A Halogen-Bonded Fluorescent Molecular Photoswitch: Transition from 3D Cubic Lattice to 1D Helical Superstructure for Polarization Inversion of Circularly Polarized Luminescence.

The fabrication of materials that can switch between circularly polarized luminescence (CPL) signals is both essential and challenging. Here, two new halogen-bonded fluorescent molecular photoswitches, namely, HB-switch 1 and HB-switch 2, containing α-cyano-substituted diarylethene compounds with different end groups were developed. Upon exposure to specific UV or visible light wavelengths, they exhibited controllable and reversible Z/E photoisomerization. When these switches were integrated into blue-phase liquid crystals (BPLCs), the temperature range of BP significantly expanded. Notably, the BP system incorporating HB-switch 1 exclusively achieved reversible polarization inversion of CPL signals under specific UV/visible light irradiation and during cooling/heating. The photo/thermal dual-response behavior of the CPL signals can be attributed to the phase transition from a high-symmetry 3D BP I lattice to a low-symmetry 1D helical superstructure induced by the Z/E photoisomerization of HB-switch 1 and temperature changes. This study underscores the significance of employing halogen-bond assembly strategies to design materials with switchable CPL signals, opening new possibilities for CPL-active systems.

The responses and tolerance of photosynthetic system in Chlorella vulgaris to the pharmaceutical pollutant carbamazepine.

Screening for sensitive toxicological indicators and understanding algal tolerance to pharmaceutical contaminants (PhCs) are essential for assessing PhCs risk and their removal by microalgae. Carbamazepine (CBZ) showed adverse effects on microalgae, but the specific toxicity mechanisms on the most sensitive algal photosynthetic system (PS) remain limited. This study delved into the impact of CBZ exposure on the growth, cell viability, pigment content, and PS of Chlorella vulgaris. The findings revealed a notable inhibition of C. vulgaris growth by CBZ, with an IC50 value of 27.2 mg/L at 96 hours. CBZ exposure induced algal membrane damage and cell viability. Intriguingly, CBZ drastically diminished intracellular pigment levels, notably showing "low promotion and high inhibition" of chlorophyll b (Chl b) by 72 hours. Moreover, the study identified a decreased number of active reaction centers (RCs) within algal PSII alongside inhibited electron transport from QA to QB on the PSII receptor side, leading to PSII disruption. As an adaptive response to CBZ stress, C. vulgaris stimulated its Chl b synthesis, increased non-photochemical quenching (NPQ), and adapted its tolerance to bright light. Additionally, the alga attempted to compensate for the CBZ-induced reduction in electron transfer efficiency at the PSII receptor side and light energy utilization by increasing its electron transfer from downstream. Principal component analysis (PCA) further verified that the parameters on non-photochemical dissipation, electron transport, and integrative performance were the most sensitive algal toxicological indicators for CBZ exposure, and algal PS has energy protection capability through negative feedback regulation. However, prolonged exposure to high doses of CBZ will eventually result in permanent damage to the algal PS. Hence, attention should be paid to the concentration of CBZ in the effluent and the exposure time, while methods to mitigate algal photodamage should be appropriately sought for algal treatment of dense effluents.

Diagnostic performance of mpox virus (MPXV) real-time PCR assays: multicenter assessment and extended sensitivity analysis.

PURPOSE: To comprehensively investigate the diagnostic performance of routinely used assays in MPXV testing, the National Center of Clinical Laboratories in China conducted a nationwide external quality assessment (EQA) scheme and an evaluated nine assays used by ≥ 5 laboratories in the EQA. METHODS: MPXV virus-like particles with 2700, 900 and 300 copies/mL were distributed to 195 EQA laboratories. For extended analysis, triple-diluted samples from 9000 to 4.12 copies/mL were repeated 20 times using the assays employed by ≥ 5 laboratories. The diagnostic performance was assessed by analyzing EQA data and calculating the limits of detection (LODs). RESULTS: The performance was competent in 87.69% (171/195) of the participants and 87.94% (175/199) of the datasets. The positive percentage agreements (PPAs) were greater than 99% for samples at 2700 and 900 copies/mL, and 95.60% (761/796) for samples at 300 copies/mL. The calculated LODs for the two clades ranged from 228.44 to 924.31 copies/mL and were greater than the LODs specified by the respective kits. EasyDiagnosis had the lowest calculated LODs and showed superior performance in EQA, whereas BioGerm and Sansure, with higher calculated LODs, did not perform well in EQA. CONCLUSION: This study provides valuable information from the EQA data and evaluation of the diagnostic performance of MPXV detection assays. It also provided insights into reagent optimization and enabled prompt public health interventions for the outbreak.

