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Yujing Xin,1 Ning Liu,2 Gang Peng,3 Xiaoyu Huang,3 Xiaojing Cao,3 Xiang Zhou3 1Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2School of Software, Shandong University, Jinan, Shandong, 250101, People’s Republic of China; 3National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaCorrespondence: Xiang Zhou, Email zhou.xiang@yeah.netPurpose: To investigate the prognostic value of inflammatory indexes based on peripheral blood cells in unresectable hepatocellular carcinoma (HCC) patients treated with Lenvatinib combined with PD-1 inhibitors.Methods: This study retrospectively collected baseline inflammatory indexes from HCC patients received Lenvatinib and PD-1 inhibitor-based combination therapy at the Cancer Hospital of the Chinese Academy of Medical Sciences between October 2018 and October 2021. The optimal threshold values for inflammatory indexes determined using X-tile. The factors related to treatment response and survival outcomes were analyzed through logistic regression and Cox regression, respectively. A novel preoperative prognostic nomogram was constructed based on inflammatory indexes, and the predictive efficacy of the nomogram and BCLC staging was compared by the area under the ROC curve.Results: 156 eligible patients with unresectable HCC were included, with median OS and PFS of 23.8 and 11.5 months, respectively, and ORR of 48.7%. The baseline SIRI was an independent factor of treatment response, with a significantly higher ORR for patients with a SIRI < 0.8 than for patients with a SIRI ≥ 0.8 (59.7% vs 41.5%, P=0.03). SIRI and PNI were independent prognostic factors of PFS, and SIRI was an independent prognostic factor of OS. The AUC value of nomogram based on baseline SIRI, PNI, and tumor distribution in predicting the 6-,12- and 18-month PFS of patients was significantly higher than that of traditional BCLC stage, and its prediction performance was substantially better than that of BCLC stage system (C-index, 0.730 vs 0.535).Conclusion: The baseline SIRI could be used as a potential non-invasive biomarker to predict the efficacy and survival benefit of immune combination therapy for HCC. The nomogram based on inflammation indexes could achieve better prediction performance and help clinicians to identify high-risk patients and formulate treatment plans.Keywords: lenvatinib, PD-1 inhibitor, inflammatory indexes, hepatocellular carcinoma

Xiaoyu Huang, Gang Peng, Yaqing Kong, Xiaojing Cao, Xiang Zhou Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaCorrespondence: Xiang Zhou, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email zhou.xiang@yeah.netPurpose: This study aimed to evaluate the prognostic value of C-reactive protein to albumin (CRP/Alb) ratio in hepatocellular carcinoma (HCC) treated with transcatheter intra-arterial therapy combined with molecular targeted agents (MTAs) and programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors.Methods: Medical records of 271 consecutive patients with HCC receiving this combination therapy in China between 2019 and 2023 were retrospectively analyzed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate Cox regression analyses. The discriminatory capability of inflammation-based prognostic scores—including the CRP/Alb ratio, C-reactive protein and alpha-fetoprotein in immunotherapy (CRAFITY) score, modified Glasgow prognostic score (mGPS), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)—was assessed using the area under the curve (AUC).Results: A total of 133 patients met the inclusion criteria. The optimal cutoff value for the binary classification of CRP/Alb ratio in predicting OS, as determined using X-tile software, was 0.02. Multivariate analysis identified the CRP/Alb ratio (hazard ratio [HR] = 2.61, p < 0.001), tumor size (HR = 2.45, p = 0.018), and extrahepatic metastases (HR = 1.93, p = 0.015) as independent predictors of OS. For PFS, significant factors included Eastern Cooperative Oncology Group Performance Status (HR = 1.55, p = 0.033) and macrovascular invasion (HR = 1.48, p = 0.046). Patients with higher CRP/Alb ratios were more likely to experience fever and fatigue. The CRP/Alb ratio demonstrated significantly higher AUCs than PLR and SII at 24 months (all p < 0.05) and showed comparable AUCs to CRAFITY score and mGPS at 12, 24, and 36 months.Conclusion: The CRP/Alb ratio is a valuable prognostic marker for predicting OS and treatment-related adverse events in HCC patients receiving transcatheter intra-arterial therapy combined with MTAs and PD-1/PD-L1 inhibitors. This ratio can be used as a simple and reliable biomarker for assessing prognosis and guiding patient selection in clinical practice.Keywords: transarterial chemoembolization, hepatic artery infusion chemotherapy, targeted therapy, immunotherapy, inflammation, C-reactive protein

Guoran Peng,1 Beibei Cheng,2 Rongzhen Ding,3 Aiguo Dai2– 4 1College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 3Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 4Department of Respiratory Medicine, First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Aiguo Dai, Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, 300 Xueshi Road, Hanpu Science & Education Park, Yuelu District, Changsha, Hunan, 410208, People’s Republic of China, Email daiaiguo@hnucm.edu.cnPurpose: Asthma and depression are prevalent conditions with significant comorbidity, impacting patients’ quality of life. This bibliometric study aims to analyze research trends and hotspots in the field from 2000 to 2023, identifying key contributions and predicting future directions.Methods: We conducted a systematic search in the Web of Science Core Collection (WoSCC) for articles on asthma and depression, published between 2000 and 2023. Bibliometrics, which involves the application of mathematical and statistical methods to analyze scholarly literature, was employed in this study to systematically assess the research trends and hotspots in the field of asthma and depression. VOSviewer and CiteSpace software were utilized for visual analysis and data visualization, enabling us to map collaboration networks and identify research hotspots and trends within the asthma and depression literature.Results: Our analysis retrieved 3067 papers from 937 journals, involving 14,631 authors and 4006 institutions across 106 countries. The United States, Columbia University, the Journal of Asthma, and Christer Janson were the most prolific contributors. Six primary research themes emerged: quality of life, childhood asthma, primary care, substance P, intervention, and emotion. Additionally, Burst detection analysis identified emerging topics, including severe asthma, other respiratory diseases, and oxidative stress.Conclusion: This bibliometric analysis has revealed significant insights into the research trends and hotspots in the field of asthma and depression. The primary findings indicate a growing body of research highlighting the impact of depression on asthma control and patients’ quality of life, the need for psychological interventions in treating comorbid asthma and depression, and the emerging focus on severe asthma and oxidative stress mechanisms. These findings underscore the importance of continued research in these areas to advance our understanding and improve clinical outcomes for patients with these comorbid conditions.Keywords: asthma, depression, bibliometric analysis, hotspots, research trends

Shuping Zhang,1,&ast; Yamei Ma,1,&ast; Xiu Zang,2 Hao Heng,2 Xuekui Liu,2 Gangshan Peng,3 Ran Liu,3 Jun Liang,1,2,&ast; Houfa Geng1,2,&ast; 1Graduate School, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3The Affiliated Xuzhou Clinical College, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houfa Geng; Jun Liang, Email genghoufa@xzhmu.edu.cn; liangjun@xzhmu.edu.cnAbstract: Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.Keywords: 17q12 microdeletion syndrome, HNF-1β gene, special-type diabetes, MODY5, polycystic kidneys, liver damage

[This corrects the article DOI: 10.1039/D1SC05435J.].

