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Summary: Abdominal ultrasonography is an important diagnostic tool in the evaluation of colic, yet primary care equine veterinary practitioners are often limited by availability and access to low‐frequency (2–5 MHz curvilinear array or sector) abdominal transducers. Use of high‐frequency (5–10 MHz linear array) transrectal transducers has not previously been compared with use of abdominal transducers for transcutaneous abdominal ultrasonography. One recent pilot study established that there was no significant difference in organ detection by the two transducers on the right side of the equine abdomen, but the stomach, liver and kidney on the left side were less likely to be detected using the transrectal transducer in healthy horses. A clinical study found that the transrectal transducer can be used successfully using the FLASH protocol in horses presenting with colic, with high‐quality images that detected abnormalities of the peritoneal fluid, small intestine and large intestine. The transrectal transducer had decreased visualisation of the stomach and left kidney and was less likely to detect pathology surrounding these organs. This is the first series of studies to evaluate use of transrectal transducers in abdominal ultrasonography of the horse, a tool that is readily accessible to the field practitioner. [ABSTRACT FROM AUTHOR]

Blood culture-negative endocarditis (BCNE) is a challenging disease because of the significant impact of delayed diagnosis on patients. In this study, excised heart valves and blood serum samples were collected from 50 BCNE patients in two central hospitals in Tehran, Iran. Sera were tested by IFA for the presence of IgG and IgM antibodies against Bartonella quintana and B. henselae. Genomic DNA extracted from the heart valves was examined for Bartonella-specific ssrA gene in a probe-based method real-time PCR assay. Any positive sample was Sanger sequenced. IgG titer higher than 1024 was observed in only one patient and all 50 patients tested negative for Bartonella IgM. By real-time PCR, the ssrA gene was detected in the valve of one patient which was further confirmed to be B. quintana. Bartonella-like structures were observed in transmission electron microscopy images of that patient. We present for the first time the involvement of Bartonella in BCNE in Iran. Future research on at-risk populations, as well as domestic and wild mammals as potential reservoirs, is recommended. [ABSTRACT FROM AUTHOR]

A new synthesized Schiff base, N-((anthracen-9-yl) methylene-2-methyl benzenamine) (AMMB), was prepared from o-toluidine and 9-anthracenecarboxaldehyde. The structure of the compound was confirmed by single crystal X-ray diffraction and characterized through various analytical tools such as high resolution mass, 1H and 13C NMR, infrared, UV-vis and elemental composition analysis. The molecular geometries of AMMB were optimized by means of DFT/B3LYP/6311-G++ (d,p) basis set. The optimized geometric parameters of the compound were concordant with the single crystal structure. The optimized structure was utilized in comparison of experimental FT-IR with calculated frequency calculation. TD-DFT analysis was performed to compute the electronic absorption of the compound. SCF-GIAO was employed to compute 1H and 13C NMR, which was consistent with the experimental results. Additionally, NLO, NBO, MEP and global reactivity parameters were also computed using the same level of theory. Hirshfield surface analysis, fingerprint plot and energy frameworks were presented to explore the intermolecular interactions within the crystal. Molecular docking study was carried out to predict the probable binding site of AMMB into lipid bilayers such as DMPC, DPPC, POPC, DLPE, DOPC and POPE. The molecular docking analysis of AMMB showed complex formation with binding affinity energy ranging from −9.3 to −3.4 kcal/mol. [ABSTRACT FROM AUTHOR]

Aiming at the problem that the existing simulation and test methods can’t evaluate the influence of aerodynamic load and temperature load on the structural strength and natural frequency of the probe when the probe is installed, the flow-thermal-solid coupling method was proposed to study the structural strength and modal characteristics of the probe measured in the simulated installation state. Firstly, the CFD (computational fluid dynamics) simulation method was used to obtain the temperature and pressure distribution of the probe surface. The temperature data was imported into the Steady-state Thermal module for steady-state thermal analysis to obtain the probe temperature distribution. The aerodynamic load and temperature load were introduced into the static strength analysis module, and the thermal stress and static stress simulation were carried out, and the maximum deformation of the probe body is calculated to be 0.336 mm and the maximum stress of the probe body is 97.867 MPa. The measured probe modal analysis under pre-stress was carried out, and it is found that the natural frequencies of the first six orders are higher than the calculation results of the traditional method, and the natural frequency of the probe differs from the engine more than 10%, and the designed probe has been installed and used, the reliability of the calculation results is verified. [ABSTRACT FROM AUTHOR]

Chlorogenic acid (CGA) is a natural product that effectively inhibits tumor growth, demonstrated in many preclinical models, and phase II clinical trials for patients with glioma. However, its direct proteomic targets and anticancer molecular mechanisms remain unknown. Herein, we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) was one of the main target proteins of CGA by using affinity-based protein profiling (AfBPP) chemical proteomic approach. We performed in-depth studies on ACAT1/CGA interactions via multiple assays including SPR, ITC, and cryo-EM. Importantly, we demonstrated that CGA impaired cancer cell proliferation by inhibiting the phosphorylation of tetrameric ACAT1 on Y407 residue through a novel mode of action in vitro and in vivo. Our study highlights the use of AfBPP platforms in uncovering unique druggable modalities accessed by natural products. And identifying the molecular target of CGA sheds light on the future clinical application of CGA for cancer therapy. Developing a photo-affinity probe PAL-CGA revealed ACAT1 as CGA's key target, and demonstrated CGA inhibits cancer proliferation by blocking ACAT1's Y407 phosphorylation, highlighting its clinical potential in cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting the lives of millions of people worldwide. Although the mechanism underlying PD pathogenesis is largely undefined, increasing evidence indicates that oxidative and nitrosative stresses play a crucial role in PD occurrence and development. Among them, the role of oxidative stress has been widely acknowledged, but there is relatively less attention given to nitrosative stress, which is mainly derived from peroxynitrite. In the present review, after briefly introducing the background of PD, we discuss the physiopathological function of peroxynitrite and especially highlight how overloaded peroxynitrite is involved in PD pathogenesis. Then, we summarize the currently reported fluorescence imaging-based peroxynitrite detection probes. Moreover, we specifically emphasize the probes that have been applied in PD research. Finally, we propose perspectives on how to develop a more applicable peroxynitrite probe and leverage it for PD theranostics. Conclusively, the present review broadens the knowledge on the pathological role of peroxynitrite in the context of PD and sheds light on how to develop and utilize fluorescence imaging-based strategies for peroxynitrite detection. [ABSTRACT FROM AUTHOR]

