A novel aptamer beacon for rapid screening of recombinant cells and in vivo monitoring of recombinant proteins.

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels.

A scoping review of intervention components of school-based oral health-related behavioural interventions using the Theoretical Domains Framework.

The aim of this study was to review the intervention components of school-based oral health-related behavioural interventions using the Theoretical Domains Framework (TDF). We identified relevant papers from the review of Cooper et al., and these papers came from both the original inclusion and exclusion article lists. We also modified and updated their search strategies (2013 - April 2019). The 53 included papers reported on 79 interventions (experimental groups = 57 interventions, control groups = 22 interventions). Most of the papers used three to nine domains (average = 5.6) in their experimental interventions, and the most commonly used domains were 'knowledge,' 'skills,' 'social influences,' and 'environmental context and resources.' Considering the complexity of intervention components in one programme, there is no one specific domain or domain set that can determine the success of behavioural interventions. The design of future programmes should be guided by a complex intervention methodology. However, the best combination set might not exist, and the choice of domains should depend on local context or resources. This study can be used as a resource for identifying previous papers, which have used the same domains.

Irisin, an exercise myokine, potently suppresses tumor proliferation, invasion, and growth in glioma.

Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G2 /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.

[Current situation and problems of national standards for Chinese medicinal materials].

To learn the current situation and strengthen the management of national standards for Chinese medicinal materials, we sorted out the relevant national standards. According to incomplete statistics, there are 1 185 kinds of Chinese medicinal materials, including 1 024 kinds of plant medicines, 106 kinds of animal medicines, and 54 kinds of mineral medicines, in addition to ethnic medicinal materials with different functions. The relevant standards include 819 Pharmacopoeia standards, 342 standards issued by the Ministry of Health or National Medicinal Products Administration, 7 standards for new medicinal materials, and 17 standards for imported medicinal materials. In this paper, the sources of standards as well as the distribution of families and genera and the distribution of medicinal parts of medicinal materials are analyzed. The suggestions are as follows:(1)to improve the coordination among different national standards of Chinese medicinal materials;(2)to improve the standardization and controllability of relevant standards;(3)to revise the issued standards for Chinese medicinal materials(including Tibetan, Uygur, and Mongolian medicinal materials).

Comparisons of tissue distributions and health risks of perfluoroalkyl acids (PFAAs) in two fish species with different trophic levels from Lake Chaohu, China.

Perfluoroalkyl acids (PFAAs) are a type of persistent organic pollutants that are widely distributed in multiple environmental media and organisms and have a teratogenic effect on and toxicity to animals and humans. The residual levels of seventeen PFAAs in the tissues of two regular consumption fish species, Culter erythropterus and Aristichthys nobilis in Lake Chaohu were measured by a high-performance liquid chromatograph - mass spectrometer (HPLC-MS). The distributions of PFAAs and the effect of the lipid contents were analyzed, and the health risks of typical PFAAs were evaluated. The results showed that perfluorohexanoic acid (PFHxA) was the predominant contaminant (80.50 ±â€¯58.31 ng/g and 19.17 ±â€¯12.57 ng/g wet weight, ww), followed by perfluorooctanesulfonic acid (PFOS) (55.02 ±â€¯34.82 and 14.79 ±â€¯6.24 ng/g, ww) in both fish. The level of total PFAAs was the highest in the liver tissues of Culter erythropterus (359.87 ng/g, ww) and the lowest in the kidney tissues in A. nobilis (10.06 ng/g, ww). Due to the higher trophic level of C. erythropteru, the total PFAA concentrations were significantly higher in all tissues than those in A. nobilis. Liver muscle ratio of C. erythropteru was the highest, indicating the most accumulation in the liver. The concentrations of PFAAs in fish tissues were influenced by the lipid content, resulting in a difference between the lipid-normalized concentrations and the wet weight concentrations of the PFAAs. The non-carcinogenic risks of PFOS were higher than those of PFOA through the ingestion of C. erythropterus and A. nobilis. Both the carcinogenic and non-carcinogenic risks of C. erythropterus were greater than those of A. nobilis, and fish tissue intake could cause an increasing of risks up to 60%, indicating that long-term and large amount ingestion of carnivorous fish and related tissues with higher trophic level, such as C. erythropterus should be avoided.

