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The major monoamine neurotransmitters, serotonin (5-HT) and catecholamines (i.e., norepinephrine (NE), epinephrine (E), and dopamine (DA)), are critical to the nervous system function, and imbalances of the neurotransmitters have been connected to a variety of diseases, making their measurement useful in a clinical setting. A simple, rapid, robust, sensitive, and specific LC-MS/MS method has been developed and validated for the simultaneous quantitation of urinary serotonin and catecholamines with low cost, which is ideal for routine clinical applications. A simple extraction from complex urine was accomplished using tailored solid phase extraction incorporating phenylboronic acid complexation on a 96-well HLB microplate for the sample extraction and resulted in significantly improved throughput, selectivity, and extraction recovery. Compared to 1–10 mL of urine typically used, this method required only 10 μL. A rapid chromatographic elution with a total cycle time of 6 min per sample compared to reported run times of 19–75 min was achieved on a PFP column. The sensitivity of l and 2 ng mL −1 for the detection of low abundant E and NE combined with the high coverage of 1024 ng mL −1 for DA enabled the multi-analyte detection of these biogenic amines in a single run. Good linearity (2.0–512, 1.0–512, 4.0–1024, and 4.0–1024 ng mL −1 for NE, E, DA, and 5-HT, respectively), accuracy (87.6–104.0%), precision (≤8.0%), extraction recovery (69.6–103.7%), and matrix effect (87.1–113.1% for catecholamines and 63.6–71.4% for 5-HT) were obtained. No autosampler carryover was observed. The analytes were stable for 5 days at 20 °C, 14 days at 4 °C, and 30 days at −20 °C and five freeze–thaw cycles. The easy sample preparation, rapid LC, and multi-analyte MS detection allow two 96-well plates of samples to be extracted within 2 h and analyzed on an LC-MS/MS system within 24 h. The applicability and reliability of the assay were demonstrated by assessment of the reference interval for authentic urine specimens from 90 healthy individuals. Graphical abstract A simple, rapid, robust, sensitive and specific LC-MS/MS method combined with a dual functional solid phase extraction has been developed and validated for the simultaneous extraction and quantitation of monoamine neurotransmitters in human urine with low cost

A novel magnetic borate-functionalized metal-organic framework nanocomposite was designed and fabricated for selective enrichment of catecholamines from human urine. Firstly, the polytannic acid (PTA) layer with natural low-cost and ecofriendly polyphenol tannic acid as the organic ligand and Fe 3+ as the cross-linker was coated onto the surface of Fe 3 O 4 . Then, the borate-functionalized metal-organic framework (MIL-100(Fe)-B) with 5-boronobenzene-1,3-dicarboxylic acid as a ligand fragment was modified onto the PTA-coated Fe 3 O 4 through a metal-ligand-fragment coassembly strategy. The obtained smart porous adsorbent Fe 3 O 4 @PTA@MIL-100(Fe)-B was confirmed by means of several characterization methods and then applied as an effective magnetic solid phase extraction (MSPE) sorbent for specific extraction of trace catecholamines in human urine. The Plackett–Burman design was used for screening the variables significantly affecting the extraction efficiency. Then, the significant factors were further investigated by the Box–Behnken design to determine the optimal extraction conditions. Under the optimal conditions, a method for selective MSPE combined with high-performance liquid chromatography with a fluorescence detector for the quantitation of catecholamines in human urine was developed and validated. With the proposed method, the linearity range was from 0.500 to 500 ng mL −1 for norepinephrine and epinephrine and from 1.00 to 500 ng mL −1 for dopamine. The detection limits were 0.050, 0.11, and 0.20 ng mL −1 for norepinephrine, epinephrine, and dopamine, respectively. The recoveries from spiking experiments varied from 91.5 to 108% with relative standard deviations (RSDs) of 0.80–4.8%. The established method is rapid, sensitive, accurate, inexpensive, and ecofriendly and was successfully applied to the determination of the target catecholamines in human urine samples. Graphical abstract