Exploring the intrinsic mechanisms of rare-earth ions entering the crystal phase has great significance for finely tuning the luminescent properties of glass–ceramics. Using Er3+ ions as a probe, X-ray diffraction was employed to precisely measure the crystallinity of SiO2-PbF2-Er2O3 glass–ceramics synthesized under various heat treatment conditions, confirming the occurrence of a rapid crystallization process. Additionally, by combining Judd–Ofelt theory with comprehensive analyses of absorption and fluorescence spectra, we calculated the relative proportions of Er3+ ions present in the crystal phase. We found that the crystallization process in the glass–ceramics and the incorporation of Er3+ ions into the crystal phase did not occur synchronously. This discovery provides new theoretical foundations and practical guidance for understanding the mechanism of rare-earth ion incorporation into crystal phases, which is significant for the development of functional materials with specific luminescent properties. [ABSTRACT FROM AUTHOR]

Mitochondria, pivotal organelles crucial for energy generation, apoptosis regulation, and cellular metabolism, have spurred remarkable advancements in targeted material development. This review surveys recent breakthroughs in targeted mitochondrial nanomaterials, illuminating their potential in drug delivery, disease management, and biomedical imaging. This review approaches from various application perspectives, introducing the specific applications of mitochondria-targeted materials in cancer treatment, probes and imaging, and diseases treated with mitochondria as a therapeutic target. Addressing extant challenges and elucidating potential therapeutic mechanisms, it also outlines future development trajectories and obstacles. By comprehensively exploring the diverse applications of targeted mitochondrial nanomaterials, this review aims to catalyze innovative treatment modalities and diagnostic approaches in medical research. This review presents the latest advancements in mitochondria-targeted nanomaterials for biomedical applications, covering diverse fields such as cancer therapy, bioprobes, imaging, and the treatment of various systemic diseases. The novelty and significance of this work lie in its systematic analysis of the intricate relationship between mitochondria and different diseases, as well as the ingenious design strategies employed to harness the therapeutic potential of nanomaterials. By providing crucial insights into the development of mitochondria-targeted nanomaterials and their applications, this review offers a valuable resource for researchers working on innovative treatment modalities and diagnostic approaches. The scientific impact and interest to the readership lie in the identification of promising avenues for future research and the potential for clinical translation of these cutting-edge technologies. [Display omitted] [ABSTRACT FROM AUTHOR]

Mitochondria, crucial intracellular organelles, are central to energy metabolism, signal transduction, apoptosis, calcium homeostasis, and a myriad of other biological processes, making them a focal point in diverse research fields. The capacity to fluorescently label and visually track mitochondria is crucial for understanding their biological roles. We present mulberrin-Cy3, a novel small molecule fluorescent probe that selectively labels mitochondria in animal cells, including cancer cells, with relative ease. This protocol details the synthesis of mulberrin-Cy3 and its use for visualizing mitochondria in living cells. The synthesis is straightforward and time-efficient, and the labeling method is more accessible than traditional approaches, providing a cost-effective option for mitochondrial visualization at room temperature. The labeling is rapid, with effective labeling achieved within 5 min of incubation. The fluorescent signal is stable and brighter, offering a significant advantage over existing methods. Mulberrin-Cy3 represents a promising mitochondrial labeling compound, providing researchers with a novel experimental tool to explore the complex biological functions of mitochondria. This innovation has the potential to significantly advance our comprehension of mitochondrial dynamics and their role in cellular health and disease. [ABSTRACT FROM AUTHOR]

Abstract Blood culture-negative endocarditis (BCNE) is a challenging disease because of the significant impact of delayed diagnosis on patients. In this study, excised heart valves and blood serum samples were collected from 50 BCNE patients in two central hospitals in Tehran, Iran. Sera were tested by IFA for the presence of IgG and IgM antibodies against Bartonella quintana and B. henselae. Genomic DNA extracted from the heart valves was examined for Bartonella-specific ssrA gene in a probe-based method real-time PCR assay. Any positive sample was Sanger sequenced. IgG titer higher than 1024 was observed in only one patient and all 50 patients tested negative for Bartonella IgM. By real-time PCR, the ssrA gene was detected in the valve of one patient which was further confirmed to be B. quintana. Bartonella-like structures were observed in transmission electron microscopy images of that patient. We present for the first time the involvement of Bartonella in BCNE in Iran. Future research on at-risk populations, as well as domestic and wild mammals as potential reservoirs, is recommended.

Chlorogenic acid (CGA) is a natural product that effectively inhibits tumor growth, demonstrated in many preclinical models, and phase II clinical trials for patients with glioma. However, its direct proteomic targets and anticancer molecular mechanisms remain unknown. Herein, we developed a novel bi-functional photo-affinity probe PAL/CGA and discovered mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) was one of the main target proteins of CGA by using affinity-based protein profiling (AfBPP) chemical proteomic approach. We performed in-depth studies on ACAT1/CGA interactions via multiple assays including SPR, ITC, and cryo-EM. Importantly, we demonstrated that CGA impaired cancer cell proliferation by inhibiting the phosphorylation of tetrameric ACAT1 on Y407 residue through a novel mode of action in vitro and in vivo. Our study highlights the use of AfBPP platforms in uncovering unique druggable modalities accessed by natural products. And identifying the molecular target of CGA sheds light on the future clinical application of CGA for cancer therapy.

