An overview of current research on cancer stem cells: a bibliometric analysis.

BACKGROUND: Cancer stem cells (CSCs) represent a potential mechanism contributing to tumorigenesis, metastasis, recurrence, and drug resistance. The objective of this study is to investigate the status quo and advancements in CSC research utilizing bibliometric analysis. METHODS: Publications related to CSCs from 2010 to 2022 were collected from the Web of Science Core Collection database. Various analytical tools including CiteSpace, VOSviewer, Scimago Graphica, and GraphPad Prism were used to visualize aspects such as co-authorship, co-occurrence, and co-citation within CSC research to provide an objective depiction of the contemporary status and developmental trajectory of the CSC field. RESULTS: A total of 22,116 publications were included from 1942 journals written by 95,992 authors. Notably, China emerged as the country with the highest number of publications, whereas the United States exerted the most significant influence within the field. MD Anderson Cancer Center emerged as the institution making the most comprehensive contributions. Wicha M.S. emerged as the most prolific and influential researcher. Among journals, Cancers emerged as a focal point for CSC research, consistently publishing a wealth of high-quality papers. Furthermore, it was observed that most journals tended to approach CSC research from molecular, biological, and immunological perspectives. The research into CSCs encompassed a broad array of topics, including isolation and enrichment techniques, biomarkers, biological characteristics, cancer therapy strategies, and underlying biological regulatory mechanisms. Notably, exploration of the tumor microenvironment and extracellular vesicles emerged as burgeoning research frontiers for CSCs. CONCLUSION: The research on CSCs has garnered growing interest. A trend toward multidisciplinary homogeneity is emerging within the realm of CSCs. Further investigation could potentially center on the patients of extracellular vesicles and the tumor microenvironment in relation to CSCs.

Biochar supported nanoscale zerovalent iron-calcium alginate composite for simultaneous removal of Mn(II) and Cr(VI) from wastewater: Sorption performance and mechanisms.

Heavy metal pollution in water caused by industrial activities has become a global environmental issue. Among them, manganese mining and smelting activities have caused the combined pollution of Cr(VI) and Mn(II) in water, posing a serious ecotoxicological risk to ecological environments and human health. To efficiently remove Cr(VI) and Mn(II) from wastewater, a novel biochar supported nanoscale zerovalent iron-calcium alginate composite (CA/nZVI/RSBC) was synthesized by liquid-phase reduction and calcium alginate embedding methods. The adsorption performance and mechanisms of Cr(VI) and Mn(II) by CA/nZVI/RSBC were investigated. The maximum adsorption capacities of Cr(VI) and Mn(II) onto CA/nZVI/RSBC fitted by the Langmuir model were 5.38 and 39.78 mg/g, respectively, which were much higher than the pristine biochar. The iron release from CA/nZVI/RSBC was comparatively lower than that of nZVI/RSBC. Mn(II) presence enhanced the reduction of Cr(VI) by CA/nZVI/RSBC. The results of XRD, XPS, and site energy distribution analysis indicated that redox was the predominant mechanism of Cr(VI) adsorption, while electrostatic attraction dominated Mn(II) adsorption. This study provides a novel alternative way for the simultaneous removal of Cr(VI) and Mn(II) in wastewater.

Light-induced LLPS of the CRY2/SPA1/FIO1 complex regulating mRNA methylation and chlorophyll homeostasis in Arabidopsis.

Light regulates chlorophyll homeostasis and photosynthesis via various molecular mechanisms in plants. The light regulation of transcription and protein stability of nuclear-encoded chloroplast proteins have been extensively studied, but how light regulation of mRNA metabolism affects abundance of nuclear-encoded chloroplast proteins and chlorophyll homeostasis remains poorly understood. Here we show that the blue light receptor cryptochrome 2 (CRY2) and the METTL16-type m6A writer FIONA1 (FIO1) regulate chlorophyll homeostasis in response to blue light. In contrast to the CRY2-mediated photo-condensation of the mRNA adenosine methylase (MTA), photoexcited CRY2 co-condenses FIO1 only in the presence of the CRY2-signalling protein SUPPRESSOR of PHYTOCHROME A (SPA1). CRY2 and SPA1 synergistically or additively activate the RNA methyltransferase activity of FIO1 in vitro, whereas CRY2 and FIO1, but not MTA, are required for the light-induced methylation and translation of the mRNAs encoding multiple chlorophyll homeostasis regulators in vivo. Our study demonstrates that the light-induced liquid-liquid phase separation of the photoreceptor/writer complexes is commonly involved in the regulation of photoresponsive changes of mRNA methylation, whereas the different photo-condensation mechanisms of the CRY/FIO1 and CRY/MTA complexes explain, at least partially, the writer-specific functions in plant photomorphogenesis.

Enhanced removal of sulfonamide antibiotics from water by phosphogypsum modified biochar composite.