[Nursing Care Experiences of Periwound Moisture-Associated Dermatitis After Simultaneous Pancreas-Kidney Transplantation].

Simultaneous pancreas-kidney (SPK) transplantation is the primary surgical treatment for type I diabetes mellitus with end-stage renal disease. However, this transplant surgery has a high-risk of surgical complications, including duodenal anastomotic leakage, which may lead to pancreas transplantation failure if the leakage worsens. This case report describes a patient who suffered from duodenal anastomotic leakage after SPK transplantation. The digestive enzymes eroded the wound and skin around the wound, resulting in periwound moisture-associated dermatitis. During the period of nursing care, the wound-care intervention was determined by interdisciplinary cooperation. In our case report, the periwound moisture-associated dermatitis healed completely under inter-hospital care. In clinical nursing practice, periwound moisture-associated dermatitis should be cared in combination with macerated wounds. We suggest the following: (1) control the moisture source; (2) use advanced dressings as the primary dressing with sterile gauze as a secondary dressing and silver antimicrobial dressings for infected wounds; (3) consider using negative pressure wound therapy for complicated chronic wounds; and (4) use a pH-neutral skin cleanser with non-woven gauze to clean the periwound skin and keep the skin clean and dry. Finally, we suggest isolating and protecting the skin with No Sting Barrier Film and a hydrocolloid dressing. We hope this nursing care experiences serves as a reference for the nursing care of periwound moisture-associated dermatitis resulting from duodenal anastomotic leakage during / after SPK transplantation.

Polyacetylated labdane-type diterpenoids, ptychantins P-R from Chinese liverwort Ptychanthus striatus.

Three new polyacetylated labdane diterpenoids ptychantins P-R (1-3) and four known compounds (4-7) were isolated from an EtOH extract of the Chinese liverwort Ptychanthus striatus (Lehm. & Lindenb.) Nees. Their structures were established by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR).

Notolutesins A-J, dolabrane-type diterpenoids from the Chinese liverwort Notoscyphus lutescens.

Ten new dolabrane-type diterpenoids, notolutesins A-J (1-10), were isolated from the Chinese liverwort Notoscyphus lutescens, along with four known compounds. The structures of the new compounds were established on the basis of extensive spectroscopic data, and that of 1 was confirmed by single-crystal X-ray crystallography. The absolute configuration of 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. All of the isolates were evaluated for their cytotoxicity against a small panel of human cancer cell lines, and compound 1 exhibited an IC50 value of 6.2 µM against the PC3 human prostate cancer cell line.

Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study.

BACKGROUND: The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM: To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS: The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION: Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.

Effect of probiotics on children with autism spectrum disorders: a meta-analysis.

BACKGROUND: Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children. METHODS: The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index). RESULTS: In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children. CONCLUSION: Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.

Clinical spectrum of neurosyphilis among HIV-negative patients in the modern era.

BACKGROUND: The clinical spectrum of neurosyphilis (NS) has changed over time. OBJECTIVE: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. METHODS: A retrospective chart review was performed for 149 in patients with NS. RESULT: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. CONCLUSIONS: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

Research status and hotspots of autoimmune gastritis: A bibliometric analysis.

BACKGROUND: As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers. AIM: To analyze the research overview and popular topics in the field of AIG using bibliometrics. METHODS: Relevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic. RESULTS: In total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, Helicobacter pylori, autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of Helicobacter pylori in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG. CONCLUSION: This bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.

A density functional theory investigation for the open-shell metal-carbide endofullerene Lu3C2@C88(D2:35) and closed-shell metal-nitride endofullerene Lu3N@C88(D2:35).