This study investigates the influence of pregnancy on the in vivo activity of the intestinal P‐glycoprotein (P‐gp) and hepatic organic anion transporters polypeptide (OATP/BCRP) using, respectively, fexofenadine and rosuvastatin as probe drugs. Eleven healthy participants were investigated during the third trimester of pregnancy (Phase 1, 28 to 38 weeks of gestation) and in the postpartum period (Phase 2, 8 to 12 weeks postpartum). In both phases, after administration of a single oral dose of fexofenadine (60 mg) and rosuvastatin (5 mg), serial blood samples were collected for up to 24 h. Rosuvastatin and fexofenadine in plasma were analyzed by LC‐MS/MS using previously validated methods. The pharmacokinetic parameters of fexofenadine and rosuvastatin (Phoenix WinNonLin software) with normal distribution (Shapiro–Wilk test) are presented as geometric mean and 90% confidence interval. Phases 1 and 2 were compared using the t test (P < .05). Fexofexadine AUC0‐24 values do not differ (P‐value: .0715) between Phase 1 (641.9 ng h/mL [500.6‐823.1]) and Phase 2 (823.8 ng h/mL [641.5‐1057.6]) showing that pregnancy (third trimester) does not alter intestinal P‐gp activity. However, rosuvastatin AUC0‐24 values are higher (P‐value: .00005) in Phase 1 (18.7 ng h/mL [13.3‐26.4]) when compared to Phase 2 (9.5 ng h/mL [6.7‐13.4]), suggesting inhibition of OATP1B1/OATP1B3 transporters. In conclusion, pregnancy assessed during the third trimester does not alter the intestinal P‐gp activity but reduces the activity of hepatic OATP1B1/OATP1B3 transporters. Therefore, adjustments in dosage regimens may be necessary for drugs with low therapeutic index, substrates of the OATP1B1/OATP1B3 transporters, administered during the third trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Bubble status monitoring is essential for designing material nanostructures and optimizing industrial processes. However, tracking the fluid dynamics of bubbles is challenging due to their random distribution and irregular dynamic changes. In this study, a tube liquid–solid triboelectric nanogenerator serves as a probe to investigate bubbles at the liquid–solid interface. The study explores the impact of bubble fluid dynamics on liquid–solid contact electrification, examining variables such as flow rates, volumes, and release intervals of bubbles. The study demonstrates that the liquid–solid triboelectric probe can work as a non‐intrusive and self‐powered sensor for monitoring bubble states in chemical fluid control. The sensor exhibits a sensitivity of 13.2 V·cm−3, a signal‐bubble volume correlation coefficient of 0.9964, and a rapid response time of 0.15 s. The sensor, integrated with a wireless module, enables continuous remote detection. This work provides a valuable tool for investigating tri‐phase contact electrification dynamics and presents promising technology for bubble state monitoring. [ABSTRACT FROM AUTHOR]

Accurately measuring the coefficient of friction (COF) is the fundamental prerequisite of superlubricity research. This study aimed to reduce the COF measurement resolution Δμ of atomic force microscopy (AFM). Based on the theoretical model, a distinctive strategy was adopted to reduce Δμ by optimizing the cantilever's cross-section of the AFM probe, inspired by civil engineering. Δμ can be reduced by decreasing the width of the horizontal side wR and the wall thickness t and increasing the width of the vertical side wH. Moreover, the I-shape demonstrates the highest reduction in Δμ, followed by the U-shape. Considering the processability, the AFM probe with the U-shaped cross-sectional cantilever was investigated further, and the dimensions are 35 µm wR, 3.5 µm wH, 0.5 µm t, 50 µm l (cantilever length), and 23 µm htip (tip height). The finite element analysis results confirm its reliability. After being fabricated and calibrated, the AFM probe achieves the minimal Δμ of 1.9×10−6 under the maximum normal force so far. Additionally, the friction detection capability of the fabricated AFM probe improves by 78 times compared to the commercial tipless-force modulation mode (TL-FM) AFM probe with the conventional solid rectangular cross-sectional cantilever. This study provides a powerful tool for measuring 10−6 COF. [ABSTRACT FROM AUTHOR]

H5, H7, and H9 are pivotal avian influenza virus (AIV) subtypes that cause substantial economic losses and pose potential threats to public health worldwide. In this study, a novel triplex fluorescence reverse transcription-loop-mediated isothermal amplification (TLAMP) assay was developed in which traditional LAMP techniques were combined with probes for detection. Through this innovative approach, H5, H7, and H9 subtypes of AIV can be simultaneously identified and differentiated, thereby offering crucial technical support for prevention and control efforts. Three primer sets and composite probes were designed based on conserved regions of the haemagglutinin gene for each subtype. The probes were labelled with distinct fluorophores at their 3' ends, which were detached to release the fluorescence signal during the amplification process. The detection results were interpreted based on the colour of the TLAMP products. Then, the reaction conditions were optimized, and three primer sets and probes were combined in the same reaction system, resulting in a TLAMP detection assay for the differential diagnosis of AIV subtypes. Sensitivity testing with in vitro-transcribed RNA revealed that the detection limit of the TLAMP assay was 205 copies per reaction for H5, 360 copies for H7, and 545 copies for H9. The TLAMP assay demonstrated excellent specificity, no cross- reactivity with related avian viruses, and 100% consistency with a previously published quantitative polymerase chain reaction (qPCR) assay. Therefore, due to its simplicity, rapidity, sensitivity, and specificity, this TLAMP assay is suitable for epidemiological investigations and is a valuable tool for detecting and distinguishing H5, H7, and H9 subtypes of AIV in clinical samples. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) are a class of hazardous gases that are widely present in the atmosphere and cause great harm to human health. In this paper, a ratiometric fluorescent probe (Dye@Eu-MOFs) based on a dye-functionalized metal–organic framework was designed to detect VOCs, which showed high sensitivity and specificity for acetaldehyde solution and vapor. A linear correlation between the integrated fluorescence intensity (I510/I616) and the concentration of acetaldehyde was investigated, enabling a quantitative analysis of acetaldehyde in the ranges of 1 × 10−4~10−5 µL/mL, with a low detection limit of 8.12 × 10−4 mg/L. The selective recognition of acetaldehyde could be clearly distinguished by the naked eye under the excitation of UV light. The potential sensing mechanism was also discussed. Significantly, a molecular logic gate was constructed based on the whole system, and finally, a molecular logic network system for acetaldehyde detection connecting basic and integrated logic operations was realized. This strategy provided an effective guiding method for constructing a molecular-level logic gate for acetaldehyde detection on a simple platform. [ABSTRACT FROM AUTHOR]