Antibiotic pollution has become a global eco-environmental issue. To reduce sulfonamide antibiotics in water and improve resource utilization of solid wastes, phosphogypsum modified biochar composite (PMBC) was prepared via facile one-step from distillers grains, wood chips, and phosphogypsum. The physicochemical properties of PMBC were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Zeta potential, X-ray diffraction (XRD), etc. The influencing factors, adsorption behaviors, and mechanisms of sulfadiazine (SD) and sulfamethazine (SMT) onto PMBC were studied by batch and fixed bed column adsorption experiments. The results showed that the removal rates of SD and SMT increased with the increase of phosphogypsum proportion, while decreased with the increase of solution pH. The maximum adsorption capacities of modified distillers grain and wood chips biochars for SD were 2.98 and 4.18 mg/g, and for SMT were 4.40 and 8.91 mg/g, respectively, which was 9.0-22.3 times that of pristine biochar. Fixed bed column results demonstrated that PMBC had good adsorption capacities for SD and SMT. When the solution flow rate was 2.0 mL/min and the dosage of PMBC was 5.0 g, the removal rates of SD and SMT by modified wood chips biochar were both higher than 50% in 4 hr. The main mechanisms of SD and SMT removal by PMBC are hydrogen bonding, π-π donor-acceptor, electrostatic interaction, and hydrophobic interaction. This study provides an effective method for the removal of antibiotics in water and the resource utilization of phosphogypsum.

More severe lung lesions in smoker patients with active pulmonary tuberculosis were associated with peripheral NK cell subsets.

BACKGROUND: Both pulmonary tuberculosis (PTB) and cigarette smoke (CS) exposure may lead to lung damage. The potential impact of CS exposure on tuberculosis-associated lung damage and the disturbance of immune cells and mediators involved, need to be further elucidated. METHODS: We firstly evaluated the chest X-ray (CXR) scores of a retrospective cohort of male patients with active PTB, followed for 6 months, and compared the scores between smoker (≥10 pack-years) and non-smoker patients. In a cross-sectional study, we measured the peripheral blood NK cell subsets and plasma inflammatory cytokines in male smoker and non-smoker patients with active PTB before anti-tuberculosis therapy, and the proportions of NK cell subsets and the levels of cytokines were analyzed for correlation with the CXR scores. RESULTS: In the retrospective cohort, male smoker patients with active PTB showed a higher CXR score, characterized by more cavitary lesions, enlarged lymph nodes and emphysema, as compared to non-smokers. The cross-sectional study revealed that the CXR score in smoker patients was correlated inversely with the percentages of blood CD107a+, NKP46+, and TIGIT+ NK cells. CONCLUSION: In patients with active PTB, CS exposure was associated with more severe lung lesions, which were correlated with peripheral NK cell subsets.

Combined Synthesis of Cerium Oxide Particles for Effective Anti-Bacterial and Anti-Cancer Nanotherapeutics.

Introduction: Kochiae Fructus has been widely used in Chinese Herbal medicine to treat various diseases. We report a rapid and eco-friendly approach for cerium oxide (CeO2) nanoparticles (NPs) synthesis using the extract of medicinally important plant "Kochiae Fructus", and the synthesized NPs were named KF-CeO2 NPs. Methods: Various spectroscopic approaches such as transmission electron microscope (TEM), powder X-ray diffraction (XRD), and energy-dispersive X-Ray (EDX) were used to characterize the KF-CeO2 NPs effectively. The antibacterial and biofilm inhibition activity of KF-CeO2 NPs against Gram-positive and Gram-negative multi-drug resistant (MDR) bacteria was determined using the serial dilution method and XTT assay. KF-CeO2 NPs were assessed for anticancer activity against HeLa cancer cells using an MTT assay. Cytobiocompatibility was determined in two normal cell lines (3T3 and hMSC). Results and Discussion: The average size of the KF-CeO2 NPs was 11.3 ± 3.9 nm with spherical morphology. KF-CeO2 NPs demonstrated a greater than 95% bactericidal efficacy against MDR microorganisms. In addition, KF-CeO2 NPs strongly suppressed (more than 79%) the biofilms of MDR bacteria, indicating their potential for addressing antibiotic resistance issues. Compared to Kochiae Fructus extract and CH-CeO2 NPs, they exhibited significant cytotoxic effects (35.60% cell viability) on HeLa cancer cells. In addition, the KF-CeO2 NPs were shown to be highly biocompatible with hMSC and 3T3 cell lines (85.13% and 81.17% cell viability, respectively), suggesting that they may be employed in biological systems. Conclusion: These data indicate that KF-CeO2 NPs synthesized using Kochiae Fructus extract are promising alternative treatments for MDR. In addition, this study will give the potential for the sustained development of biocompatible NPs with enhanced biological capabilities derived from vital pharmaceutical plants.