A boronate-modified magnetic affinity sorbent was prepared by adopting hyperbranched polyethyleneimine as the scaffold to amplify initiator sites. 3-Acrylamidophenylboronic acid was employed as monomer to proceed in situ free-radical polymerization on magnetite (Fe 3 O 4 ) nanoparticles. Due to the improved density of boronic acid polymers, the adsorbent exhibited high adsorption capacity, typically (134 ± 8) μg mg −1 for dopamine, (92 ± 7) μg mg −1 for catechol, (363 ± 14) μg mg −1 for ovalbumin and (464 ± 22) μg mg −1 for horseradish peroxidase. These capacities are much higher than those of other adsorbents. The sorbent was applied to the enrichment of catecholamines from spiked human urine. Owing to the high adsorption capacity, only 1.0 mg of adsorbent was sufficient to eliminate the interferences and enrich the targets (dopamine, norepinephrine and epinephrine) within 5 min. They were quantified by HPLC. The recoveries from spiked samples range between 83.5% ~106%, with relative standard deviations of 3.2 ~ 9.4% ( n  = 5). The separation of glycoproteins from egg white was also accomplished prior to their analysis by PAGE. In the authors’ perception, this approach is promising in that the density of functional groups on the adsorbent is strongly increased. Graphical abstract The preparation routine of boronate affinity magnetic adsorbent (Fe 3 O 4 @HpAAPBA). The adsorbent is used for the magnetic solid phase extraction of cis -dol compounds from real sample.

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal–organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH 2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence “turn-on” response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6–350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases. Graphic Abstract

Herein, we developed a sophisticated dual-mode sensor that utilized 3-aminophenylboric acid functionalized carbon dots (APBA-CDs) to accurately detect uric acid (UA). Our innovative process involved synthesizing APBA-CDs that emitted at 369 nm using a one-step hydrothermal method with 3-aminophenylboric acid and L-glutamine as precursors, ethanol and deionized water as solvents. Once UA was introduced to the APBA-CDs, the fluorescence of the system became visibly quenched. The results of Zeta potential, Fourier transformed infrared (FTIR) spectra, fluorescence lifetime, and other characteristics were analyzed to determine that the reaction mechanism was static quenching. This meant that after UA was mixed with APBA-CDs, it combined with the boric acid function on the surface to form complexes, resulting in a decrease in fluorescence intensity and a blue shift in the absorption peak at about 295 nm in the Ultraviolet–visible (UV–vis) absorption spectra. We were pleased to report that we have successfully used the dual-reading platform to accurately detect UA in serum and human urine. It provided a superior quantitative and visual analysis of UA without the involvement of enzymes. We firmly believe that our innovative dual-mode sensor has immense potential in the fields of biosensing and health monitoring.

An innovative supramolecular architecture is reported for bienzymatic glucose biosensing based on the use of a nanohybrid made of multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with a Schiff base modified with two phenylboronic acid residues (SB-dBA) as platform for the site-specific immobilization of the glycoproteins glucose oxidase (GOx) and horseradish peroxidase (HRP). The analytical signal was obtained from amperometric experiments at − 0.050 V in the presence of 5.0 × 10 −4  M hydroquinone as redox mediator. The concentration of GOx and HRP and the interaction time between the enzymes and the nanohybrid MWCNT–SB-dBA deposited at glassy carbon electrodes (GCEs) were optimized through a central composite design (CCD)/response surface methodology (RSM). The optimal concentrations of GOx and HRP were 3.0 mg mL −1 and 1.50 mg mL −1 , respectively, while the optimum interaction time was 3.0 min. The bienzymatic biosensor presented a sensitivity of (24 ± 2) × 10 2 µA dL mg −1 ((44 ± 4) × 10 2 µA M −1 ), a linear range between 0.06 mg dL −1 and 21.6 mg dL −1 (3.1 µM–1.2 mM) ( R 2  = 0.9991), and detection and quantification limits of 0.02 mg dL −1 (1.0 µM) and 0.06 mg dL −1 (3.1 µM), respectively. The reproducibility for five sensors prepared with the same MWCNT–SB-dBA nanohybrid was 6.3%, while the reproducibility for sensors prepared with five different nanohybrids and five electrodes each was 7.9%. The GCE/MWCNT–SB-dBA/GOx-HRP was successfully used for the quantification of glucose in artificial human urine and commercial human serum samples. Graphical Abstract