The issue of food safety has received significant attention in recent years. Heavy metal ions in food can accumulate in living organisms and significantly threaten human health. Therefore, it is crucial to detect heavy metal ions. Conventional instrumental analysis methods have high accuracy, but the disadvantage is the high cost and the complexity of the operation process, so it is very urgent to establish a low-cost, rapid, and continuous detection method for heavy metal ions. Field effect transistor (FET) biosensors are one of the most promising detection tools for heavy metal ion detection due to demonstrated advantages of rapidity, accuracy, and continuity in hazard detection. This review first introduces the structure and principle of graphene FETs in detail, then lists some examples of graphene FETs for detecting common heavy metal ions, and analyzes their advantages and disadvantages in depth. Finally, the development direction of graphene FET biosensors in heavy metal ion detection highlighted in this paper. [ABSTRACT FROM AUTHOR]

A great deal of attention has been pressed to the hazards caused by the remains of antibiotics in the environment. Fluorescent sensing materials are favored for their rapid qualitative and quantitative detection of antibiotics, with carbon quantum dots (CQDs) being widely used as typical fluorescent materials. CQDs have demonstrated superior performances in conducting antibiotic diagnosis, which makes them a key tool for tackling antibiotic residues. This review article investigates recent advances in CQDs for the assessment and determination of antibiotics residues, involved antibiotic assay components are classified according to the assay mechanism as Static quenching effect (SQE), Dynamic quenching effect (DQE), Internal filtering effect (IFE), and Förster resonance energy transfer (FRET) quenching mechanisms. We hope to provide valuable guidelines for the preparation of high-quality probes as well as limited detection of antibiotics, so as to promote the advancement of CQDs in the antimicrobial field. [ABSTRACT FROM AUTHOR]

The loop-mediated isothermal amplification (LAMP) technique is a great alternative to PCR-based methods, as it is fast, easy to use and works with high sensitivity and specificity without the need for expensive instruments. However, one of the limitations of LAMP is difficulty in achieving the simultaneous detection of several targets in a single tube, as the methodologies that allow this rely on fluorogenic probes containing specific target sequences, complicating their adaptation and the optimization of assays. Here, we summarize different methods for the development of multiplex LAMP assays based on sequence-specific detection, illustrated with a schematic representation of the technique, and evaluate their practical application based on the real-time detection and quantification of results, the possibility to visualize the results at a glance, the prior stabilization of reaction components, promoting the point-of-care use, the maximum number of specific targets amplified, and the validation of the technique in clinical samples. The various LAMP multiplexing methodologies differ in their operating conditions and mechanism. Each methodology has its advantages and disadvantages, and the choice among them will depend on specific application interests. [ABSTRACT FROM AUTHOR]

Recently, the construction of the trisubstituted olefin-type probe molecules has elicited the attention of many researchers. However, the synthesis of the trisubstituted olefin-type probes containing two N-heterocycles simultaneously has been rarely reported. In this study, starting from the inexpensive mucobromic acid 1 and N-heterocyclic compound 2, we first utilized a simple one-step reaction to synthesize a series of trisubstituted olefin-type compounds 3 simultaneously bearing with the structure of two N-heterocyclic rings in the absence of transition metal catalysts with a yield of 62–86%. The optimal reaction conditions were systematically explored, and the structure of the obtained compounds 3 were well characterized with 1H NMR, 13C NMR, X-ray single-crystal and HR-MS. The preliminary observation showed that, in the presence of base, mucobromic acid 1 reacts as its ring-opening structure, and the successive nucleophilic substitution reaction and Michael addition reaction can generate the target product 3. Considering that the aldehyde group in the molecular structure of the trisubstituted olefin-type compounds 3 may react with malononitrile, we carried out some relevant investigations so as to realize the visual detection of malononitrile. Interestingly, among the products, compounds 3a–3c can be prepared in portable test strips through a simple process and used to achieve the naked-eye detection of malononitrile in environmental systems as designed. [ABSTRACT FROM AUTHOR]

This article explores a restriction on non-local binding in Vietnamese—the blocking effect—including a systematic comparison with its Mandarin Chinese counterpart. Our finding is that the blocking effect in Vietnamese appeared to be rather different from that in Mandarin but, in fact, employs essentially the same syntactic mechanism. While binding of Mandarin ziji is governed by a [+participant] feature, binding of the Vietnamese anaphor mình is governed by a [+author] feature. Together with the assumption of the presence of a silent performative frame, this derives that binding of Vietnamese mình yields what one may call an Author effect. [ABSTRACT FROM AUTHOR]