By means of the density functional theory calculations, two C88(D2:35)-based endohedral fullerenes, Lu3C2@C88(D2:35) and Lu3N@C88(D2:35) which encapsulate tri-lutetium carbide and tri-lutetium nitride cluster were investigated. For the cores in Lu3C2@C88 and Lu3N@C88, the trivalent C2 and N respectively template a butterfly-shaped endohedral moiety and a planar tri-lutetium cluster within the same D2-symmetric C88 cage. Moreover, Lu3N@C88 - D2 has a closed-shell electronic structure but for LuC3C2@C88 - D2, it owns an unpaired electron mainly localized on the internal Lu3C2 cluster. These results clearly showed that the core unit C2(3) as well as N3- play an important role in constructing molecular structures and electronic features of metallofullerenes. Furthermore, the electrochemical redox potentials, and vibrational frequencies of the two endofullerenes agree well with our experimental results. The electronic structures, ionization energies, electron affinities, inner clusters' dynamic motions of them have been predicted to further disclose the characters of these two metallofullerenes.

Pembrolizumab-induced Stevens-Johnson syndrome in advanced squamous cell carcinoma of the lung: A case report and review of literature.

BACKGROUND: For advanced lung squamous cell carcinoma, immune checkpoint inhibitors (ICIs) have been regarded as one of the optimal therapies. While immune-related adverse events (irAEs) are common in ICI treatment, cutaneous toxicities are among the most common irAEs. Most immune-related skin toxicity grades are low, and the prognosis is good. However, Stevens-Johnson syndrome (SJS) is a rare but extremely severe cutaneous adverse drug reaction with high mortality. CASE SUMMARY: We report a rare case of SJS induced by pembrolizumab. The case involved a 68-year-old female who was diagnosed with advanced squamous cell carcinoma of the lung. SJS appeared after one cycle of immunotherapy combined with chemotherapy. After treatment with prednisone hormone symptoms, anti-infection, gamma globulin, and antipruritic agents, the skin toxicity of the patients gradually decreased and eventually disappeared. Although the antitumor treatment was stopped due to serious adverse reactions, the tumor of the patient remained stable for nearly half a year after one cycle of immune therapy combined with chemotherapy, which also corroborates the delayed effect of immunotherapy. CONCLUSION: We believe our report can provide some references for the treatment of SJS and the treatment of immune-related adverse reactions.

Long-term fasting glucose variability and risk of cancer in patients with type 2 diabetes mellitus: A retrospective population-based cohort study in Shanghai.

BACKGROUNDS: Fasting blood glucose (FBG) variability may make an impact on adverse events in patients with diabetes mellitus. However, the association between long-term changes in FBG and cancer remains unclear. We aimed to investigate this association in a large-scale longitudinal study. METHODS: Data were collected from 46 761 patients with type 2 diabetes mellitus aged 20-80 years who participated in the Diabetes Standardized Management Program in Shanghai, China. We adopted four indicators, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average real variability (ARV) to describe FBG variability. Adjusted multivariable Cox regression analyses and restricted cubic splines were used to investigate the association between long-term FBG variability and cancer risk. We also determined the interactive effect of FBG variability with hypertension and FBG-mean with hypertension on cancer risk, respectively. RESULTS: In this study, we confirmed 2218 cancer cases (51.1% male) over a median follow-up of 2.86 years. In the multivariable-adjusted models, participants in the highest quartile of FBG variability had an increased risk of cancer compared with those in the lowest quartile. The nonlinear association was found when using FBG-VIM, FBG-ARV, and FBG-SD in restricted cubic spline plots. There was a significant interaction effect of FBG variability with hypertension on cancer, whereas the effect of FBG-mean with hypertension did not attain significance. CONCLUSIONS: Our retrospective cohort study demonstrated a positive association between the long-term changes in FBG and cancer risk in patients with type 2 diabetes mellitus. FBG variability may independently predict cancer incidence.

Surface-confined conformers and coassembly-induced conformer resolution.

Stereoisomerism is a fundamental chemistry issue and has been intensively investigated because of its importance in organic chemistry, biology, and pharmacology. Molecules with freely rotatable single bonds have many interconvertable conformers. Herein, we report the surface-adsorption-induced conformer resolution by employing azobenzene-3,3-dicarboxylic acid (ADA-33) as a model compound. Two linear assembly phases composed of trans conformers on a highly oriented pyrolytic graphite (HOPG) surface are observed by scanning tunneling microscopy. With the codeposition with 1-octanoic acid (OA), only one trans conformer of ADA-33 can be recognized by OA to form a two-component assembly with alternately arranged ADA-33 and OA stripes, which can be attributed to the epitaxial assembly of ADA-33 and OA on the HOPG surface, and weak hydrogen bonding exists between conformer I and OA molecules. The results are of significance with respect to the discrimination and resolution of conformers on a solid surface and provide molecular insights into the coadsorption assembly on the surface.

