Novel Enzyme-Assisted Recycle Amplification Strategy for Tetracycline Detection Based on Oxidized Single-Walled Carbon Nanohorns.

In this study, oxidized single-walled carbon nanohorns (oxSWCNHs) were prepared using nitric acid oxidation and subsequently combined with 3'6-carboxyfluorescein through charge transfer to prepare fluorescent probes. These oxSWCNHs were used to quench fluorogen signals at short distances and dissociate ssDNA using cryonase enzymes. We established a method for rapidly detecting tetracycline (TC) in complex samples based on the amplification of cryonase enzyme signals. After optimizing the experimental conditions, our method showed a detection limit of 5.05 ng/mL, with good specificity. This method was used to determine the TC content in complex samples, yielding a recovery rate of 90.0-103.3%. This result validated the efficacy of our method in detecting TC content within complex samples.

An all-in-one tetrazine reagent for cysteine-selective labeling and bioorthogonal activable prodrug construction.

The prodrug design strategy offers a potent solution for improving therapeutic index and expanding drug targets. However, current prodrug activation designs are mainly responsive to endogenous stimuli, resulting in unintended drug release and systemic toxicity. In this study, we introduce 3-vinyl-6-oxymethyl-tetrazine (voTz) as an all-in-one reagent for modular preparation of tetrazine-caged prodrugs and chemoselective labeling peptides to produce bioorthogonal activable peptide-prodrug conjugates. These stable prodrugs can selectively bind to target cells, facilitating cellular uptake. Subsequent bioorthogonal cleavage reactions trigger prodrug activation, significantly boosting potency against tumor cells while maintaining exceptional off-target safety for normal cells. In vivo studies demonstrate the therapeutic efficacy and safety of this prodrug design approach. Given the broad applicability of functional groups and labeling versatility with voTz, we foresee that this strategy will offer a versatile solution to enhance the therapeutic range of cytotoxic agents and facilitate the development of bioorthogonal activatable biopharmaceuticals and biomaterials.

Efficient removal of tetracycline and Cu2+ by honeycomb derived magnetic carbon: Adsorption mechanism and advanced oxidation regeneration mechanism.

The honeycomb magnetic carbons (xFe@HCNs) were prepared by sacrificial template method novelty using polyacrylamide resin (PAAS) as template and ammonium pyrrolidine dithioate/Fe3+ complex (APDC-Fe) as carbon skeleton and metal source. Tetracycline (TC) and copper (Cu2+) as target pollutants were used to investigate the adsorption properties of xFe@HCNs in single or binary TC and Cu2+ systems. The adsorption capacity sequence for TC among the adsorbents was (mmol·g-1): 2Fe@HCNs (0.088) > 8Fe@HCNs (0.061) > HCNs (0.054) > RC (0.036), and for Cu2+ was (mmol·g-1): 2Fe@HCNs (1.120) > 8Fe@HCNs (1.026) > RC (0.792) > HCNs (0.681). 2Fe@HCNs demonstrated notable affinity for adsorbing both TC and Cu2+. Additionally, the influence of hydrochemical factors (i.e., cation species, anion species, and pH) on the adsorption properties of 2Fe@HCNs. Combined with advanced oxidation technology, the regeneration methods of magnetic adsorbent were explored using oxidizing agents (e.g., H2O2 and peroxymonosulfate) as eluents which could increase the adsorption sites of magnetic carbon adsorbents during the regenerating process, which was the novelty of the study. Furthermore, the regeneration mechanisms of H2O2 as eluent were investigated. This study discussed the application and regeneration methods of magnetic adsorbents in water treatment, offering new insights into environmental remediation using magnetic materials.

Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Facile One-Pot Synthesis and Anti-Microbial Activity of Novel 1,4-Dihydropyridine Derivatives in Aqueous Micellar Solution under Microwave Irradiation.

The current study describes a novel and eco-conscious method to synthesize 1,4-dihydropyridine derivatives utilizing an aqueous micellar solution containing aluminum dodecyl sulfate, Al(DS)3, using readily available starting material. The final products were synthesized with excellent yields within remarkably quick reaction durations, promoting remarkable atom economy and minimizing environmental impacts. The present protocol has several advantages over other methodologies in terms of high yield (up to 97%) with excellent purity. Further, the synthesized 1,4-DHPs exhibit favorable to excellent resistance against examined bacterial and fungal species. Intriguingly, polar groups on the phenyl ring (5b, 5c, 5i and 5j) make the 1,4-DHPs equally potent against the microbes as compared to the standard drugs.