Tissue imaging is crucial in oral cancer diagnostics. Imaging techniques such as X-ray imaging, magnetic resonance imaging, optical coherence tomography (OCT) and computed tomography (CT) enable the visualization and analysis of tissues, aiding in the detection and diagnosis of cancers. A significant amount of research has been conducted on designing OCT probes for tissue imaging, but most probes are either heavy, bulky and require external mounting or are lightweight but straight. This study addresses these challenges, resulting in a curved lightweight, low-voltage and compact handheld imaging probe for oral soft tissue examination. To the best of our knowledge, this is the first curved handheld OCT probe with its shape optimized for oral applications. This probe features highly compact all-fiber optics with a diameter of 125 μm and utilizes innovative central deflection magnetic actuation for controlled beam scanning. To ensure vertical stability while scanning oral soft tissues, the fiber was secured through multiple narrow slits at the probe's distal end. This apparatus was encased in a 3D-printed angular cylinder tube (15 mm outer diameter, 12 mm inner diameter and 160 mm in length, weighing < 20 g). An angle of 115° makes the probe easy to hold and suitable for scanning in space-limited locations. To validate the feasibility of this probe, we conducted assessments on a multi-layered imaging phantom and human tissues, visualizing microstructural features with high contrast. [ABSTRACT FROM AUTHOR]

Recently, the construction of the trisubstituted olefin-type probe molecules has elicited the attention of many researchers. However, the synthesis of the trisubstituted olefin-type probes containing two N-heterocycles simultaneously has been rarely reported. In this study, starting from the inexpensive mucobromic acid 1 and N-heterocyclic compound 2, we first utilized a simple one-step reaction to synthesize a series of trisubstituted olefin-type compounds 3 simultaneously bearing with the structure of two N-heterocyclic rings in the absence of transition metal catalysts with a yield of 62–86%. The optimal reaction conditions were systematically explored, and the structure of the obtained compounds 3 were well characterized with 1H NMR, 13C NMR, X-ray single-crystal and HR-MS. The preliminary observation showed that, in the presence of base, mucobromic acid 1 reacts as its ring-opening structure, and the successive nucleophilic substitution reaction and Michael addition reaction can generate the target product 3. Considering that the aldehyde group in the molecular structure of the trisubstituted olefin-type compounds 3 may react with malononitrile, we carried out some relevant investigations so as to realize the visual detection of malononitrile. Interestingly, among the products, compounds 3a–3c can be prepared in portable test strips through a simple process and used to achieve the naked-eye detection of malononitrile in environmental systems as designed.

Proteolysis targeting chimeras (PROTACs), as a novel therapeutic drug model, has received widespread attention from academia and the pharmaceutical industry. PROTAC technology has led researchers to focus on developing chemical biology tool properties due to the unique operating mechanism and protein dynamic regulatory properties. In recent years the rapid development of PROTAC technology has gradually made PROTACs an essential tool for target identification and validation. To further promote the application of PROTAC tools in drug discovery and basic medical science research, this review distinguished target identification and validation concepts. Furthermore, research progress in PROTAC technology was summarized.

Autophagy is important for many physiological processes; and disordered autophagy can contribute to the pathogenesis of a broad range of systemic disorders. C. elegans is a useful model organism for studying the genetics of autophagy, however, current methods for studying autophagy are labor-intensive and not readily amenable to high-throughput procedures. Here we describe a fluorescent reporter, GFP::LGG-1::mKate2, which is useful for monitoring autophagic flux in live animals. In the intestine, the fusion protein is processed by endogenous ATG-4 to generate GFP::LGG-1 and mKate2 proteins. We provide data indicating that the GFP:mKate ratio is a suitable readout for measuring cellular autophagic flux. Using this reporter, we measured autophagic flux in L1 larvae to day 7 adult animals. We show that basal autophagic flux is relatively low during larval development but increases markedly in reproductive adults before decreasing with age. Furthermore, we show that wild-type, eat-2, and daf-2 mutant animals have distinct autophagic flux profiles through post-embryonic development. Finally, we demonstrate the utility of this reporter by performing a high-content small molecule screen to identify compounds that alter autophagic flux in C. elegans.

In this study, two "on–off" probes (BF2-cur-Ben and BF2-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF2-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (Km = 16 ± 1.6 μM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF2-cur-Ben forms more hydrogen bonds (seven, while BF2-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of Km values. These two probes could enable recognition of intracellular AChE and probe BF2-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF2-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment. [ABSTRACT FROM AUTHOR]

Millions of deaths occur each year due to the late diagnosis of abnormal cellular growth within the body. However, the devastating impact of this can be significantly reduced if cancer metastasis is detected early through the use of enzymatic biomarkers. Among several biomarkers, γ-glutamyltranspeptidase (GGT) stands out as a member of the aminopeptidase family. It is primarily found on the surface of cancer cells such as glioma, ovarian, lung, and prostate cancer, without being overexpressed in normal cells or tissues. Recent years have witnessed significant progress in the field of cancer monitoring and imaging. Fluorescence sensing techniques have been employed, utilizing organic small molecular probes with enzyme-specific recognition sites. These probes emit a fluorescent signal upon interacting with GGT, enabling the imaging, identification, and differentiation of normal and cancerous cells, tissues, and organs. This review article presents a concise overview of recent progress in fluorescent probes developed for the selective detection of GGT, focusing on their applications in cancer imaging. It highlights the observed alterations in the fluorescence and absorption spectra of the probes before and after interaction with GGT. Additionally, the study investigates the changes in the probe molecule's structure following enzyme treatment, evaluates the sensor's detection limit, and consolidated imaging studies conducted using confocal fluorescence analysis. This comprehensive survey is expected to contribute to the advancement of sensing techniques for biomarker detection and cancer imaging, providing valuable insights for refining methodologies and inspiring future developments in this field. [ABSTRACT FROM AUTHOR]

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Development of effective methods for analyzing hypochlorite is of great significance due to the crucial role of hypochlorite in live organisms, as an endogenously produced reactive oxygen species (ROS) in the human immune system. In this paper, a novel fluorescent probe based on 6-methylthiocoumarinyl formate was designed and synthesized in one step for detection of hypochlorite in MeCN/PBS (8:2, v/v, pH 7.4) medium. The probe showed high specificity for hypochlorite over other competitive ROS analytes, extreme large Stokes shift of 265 nm, rapid response to hypochlorite within 20 s, low detection limit of 1.57 μM, and a wide applicable range of pH 3–10. The sensing mechanism was demonstrated to be based on oxidation of methyl phenyl sulfide to sulfoxide by hypochlorite. The probe may have extensive application for selective and convenient detection of hypochlorite due to its multiple advantages. [ABSTRACT FROM AUTHOR]

Simple Summary: Long Interspersed Element-1 (LINE-1 or L1) is an autonomous transposable element, meaning that its DNA sequences are able to replicate themselves throughout the human genome. This activity may lead to genomic instability and is associated with several different diseases. Additionally, L1s are also capable of replicating other non-autonomous sequences, thereby increasing their disruptive impact. Although there are different tools available that may be used for L1 detection, the heuristics involved affect their accuracy. L1PD (LINE-1 Pattern Detection) uses a novel pattern-matching approach to detect L1s in human genomes, using a fixed set of k-mer probes of length 50 that were generated using the human reference genome GRCh38. This research aims to improve L1PD by using longer probes and testing whether this leads to better results. Additionally, experiments were performed to test the effectiveness of L1PD in detecting L1s in other species, such as dogs, horses, and cows. The results showed that longer probes did improve precision and recall of L1s, not only in humans but in the other species as well. Long Interspersed Element-1 (LINE-1 or L1) is an autonomous transposable element that accounts for 17% of the human genome. Strong correlations between abnormal L1 expression and diseases, particularly cancer, have been documented by numerous studies. L1PD (LINE-1 Pattern Detection) had been previously created to detect L1s by using a fixed pre-determined set of 50-mer probes and a pattern-matching algorithm. L1PD uses a novel seed-and-pattern-match strategy as opposed to the well-known seed-and-extend strategy employed by other tools. This study discusses an improved version of L1PD that shows how increasing the size of the k-mer probes from 50 to 75 or to 100 yields better results, as evidenced by experiments showing higher precision and recall when compared to the 50-mers. The probe-generation process was updated and the corresponding software is now shared so that users may generate probes for other reference genomes (with certain limitations). Additionally, L1PD was applied to other non-human genomes, such as dogs, horses, and cows, to further validate the pattern-matching strategy. The improved version of L1PD proves to be an efficient and promising approach for L1 detection. [ABSTRACT FROM AUTHOR]

The precise release and characterization of nitroxyl (HNO) gas signaling molecule remain a challenge due to its short lifetime to date. To solve this issue, an azobenzene-based HNO donor (Azo-D1) was proposed as a colorimetric and fluorometric chemosensor for HNO releasing, to release both HNO and an azobenzene fluorescent reporter together. Specifically, the Azo-D1 has an HNO release half-life of ∼68 min under physiological conditions. The characteristic color change from the original orange to the yellow color indicated the decomposition of the donor molecule. In addition, the stoichiometry release of HNO was qualitatively and quantitatively verified through the classical phosphine compound trap. As compared with the donor molecule by itself, the decomposed product demonstrates a maximum fluorescence emission at 424 nm, where the increase of fluorescence intensity by 6.8 times can be applied to infer the real-time concentration of HNO. Moreover, cellular imaging can also be achieved using this Azo-D1 HNO donor through photoexcitation at 405 and 488 nm, where the real-time monitoring of HNO release was achieved without consuming the HNO source. Finally, the Azo-D1 HNO donor would open a new platform in the exploration of the biochemistry and the biology of HNO. [Display omitted] • The first azobenzene-based HNO donor (Azo-D1) was developed. • Azo-D1 can release HNO (t 1/2 –68 min) under physiological conditions. • HNO release can be monitored by colorimetric and fluorometric changes. • Cell imagines were successfully obtained using Azo-D1 donor. [ABSTRACT FROM AUTHOR]

Summary: Pratylenchus crenatus , P. neglectus , P. penetrans and P. thornei are globally the most commonly occurring species of root-lesion nematodes (RLN). Correct identification and quantification of these nematodes is important for strategic management interventions such as rotation choice and nematicide use. A real-time quantitative PCR can provide a fast and reliable alternative to morphological identification, which requires significant taxonomic experience. A TaqMan hydrolysis probe method based on the 28S rDNA D2-D3 expansion region was developed and validated for the identification and quantification of these four root-lesion nematode species. Standard curves for each target RLN species were generated by plotting known gene copy number, obtained by a ten-fold serial dilution of purified plasmids, with corresponding Ct values. Each standard curve had a strong linear correlation ( R 2 ⩾ 0.9901) between Ct value and gene copy number. There was consistent amplification of samples with target species from different geographic locations within the UK, whereas a lack of amplification was noted for selected non-target species: P. coffeae , P. pseudocoffeae , P. vulnus , P. fallax , Globodera rostochiensis , Meloidogyne hapla , Trichodorus primitivus and Bitylenchus hispaniensis. Specificity and sensitivity of the methods were confirmed by three experiments that explored different life stages, increasing the number of target species, and had mixed Pratylenchus samples. Finally, estimates obtained by qPCR methods were compared with counting carried out by microscopy showing a good correlation ( R 2 = 0.789). The TaqMan real-time PCR developed in this study provides a specific, fast and accurate quantification of P. crenatus , P. neglectus , P. penetrans and P. thornei. [ABSTRACT FROM AUTHOR]

The injectable hydrogels can deliver the loads directly to the predetermined sites and form reservoirs to increase the enrichment and retention of the loads in the target areas. The preparation and injection of injectable hydrogels involve the sol–gel transformation of hydrogels, which is affected by factors such as temperature, ions, enzymes, light, mechanics (self‐healing property), and pH. However, tracing the injection, degradation, and drug release from hydrogels based on different ways of gelation is a major concern. To solve this problem, contrast agents are introduced into injectable hydrogels, enabling the hydrogels to be imaged under techniques such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging, and radionuclide imaging. This review details methods for causing the gelation of imageable hydrogels; discusses the application of injectable hydrogels containing contrast agents in various imaging techniques, and finally explores the potential and challenges of imageable hydrogels based on different modes of gelation. [ABSTRACT FROM AUTHOR]