Up-regulation of BTLA expression in myeloid dendritic cells associated with the treatment outcome of neonatal sepsis.

Dentritic cells (DCs) dysfunction has been verified detrimental for sepsis and B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to be associated with DCs dysfunction. However, the role of BTLA expression in myeloid DCs (mDCs) in neonatal sepsis is unknown. In the current study, we found BTLA-expressing mDCs were elevated in neonates with sepsis and the BTLA expression level in mDCs was positively correlated to the severity of sepsis. The presence of BTLA negatively regulated the phagocytosis capacity and bactericidal ability of mDCs as well as the maturation markers expression of mDCs. Our data also showed BTLA+mDCs shifted into an anti-inflammatory phenotype with decreased expression of IL-6, TNF-α and IL-12, but increased IL-10. in addition, we found BTLA expression indeedly altered the mDCs allo-stimulatory capacity. Therefore, BTLA expression in mDCs could be a useful predictive marker for neonatal sepsis and targeting BTLA expression in mDCs may be a new therapeutic strategy.

Planar quinary cluster inside a fullerene cage: synthesis and structural characterizations of Sc(3)NC@C(80)-I(h).

The endohedral fullerene Sc(3)NC@C(80)-I(h) has been synthesized and characterized; it has an unprecedented planar quinary cluster in a fullerene cage. It is also the first chemical compound in which the presence of an unprecedented (NC)(3-) trianion has been disclosed. The fascinating intramolecular dynamics in Sc(3)NC@C(80)-I(h) enables the whole molecule to display high polarity and promising ferroelectricity. This finding inspires the possibility that such a planar quinary cluster may be useful in constructing many other endohedral fullerenes.

Russian-doll-type metal carbide endofullerene: synthesis, isolation, and characterization of Sc4C2@C80.

For the first time, we have produced the stable compound Sc(4)C(2)@C(80)-I(h) and characterized it as a metal carbide endofullerene by FTIR and Raman spectroscopies in combination with DFT calculations. Furthermore, DFT calculations have demonstrated that this molecule has a Russian-doll-type structure, C(2)@Sc(4)@C(80).

Effects of fluorescent dissolved organic matters (FDOMs) on perfluoroalkyl acids (PFAAs) in lake and river water.

This study presents the effects of fluorescent dissolved organic matters (FDOM) on perfluoroalkyl acids (PFAAs) in western Lake Chaohu and its inflow rivers. The surface water samples from the 27 sites in western Lake Chaohu and its inflow rivers were collected in March and September 2013. The contents of PFAAs and the FDOM in the water samples were measured by a high-performance liquid chromatograph - mass spectrometer (HPLC-MS) and by a fluorescence spectrophotometer, respectively. The temporal-spatial distributions of PFAAs and FDOM, as well as their interrelationships, were investigated. Eleven PFAA components were detected, and the mean concentration of total PFAAs (TPFAAs) in western Lake Chaohu and its inflow rivers were 12.93 ±â€¯5.19 ng/L and 11.84 ±â€¯9.50 ng/L, respectively. PFOA was the predominant contaminant in two regions (7.13 ±â€¯3.07 ng/L and 4.30 ±â€¯2.14 ng/L) followed by PFHxA (1.72 ±â€¯0.80 ng/L and 1.42 ±â€¯1.41 ng/L) and PFBA (1.44 ±â€¯0.78 ng/L and 1.37 ±â€¯0.78 ng/L). The mean concentration of total FDOM in western Lake Chaohu and its inflow rivers were 220.0 ±â€¯40.30 µg quinine sulfate units (Q.S.)/L and 406.3 ±â€¯213.1 µg Q.S./L, respectively. The significant, positive correlations were observed between the PFAAs and FDOMs in both the lake area and the inflow rivers. However, no significant correlation was observed between PFAAs and the dissolved organic carbon (DOC) in the lake area. This finding indicated that the residues and distributions of PFAAs were significantly dependent on the compositions of dissolved organic matters (DOM) and not on the total content of DOM.