Wei Jia,1 Lei Liu,1 Gang Peng2 1School of Politics and Public Administration, Qingdao University, Qingdao, Shandong, People’s Republic of China; 2School of Statistics, Southwestern University of Finance and Economics, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lei Liu, School of Politics and Public Administration, Qingdao University, 308 Ningxia Road, Laoshan District, Qingdao, Shandong, 266071, People’s Republic of China, Tel +86-15110224681, Email ll15450176@163.comPurpose: The integration of social media into all areas of society has become a typical phenomenon of the Internet era. This study’s core objective is to dissect the relationship between social media, self-efficacy and loneliness, especially emphasizing the mediating function of social support.Patients and Methods: The research data is derived from the pooled cross-sectional data combined from the four-period data of the China Family Panel Studies (CFPS). The study employs Ordinary Least Squares (OLS) regression as the basic research method, and utilizes Instrumental Variables (IV) and other methods to conduct robustness checks.Results: Social media usage frequency (SMUF) enhances self-efficacy and loneliness through social support. Social support promotes self-efficacy and alleviates users’ loneliness. In self-efficacy, social support plays a fully mediating role. Moreover, education (human capital) has a significant moderating effect. There are noticeable differences in the response of different characteristics groups to SMUF.Conclusion: This study reveals how social media impacts self-efficacy and loneliness through social support. Based on the research results, avoiding prolonged usage of social media and improving digital literacy are the crucial means to exert the positive benefits of social media.Keywords: social media, self-efficacy, loneliness, social support, mediation analysis

Bisected N-glycans represent a unique class of protein N-glycans that play critical roles in many biological processes. Herein, we describe the systematic synthesis of these structures. A bisected N-glycan hexasaccharide was chemically assembled with two orthogonal protecting groups attached at the C2 of the branching mannose residues, followed by sequential installation of GlcNAc and LacNAc building blocks to afford two asymmetric bisecting "cores". Subsequent enzymatic modular extension of the "cores" yielded a comprehensive library of biantennary N-glycans containing the bisecting GlcNAc and presenting 6 common glycan determinants in a combinatorial fashion. These bisected N-glycans and their non-bisected counterparts were used to construct a distinctive glycan microarray to study their recognition by a wide variety of glycan-binding proteins (GBPs), including plant lectins, animal lectins, and influenza A virus hemagglutinins. Significantly, the bisecting GlcNAc could bestow (PHA-L, rDCIR2), enhance (PHA-E), or abolish (ConA, GNL, anti-CD15s antibody, etc.) N-glycan recognition of specific GBPs, and is tolerated by many others. In summary, synthesized compounds and the unique glycan microarray provide ideal standards and tools for glycoanalysis and functional glycomic studies. The microarray data provide new information regarding the fine details of N-glycan recognition by GBPs, and in turn improve their applications.

Gangliosides are sialic acid-containing glycosphingolipids that have been found in the cell membranes of all vertebrates. Their important biological functions are contributed by both the glycan and the ceramide lipid components. GM3 is a major ganglioside and a precursor for many other more complex gangliosides. To obtain structurally diverse GM3 gangliosides containing various sialic acid forms and different fatty acyl chains in low cost, an improved process was developed to chemically synthesize lactosyl sphingosine from an inexpensive l-serine derivative. It was then used to obtain GM3 sphingosines from diverse modified sialic acid precursors by an efficient one-pot multienzyme sialylation system containing Pasteurella multocida sialyltransferase 3 (PmST3) with in situ generation of sugar nucleotides. A highly effective chemical acylation and facile C18-cartridge purification process was then used to install fatty acyl chains of varying lengths and different modifications. The chemoenzymatic method represents a powerful total synthetic strategy to access a library of structurally defined GM3 gangliosides to explore their functions.

Glycans mediate a wide variety of biological roles via recognition by glycan-binding proteins (GBPs). Comprehensive knowledge of such interaction is thus fundamental to glycobiology. While the primary binding feature of GBPs can be easily uncovered by using a simple glycan microarray harboring limited numbers of glycan motifs, their fine specificities are harder to interpret. In this study, we prepared 98 closely related N-glycoforms that contain 5 common glycan epitopes which allowed the determination of the fine binding specificities of several plant lectins and anti-glycan antibodies. These N-glycoforms differ from each other at the monosaccharide level and were presented in an identical format to ensure comparability. With the analysis platform we used, it was found that most tested GBPs have preferences toward only one branch of the complex N-glycans, and their binding toward the epitope-presenting branch can be significantly affected by structures on the other branch. Fine specificities described here are valuable for a comprehensive understanding and applications of GBPs.