Background: Arthroscopic knee procedures are one amongst the common surgical interventions for problems in the knee. It is technically more demanding than an open procedure and is associated with several potential complications. During arthroscopy procedures, several technical challenges may arise, and even experienced surgeons may encounter new issues. However, careful attention to the surgical technique can help prevent or resolve them. Methodology: The study was conducted on all patients who underwent knee arthroscopy procedure during study period. We recorded details of the implants used and any unexpected situations related to them, as well as how they were managed. Instrumentation-related parameters such as screwdriver issues, radiofrequency ablator issues, scope damages, shaver complications, probe complications, and meniscus suture passing devices were also assessed. Results: In total, there were 12 (3.73%) implant and instrument-related incidents and complications, of which 5 (1.55%) were implant-related and 7 (2.17%) were instrument related. Among the instrumentation-related incidents and complications, two (0.62%) were screwdriver breakage incidents, two (0.62%) were radiofrequency ablator-related incidents, one was arthroscopic probe (0.31%) related incident, one (0.31%) was meniscus suture passing device related complication and one (0.31%) was arthroscope related incident. Conclusion: Surgeons must be ready to anticipate and effectively manage any technical difficulties that may arise during the procedure, maintaining composure in the face of unexpected challenges and guiding the team. In most cases, incidents can be addressed intra operatively and may not have long-term effects on patient outcomes. It is crucial to have multiple implant and instrument backup options available for successful surgery. [ABSTRACT FROM AUTHOR]

Biomacromolecular probes have been extensively employed in the detection of metal ions for their prominent biocompatibility, water solubility, high selectivity, and easy modification of fluorescent groups. In this study, a fluorescent probe FP was constructed. The probe FP exhibited high specificity recognition for Cu2+. With the combination of Cu2+, the probe was subjected to fluorescence quenching. The research suggested that the probe FP carried out the highly sensitive detection of Cu2+ with detection limits of 1.7 nM. The fluorescence quenching of fluorescamine was induced by Cu2+ perhaps due to the PET (photoinduced electron transfer) mechanism. The FP-Cu2+ complex shows weak fluorescence, which is likely due to the PET quenching effect from Cu2+ to fluorescamine fluorophore. Moreover, the probe FP can be employed for imaging Cu2+ in living cells. The new fluorescent probe developed in this study shows the advantages of good biocompatibility and low cytotoxicity. It can be adopted for the targeted detection of Cu2+ in cells, and it has promising applications in the mechanism research and diagnosis of Cu2+-associated diseases. [ABSTRACT FROM AUTHOR]

The rapid detection of Ni ions has important research and application value. This paper presents a novel specific turn-off fluorescence probe PCTMP-FS for detecting Ni2+ ions. The carbazole-based compound PCTMP is first synthesized via a two-step reaction. PCTMP-FS comprises PCTMP dispersed into a DMSO-H2O (fw = 30% v/v) mixed solvent. The probe demonstrates prominent selectivity and anti-interference abilities for detecting Ni2+ with a limit of detection (LOD) of 0.233 μM. The probe exhibits good applicability over a wide range of acidities. The detecting mechanism of the probe is due to the complex formed by PCTMP and Ni2+ (2:1), which destroys intramolecular charge transfer in the compound. The probe has good repeatability and demonstrates excellent stability and sensitivity for the detection of Ni2+ in real water samples. [ABSTRACT FROM AUTHOR]

Carbon quantum dots (CQDs) have already demonstrated their utility as lubricant additives, and non-contact temperature sensing based on CQDs offers considerable potential for condition monitoring in mechanical, electrical, and other fields, as well as lubrication-temperature multifunctional applications in lubricants. In this paper, we have successfully synthesized and designed high-brightness carbon quantum dots/polyvinyl alcohol (PVA) temperature sensor thin film and dispersions of CQDs in a liquid paraffin lubrication system. Based on fluorescence intensity and the fluorescence intensity ratio, the carbon quantum dot/PVA film exhibited exponential temperature-dependent properties with a wide applicability range, a high goodness of fit (R2 > 0.99), and high relative thermal sensitivity (relative sensitivities of 1.74% K−1 and 1.39% K−1 for fluorescence intensity and fluorescence intensity ratio, respectively). In addition, based on the fluorescence intensity, the CQDs exhibited a wide temperature range (20–90 °C), a high goodness of fit (R2 > 0.99), and higher sensitivity (2.84% K−1) in a liquid paraffin lubrication system, which reflects the temperature responsive properties of carbon quantum dots as additives in lubrication systems. These findings provide convenient and effective possibilities for the sensing and monitoring of carbon quantum dots and their multifunctional applications under lubrication systems. [ABSTRACT FROM AUTHOR]

Fluorescence-based probes have been the key interest of researchers working at the intersection of chemistry and biology. Such probes are crucial for strengthening our understanding about biochemical processes, drug delivery, and fluorescence-guided surgery. A challenge in this regard is optimizing the probe's aqueous solubility while maintaining its lipophilicity to allow cell membrane permeation. This review summarizes the recent progress in water-soluble fluorescence-based probes for different types of biomolecules including carbohydrates, proteins, enzymes, amino acids, neurotransmitters and biologically relevant reactive species. A comprehensive overview of the crucial parameters for such probes' design, potential sensing mechanism for specific analytes, and experimental conditions for sensing has been provided. Incorporation of hydrophilic functional groups, ionic charge(s), absorption-emission characteristics and pH-stability in biological window are pivotal to develop optimized probes with high sensitivity for target biomarkers. We further underline the limitations of the probes that hinder their translation to clinical research and also indicate major research gap in optimizing any single probe for a certain biomarker.