Key Points There is currently no uniform standard of care for the treatment of patients with relapsed and/or refractory multiple myeloma (MM), but combination regimens are generally preferred over monotherapy Incorporation of immunomodulatory drugs and proteasome inhibitors into anti-MM treatment regimens has improved survival rates in these difficult-to-treat patients Each anti-MM agent is associated with a distinct safety profile that can impact treatment selection and its use in combination with other agents An understanding of disease-related and patient-related factors, as well as treatment-related toxicities, is critical for evaluating appropriate therapeutic options for each patient Recent developments in the treatment of multiple myeloma have led to improvements in response rates and to increased survival; however, relapse is inevitable in almost all patients. Currently, there is no standard treatment for patients with relapsed and/or refractory disease. This Review discusses the current treatment landscape for patients with relapsed and/or refractory multiple myeloma and highlights disease-related and patient-related factors that are important considerations for clinicians when selecting an appropriate treatment. Recent developments in the treatment of multiple myeloma have led to improvements in response rates and to increased survival; however, relapse is inevitable in almost all patients. Recurrence of myeloma is typically more aggressive with each relapse, leading to the development of treatment-refractory disease, which is associated with a shorter survival. Several phase II and III trials have demonstrated the efficacy of recently approved agents in the setting of relapsed and/or refractory multiple myeloma, including immunomodulatory agents, such as lenalidomide and pomalidomide, and proteasome inhibitors, such as bortezomib and carfilzomib. Currently, however, there is no standard treatment for patients with relapsed and/or refractory disease. This Review discusses the current treatment landscape for patients with relapsed and/or refractory multiple myeloma and highlights disease-related and patient-related factors—such as pre-existing comorbidities or toxicities—that are important considerations for clinicians when selecting an appropriate treatment regimen.

Poly(3-acrylamidophenylboronic acid) (PAAPBA) was grafted onto polydopamine-coated magnetic graphene oxide via surface-initiated atom transfer radical polymerization to obtain a new kind of boronate affinity material (BAM). The BAM possesses good water dispersity and adsorption capacities as high as 154, 357, 588 and 1111 μmol·g −1 for adenosine, salbutamol, dopamine and catechol, respectively. For the molecules without nitrogen atoms, the BAM can selectively capture the cis -diols under the interference of non- cis -diols. For molecules containing nitrogen, the non- cis -diols are also retained, but much less than the cis -diols. The selectivity can be improved by adding salts to facilitate complexation and to suppress the electrostatic interaction between cis -diols and the boronic acid ligand. The BAM was successfully employed to the enrichment of catecholamines from real urine samples. Results indicate that it is a promising material for the pretreatment of real samples. Graphical abstract Schematic of the preparation of an ultrahigh capacity boronate affinity material by grafting polymer brush from polydopamine coated magnetic graphene oxide. The material has good selectivity to cis -diol-containing molecules and can be applied to enrich catecholamines in urine samples.

A novel polymerized crystalline colloidal array (PCCA) sensing material for the detection of urine glucose was developed by embedding a two-dimensional (2-D) polystyrene crystalline colloidal array (CCA) in 3-acrylamidophenylboronic acid (3-APBA)-functionalized hydrogel. After adjusting the cross-linker concentration, this material showed significant sensitivity for glucose under lab conditions, the particle spacing of the PCCA changed from 917 to 824 nm (93 nm) within 3 min as the glucose concentration increased from 0 to 10 mM, and the structural color of the PCCA changed from red through orange, to green, and finally, to cyan. In further experiments, this material was used to semi-quantitatively detect glucose in 20 human urine (HU) samples. Compared with the traditional dry-chemistry method, which was applied widely in clinical diagnosis, the PCCA method was more accurate and cost-effective. Moreover, this method can efficiently avoid the errors induced by most of the urine-interfering elements like vitamin C and ketone body. With a homemade portable optical detector, this low-cost intelligent sensing material can provide a more convenient and efficient strategy for the urine glucose detection in clinical diagnosis and point-of-care monitoring.

Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in massive porphyrin accumulation in blood cells, which is responsible for hemolytic anemia and skin photosensitivity. Among the missense mutations actually described up to now in CEP patients, the C73R and the P248Q mutations lead to a profound UROS deficiency and are usually associated with a severe clinical phenotype. We previously demonstrated that the UROS C⁷³ᴿ mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. We show evidence that the reduced kinetic stability of the UROS ᴾ²⁴⁸Q mutant is also responsible for increased protein turnover in human erythroid cells. Through the analysis of EGFP-tagged versions of UROS enzyme, we demonstrate that both UROS C⁷³ᴿ and UROS ᴾ²⁴⁸Q are equally destabilized in mammalian cells and targeted to the proteasomal pathway for degradation. We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. Finally, in CEP mice (Uros ᴾ²⁴⁸Q/ᴾ²⁴⁸Q) treated with bortezomib (Velcade), a clinically approved proteasome inhibitor, we observed reduced porphyrin accumulation in circulating RBCs and urine, as well as reversion of skin photosensitivity on bortezomib treatment. These results of medical importance pave the way for pharmacologic treatment of CEP disease by preventing certain enzymatically active UROS mutants from early degradation by using proteasome inhibitors or chemical chaperones.