Synthesis and preclinical evaluation of a novel molecular probe [18F]AlF-NOTA-PEG2-Asp2-PDL1P for PET imaging of PD-L1 positive tumor.

Immunotherapy has brought great benefits to cancer patients, but only some patients benefit from it. Noninvasive, real-time and dynamic monitoring of the effectiveness of immunotherapy through PET imaging may provide assistance for the treatment plan of immunotherapy. In this study, we designed and synthesized a new targeted PD-L1 peptide NOTA-PEG2-Asp2-PDL1P, which was labeled with nuclide 18F to obtain a new imaging agent [18F]AlF-NOTA-PEG2-Asp2-PDL1P. The total radiochemical yield of [18F]AlF-NOTA-PEG2-Asp2-PDL1P was 13.7 % (Uncorrected radiochemical yield, n > 5). [18F]AlF-NOTA-PEG2-Asp2-PDL1P achieved high radiochemical purity (>95 %) with a molar activity more than 51.2 GBq/µmol. [18F]AlF-NOTA-PEG2-Asp2-PDL1P exhibited good hydrophilicity and had good stability both in vivo and in vitro, it can specifically targets B16F10 tumor with PD-L1 expression, and had a relatively high retention in tumor, a relatively fast clearance in vivo and a higher tumor-to-non-target ratio, all of which could make [18F]AlF-NOTA-PEG2-Asp2-PDL1P a potential tracer for PD-L1 prediction before clinical immunotherapy.

Nanozyme-induced deep learning-assisted smartphone integrated colorimetric and fluorometric dual-mode for detection of tetracycline analogs.

In this work, a colorimetric and fluorescent dual-mode probe controlled by NH2-MIL-88 B (Fe, Ni) nanozymes was developed to visually detect tetracycline antibiotics (TCs) residues quantitatively, as well as accurately distinguish the four most widely used tetracycline analogs (tetracycline (TC), chrycline (CTC), oxytetracycline (OTC), and doxycycline (DC)). Colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) may be oxidized to blue oxidized TMB by the Fe Fenton reaction, which was catalyzed by the NH2-MIL-88 B (Fe, Ni) nanozyme with POD-like activity. The colorimetric detection system allows TCs to interact with NH2-MIL-88 B (Fe, Ni). This inhibits the production of ·OH, weakens the oxidation process of TMB, and ultimately lightens the blue color in the system by blocking the electron transfer between NH2-MIL-88 B (Fe, Ni) and H2O2. Furthermore, TCs can interact with NH2-MIL-88 B (Fe, Ni) as a result of the internal filtering effect, which causes the fluorescence intensity to decrease as TCs concentration increases. Additionally, a portable instrument that combines a smartphone sensing platform with colorimetric and fluorescent signals was created for the quick, visual quantitative detection of TCs. The colorimetric and fluorescent dual-mode nano platform enables color change, with detection limits (LODs) of 0.182 µM and 0.0668 µM for the spectrometer and smartphone sensor, respectively, based on the inhibition of fluorescence and enzyme-like activities by TCs. Overall, the colorimetric and fluorescence dual-mode sensor has good stability, high specificity, and an efficient way to eliminate false-positive issues associated with a single detection mode.

First Use of Combination Oral Deucravacitinib With Tapinarof Cream for Treatment of Severe Plaque Psoriasis.

Plaque psoriasis is a chronic, immune-mediated, cutaneous, and systemic inflammatory dermatosis. Its pathogenesis involves the dysregulation of the interleukin (IL)-23/IL-17 signaling pathway. There are a range of treatment options available, encompassing topical agents, biologics, oral systemic therapy, and phototherapy. The utility of combination treatment has also been described and is a budding field of research. Here we describe the first case of adult severe generalized plaque psoriasis treated with once-daily oral deucravacitinib 6 mg combined with tapinarof cream 1% applied once daily. To our knowledge, the combination of these agents has not yet been described in the literature. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8091.

G-CSF + plerixafor versus G-CSF alone mobilized hematopoietic stem cells in patients with multiple myeloma and lymphoma: a systematic review and meta-analysis.

AIM: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. METHODS: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). RESULTS: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). CONCLUSIONS: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.

Minimalist Tetrazine N-Acetyl Muramic Acid Probes for Rapid and Efficient Labeling of Commensal and Pathogenic Peptidoglycans in Living Bacterial Culture and During Macrophage Invasion.