Yan Sun, Lumi Zhang, Ping Liu, Guoping Peng Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Guoping Peng, Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, &num;79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Tel +86 13588150613, Email guopingpeng@zju.edu.cnAbstract: Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases with heterogenous clinical, genetic, and pathological characteristics that show similar impairment of areas in the frontal and/or temporal lobes. Prime doctors’ lack of awareness of this complex disease makes early identification and accurate intervention difficult. Autoimmune diseases and autoantibodies are manifestations of different levels of autoimmune reactions. This review presents research findings examining the relationship between autoimmunity and FTLD in terms of autoimmune diseases and autoantibodies with a focus on identifying potential diagnosis and treatment approaches. The findings indicate that the same or similar pathophysiological mechanisms may exist from clinical, genetic, and pathological perspectives. However, the existing evidence is not sufficient to extract substantial conclusions. On the basis of the current situation, we propose future research patterns using prospective studies on large populations and combined clinical and experimental research. Autoimmune reactions or, more generally, inflammatory reactions should receive increased attention from doctors and scientists of all disciplines.Keywords: frontotemporal lobar degeneration, autoimmunity, autoimmune disorders, autoantibodies, diagnosis, treatment

Liuyang Wu,1,2 Wei Wang,2 Yang Gui,2 Qiqi Yan,1,2 Guangxin Peng,2 Xin Zhang,2 Lifang Ye,2 Lihong Wang2 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, People’s Republic of ChinaCorrespondence: Lihong Wang, Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), No. 158 Shangtang Road, Hangzhou, Zhejiang Province, 310014, People’s Republic of China, Tel +86 136-6669-0589, Email wanglhnew@126.com; wlhhz2013@126.comPurpose: Our study aimed to identify new-onset atrial fibrillation (NOAF) risk factors in acute myocardial infarction (AMI) patients after treatment with percutaneous coronary intervention (PCI) and investigate whether their nutritional status can be a predicting factor of NOAF.Patients and Methods: We analyzed 662 AMI patients after PCI for NOAF occurrence during follow-up hospitalization and divided them into an NOAF and non-NOAF group. The patients’ nutritional status was assessed using the controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI). The Kaplan‒Meier analysis was used to assess NOAF-free survival in varying degrees of malnutrition. Cox proportional hazards models were used to identify the risk factors for NOAF.Results: Eighty-four (12.7%) patients developed NOAF during hospitalization. There was a statistically significant difference in the occurrence of NOAF among different categories of nutritional status. The CONUT score and GNRI classifications were independent predictors of NOAF. NOAF occurrence was associated with older age, higher uric acid levels, higher N-terminal pro-B-type natriuretic peptide levels, greater left atrial size, and worse Killip class upon admission.Conclusion: The nutritional status can affect NOAF occurrence in AMI patients after PCI. The CONUT score and GNRI are ideal tools for evaluating the nutritional status of AMI patients, with an excellent predictive effect on NOAF.Keywords: atrial fibrillation, acute myocardial infarction, malnutrition, controlling nutritional status, geriatric nutritional risk index

Genetically introducing covalent bonds into proteins in vivo with residue specificity is affording innovative ways for protein research and engineering, yet latent bioreactive unnatural amino acids (Uaas) genetically encoded to date react with one to few natural residues only, limiting the variety of proteins and the scope of applications amenable to this technology. Here we report the genetic encoding of (2 R)-2-amino-3-fluoro-3-(4-((2-nitrobenzyl)oxy) phenyl) propanoic acid (FnbY) in Escherichia coli and mammalian cells. Upon photoactivation, FnbY generated a reactive quinone methide (QM), which selectively reacted with nine natural amino acid residues placed in proximity in proteins directly in live cells. In addition to Cys, Lys, His, and Tyr, photoactivated FnbY also reacted with Trp, Met, Arg, Asn, and Gln, which are inaccessible with existing latent bioreactive Uaas. FnbY thus dramatically expanded the number of residues for covalent targeting in vivo. QM has longer half-life than the intermediates of conventional photo-cross-linking Uaas, and FnbY exhibited cross-linking efficiency higher than p-azido-phenylalanine. The photoactivatable and multitargeting reactivity of FnbY with selectivity toward nucleophilic residues will be valuable for addressing diverse proteins and broadening the scope of applications through exploiting covalent bonding in vivo for chemical biology, biotherapeutics, and protein engineering.

Expansion of the genetic code with unnatural amino acids (Uaas) has significantly increased the chemical space available to proteins for exploitation. Due to the inherent limitation of translational machinery and the required compatibility with biological settings, function groups introduced via Uaas to date are restricted to chemically inert, bioorthogonal, or latent bioreactive groups. To break this barrier, here we report a new strategy enabling the specific incorporation of biochemically reactive amino acids into proteins. A latent bioreactive amino acid is genetically encoded at a position proximal to the target natural amino acid; they react via proximity-enabled reactivity, selectively converting the latter into a reactive residue in situ. Using this Genetically Encoded Chemical COnversion (GECCO) strategy and harnessing the sulfur-fluoride exchange (SuFEx) reaction between fluorosulfate-l-tyrosine and serine or threonine, we site-specifically generated the reactive dehydroalanine and dehydrobutyrine into proteins. GECCO works both inter- and intramolecularly, and is compatible with various proteins. We further labeled the resultant dehydroalanine-containing protein with thiol-saccharide to generate glycoprotein mimetics. GECCO represents a new solution for selectively introducing biochemically reactive amino acids into proteins and is expected to open new avenues for exploiting chemistry in live systems for biological research and engineering.

Su’e Shao,1 Meifang Huang,2 Heng Zhang,1 Gangqiang Peng,1 Min Song,1 Jing Liu,1 Dan Xu1 1Department of Gastroenterology, The Central Hospital of Wuhan, Wuhan, People’s Republic of China; 2Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Meifang Huang, Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169 East Lake Road, Wuchang District, Wuhan, Hubei, 430061, People’s Republic of China, Tel +86-13307110223, Email 1657791068@qq.com Heng Zhang, Department of Gastroenterology, the Central Hospital of Wuhan, No. 26 Shengli Street, Jiang’an District, Wuhan, Hubei, 430014, People’s Republic of China, Tel +86-18627886610, Email 653262549@qq.comPurpose: To retrospectively collect and analyze demographic information as well as symptoms, laboratory results, endoscopic and pathologic findings, and treatment of ulcerative colitis (UC) and Crohn’s disease (CD) patients in Wuhan, China.Methods: Patients who were diagnosed as inflammatory bowel disease (IBD) and hospitalized from January 2012 to December 2017 were enrolled in this study. The clinical characteristics including symptoms, laboratory results, and treatment were reviewed and analyzed.Results: Totally 821 cases were screened, and finally 430 UC patients and 286 CD patients were selected and enrolled in this study. The most common symptom in UC patients was bloody stool (90.7%) followed by diarrhea (87.7%), mucus in stool (72.1%), and abdominal pain (66.3%), which were significantly different from those of CD patients (P < 0.01). In contrast, the most common symptom in CD patients was abdominal pain (80.0%) followed by diarrhea (58.4%), bloody stool (27.6%), and fever (18.2%). Erythrocyte sedimentation, C-reactive protein, and platelets were significantly increased, while hemoglobin was decreased, in the moderately or highly active IBD. The percentage of positive perinuclear anti-neutrophil cytoplasmic antibody was significantly higher in UC patients (31.1%) than that in CD patients (4.8%, P < 0.001), while the percentage of positive anti-intestinal goblet cell antibody was significantly higher in CD patients (23.1%) than that in UC patients (14.9%, P = 0.037).Conclusion: The findings of the current study may provide evidence-based information for Chinese gastroenterologists to treat IBD more effectively in the future.Keywords: inflammatory bowel disease, Crohn’s disease, ulcerative colitis

Ping Liu,1 Yunyun Wang,1,2 Yan Sun,1 Guoping Peng1 1Department of Neurology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Neurology, Shengzhou People’s Hospital, Shaoxing, People’s Republic of ChinaCorrespondence: Guoping Peng, Department of Neurology, the First Affiliated Hospital, Zhejiang University School of Medicine, #79 Qingchun Road, Hangzhou, Zhejiang Province, 310003, People’s Republic of China, Tel +86 13588150613, Email guopingpeng@zju.edu.cnAbstract: Although amyloid-β (Aβ) peptide accumulation is considered as a key early event in the pathogenesis of Alzheimer’s disease (AD), the precise pathophysiology of this deadly illness remains unclear and no effective remedies capable of inhibiting disease progression have been discovered. In addition to deposition of extracellular Aβ plaques and intracellular neurofibrillary tangles, neuroinflammation has been identified as the third core characteristic crucial in the pathogenesis of AD. More and more evidence from laboratory and clinical studies have suggested that anti-inflammatory treatments could defer or prevent the occurrence of AD. In this review, we will discuss multifaceted evidence of neuroinflammation presented in AD and the newly emerged anti-inflammatory targets both in pre-clinical and clinical AD.Keywords: Alzheimer’s disease, neuroinflammation, disease‐modifying therapy, anti-inflammatory treatment

Analogous to reversible post-translational protein modifications, the ability to attach and subsequently remove modifications on proteins would be valuable for protein and biological research. Although bioorthogonal functionalities have been developed to conjugate or cleave protein modifications, they are introduced into proteins on separate residues and often with bulky side chains, limiting their use to one type of control and primarily protein surface. Here we achieved dual control on one residue by genetically encoding S-propargyl-cysteine (SprC), which has bioorthogonal alkyne and propargyl groups in a compact structure, permitting usage in protein interior in addition to surface. We demonstrated its incorporation at the dimer interface of glutathione transferase for in vivo crosslinking via thiol-yne click chemistry, and at the active site of human rhinovirus 3C protease for masking and then turning on enzyme activity via Pd-cleavage of SprC into Cys. In addition, we installed biotin onto EGFP via Sonogashira coupling of SprC and then tracelessly removed it via Pd cleavage. SprC is small in size, commercially available, nontoxic, and allows for bond building and breaking on a single residue. Genetically encoded SprC will be valuable for chemically controlling proteins with an essential Cys and for reversible protein modifications.

A highly efficient streamlined chemoenzymatic strategy for total synthesis of four prioritized ganglioside cancer antigens GD2, GD3, fucosyl GM1, and GM3 from commercially available lactose and phytosphingosine is demonstrated. Lactosyl sphingosine (LacβSph) was chemically synthesized (on a 13 g scale), subjected to sequential one-pot multienzyme (OPME) glycosylation reactions with facile C18-cartridge purification, followed by improved acylation conditions to form target gangliosides, including fucosyl GM1 which has never been synthesized before.

Introducing new chemical reactivity into proteins in living cells would endow innovative covalent bonding ability to proteins for research and engineering in vivo. Latent bioreactive unnatural amino acids (Uaas) can be incorporated into proteins to react with target natural amino acid residues via proximity-enabled reactivity. To expand the diversity of proteins amenable to such reactivity in vivo, a chemical functionality that is biocompatible and able to react with multiple natural residues under physiological conditions is highly desirable. Here we report the genetic encoding of fluorosulfate-l-tyrosine (FSY), the first latent bioreactive Uaa that undergoes sulfur-fluoride exchange (SuFEx) on proteins in vivo. FSY was found nontoxic to Escherichia coli and mammalian cells; after being incorporated into proteins, it selectively reacted with proximal lysine, histidine, and tyrosine via SuFEx, generating covalent intraprotein bridge and interprotein cross-link of interacting proteins directly in living cells. The proximity-activatable reactivity, multitargeting ability, and excellent biocompatibility of FSY will be invaluable for covalent manipulation of proteins in vivo. Moreover, genetically encoded FSY hereby empowers general proteins with the next generation of click chemistry, SuFEx, which will afford broad utilities in chemical biology, drug discovery, and biotherapeutics.

Yalan Li,1,&ast; Na Li,1,&ast; Jiajing Liu,1 Tieshan Wang,2 Ruijuan Dong,3 Dongyu Ge,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiying Peng, Email penggy@bucm.edu.cnObjective: Ulcerative colitis (UC) as one of the intractable diseases in gastroenterology seriously threatens human health. Respiratory pathology is a representative extraintestinal manifestation of UC affecting the quality of life of patients. Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine prescription for UC or acute lung injury. This study was aimed to reveal the therapeutic effect of GQD on UC and its pulmonary complications and uncover its molecular mechanism mediated by myeloid cells and microbiota.Methods: Mice with DSS-induced colitis were orally administrated with GQD. Overall vital signs were assessed by body weight loss and disease activity index (DAI). Pulmonary general signs were evaluated by pulmonary pathology and lung function. The mechanism of GQD relieving UC was characterized by detecting myeloid cells (neutrophils, macrophages, inflammatory monocytes, and resident monocytes) in colonic and lung tissues, related inflammatory cytokines, as well as the microbiota in bronchoalveolar lavage fluid (BALF) and feces.Results: GQD significantly reduced weight loss, DAI scores, and lung injury but improved the lung function of colitis mice. The DSS-induced colonic and concurrent pulmonary inflammation were also alleviated by GQD, as indicated by the down-regulated expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6, CCR2, and CCL2) and the suppressed recruitment of neutrophils and inflammatory monocytes. Meanwhile, GQD greatly improved intestinal microbiota imbalance by enriching Ruminococcaceae UCG-013 while decreasing Parabacteroides, [Eubacterium]_fissicatena_group, and Akkermansia in the feces of colitis mice. Expectantly, GQD also restored lung microbiota imbalance by clearing excessive Coprococcus 2 and Ochrobactrum in the BALF of colitis mice. Finally, significant correlations appeared between GQD-mediated specific bacteria and inflammatory cytokines or immune cells.Conclusion: GQD could alleviate UC by decreasing excessive inflammatory myeloid cells and cytokines, and reshaping the microbiota between the colon and lung, which contributes to clarifying the mechanism by which GQD ameliorates colitis-associated pulmonary inflammation.Keywords: Gegen Qinlian Decoction, ulcerative colitis, lung and intestinal microbiota, pulmonary inflammation, myeloid cells

Shijie Tang,1– 4,&ast; Penghong Chen,1– 4,&ast; Haoruo Zhang,1– 4 Haiyan Weng,1– 4 Zhuoqun Fang,1– 4 Caixiang Chen,1– 4 Guohao Peng,1– 4 Hangqi Gao,1– 4 Kailun Hu,1– 4 Jinghua Chen,5 Liangwan Chen,3,6 Xiaosong Chen1– 3 1Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China; 2Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou, 350001, People’s Republic of China; 3Engineering Research Center of Tissue and Organ Regeneration, Fujian Province University, Fuzhou, 350001, People’s Republic of China; 4Oncology Institution, Fujian Medical University, Fuzhou, 350004, People’s Republic of China; 5Department of Pharmaceutical Analysis, the School of Pharmacy, Fujian Medical University, Fuzhou, 350100, People’s Republic of China; 6Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaosong Chen; Liangwan Chen Email chenxiaosong74@163.com; chenliangwan@fjmu.edu.cnIntroduction: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and their small extracellular vesicles (hUC-MSC-sEVs) have shown attractive prospects applying in regenerative medicine. This study aimed to compare the therapeutic effects of two agents on osteoarthritis (OA) and investigate underlying mechanism using proteomics.Methods: In vitro, the proliferation and migration abilities of chondrocytes treated with hUC-MSCs or hUC-MSC-sEVs were detected by Cell Counting Kit-8 assay and scratch wound assay. In vivo, hUC-MSCs (a single dose of 5 × 105) or hUC-MSC-sEVs (30 μg/time) were injected into the knee joints of anterior cruciate ligament transection-induced OA model. Hematoxylin and eosin, Safranin O/Fast Green staining were used to observe cartilage degeneration. The levels of cartilage matrix metabolic molecules (Collagen II, MMP13 and ADAMTS5) and macrophage polarization markers (CD14, IL-1β, IL-10 and CD206) were assessed by immunohistochemistry. Finally, proteomics analysis was performed to characterize the proteinaceous contents of two agents.Results: In vitro data showed that hUC-MSC-sEVs were taken up by chondrocytes. A total of 15 μg/mL of sEVs show the greatest proliferative and migratory capacities among all groups. In the animal study, hUC-MSCs and hUC-MSC-sEVs alleviated cartilage damage. This effect was mediated via maintaining cartilage homeostasis, as was confirmed by upregulation of the COL II and downregulation of the MMP13 and ADAMTS5. Moreover, the M1 macrophage markers (CD14) were significantly reduced, while the M2 macrophage markers (CD206 and IL-10) were increased in the hUC-MSCs and hUC-MSC-sEVs relative to the untreated group. Mechanistically, we found that many proteins connected to cartilage repair were more abundant in sEVs. Notably, compared to hUC-MSCs, the upregulated proteins in sEVs were mostly involved in the regulation of immune effector process, extracellular matrix organization, PI3K-AKT signaling pathways, and Rap1 signaling pathway.Conclusion: Our study indicated that hUC-MSC-sEVs protect cartilage from damage and many cartilage repair-related proteins are probably involved in the restoration process. These data suggest the promising potential of hUC-MSC-sEVs as a therapeutic agent for OA.Keywords: human umbilical cord-derived mesenchymal stem cells, small extracellular vesicles, osteoarthritis, proteomics, cell-free therapy

Yongan Wang,1,&ast; Na Li,1,&ast; Qiuyi Li,1 Zirui Liu,1 Yalan Li,1 Jingwei Kong,1 Ruijuan Dong,2 Dongyu Ge,2 Jie Li,3 Guiying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiying Peng; Jie Li Email penggy@bucm.edu.cn; lijie2007@126.comPurpose: Chronic obstructive pulmonary disease (COPD), a prevalent obstructive airway disease, has become the third most common cause of death globally. Xuanbai Chengqi decoction (XBCQ) is a traditional Chinese medicine prescription for the acute exacerbation of COPD. Here, we aimed to reveal the therapeutic effects of XBCQ administration and its molecular mechanisms mediated by Th17/Treg balance and gut microbiota.Methods: We determined the counts of Th17 and Treg cells in the serum of 15 COPD and 10 healthy subjects. Then, cigarette smoke extract-induced COPD mice were gavaged with low, middle, and high doses of XBCQ, respectively. Weight loss, pulmonary function and inflammation, Th17/Treg ratio, and gut microbiota were measured to evaluate the efficacy of XBCQ on COPD.Results: COPD patients had a higher Th17/Treg ratio in the serum than healthy controls, which was consistent with the results in the lung and colon of COPD mice. The middle dose of XBCQ (M-XBCQ) significantly decreased the weight loss and improved the pulmonary function (FEV0.2/FVC) in COPD mice. Moreover, M-XBCQ alleviated lung inflammation by rectifying the Th17/Treg imbalance, reducing the expressions of TNF-α, IL-1β, and MMP-9, and suppressing inflammatory cells infiltration. Meanwhile, M-XBCQ greatly improved the microbial homeostasis in COPD mice by accumulating probiotic Gordonibacter and Akkermansia but inhibiting the growth of pathogenic Streptococcus, which showed significant correlations with pulmonary injury.Conclusion: Oral M-XBCQ could alleviate COPD exacerbations by reshaping the gut microbiota and improving the Th17/Treg balance, which aids in elucidating the mechanism through which XBCQ as a therapy for COPD.Keywords: XBCQ, COPD, intestinal microbiota, Th17/Treg, pulmonary inflammation

Panghua Ding,1,&ast; Jiajing Liu,2,&ast; Qiuyi Li,2 Qiongqiong Lu,3 Junxiang Li,3 Rui Shi,3 Lei Shi,2 Tangyou Mao,3 Dongyu Ge,4 HaiJun Niu,5 Guiying Peng,2 Zhibin Wang3 1Department of Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Gastroenterology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Anhui Joyfar Pharmaceutical Research Institute Co. Ltd, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiying Peng; Zhibin Wang Email penggy@bucm.edu.cn; wangsanger@126.comBackground: Hudi enteric-coated capsule (HDC) is a Chinese medicine prescribed to treat ulcerative colitis (UC). However, its anti-inflammatory active ingredients and mechanisms remain unknown. This study aimed to investigate the active components of HDC and explore its potential mechanisms against UC by integrating network pharmacology and experimental verification.Methods: A DSS-induced colitis murine model was established to validate the efficacy of HDC by detecting disease activity index (DAI) and histopathological changes. Network pharmacological analysis was performed to identify the active compounds and core targets of HDC for the treatment of UC. The main compounds in HDC were identified by high-performance liquid chromatography. The relative expressions of HDC’s core targets were also determined in vivo. Finally, molecular docking was applied to model the interaction between HDC and target proteins.Results: In an in vivo experiment, HDC, especially the middle-dose HDC, effectively reduced clinical symptoms of UC, including weight loss, bloody stool, and colon shortening. Besides, the severity of colitis was considerably suppressed by HDC as evidenced by reduced DAI scores. A total of 118 active compounds and 69 candidate targets from HDC closely related to UC progression were identified via network pharmacology. Enrichment analysis revealed that the key targets of HDC correlated with the expressions of PTGS2, TNF-α, IL-6, and IL-1β. Meanwhile, these cytokines were enriched in various biological processes through the IL-17/JAK2/STAT3 signaling pathway. The middle-dose HDC contributed more to ameliorating DSS-induced colitis through this signaling pathway than other dosages. Nine components binding to JAK2, STAT3, IL-17 and IL-6 were identified by molecular docking, confirming again the inhibition effects of HDC on the IL-17/JAK2/STAT3 signaling pathway.Conclusion: The HDC treatment, particularly the middle-dose, exerted an anti-UC effect in a multi-component, multi-target, and multi-mechanism manner, especially inhibiting the IL-17/JAK2/STAT3 signaling pathway to downregulate the secretion of proinflammatory cytokines.Keywords: Hudi enteric-coated capsule, ulcerative colitis, network pharmacology, IL-17/JAK2/STAT3 pathway

Helicobacter pylori α1-3/4-fucosyltransferase (Hp3/4FT) was expressed in Escherichia coli at a level of 30 mg L-1 culture and used as a diverse catalyst in a one-pot multienzyme (OPME) system for high-yield production of l-fucose-containing carbohydrates including Lewis antigens such as Lewis a, b, and x, O-sulfated Lewis x, and sialyl Lewis x and human milk fucosides such as 3-fucosyllactose (3-FL), lacto-N-fucopentaose (LNFP) III, and lacto-N-difuco-hexaose (LNDFH) II and III. Noticeably, while difucosylation of tetrasaccharides was readily achieved using an excess amount of donor, the synthesis of LNFP III was achieved by Hp3/4FT-catalyzed selective fucosylation of the N-acetyllactosamine (LacNAc) component in lacto-N-neotetraose (LNnT).

Jinglong Chen,1,2,&ast; Changbin Jiang,1,&ast; Youlan Zheng,1,&ast; Dongxing Zhao,1,&ast; Fan Wu,1 Zhuxiang Zhao,3 Jun Zhao,2 Qing Li,2 Bing Li,4 Gongyong Peng,1 Yumin Zhou,1 Pixin Ran1 1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Geriatrics, National Clinical Key Specialty, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3The Pulmonary Medicine, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 4GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin RanNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of ChinaEmail pxran@gzhmu.edu.cnBackground and Objective: To determine the effects of BSE (biomass smoke exposure) on pulmonary and non-pulmonary changes in patients with COPD compared with normal individuals.Methods: Using a cohort, we recruited 16 healthy individuals with BSE (BSE normal), 19 patients with BSE+COPD, 13 healthy individuals with cigarette smoke exposure (CSE normal), 25 patients with CSE+COPD, and 25 healthy controls. Patients with GOLD stage I and II COPD were included. Baseline data (demographic data, BSE or CSE, lung function, and CT findings) and follow-up lung function data were collected. CT parameters of emphysema, pulmonary small vessels, airway remodeling, pectoralis muscles, and erector spinae muscle were measured.Results: Individuals with BSE were mainly women (32/35, 91.43%). Compared with the CSE+COPD group, the BSE+COPD group demonstrated slower lung function decline, increased lower lung emphysema, narrower airway lumen dimensions and increased airway wall thickening in the moderate and small airways (all P< 0.05). Compared with healthy controls, the CSE normal and BSE normal groups exhibited significant reductions in pulmonary small vessel area and obvious airway remodeling in small airways (P< 0.05). Compared with the BSE normal group, the BSE+COPD group showed significantly more severe emphysema and airway remodeling, as well as reduced left pectoralis major muscle area (all P< 0.05).Conclusion: Healthy individuals with BSE had reduced pulmonary small vessel area and evidence of airway remodeling; patients with BSE and COPD showed more severe emphysema, airway remodeling, and reductions in pectoralis major muscle area.Clinical Trial Registration: ChiCTR-OO-14004264.Keywords: biomass smoke, chronic obstructive pulmonary disease, computed tomography, pulmonary function

Substrate specificity studies of human FUT8 using 77 structurally-defined N-glycans as acceptors showed a strict requirement towards the α1,3-mannose branch, but a great promiscuity towards the α1,6-mannose branch. Accordingly, a chemoenzymatic strategy was developed for the efficient synthesis of core-fucosylated asymmetric N-glycans.

