, Dy3+ water soluble and stable nanoparticles are synthesize using a modified Sol-Gel method followed by the grinding and coating with APTES. The surface coating of the afterglow with APTES and the conjugation with PpIX and folic acid not only improve their water solubility but also enhance the PpIX luminescence by 10 times. More importantly, these strategies make it possible to produce singlet oxygen under X-ray irradiation, which is a very important result for deep cancer treatment. In addition, the surface coating and conjugation largely increase the cell uptake and greatly reduce their dark cytotoxicity. All these results indicate the methods reported here for afterglow nanoparticle synthesis, coating and conjugation are successful, and consequently, the prepared Sr2MgSi2O7:Eu2+, Dy3+/PPIX/Folic acid nano-conjugates are promising for X-ray induced photodynamic therapy on cancer treatment.