N-Acetyl muramic acid (NAM) probes containing alkyne or azide groups are commonly used to investigate aspects of cell wall synthesis because of their small size and ability to incorporate into bacterial peptidoglycan (PG). However, copper-catalyzed alkyne-azide cycloaddition (CuAAC) reactions are not compatible with live cells, and strain-promoted alkyne-azide cycloaddition (SPAAC) reaction rates are modest and, therefore, not as desirable for tracking the temporal alterations of bacterial cell growth, remodeling, and division. Alternatively, the tetrazine-trans-cyclooctene ligation (Tz-TCO), which is the fastest known bioorthogonal reaction and not cytotoxic, allows for rapid live-cell labeling of PG at biologically relevant time scales and concentrations. Previous work to increase reaction kinetics on the PG surface by using tetrazine probes was limited because of low incorporation of the probe. Described here are new approaches to construct a minimalist tetrazine (Tz)-NAM probe utilizing recent advancements in asymmetric tetrazine synthesis. This minimalist Tz-NAM probe was successfully incorporated into pathogenic and commensal bacterial PG where fixed and rapid live-cell, no-wash labeling was successful in both free bacterial cultures and in coculture with human macrophages. Overall, this probe allows for expeditious labeling of bacterial PG, thereby making it an exceptional tool for monitoring PG biosynthesis for the development of new antibiotic screens. The versatility and selectivity of this probe will allow for real-time interrogation of the interactions of bacterial pathogens in a human host and will serve a broader utility for studying glycans in multiple complex biological systems.

trans-IV restriction: a new configuration for metal bis-cyclam complexes as potent CXCR4 inhibitors.

The chemokine receptor CXCR4 is implicated in multiple diseases including inflammatory disorders, cancer growth and metastasis, and HIV/AIDS. CXCR4 targeting has been evaluated in treating cancer metastasis and therapy resistance. Cyclam derivatives, most notably AMD3100 (Plerixafor™), are a common motif in small molecule CXCR4 antagonists. However, AMD3100 has not been shown to be effective in cancer treatment as an individual agent. Configurational restriction and transition metal complex formation increases receptor binding affinity and residence time. In the present study, we have synthesized novel trans-IV locked cyclam-based CXCR4 inhibitors, a previously unexploited configuration, and demonstrated their higher affinity for CXCR4 binding and CXCL12-mediated signaling inhibition compared to AMD3100. These results pave the way for even more potent CXCR4 inhibitors that may provide significant efficacy in cancer therapy.

Research progress of the chemokine/chemokine receptor axes in the oncobiology of multiple myeloma (MM).

BACKGROUND: The incidence of multiple myeloma (MM), a type of blood cancer affecting monoclonal plasma cells, is rising. Although new drugs and therapies have improved patient outcomes, MM remains incurable. Recent studies have highlighted the crucial role of the chemokine network in MM's pathological mechanism. Gaining a better understanding of this network and creating an overview of chemokines in MM could aid in identifying potential biomarkers and developing new therapeutic strategies and targets. PURPOSE: To summarize the complicated role of chemokines in MM, discuss their potential as biomarkers, and introduce several treatments based on chemokines. METHODS: Pubmed, Web of Science, ICTRP, and Clinical Trials were searched for articles and research related to chemokines. Publications published within the last 5 years are selected. RESULTS: Malignant cells can utilize chemokines, including CCL2, CCL3, CCL5, CXCL7, CXCL8, CXCL12, and CXCL13 to evade apoptosis triggered by immune cells or medication, escape from bone marrow and escalate bone lesions. Other chemokines, including CXCL4, CCL19, and CXCL10, may aid in recruiting immune cells, increasing their cytotoxicity against cancer cells, and inducing apoptosis of malignant cells. CONCLUSION: Utilizing anti-tumor chemokines or blocking pro-tumor chemokines may provide new therapeutic strategies for managing MM. Inspired by developed CXCR4 antagonists, including plerixafor, ulocuplumab, and motixafortide, more small molecular antagonists or antibodies for pro-tumor chemokine ligands and their receptors can be developed and used in clinical practice. Along with inhibiting pro-tumor chemokines, studies suggest combining chemokines with chimeric antigen receptor (CAR)-T therapy is promising and efficient.

The efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial.