Extraction, characterization and intestinal anti-inflammatory and anti-oxidative activities of polysaccharide from stems and leaves of Chuanminshen violaceum M. L. Sheh & R. H. Shan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear. AIM OF THE STUDY: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms. MATERIALS AND METHODS: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action. RESULTS: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway. CONCLUSION: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases.

Accelerating diabetic wound healing by ROS-scavenging lipid nanoparticle-mRNA formulation.

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy to accelerate diabetic wound healing by repairing and reprogramming the microenvironment of the wounds. A library of reactive oxygen species (ROS)-responsive TS LNPs was designed and developed to encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at the wound site and induces the expression of IL4 in macrophages, promoting the polarization from the proinflammatory M1 to the anti-inflammatory M2 phenotype at the wound site. In a diabetic wound model of db/db mice, treatment with this formulation significantly accelerates wound healing by enhancing the formation of an intact epidermis, angiogenesis, and myofibroblasts. Overall, this TS LNP-mRNA platform not only provides a safe, effective, and convenient therapeutic strategy for diabetic wound healing but also holds great potential for clinical translation in both acute and chronic wound care.

Corrigendum: Comparison of indocyanine green angiography and swept-source wide-field optical coherence tomography angiography in posterior uveitis.

[This corrects the article DOI: 10.3389/fmed.2022.853315.].

[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

Latent Class Analysis of Sleep in Mild Cognitive Impairment Patients and its Influencing Factors.

Background: Individuals with mild cognitive impairment (MCI) frequently experience sleep disorders, which may elevate the risk of developing Alzheimer's disease. Yet, sleep types in MCI patients and the factors influencing them have not been sufficiently investigated. Objective: The objective of this study was to explore potential sleep typing and its influencing factors in patients with MCI using latent class analysis. Methods: A cross-sectional survey was conducted in Jiangsu Province, China. Cognitive function in older adults was assessed using neuropsychological tests, including the Montreal Cognitive Assessment Scale-Beijing version (MoCA), the Mini-Mental State Examination (MMSE), the Activities of Daily Living Scale (ADL), and the Clinical Dementia Rating Scale (CDR). Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Latent class analysis based on PSQI scores and multinomial logistic regression analyses were employed to explore the influencing factors of sleep typing. Results: The study included a total of 611 patients with MCI. Latent class analysis identified three latent classes to categorize the sleep patterns of MCI patients: the good sleep type (56.6%), the insufficient sleep type (29.6%), and the difficulty falling asleep type (13.7%). Potential sleep typing is influenced by gender, chronic disease, physical exercise, social activity, brain exercise, smoking, frailty, subjective cognitive status, and global cognitive function. Conclusions: The findings of this study underscore the notable heterogeneity in the sleep patterns of patients with MCI. Future research may provide targeted prevention and interventions to address the characteristics and influencing factors of patients with different subtypes of sleep MCI.

Strain and Temperature Sensing Based on Different Temperature Coefficients fs-FBG Arrays for Intelligent Buoyancy Materials.

The temperature and strain fields monitoring during the preparation process of buoyancy materials, as well as the health status after molding, are important for mastering the mechanical properties of buoyancy materials and ensuring the safety of operators and equipment. This paper proposes a short and high-density femtosecond fiber Bragg grating (fs-FBG) array based on different temperature coefficients fibers. By optimizing the parameters of femtosecond laser point-by-point writing technology, high-performance fs-FBG arrays with millimeter level gating length and millimeter level spatial resolution were prepared on two types of fibers. These were successfully embedded in buoyancy materials to achieve in-situ online monitoring of the curing process and after molding. The experimental results show that the fs-FBG array sensor has good anti-chirp performance and achieves online monitoring of millimeter-level spatial resolution. Intelligent buoyancy materials can provide real-time feedback on the health status of equipment in harsh underwater environments. The system can achieve temperature monitoring with an accuracy of 0.56 °C and deformation monitoring with sub-millimeter accuracy; the error is in the order of micrometers, which is of great significance in the field of deep-sea exploration.

Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro.

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.

An exosomal strategy for targeting cancer-associated fibroblasts mediated tumors desmoplastic microenvironments.

Tumors desmoplastic microenvironments are characterized by abundant stromal cells and extracellular matrix (ECM) deposition. Cancer-associated fibroblasts (CAFs), as the most abundant of all stromal cells, play significant role in mediating microenvironments, which not only remodel ECM to establish unique pathological barriers to hinder drug delivery in desmoplastic tumors, but also talk with immune cells and cancer cells to promote immunosuppression and cancer stem cells-mediated drug resistance. Thus, CAFs mediated desmoplastic microenvironments will be emerging as promising strategy to treat desmoplastic tumors. However, due to the complexity of microenvironments and the heterogeneity of CAFs in such tumors, an effective deliver system should be fully considered when designing the strategy of targeting CAFs mediated microenvironments. Engineered exosomes own powerful intercellular communication, cargoes delivery, penetration and targeted property of desired sites, which endow them with powerful theranostic potential in desmoplastic tumors. Here, we illustrate the significance of CAFs in tumors desmoplastic microenvironments and the theranostic potential of engineered exosomes targeting CAFs mediated desmoplastic microenvironments in next generation personalized nano-drugs development.

Charge-Reversal NaCl/G-Quartets for Aggregation-Induced Mitochondrial MicroRNA Imaging and Ion-Interference Therapy.

Mitochondrial therapy is a promising new strategy that offers the potential to achieve precise disease diagnosis or maximum therapeutic response. However, versatile mitochondrial theranostic platforms that integrate biomarker detection and therapy have rarely been exploited. Here, we report a charge-reversal nanomedicine activated by an acidic microenvironment for mitochondrial microRNA (mitomiR) detection and ion-interference therapy. The transporter liposome (DD-DC) was constructed from a pH-responsive polymer and a positively charged phospholipid, encapsulating NaCl nanoparticles with coloading of the aggregation-induced emission (AIE) fluorogens AIEgen-DNA/G-quadruplexes precursor and brequinar (NAB@DD-DC). The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na+ in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.

[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

Vineyard microclimate alterations induced by black inter-row mulch through transcriptome reshaped the flavoromics of cabernet sauvignon grapes.

BACKGROUND: Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016-2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate. RESULTS: Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified. CONCLUSION: This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes.

Downregulation of GPX8 in hepatocellular carcinoma: impact on tumor stemness and migration.

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.

Therapeutic effects and mechanisms of isoxanthohumol on DSS-induced colitis: regulating T cell development, restoring gut microbiota, and improving metabolic disorders.

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.

YY1 Lactylation Aggravates Autoimmune Uveitis by Enhancing Microglial Functions via Inflammatory Genes.

Activated microglia in the retina are essential for the development of autoimmune uveitis. Yin-Yang 1 (YY1) is an important transcription factor that participates in multiple inflammatory and immune-mediated diseases. Here, an increased YY1 lactylation in retinal microglia within in the experimental autoimmune uveitis (EAU) group is observed. YY1 lactylation contributed to boosting microglial activation and promoting their proliferation and migration abilities. Inhibition of lactylation suppressed microglial activation and attenuated inflammation in EAU. Mechanistically, cleavage under targets & tagmentation ï¼ˆCUT&Tag） analysis revealed that YY1 lactylation promoted microglial activation by regulating the transcription of a set of inflammatory genes, including STAT3, CCL5, IRF1, IDO1, and SEMA4D. In addition, p300 is identified as the writer of YY1 lactylation. Inhibition of p300 decreased YY1 lactylation and suppressed microglial inflammation in vivo and in vitro. Collectively, the results showed that YY1 lactylation promoted microglial dysfunction in autoimmune uveitis by upregulating inflammatory cytokine secretion and boosting cell migration and proliferation. Therapeutic effects can be achieved by targeting the lactate/p300/YY1 lactylation/inflammatory genes axis.

Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

Arthroscopic debridement improves range of motion for heterotopic ossification after total knee replacement: a retrospective cohort study.

The presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3-6 months. The maximum size of the ossification was < 2 cm in 23 knees, 2 cm < heterotopic bone < 5 cm in 6 knees and > 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was - 15.2-90.6°, which postoperatively increased to - 4.2-110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness.