An in-situ-tag-generation proximity labeling technology for recording cellular interactions.

Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.

Characterization of Responses to Lenvatinib plus Pembrolizumab in Patients with Advanced Renal Cell Carcinoma at the Final Prespecified Survival Analysis of the Phase 3 CLEAR Study.

In the phase 3 CLEAR trial, lenvatinib plus pembrolizumab (L + P) showed superior efficacy versus sunitinib in treatment-naïve patients with advanced renal cell carcinoma (aRCC). The combination treatment was associated with a robust objective response rate of 71%. Here we report tumor responses for patients in the L + P arm in CLEAR, with median follow-up of ∼4 yr at the final prespecified overall survival (OS) analysis. Tumor responses were assessed by independent review using Response Evaluation Criteria in Solid Tumors v1.1. Patients with a complete response (CR; n = 65), partial response (PR) with maximum tumor shrinkage ≥75% (near-CR; n = 59), or PR with maximum tumor shrinkage <75% (other PR; n = 129), were characterized in terms of their baseline characteristics. The median duration of response was 43.7 mo (95% confidence interval [CI] 39.2-not estimable) for the CR group, 30.5 mo (95% CI 22.4-not estimable) for the near-CR group, and 17.2 mo (95% CI 12.5-21.4) for the other PR group. The 36-mo OS rates were consistently high in the CR (97%), near-CR (86%), and other PR (62%) groups. Robust objective response rates were observed across International Metastatic RCC Database Consortium favorable-risk (69%, 95% CI 60-78%), intermediate-risk (73%, 95% CI 67-79%), and poor-risk (70%, 95% CI 54-85%) subgroups. The robust response to L + P supports this combination as a standard-of-care first-line treatment for patients with aRCC. PATIENT SUMMARY: The CLEAR trial enrolled patients with advanced kidney cancer who had not previously received any treatment for their cancer. Here we report results for tumor shrinkage observed in the group that received lenvatinib plus pembrolizumab combination treatment during the trial. Shrinkage of target tumors with this combination was long-lasting and was observed in patients irrespective of their disease severity. This trial is registered on ClinicalTrials.gov as NCT02811861.

Single-Molecule Discrimination of Saccharides Using Carbon Nitride Nanopores.

Structural complexity brings a huge challenge to the analysis of sugar chains. As a single-molecule sensor, nanopores have the potential to provide fingerprint information on saccharides. Traditionally, direct single-molecule saccharide detection with nanopores is hampered by their small size and weak affinity. Here, a carbon nitride nanopore device is developed to discern two types of trisaccharide molecules (LeApN and SLeCpN) with minor structural differences. The resolution of LeApN and SLeCpN in the mixture reaches 0.98, which has never been achieved in solid-state nanopores so far. Monosaccharide (GlcNAcpN) and disaccharide (LacNAcpN) can also be discriminated using this system, indicating that the versatile carbon nitride nanopores possess a monosaccharide-level resolution. This study demonstrates that the carbon nitride nanopores have the potential for conducting structure analysis on single-molecule saccharides.

Safety, tolerability, and pharmacokinetics of aildenafil citrate tablets, a novel oral PDE5 inhibitor, in healthy Chinese volunteers after multiple-dose administration.

Background: Aildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, developed for the treatment of erectile dysfunction (ED). Aim: This study aimed to assess the pharmacokinetics, safety, and tolerability of aildenafil citrate tablets after multiple doses in healthy Chinese males. Methods: Twenty participants were divided into 2 groups, 10 participants each. Participants were administered multiple doses of aildenafil citrate tablets at 30 and 60 mg. Outcomes: The safety evaluation was based on clinical symptoms and adverse events. Concentrations of aildenafil and its key metabolites (M1, M5, and M12) in human serum were measured by liquid chromatography-tandem mass spectrometry. Results: Pharmacokinetic analysis showed rapid absorption and elimination of aildenafil, with a median time to maximum serum concentration of 1 hour and mean terminal half-lives of 2.75 and 3.26 hours in the respective dose groups. The mean maximum concentration was proportional to the aildenafil dose in the range of 30 to 60 mg, although the area under the curve was not proportional for serum concentration vs time 0 to the last measurable time point (24 hours). Multiple doses of aildenafil were well tolerated, with 60.0% of men experiencing treatment-emergent adverse events, notably myalgia and fatigue, particularly in the 60-mg group. Clinical Implications: Aildenafil citrate tablets demonstrated favorable tolerability with once-daily administration over the clinical dose range. The occurrence of myalgia and fatigue was more prevalent in the 60-mg group. From a pharmacokinetic perspective, optimal administration of aildenafil citrate tablets appears to be 1 hour before sexual intercourse in men with ED. Strengths and Limitations: This study presents robust safety and pharmacokinetic data at expected therapeutic doses, unaffected by clinical factors. The efficacy of aildenafil citrate tablets warrants further validation in individuals with ED. Conclusion: Aildenafil citrate tablets exhibited good tolerability in healthy Chinese males following multiple doses at 30 and 60 mg. The 60-mg group showed an increased incidence of myalgia and fatigue, suggesting the need for heightened clinical vigilance. The mean maximum concentration, but not the area under the curve, displayed dose proportionality within the 30- to 60-mg dose range, and no significant drug accumulation was observed with repeated daily administration. Clinical Trial Registration: CTR20192473 (http://www.chinadrugtrials.org.cn).

A first-in-human study of Brozopentyl Sodium, following single and multiple ascending intravenous infusion in Chinese healthy volunteers.

BACKGROUND: Brozopentyl Sodium (BZP), a novel agent for ischemic stroke, has shown promising results in preclinical pharmacological studies, prompting the initiation of the first-in-human investigation. PURPOSE: This study aimed to assess the safety, tolerability, and pharmacokinetic (PK) characteristics of BZP in Chinese healthy volunteers. METHODS: The study consisted of two parts. Part I was a single-center, randomized, single-blinded, placebo-controlled, single-ascending study with six BZP dose cohorts (SAD: 25, 50, 100, 200, 300, and 400 mg). Part II was a single-center, randomized, single-blinded, placebo-controlled, multi-dose- and dose-elevated study with three BZP dose cohorts (MAD: 50, 100, and 200 mg). Doses were administered once daily on days 1 and 7 and twice daily on days 2-6. The PK properties of BZP and its bioactive metabolites, BNBP, were assessed. Safety and tolerability evaluations were also conducted. RESULTS: In the SAD study, BZP reached peak plasma concentrations (Tmax) at the end of administration, with median Tmax values ranging from 1 to 1.03 h, while BNBP reached Tmax between 1.25 to 1.38 h. The terminal half-lives (T1/2) were approximately 8 h for BZP and 15 h for BNBP. In the MAD study, steady-state plasma concentrations of BZP were reached by day 5. There was minimal accumulation of both BZP and BNBP after 7 days of administration. The area under the plasma concentration-time curve from 0 to time of the last measurable concentration (AUC0-t) and maximum plasma drug concentration (Cmax) showed dose-proportional increases for BZP but not for BNBP in both study parts. Single and multiple doses of BZP demonstrated a good safety profile and were well-tolerated. CONCLUSION: BZP displayed safety, good tolerability and predictable PK characteristics following both single and multiple ascending intravenous administrations. These findings provide a basis for further clinical development of BZP for ischemic stroke patients.

Selenium-based metabolic oligosaccharide engineering strategy for quantitative glycan detection.

Metabolic oligosaccharide engineering (MOE) is a classical chemical approach to perturb, profile and perceive glycans in physiological systems, but probes upon bioorthogonal reaction require accessibility and the background signal readout makes it challenging to achieve glycan quantification. Here we develop SeMOE, a selenium-based metabolic oligosaccharide engineering strategy that concisely combines elemental analysis and MOE,enabling the mass spectrometric imaging of glycome. We also demonstrate that the new-to-nature SeMOE probes allow for detection, quantitative measurement and visualization of glycans in diverse biological contexts. We also show that chemical reporters on conventional MOE can be integrated into a bifunctional SeMOE probe to provide multimodality signal readouts. SeMOE thus provides a convenient and simplified method to explore the glyco-world.

Site-selected in situ polymerization for living cell surface engineering.

The construction of polymer-based mimicry on cell surface to manipulate cell behaviors and functions offers promising prospects in the field of biotechnology and cell therapy. However, precise control of polymer grafting sites is essential to successful implementation of biomimicry and functional modulation, which has been overlooked by most current research. Herein, we report a biological site-selected, in situ controlled radical polymerization platform for living cell surface engineering. The method utilizes metabolic labeling techniques to confine the growth sites of polymers and designs a Fenton-RAFT polymerization technique with cytocompatibility. Polymers grown at different sites (glycans, proteins, lipids) have different membrane retention time and exhibit differential effects on the recognition behaviors of cellular glycans. Of particular importance is the achievement of in situ copolymerization of glycomonomers on the outermost natural glycan sites of cell membrane, building a biomimetic glycocalyx with distinct recognition properties.

Development of the mirror-image sensitivity for different object categories-Evidence from the mirror costs of object images in children and adults.

Object recognition relies on a multitude of factors, including size, orientation, and so on. Mirrored orientation, particularly due to children's mirror confusion in reading, holds special significance among various object orientations. Brain imaging studies suggest that the visual ventral and dorsal streams exhibit distinct orientation sensitivity across diverse object categories. Yet, it remains unclear whether mirror orientation sensitivity also varies among these categories during development at the behavioral level. Here, we explored the mirror sensitivity of children and adults across five distinct categories, which encompass tools that activate both the visual ventral stream for function information and the dorsal stream for manipulation information, and animals and faces that mainly activate the ventral stream. Two types of symbols, letters and Chinese characters, were also included. Mirror sensitivity was assessed through mirror costs-that is, the additional reaction time or error rate in the mirrored versus the same orientation condition when judging the identity of object pairs. The mirror costs in reaction times and error rates consistently revealed that children exhibited null mirror costs for tools, and the mirror costs for tools in adults were minimal, if any, and were smaller than those for letters and characters. The mirror costs reflected in absolute reaction time and error rate were similar across adults and children, but when the overall difference in reaction times was considered, adults showed a larger mirror cost than children. Overall, our investigation unveils categorical distinctions and development in mirror sensitivity of object recognition across the ventral and dorsal streams.

Traceless Protein-Selective Glycan Labeling and Chemical Modification.

Executing glycan editing at a molecular level not only is pivotal for the elucidation of complicated mechanisms involved in glycan-relevant biological processes but also provides a promising solution to potentiate disease therapy. However, the precision control of glycan modification or glyco-editing on a selected glycoprotein is by far a grand challenge. Of note is to preserve the intact cellular glycan landscape, which is preserved after editing events are completed. We report herein a versatile, traceless glycan modification methodology for customizing the glycoforms of targeted proteins (subtypes), by orchestrating chemical- and photoregulation in a protein-selective glycoenzymatic system. This method relies on a three-module, ligand-photocleavable linker-glycoenzyme (L-P-G) conjugate. We demonstrated that RGD- or synthetic carbohydrate ligand-containing conjugates (RPG and SPG) would not activate until after the ligand-receptor interaction is accomplished (chemical regulation). RPG and SPG can both release the glycoenzyme upon photoillumination (photoregulation). The adjustable glycoenzyme activity, combined with ligand recognition selectivity, minimizes unnecessary glycan editing perturbation, and photolytic cleavage enables precise temporal control of editing events. An altered target protein turnover and dimerization were observed in our system, emphasizing the significance of preserving the native physiological niche of a particular protein when precise modification on the carbohydrate epitope occurs.

Identification of immune-associated signatures and potential therapeutic targets for pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) comprises a heterogeneous group of diseases with diverse aetiologies. It is characterized by increased pulmonary arterial pressure and right ventricular (RV) failure without specific drugs for treatment. Emerging evidence suggests that inflammation and autoimmune disorders are common features across all PAH phenotypes. This provides a novel idea to explore the characteristics of immunological disorders in PAH and identify immune-related genes or biomarkers for specific anti-remodelling regimens. In this study, we integrated three gene expression profiles and performed Gene Ontology (GO) and KEGG pathway analysis. CIBERSORT was utilized to estimate the abundance of tissue-infiltrating immune cells in PAH. The PPI network and machine learning were constructed to identify immune-related hub genes and then evaluate the relationship between hub genes and differential immune cells using ImmucellAI. Additionally, we implemented molecular docking to screen potential small-molecule compounds based on the obtained genes. Our findings demonstrated the density and distribution of infiltrating CD4 T cells in PAH and identified four immune-related genes (ROCK2, ATHL1, HSP90AA1 and ACTR2) as potential targets. We also listed 20 promising molecules, including TDI01953, pemetrexed acid and radotinib, for PAH treatment. These results provide a promising avenue for further research into immunological disorders in PAH and potential novel therapeutic targets.

Benign pancreatic lesion on 18F-FDG PET-MRI: A case report.

RATIONALE: Differentiation of benign and malignant lesions in the head of pancreas is the key. When the mass is small, it is difficult to distinguish via conventional imaging modalities. Positron emission tomography and magnetic resonance imaging (PET/MRI) can distinguish benign and malignant lesions from the perspective of metabolism, which provides a new idea for the diagnosis of pancreatic head mass. PATIENT CONCERNS: We report the case of a 44-year-old male patient who underwent an 18F-fluorodeoxyglucose PET/MRI for medical examination. The patient did not complain of special discomfort. DIAGNOSES: PET-MRI revealed in the head of the pancreas, there is a circular space-occupying lesion without obvious fluorodeoxyglucose accumulation, which tends to be benign based on its MRI and metabolic characteristics. INTERVENTIONS: The patient refused further laboratory examination or ultrasound gastroscopy as there is no discomfort. OUTCOMES: No special discomfort was found in the patient after 6 months follow-up. LESSONS: If routine examination fails to diagnose benign or malignant pancreatic head occupying, and the patient refuses invasive examination, PET-MRI can be performed for identification.

A novel immunogenic cell death-related subtype classification and risk signature for predicting prognosis and immunotherapy efficacy in gastric cancer.

The majority of gastric cancer (GC) patients are in a progressive stage at the initial stage of treatment, and the overall response rate to immunotherapy remains unsatisfactory largely due to the lack of effective prognostic biomarkers. Immunogenic cell death (ICD) was identified as a new form of regulated cell death that can activate adaptive immune responses and further promote immunotherapy efficacy. Therefore, we attempted to characterize the ICD-associated signature to stratify patients who could benefit from immunotherapy. In our study, two subgroups of patients were identified based on the data of 34 ICD-related genes extracted from The Cancer Genome Atlas database via consensus clustering. The estimated scores, stromal scores, immune scores, tumor purity, and survival rate showed significant differences between the low and high ICD groups. Then, we constructed an ICD-related risk signature, including IFNB1, IL6, LY96, and NT5E, using least absolute shrinkage and selection operator Cox regression analysis; then, high- and low-risk groups could be clearly distinguished. Notably, the risk score is a reliable predictor of the prognosis and immunotherapy outcome in GC, which was further validated in an immunohistochemistry assay. These results suggest that ICD is closely associated with the prognosis and tumor immune microenvironment in GC. Taken together, this study first constructed and validated a prognostic ICD-related signature to predict the survival and effect of immunotherapy in GC, which provided new insight for potent individualized immunotherapy strategies.

Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab.

BACKGROUND: Lenvatinib plus pembrolizumab showed significantly improved progression-free and overall survival outcomes compared with sunitinib in patients with advanced renal cell carcinoma in the CLEAR study (NCT02811861). Here, we used CLEAR data to characterize common adverse reactions (ARs; adverse-event preferred terms grouped in accordance with regulatory authority review) associated with lenvatinib plus pembrolizumab and review management strategies for select ARs. MATERIALS AND METHODS: Safety data from the 352 patients who received lenvatinib plus pembrolizumab in the CLEAR study were analyzed. Key ARs were chosen based on frequency of occurrence (≥30%). Time to first onset and management strategies for key ARs were detailed. RESULTS: The most frequent ARs were fatigue (63.1%), diarrhea (61.9%), musculoskeletal pain (58.0%), hypothyroidism (56.8%), and hypertension (56.3%); grade ≥3 severity ARs that occurred in ≥5% of patients were hypertension (28.7%), diarrhea (9.9%), fatigue (9.4%), weight decreased (8.0%), and proteinuria (7.7%). Median times to first onset of all key ARs were within approximately 5 months (approximately 20 weeks) of starting treatment. Strategies for effectively managing ARs included baseline monitoring, drug-dose modifications, and/or concomitant medications. CONCLUSION: The safety profile of lenvatinib plus pembrolizumab was consistent with the known profile of each monotherapy; ARs were considered manageable with strategies including monitoring, dose modifications, and supportive medications. Proactive and prompt identification and management of ARs are important for patient safety and to support continued treatment. CLINICALTRIALS.GOV ID: NCT02811861.

Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study.

BACKGROUND: In the primary analysis of the CLEAR study, lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival versus sunitinib in patients with advanced renal cell carcinoma (data cutoff Aug 28, 2020). We aimed to assess overall survival based on 7 months of additional follow-up. METHODS: This is a protocol-prespecified updated overall survival analysis (data cutoff March 31, 2021) of the open-label, phase 3, randomised CLEAR trial. Patients with clear-cell advanced renal cell carcinoma who had not received any systemic anticancer therapy for renal cell carcinoma, including anti-vascular endothelial growth factor therapy, or any systemic investigational anticancer drug, were eligible for inclusion from 200 sites (hospitals and cancer centres) across 20 countries. Patients were randomly assigned (1:1:1) to receive lenvatinib (20 mg per day orally in 21-day cycles) plus pembrolizumab (200 mg intravenously every 21 days; lenvatinib plus pembrolizumab group), lenvatinib (18 mg per day orally) plus everolimus (5 mg per day orally; lenvatinib plus everolimus group [not reported in this updated analysis]) in 21-day cycles, or sunitinib (50 mg per day orally, 4 weeks on and 2 weeks off; sunitinib group). Eligible patients were at least 18 years old with a Karnofsky performance status of 70 or higher. A computer-generated randomisation scheme was used, and stratification factors were geographical region and Memorial Sloan Kettering Cancer Center prognostic groups. The primary endpoint was progression-free survival assessed by independent imaging review according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). In this Article, extended follow-up analyses for progression-free survival and protocol-specified updated overall survival data are reported for the intention-to-treat population. No safety analyses were done at this follow-up. This study is closed to new participants and is registered with ClinicalTrials.gov, NCT02811861. FINDINGS: Between Oct 13, 2016, and July 24, 2019, 1417 patients were screened for inclusion in the CLEAR trial, of whom 1069 (75%; 273 [26%] female, 796 [74%] male; median age 62 years [IQR 55-69]) were randomly assigned: 355 (33%) patients (255 [72%] male and 100 [28%] female) to the lenvatinib plus pembrolizumab group, 357 (33%) patients (275 [77%] male and 82 [23%] female) to the sunitinib group, and 357 (33%) patients to the lenvatinib plus everolimus group (not reported in this updated analysis). Median follow-up for progression-free survival was 27·8 months (IQR 20·3-33·8) in the lenvatinib plus pembrolizumab group and 19·4 months (5·5-32·5) in the sunitinib group. Median progression-free survival was 23·3 months (95% CI 20·8-27·7) in the lenvatinib plus pembrolizumab group and 9·2 months (6·0-11·0) in the sunitinib group (stratified hazard ratio [HR] 0·42 [95% CI 0·34-0·52]). Median overall survival follow-up was 33·7 months (IQR 27·4-36·9) in the lenvatinib plus pembrolizumab group and 33·4 months (26·7-36·8) in the sunitinib group. Overall survival was improved with lenvatinib plus pembrolizumab (median not reached [95% CI 41·5-not estimable]) versus sunitinib (median not reached [38·4-not estimable]; HR 0·72 [95% CI 0·55-0·93]). INTERPRETATION: Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma. FUNDING: Eisai and Merck Sharp & Dohme.

Site-Specific Introduction of Bioorthogonal Handles to Nanopores by Genetic Code Expansion.

Site-specific functionalization of natural amino acid-containing biological nanopores is pivotal in single molecule sensing. However, pore engineering methodologies are restricted to a limited choice and introduction of unnatural chemical components is extremely difficult. Herein we report the genetic code expansion (GCE) strategy to introduce unnatural amino acid (UAA) to an octameric Mycobacterium smegmatis porin A (MspA) nanopore. GCE allows for rapid and efficient introduction of bioorthogonal reactive site (i.e., azide) to the pore rim, and conjugation of single stranded DNA or lysozyme was demonstrated. The lysozyme-conjugated pore was further used for the discrimination of different oligosaccharides, demonstrating a sensing capacity that a bare MspA nanopore does not possess. GCE with bioorthogonal handles, which has never been previously applied in the preparation of nanopores, is a versatile strategy for pore engineering and may further expand the application scenarios of nanopores.

Role of 18F-fluorodeoxyglucose PET/computed tomography in the diagnosis and treatment response assessment of primary bone lymphoma.