β1-3-N-Acetylglucosaminyltransferases (β3GlcNAcTs) and β1-4-galactosyltransferases (β4GalTs) have been broadly used in enzymatic synthesis of N-acetyllactosamine (LacNAc)-containing oligosaccharides and glycoconjugates including poly-LacNAc, and lacto-N-neotetraose (LNnT) found in the milk of human and other mammals. In order to explore oligosaccharides and derivatives that can be synthesized by the combination of β3GlcNAcTs and β4GalTs, donor substrate specificity studies of two bacterial β3GlcNAcTs from Helicobacter pylori (Hpβ3GlcNAcT) and Neisseria meningitidis (NmLgtA), respectively, using a library of 39 sugar nucleotides were carried out. The two β3GlcNAcTs have complementary donor substrate promiscuity and 13 different trisaccharides were produced. They were used to investigate the acceptor substrate specificities of three β4GalTs from Neisseria meningitidis (NmLgtB), Helicobacter pylori (Hpβ4GalT), and bovine (Bβ4GalT), respectively. Ten of the 13 trisaccharides were shown to be tolerable acceptors for at least one of these β4GalTs. The application of NmLgtA in one-pot multienzyme (OPME) synthesis of two trisaccharides including GalNAcβ1-3Galβ1-4GlcβProN3 and Galβ1-3Galβ1-4Glc was demonstrated. The study provides important information for using these glycosyltransferases as powerful catalysts in enzymatic and chemoenzymatic syntheses of oligosaccharides and derivatives which can be useful probes and reagents.

Saijun Huang1,2 *,* Tao Sun1,2 *,* Yanna Zhu,3 Shanshan Song,1,2 Jie Zhang,4 Linjuan Huang,5 Qiang Chen,6 Guangyang Peng,7 Dongmei Zhao,8 Hong Yu,1,2 Jin Jing3 1Department of Child Healthcare, Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan, Guangdong, 528000, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China; 3Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, Guangdong, Guangzhou, 510080, People’s Republic of China; 4Department of Child Healthcare, Xi’an Children’s Hospital, Xi’an, Shaanxi, 710003, People’s Republic of China; 5Health Management Center, Fuzhou Children’s Hospital of Fujian Medical University, Fuzhou, Fujian, 350005, People’s Republic of China; 6Department of Child Psychological Health, Zhuhai Women and Children’s Hospital, Zhuhai, Guangdong, 519001, People’s Republic of China; 7 Department of Child Rehabilitation, Huanggang Ping’an Rehabilitation Hospital, Huanggang, Hubei, 438000, People’s Republic of China; 8Department of Child Healthcare, Jinan Children’s Hospital, Jinan, Shandong, 250022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Yu; Jin Jing Email yu376@163.com; jingjin@mail.sysu.edu.cnBackground: The COVID-19 pandemic and lockdown will have short-term and long-term psychosocial and mental health implications for children. Children with autism may have some specific needs for support because of their difficulties in social communication, stereotyped behavior patterns, and other specificities brought about by autism.Purpose: The purpose of this study was to investigate the impact of the COVID-19 pandemic on ASD children and their families.Patients and Methods: A total of 406 parents of ASD children completed an online survey investigating basic information; sleep, outdoor activities, and rehabilitation training; ASD children’s frequency of abnormal behaviors; and stress and emotional status of parents.Results: 50.3% of the parents thought their children had sleep problems, and 47.3% of the parents thought their children’s outdoor activity time was reduced. About 40% of parents think that their children have improved cognitive ability, language expression, and understanding. 36.2% of the families reported that their children’s emotional and social performance became worse. 60.8% of parents reported that their children’s training intensity decreased. The most common abnormal behaviors observed in children with ASD were being easily distracted, losing temper, and crying. 81.3% of parents did not have anxiety, but 98% of parents reported that family training was under pressure.Conclusion: The main impact of the COVID-19 pandemic on children with ASD is that they do not have access to professional rehabilitation training. These families need more medical support, especially in family training, to help parents improve the social and emotional control skills of ASD children.Keywords: COVID-19, ASD, child, behavior, rehabilitation training, China

Hao-cheng Zheng,1,* Yong-an Wang,1,* Zi-rui Liu,1 Ya-lan Li,1 Jing-wei Kong,1 Dong-yu Ge,2 Gui-ying Peng1 1Department of Immunology and Microbiology, School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Experimental Teaching Center, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gui-ying PengBeijing University of Chinese Medicine, No. 11, East Road North Ring 3rd, Chao-Yang District, Beijing 100029, People’s Republic of ChinaTel +86-010-53912169Email penggy@bucm.edu.cnObjective: In China, lamb and fish are well-known triggers for an asthma attack. Our investigation aims at assessing whether the long-term intake of lamb meat or Basa fish would aggravate pulmonary inflammation as well as exploring changes in the intestinal microbiota and immune cells in asthmatic mice.Materials and Methods: The murine asthmatic model was established by intraperitoneal injection of ovalbumin (OVA) plus aluminum on day 0 and 14 and nebulization of OVA from day 21 to 27. Lamb meat or fish was administered to asthmatic mice by oral gavage from day 0 to 27.Results: Our results showed that long-term consumption of lamb meat or Basa fish in asthmatic mice increased the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), enhanced levels of IL-5, IL-13 in BALF and total IgE in serum, aggravated pulmonary inflammatory cell infiltration and mucus secretion. Long-term oral lamb enhanced the proportion of type 2 innate lymphoid cells (ILC2) from small intestine while it inhibited that of Treg from lung in asthmatic mice. Oral fish showed no remarkable effect on that of ILC2 from lung and small intestine but inhibited that of intestinal Treg in asthmatic mice. What’s more, the chao-1 and observed species richness as well as PD whole tree diversity increased in asthmatic mice while these increments were inhibited after lamb treatment. PCA analysis indicated that there were significant differences in the bacterial community composition after lamb or fish treatment in asthmatic mice. Both lamb and fish treatment enhanced the abundance of colonic Alistipes in asthmatic mice.Conclusion: Collectively, long-term intake of lamb or fish shapes colonic bacterial communities and aggravates pulmonary inflammation in asthmatic mice, which provides reasonable food guidance for asthmatic patients.Keywords: asthma, intestinal microbiota, lamb, fish, ILC2, Treg

Galacto-N-biose (GNB) derivatives were efficiently synthesized from galactose derivatives via a one-pot two-enzyme system containing two promiscuous enzymes from Bifidobacterium infantis: a galactokinase (BiGalK) and a d-galactosyl-β1-3-N-acetyl-d-hexosamine phosphorylase (BiGalHexNAcP). Mono-sialyl and di-sialyl galacto-N-biose derivatives were then prepared using a one-pot two-enzyme system containing a CMP-sialic acid synthetase and an α2-3-sialyltransferase or an α2-6-sialyltransferase.