BACKGROUND: Vulvar lichen planus (VLP) is a chronic vulvar dermatosis that is difficult to treat and can severely impair quality of life in the absence of adequate treatment. There is a lack of high-quality evidence to direct therapy for VLP. This randomised controlled trial will be the first double-blinded study comparing systemic treatments in VLP and aims to investigate the safety and efficacy of deucravacitinib compared to methotrexate, in patients with VLP who have failed treatment with potent topical corticosteroids. METHODS: A total of 116 women aged ≥ 18 years with moderate to severe VLP (Genital Erosive Lichen Planus (GELP) score ≥ 5) will be recruited. All participants will initially be treated with Diprosone® OV daily, and their outcome will be assessed using the GELP score. At 8 weeks' follow-up, responders (GELP < 5) will be continued on Diprosone® OV. Non-responders (GELP ≥ 5) will be randomised 1:1 in a blinded fashion to receive (i) methotrexate 10 mg weekly + placebo tablet twice daily + folic acid 5 mg weekly or (ii) deucravacitinib 6 mg twice daily + placebo tablet weekly + folic acid 5 mg weekly. The primary endpoint is the difference in the mean change of GELP scores from baseline to week 32 between deucravacitinib and methotrexate groups. DISCUSSION: High-quality evidence guiding the management of women with VLP is lacking. Once completed, this will be the first double-blinded RCT to compare systemic treatments in VLP. The results of this study will provide valuable, high-quality data to guide second-line therapy options for VLP that is recalcitrant to potent topical corticosteroids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000682640. Registered on 26 June 2023.

A Molecular Hybrid of the GFP Chromophore and 2,2'-Bipyridine: An Accessible Sensor for Zn2+ Detection with Fluorescence Microscopy.

The few commercially available chemosensors and published probes for in vitro Zn2+ detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2'-bipyridine chelator moiety (GFZnP BIPY) for Zn2+ detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented. Excellent photophysical characteristics are reported, including a 53-fold fluorescence enhancement with excitation and emission maxima at 422 nm and 492 nm, respectively. A high two-photon cross section of 3.0 GM at 840 nm as well as excellent metal ion selectivity are reported. In vitro experiments on HEK 293 cell culture were carried out using two-photon microscopy to demonstrate the applicability of the novel sensor for zinc bioimaging.

Video-assisted anal fistula treatment (VAAFT) combined with ozonide oil dressing: standardization of technique in pediatric patients.

BACKGROUND: Anal fistula and perianal abscess are commonly acquired anorectal pathologies in children. Surgical treatment options commonly adopted are fistulotomy, fistulectomy, cutting seton placement, and more recently video-assisted anal fistula treatment (VAAFT). Optimal postoperative wound dressing remains debated. This study aimed to report our series of pediatric patients, who received VAAFT and postoperative wound dressing using ozonide oil. METHODS: All patients who underwent VAAFT between August 2018 and May 2023 were included in the study. Demographics, clinical features, pre-operative imaging, surgical details, outcome, and mid-term outcome data were retrospectively reviewed for each patient. All VAAFT procedures were performed under general anesthesia and using a 10-Ch fistuloscope. RESULTS: Thirty-three VAAFT procedures were performed in 30 patients over the study period. The median patient age was 5.7 years (range 1.75-14). Anal fistula was idiopathic in 26/30 (86.6%), iatrogenic in 2/30 (6.7%), and secondary to Crohn's disease in 2/30 (6.7%). The median duration of surgery was 23 min (range 18-40). All patients received ozonide oil dressing twice a day for 5 weeks postoperatively. The median hospital stay was 24 h (range 9-36). The median healing time was 28 days (range 17-39). With a median follow-up of 2 years (range 0.5-5), disease recurrence occurred in 3/30 (10%) patients with idiopathic fistula, who were re-operated using the same technique, with no further recurrence. No fecal incontinence or soiling was observed. CONCLUSION: Our series confirmed that VAAFT is a safe and effective technique to treat children with perianal fistula. The technique is versatile, allowing to treat fistulae of different etiologies. Postoperative course was painless and fast. Future comparative prospective studies are needed to better establish these conclusions.

Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study.

Breast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthesized compounds were evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) method using MCF-7 and MDA-MB-231 breast cancerous cells, compound 17 had the maximum anticancer activity against both breast cancerous cells, recording the lowest half-maximal inhibitory concentration (IC50) values (56.712 µg/mL for MCF-7 cells and 48.743 µg/mL for MDA-MB-231 cells). The results were confirmed in terms of the intrinsic mechanism of apoptosis, where compound 17 had the highest percentage in the case of both cancer cells and recorded Bax (Bcl-2 associated X)/Bcl-2 (B-cell lymphoma 2) ratio 17.5 and 96.667 for MCF-7 and MDA-MB-231 cells, while compound 19 came after 17 in the ability for induction of apoptosis, where the Bax/Bcl-2 ratio was 15.789 and 44.273 for both cancerous cells, respectively. Also, compound 11 recorded a high Bax/Bcl-2 ratio for both cells. The safety of the synthesized compounds was applied on normal WI-38 cells, showing minimum cytotoxic effect with undetectable IC50. Compounds 17, 11, and 19 recorded a significant increase of p53 upregulated modulator of apoptosis (PUMA) expression levels in the cancerous cells. The DFT method was also used to establish a connection between the experimentally determined values of the present investigated compounds and their predicted quantum chemical parameters. It was concluded that Compounds 17, 11, and 19 had anti-breast cancer potential through the induction of apoptotic Bax/Bcl-2 and PUMA expression levels.