OBJECTIVE: Primary bone lymphoma (PBL) is a rare type of extranodal lymphoma, and the clinical application value of 18F-fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) in PBL has not been fully evaluated. This study aimed to determine the imaging characteristics of PBL and investigate the value of 18 F-FDG PET/CT parameters. METHODS: A total of 25 patients with PBL who underwent PET/CT examination before treatment were included in this study. The clinicopathological parameters and PET/CT parameters were analyzed. RESULTS: Among the 25 patients, 7 patients had single lesions, 15 patients had nonsingle lesions (≥2) and 3 patients had diffuse distribution in the medullary cavity. The bone destruction types included osteolytic, osteogenic, normal density, mixed lytic and osteogenic. All patients showed increased FDG uptake, and the CT detection rate was 88%. Five patients underwent PET/CT assessment mid-treatment, and when assessed using the Deauville five-point scale, four patients were PET-negative and one patient was PET-positive. There were two PET-positive and three PET-negative patients when assessed using the Δ maximum standardized uptake value (SUV max ) method. Six patients underwent PET/CT imaging at the end of treatment. When assessed using the Deauville five-point scale, five patients (83%) were PET-negative and one patient (17%) was PET-positive. The same results were obtained when evaluated by the ΔSUV max method. CONCLUSION: PET/CT plays a substantial role in the diagnosis and treatment efficacy evaluation of PBL, and it should be recognized by clinicians and radiologists. Changes in metabolic parameters such as SUV, metabolic tumor volume and total lesion glycolysis have considerable potential for application in PBL diagnostics and treatment efficacy evaluation.

Recent Advances in Protein-Specific Glycan Imaging and Editing.

Glycosylation in live cell and animal modulate a constellation of biological functions. The advent of Chemical Biology has revolutionized the analysis and tailoring of glycans, by introducing myriads of glycan engineering methods. However, the ideal scenario to achieve glycan monitoring and structural manipulation at any hierarchical levels is unmet yet. Herein we review recent advances in the methodological innovation and the versatile applications of the protein-specific glycan visualization and editing in deciphering the biological functions of glycans. An outlook for future directions toward specific sugar-chain editing is also included.

[Determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis by gel permeation chromatography-gas chromatography-ion trap mass spectrometry].

With the growing global popularity of traditional medicine and natural drugs， especially in Southeast Asia， the quality of traditional Chinese medicines （TCMs） has attracted the attention of regulators. China's major TCM export destinations， such as South Korea， Japan， and Europe， have formulated strict maximum residue limits （MRLs） of pesticides in TCMs. Therefore， a sensitive and high-throughput method for the simultaneous determination of 101 pesticide residues in Platycodonis radix and extracts of Angelica sinensis was established， involving gel permeation chromatography （GPC） coupled with gas chromatography-ion trap mass spectrometry （GC-ITMS）. In this method， the samples were first ground into fine powder and extracted twice with 20 mL acetonitrile in an ultrasonic cleaner for 30 min. After centrifugation for 10 min at 6000 r/min， the supernatants were combined and dried at 40 ℃ using a rotary vacuum evaporator. The residue was re-dissolved in 2 mL ethyl acetate-cyclohexane （1∶1， v/v） and purified by gel permeation chromatography using a 40 cm×20 mm column. The eluent collecting time was optimized as 17-30 min to ensure both the recovery of target compounds and the removal of interferences such as pigments and lipids from the target compounds. The eluent was then dried and re-dissolved with 1 mL toluene for analysis. The 101 pesticide residues were separated using the DB-5MS capillary column and analyzed by ion trap mass spectrometry. The pretreatment conditions and ion trap mass spectrometry parameters were optimized to effectively reduce the interference of complex TCM matrices and greatly improve the quantitative accuracy of the analysis and recovery of the target pesticides. Three spiked levels of 101 pesticides were tested. The average recovery range was 58.3%-108.9% and the relative standard deviations （RSDs） at the three spiked levels （n=10） ranged from 0.4% to 16.5%. The limits of detection （LODs， S/N=3） of the 101 pesticide compounds ranged from 0.2 to 40.0 µg/kg， while the limits of quantification （LOQs， S/N=10） ranged from 0.6 to 120.0 µg/kg， which met the maximum residue limits of China's main TCM export countries and organizations. This rapid analysis method was easy to operate and high throughput， with strong sensitivity and good repeatability. The employment of gel permeation chromatography overcame the drawback of inadequate cleanup of the solid phase extraction column during TCM analysis. The application of ion trap technology further eliminated the interference of matrix impurities and increased the accuracy of the quantitative and qualitative analyses. This method fills the knowledge gap in multiple pesticide residue determination in TCMs using gas chromatography-ion trap mass spectrometry and is a useful and beneficial alternative to current analytical methods of TCMs.