Arabidopsis thaliana glucuronokinase (AtGlcAK) was cloned and shown to be able to use various uronic acids as substrates to produce the corresponding uronic acid-1-phosphates. AtGlcAK or Bifidobacterium infantis galactokinase (BiGalK) was used with a UDP-sugar pyrophosphorylase, an inorganic pyrophosphatase, with or without a glycosyltransferase for highly efficient synthesis of UDP-uronic acids and glucuronides. These improved cost-effective one-pot multienzyme (OPME) systems avoid the use of nicotinamide adenine dinucleotide (NAD(+))-cofactor in dehydrogenase-dependent UDP-glucuronic acid production processes and can be broadly applied for synthesizing various glucuronic acid-containing molecules.

Lin-lin Pei,1,* Wen-zhu Yang,1,* Jing-yuan Fu,1,* Meng-xi Liu,1 Ting-ting Zhang,1 Dong-bo Li,1 Ruo-yue Huang,1 Li Zhang,1 Guang-neng Peng,1 Gang Shu,1 Zhi-xiang Yuan,2 Ju-chun Lin,1 Wei Zhang,1 Zhi-jun Zhong,1 Ling Zhao,1 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, People’s Republic of China; 2College of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua-lin FuDepartment of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, People’s Republic of ChinaTel +86 028-86291162Email fuhl2005@sohu.comIntroduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use.Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated.Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01± 4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride.Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.Keywords: enrofloxacin mesylate, characterization, antibacterial effect, acute toxicity, pharmacokinetics

Ye Tao,*,1,2 Miao He,*,3 Qinghua Yang,1 Zhao Ma,3 Yingxin Qu,1 Wen Chen,3 Guanghua Peng,1 Dengke Teng41Department of Physiology, Basic Medical College, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 2Lab of Visual Cell Differentiation, Basic Medical College, Zhengzhou University, Zhengzhou 450001, People’s Republic of China; 3Department of Neurosurgery, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, People’s Republic of China; 4Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China*These authors contributed equally to this workObjective: Retinitis pigmentosa causes progressive photoreceptor degeneration in the subjects while no clinical therapy exists. The present study sought to evaluate the potential protective effects of taurine on a pharmacologically induced RP animal model.Methods: Photoreceptor degeneration in mice was induced by an intraperitoneal injection of N-methyl-N-nitrosourea (MNU). The MNU-administrated mouse received taurine treatment and then they were examined by electroretinography, spectral-domain optical coherence tomography, optokinetic test, and histological and immunohistochemistry assay.Results: Prominent taurine deficiency was found in the retinas of MNU-administered mice. Intravenous taurine treatment increased significantly the retinal taurine level. Morphological studies showed that taurine could alleviate the retinal disorganizations in the MNU-induced mice. Taurine also ameliorated the visual impairments in the MNU-induced mice as evidenced by functional examinations. Immunostaining experiments demonstrated that both the M-cone and S-cone populations in the degenerative retinas are rescued by taurine. In particular, the M-cone photoreceptors in superior-temporal quadrant and the S-cone photoreceptors in inferior-nasal quadrant were preferentially rescued. Mechanism study showed that the photoreceptor apoptosis and oxidative stress in the degenerative retina were effectively alleviated by taurine treatment.Conclusion: Taurine is protective against the MNU-induced photoreceptor degeneration. Systemic taurine administration may act as a promising therapeutic potion for retinopathies with chronic cycle.Keywords: neural degeneration, retina, therapeutics

O-Linked β-N-acetylglucosaminyl transferase (OGT) plays an important role in the glycosylation of proteins, which is involved in various cellular events. In human, three isoforms of OGT (short OGT [sOGT]; mitochondrial OGT [mOGT]; and nucleocytoplasmic OGT [ncOGT]) share the same catalytic domain, implying that they might adopt a similar catalytic mechanism, including sugar donor recognition. In this work, the sugar-nucleotide tolerance of sOGT was investigated. Among a series of uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) analogs tested using the casein kinase II (CKII) peptide as the sugar acceptor, four compounds could be used by sOGT, including UDP-6-deoxy-GlcNAc, UDP-GlcNPr, UDP-6-deoxy-GalNAc and UDP-4-deoxy-GlcNAc. Determined values of Km showed that the substitution of the N-acyl group, deoxy modification of C6/C4-OH or epimerization of C4-OH of the GlcNAc in UDP-GlcNAc decreased its affinity to sOGT. A molecular docking study combined with site-directed mutagenesis indicated that the backbone carbonyl oxygen of Leu653 and the hydroxyl group of Thr560 in sOGT contributed to the recognition of the sugar moiety via hydrogen bonds. The close vicinity between Met501 and the N-acyl group of GlcNPr, as well as the hydrophobic environment near Met501, were responsible for the selective binding of UDP-GlcNPr. These findings illustrate the interaction of OGT and sugar nucleotide donor, providing insights into the OGT catalytic mechanism.

Qianling Lu,1,* Xinyu Dai,1,* Peng Zhang,1,* Xiao Tan,2 Yuejiao Zhong,3 Cheng Yao,4 Mei Song,4 Guili Song,4 Zhenghai Zhang,4 Gang Peng,5 Zhirui Guo,6 Yaoqi Ge,7 Kangzhen Zhang,7 Yuntao Li7 1Department of Neurology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 2Department of Emergency, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 3Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China; 4Office of Academic Research, Kizilsu Kirghiz Autonomous Prefecture People’s Hospital, Atush, China; 5Department of Neurosurgery, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 6Department of Geratology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China; 7Department of General Practice, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Background: Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe3O4@Au magnetic nanoparticles (Fe3O4@Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. Methods: The core-shell Fe3O4@Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe3O4@Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe3O4@Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. Results: The inhibitory and apoptotic rates of Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe3O4@Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. Conclusion: Our studies illustrated that Fe3O4@Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future. Keywords: Fe3O4@Au-C225 composite-targeted magnetic nanoparticles, U251 cells, human glioma therapy, magnetic fluid hyperthermia, near-infrared hyperthermia