Silver and Gold Complexes with NHC-Ligands Derived from Caffeine: Catalytic and Pharmacological Activity.

N-heterocyclic carbene (NHC) silver(I) and gold(I) complexes have found different applications in various research fields, as in medicinal chemistry for their antiproliferative, anticancer, and antibacterial activity, and in chemistry as innovative and effective catalysts. The possibility of modulating the physicochemical properties, by acting on their ligands and substituents, makes them versatile tools for the development of novel metal-based compounds, mostly as anticancer compounds. As it is known, chemotherapy is commonly adopted for the clinical treatment of different cancers, even though its efficacy is hampered by several factors. Thus, the development of more effective and less toxic drugs is still an urgent need. Herein, we reported the synthesis and characterization of new silver(I) and gold(I) complexes stabilized by caffeine-derived NHC ligands, together with their biological and catalytic activities. Our data highlight the interesting properties of this series as effective catalysts in A3-coupling and hydroamination reactions and as promising anticancer, anti-inflammatory, and antioxidant agents. The ability of these complexes in regulating different pathological aspects, and often co-promoting causes, of cancer makes them ideal leads to be further structurally functionalized and investigated.

Selective Late-Stage Functionalization of Tryptophan-Containing Peptides To Facilitate Bioorthogonal Tetrazine Ligation.

Site-selective modification of complex peptides and the functionalization of their C-H bonds hold great promise for expanding their use in therapeutics and biomedical research. Herein, we leverage the power of late-stage chemoenzymatic catalysis using an indole prenyltransferase (IPT) enzyme and alkyl diphosphates to specifically modify the indole ring of tryptophan in clinically relevant peptides. Furthermore, the installed handle enables bioorthogonal click chemistry through an inverse electron-demand Diels-Alder (IEDDA) reaction with a biotin-conjugated tetrazine probe.

Design, synthesis, and biological evaluation of piperazine derivatives as pan-PPARs agonists for the treatment of liver fibrosis.

Liver fibrosis is commonly occurred in chronic liver diseases, but there is no approved drug for clinical use. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) could not only regulate metabolic homeostasis but also possess anti-inflammatory and antifibrotic effects, and pan-PPARs agonist was considered as a potential anti-liver fibrosis agent. In this study, a series of novel piperazine pan-PPARs agonists were developed, and the preferred compound 12 displayed potent and well-balanced pan-PPARs agonistic activity. Moreover, compound 12 could dose-dependently stimulate the PPARs target genes expression and showed high selectivity over other related nuclear receptors. Importantly, compound 12 exhibited excellent pharmacokinetic profiles and good anti-liver fibrosis effects in vivo. Collectively, compound 12 holds promise for developing an anti-liver fibrosis agent.

An asynchronous response fluorescence sensor combines machine learning theory to qualitatively and quantitatively detect tetracyclines.

Excess use of tetracyclines poses significant health risks arising from animal-derived foods, meaning simple and sensitive methods to detect tetracyclines would be beneficial given current laboratory methods are complex and expensive. Herein, we describe an asynchronous response fluorescence sensor constructed based on Zn-based metal-organic framework and Ru(bpy)32+ (denoted as Ru@Zn-BTEC) for the qualitative and quantitative detection of tetracyclines in foods. Under excitation at 365 nm, the sensor emitted red fluorescence at 609 nm. When tetracyclines were present, these molecules aggregated in the Ru@Zn-BTEC framework, causing green fluorescence emission at 528 nm. The developed sensing system accurately distinguished the different categories of tetracyclines with a classifier accuracy of 94 %. The Ru@Zn-BTEC sensor demonstrated a detection limit of 0.012 µM and satisfactory recovery (87.81 %-113.84 %) for tetracyclines in food samples. This work provides a pathway for constructing asynchronous response fluorescence sensors for food analysis.