Subdiaphragmatic bronchogenic cysts: Case series and literature review.

Bronchogenic cysts are congenital malformations caused by aberrant foregut budding. They major occur in the thorax, with subdiaphragmatic cases being uncommon. Here, we present a series of 19 patients diagnosed with subdiaphragmatic bronchogenic cysts histopathologically at a single institution in China from 2012 to 2021. A literature review was also conducted by searching the PubMed database using keywords related to "bronchogenic cysts" and "subdiaphragmatic," yielding 107 cases. Taken together, the 126 cases had a median age of 41.0 years (interquartile range, 30.0-51.0 years) and 62 of them were male (49.2%). The cysts were most commonly detected in the left adrenal region (36.2%), followed by the pancreatic region (11.5%) and gastric cardia/lesser curvature of the stomach (9.2%). All patients except two underwent surgery for a definite diagnosis, symptom alleviation, and (or) malignancy prevention. Most patients recovered fast and were discharged from the hospital within 1 week after surgery, and the surgical complications were infrequent. The prognosis was generally favorable, as no recurrence was reported during the follow-up as long as 77 months.

Etiology of Emergency Visit and In-Hospital Outcomes of Patients with COPD.

Backgrounds: Patients with COPD often visit the emergency department (ED) due to exacerbation of respiratory symptoms (dyspnea, cough, and sputum production). Because manifestations of acute exacerbation of COPD (AECOPD) are nonspecific, differential diagnosis is critical in this acute setting. The causes for emergency visiting and the in-hospital outcomes are varied in patients with COPD. This study aimed to investigate the distributions of etiologies and the in-hospital outcomes of patients with COPD who presented to the ED because of exacerbation of respiratory symptoms. Methods: This was a retrospective study on COPD patients who had visited the ED and been hospitalized in a tertiary hospital because of worsening respiratory symptoms including cough, sputum production, and dyspnea from January 2017 to April 2020. Demographics, clinical manifestations, and laboratory studies in the ED were collected as the baseline data. The primary diagnosis at discharge or death was recorded. The hospitalization settings (general wards and ICU), the in-hospital outcomes, and associated factors were analyzed. Results: During the study period, 392 patients with COPD (male 302 (77.0%)), with a median age of 78 years, visited the ED and hospitalized in this hospital. The first 3 causes for emergency visit were AECOPD (n = 314, 80.1%), acute coronary artery syndrome with or without congestive heart failure (n = 24, 6.1%), and pulmonary embolism (n = 13, 3.3%). For patients with AECOPD (n = 314), 51.6% (n = 162) was admitted to ICU, and 6.4% (n = 20) died. Multivariate logistic analysis showed that age, atrial fibrillation, NT-pro BNP ≥300 pg/ml, and blood pH <7.3 were independent risk factors for ICU admission. Age, comorbid malignancy, NT-pro BNP ≥1800 pg/ml, and pneumonia on CT scan were independent risk factors for hospital mortality in patients with AECOPD. Conclusion: In COPD patients visiting the ED because of worsening respiratory symptoms, nearly 20% were due to non-AECOPD causes. For those with AECOPD, age, atrial fibrillation, NT-pro BNP ≥300 pg/ml, and blood pH <7.3 were independent risk factors for ICU admission, while advanced age, underlying malignancy, elevated NT-pro BNP, and pneumonia on CT scan were risk factors for hospital mortality.

Microwave-assisted pyrolysis derived biochar for volatile organic compounds treatment: Characteristics and adsorption performance.

Biochar derived from corn stalk doping with activated carbon was produced by microwave-assisted pyrolysis and applied to sorb volatile organic compounds (VOCs: benzene and o-xylene). Specific surface area (SSA), total pore volume (TPV) and micropore volume (MV) of microwave biochar increased with increasing microwave power with the maximum values 325.2 m2·g-1, 0.181 mL·g-1 and 0.1420 mL·g-1, respectively. Adsorption capacities of benzene and o-xylene on microwave biochar ranged 6.82-54.75 mg·g-1 and 7.43-48.73 mg·g-1, which were separate positively related with SSA, TPV, and MV. Benzene adsorption was mainly dominated by surface interaction and partition mechanisms, while o-xylene adsorption was governed by pore filling. The adsorption capacities of microwave biochar for benzene and o-xylene decreased by only 0.30% and 0.99% on the 5th cycle that illustrated the reasonably good reusability of microwave biochar. The results of this research demonstrate that microwave biochar is a promising adsorbent for VOCs removal.

Effect of a neodymium-doped yttrium aluminium garnet laser on the physicochemical properties of contaminated titanium surfaces and macrophage polarization.