Criminalitatea organizată, ca fenomen socialmente extrem de periculos, este menționată de multe ori, pe bună dreptate, ca fiind o criminalitate „perfecționată”. Desigur, infracțiunile comise de grupările criminale organizate s-au manifestat întotdeauna printr-un grad de pericol social mult mai avansat decât faptele comise, în particular, de persoane. În primul caz, în activitatea infracțională sunt antrenate mai multe persoane, unite printr-un scop unic infracțional, pregătiți pentru realizarea lui, și sunt cauzate prejudicii substanțiale, ceea ce determină un anumit specific al mecanismului activității criminale și în raport cu particularitățile metodice de cercetare a unor asemenea fapte. Elaborarea unui mecanism metodico-criminalistic sigur de investigare a faptelor infracționale comise de grupările criminale organizate este un lucru posibil de realizat pe durata mai multor ani. În conținutul acestui articol a fost întreprinsă o încercare de sistematizare a materialului faptico-doctrinar referitor la metodele identificare, descoperire și investigare a activității infracționale organizate și elaborarea, în baza lor, a recomandărilor criminalistice corespunzătoare. Or, studiul nu are ca scop examinarea întregului spectru de probleme actuale în domeniul investigării faptelor comise de grupurile criminale organizate, reflectând doar unele chestiuni legate de eficientizarea cercetării acestor categorii de infracțiuni.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting the lives of millions of people worldwide. Although the mechanism underlying PD pathogenesis is largely undefined, increasing evidence indicates that oxidative and nitrosative stresses play a crucial role in PD occurrence and development. Among them, the role of oxidative stress has been widely acknowledged, but there is relatively less attention given to nitrosative stress, which is mainly derived from peroxynitrite. In the present review, after briefly introducing the background of PD, we discuss the physiopathological function of peroxynitrite and especially highlight how overloaded peroxynitrite is involved in PD pathogenesis. Then, we summarize the currently reported fluorescence imaging-based peroxynitrite detection probes. Moreover, we specifically emphasize the probes that have been applied in PD research. Finally, we propose perspectives on how to develop a more applicable peroxynitrite probe and leverage it for PD theranostics. Conclusively, the present review broadens the knowledge on the pathological role of peroxynitrite in the context of PD and sheds light on how to develop and utilize fluorescence imaging-based strategies for peroxynitrite detection.

Exploring the intrinsic mechanisms of rare-earth ions entering the crystal phase has great significance for finely tuning the luminescent properties of glass–ceramics. Using Er3+ ions as a probe, X-ray diffraction was employed to precisely measure the crystallinity of SiO2-PbF2-Er2O3 glass–ceramics synthesized under various heat treatment conditions, confirming the occurrence of a rapid crystallization process. Additionally, by combining Judd–Ofelt theory with comprehensive analyses of absorption and fluorescence spectra, we calculated the relative proportions of Er3+ ions present in the crystal phase. We found that the crystallization process in the glass–ceramics and the incorporation of Er3+ ions into the crystal phase did not occur synchronously. This discovery provides new theoretical foundations and practical guidance for understanding the mechanism of rare-earth ion incorporation into crystal phases, which is significant for the development of functional materials with specific luminescent properties.

Mitochondria, crucial intracellular organelles, are central to energy metabolism, signal transduction, apoptosis, calcium homeostasis, and a myriad of other biological processes, making them a focal point in diverse research fields. The capacity to fluorescently label and visually track mitochondria is crucial for understanding their biological roles. We present mulberrin-Cy3, a novel small molecule fluorescent probe that selectively labels mitochondria in animal cells, including cancer cells, with relative ease. This protocol details the synthesis of mulberrin-Cy3 and its use for visualizing mitochondria in living cells. The synthesis is straightforward and time-efficient, and the labeling method is more accessible than traditional approaches, providing a cost-effective option for mitochondrial visualization at room temperature. The labeling is rapid, with effective labeling achieved within 5 min of incubation. The fluorescent signal is stable and brighter, offering a significant advantage over existing methods. Mulberrin-Cy3 represents a promising mitochondrial labeling compound, providing researchers with a novel experimental tool to explore the complex biological functions of mitochondria. This innovation has the potential to significantly advance our comprehension of mitochondrial dynamics and their role in cellular health and disease.

High‐contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue‐based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical "OFF‐to‐ON" absorption transition for high‐contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue‐based probe for cysteine (MB‐Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π‐conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130‐fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high‐contrast manner. Therefore, this work established an up‐to‐date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo. [ABSTRACT FROM AUTHOR]

Scavengers that capture reactive chemical substances are used to prevent the decomposition of materials. However, in the field of catalysis, the development of scavengers that inhibit background pathways has attracted little attention, although the concept will open up an otherwise inaccessible reaction space. In catalytic bromination, fast non‐catalyzed background reactions disturb the catalytic control of the selectivity, even when using N‐bromoamide reagents, which have a milder reactivity than bromine (Br2). Here, we developed a trans‐cyclooctene (TCO) bearing a 2‐pyridylethyl group to efficiently retard background reactions by capturing Br2 in bromocyclization using N‐bromosuccinimide. The use of less than a stoichiometric amount of the TCO was sufficient to inhibit non‐catalyzed reactions, and mechanistic studies using the TCO revealed that in situ‐generated Br2 provides non‐catalyzed reaction pathways based on a chain mechanism. The TCO is useful as an additive for improving enantioselectivity and regioselectivity in catalytic reactions. Cooperative systems using the TCO with selective catalysts offer an alternative strategy for optimizing catalyst‐controlled selectivity during bromination. Moreover, it also served as an indicator of Br2 involved in catalytic reaction pathways; thus, the TCO was useful as a probe for mechanistic investigations into the involvement of Br2 in bromination reactions of interest. [ABSTRACT FROM AUTHOR]