AIM(S): The objective of this study was to evaluate the changes in the physical and chemical properties of titanium surfaces contaminated by a Nd:YAG laser with different levels of energy and the regulation of macrophage polarization. MATERIALS AND METHODS: The titanium specimens were divided into four groups. The blank control group consisted of the above-mentioned contaminated titanium specimens, and the conditioned control group consisted of sandblasted and acid-etched (SLA) titanium surfaces. The blank control and condition control groups were sealed and preserved in a sterile dark box. There were two experimental groups treated with the Nd:YAG laser-one with 0.5 W and the second with 1.0 W. Surface characteristics were evaluated using scanning electron microscopy, surface profilometry, and contact angle assays. The macrophage viability and proliferation of mouse RAW246.7 were analysed, and the macrophage surface markers, macrophage cytokines, and inflammatory and anti-inflammatory genes were expressed. RESULTS: The Nd:YAG laser increased the hydrophilicity and roughness of the titanium surface after decontamination. Fewer RAW264.7 cells were observed on the titanium surface after Nd:YAG decontamination than on the contaminated titanium surface expressing the M1-type macrophage marker CCR7, whereas more cells were observed after decontamination than on the contaminated titanium surface expressing the M2-type macrophage marker CD206. Following Nd:YAG laser treatment, the secretion of the inflammatory cytokines IL-1ß and TNF-α by RAW264.7 cells on the titanium surface was decreased, whereas the secretion of the anti-inflammatory cytokines IL-4 and IL-10 was increased. RAW264.7 cells cultured for 3 days on the titanium surface after Nd:YAG decontamination treatment expressed significantly reduced levels of the inflammation-related genes IL-1ß, TNF-α, IL-6 and iNOS. The expression of the anti-inflammatory genes Arg-1, IL-4, IL-10 and TGF-ß by RAW264.7 cells was significantly up-regulated after 3 days of incubation on the titanium surface after Nd:YAG decontamination treatment. CONCLUSION(S): The Nd:YAG laser increased the hydrophilicity and roughness of the titanium surface after decontamination, and this change inhibited M1-type macrophage polarization and promoted M2-type macrophage polarization.

Release characteristics of phosphate from ball-milled biochar and its potential effects on plant growth.

Ball-milled biochar could potentially supply phosphorus, an essential element for plant growth. To realize resource reuse and phosphorus recovery, three feedstocks (rice straw, distillers grains, and Eupatorium adenophorum) were used to prepare ball-milled biochar to evaluate its release characteristics of phosphorus and potential effects on germination and growth. The results showed that the phosphate release performance of ball-milled distillers grains biochar (DM) at 300 and 600 °C was better than that of other biochars ball-milled for 12 h. The DM prepared at 600 °C and incubated for 12 (DM-12) or 24 h (DM-24) had the best phosphate release capacity. The solution with pH 3.0 was beneficial to the release of phosphate from DM-12. The pseudo-second-order model could better fit the phosphate release of DM-12. A germination and seedling growth experiment suggested that adding 2.5 wt% DM-12 was beneficial to the height of mung beans. This study shows that DM-12 can be used as a slow-release fertilizer for the growth of mung beans, which provides a new way for resource utilization of distillers grains and phosphorus-rich biochar.

Biogenic Synthesis of MnO2 Nanoparticles With Leaf Extract of Viola betonicifolia for Enhanced Antioxidant, Antimicrobial, Cytotoxic, and Biocompatible Applications.

In this study, we propose to synthesize NPs using plant extract containing active biomedical components, with the goal of obtaining NPs that inherit the biomedical activities of the plant. Herein, we report the synthesis of manganese dioxide nanoparticles (VBLE-MnO2 NPs) using the leaves extract of Viola betonicifolia, in which the biological active plant's secondary metabolites function as both reducing and capping agents. The synthesized NPs were successfully characterized with different spectroscopic techniques. The antibacterial, antifungal, and biofilm inhibition properties of the synthesized VBLE-MnO2 NPs were further explored against a variety of bacteria (Gram-positive and Gram-negative) and mycological species. Additionally, their antioxidant ability against linoleic acid peroxidation inhibition, cytobiocompatibility with hMSC cells, and cytotoxicity against MCF-7 cells were investigated compared to leaves extract and chemically synthesized manganese dioxide NPs (CH-MnO2 NPs). The results were demonstrated that the synthesized VBLE-MnO2 NPs presented excellent antibacterial, antifungal, and biofilm inhibition performance against all the tested microbial species compared to plant leaves extract and CH-MnO2 NPs. Moreover, they also exhibited significant antioxidant potential, which was comparable to the external standard (ascorbic acid); however, it was higher than plant leaves extract and CH-MnO2 NPs. Furthermore, the synthesized CH-MnO2 NPs displayed good cytobiocompatibility with hMSC cells compared to CH-MnO2 NPs. The enhanced antioxidant, antibacterial, antifungal, and biofilm inhibition efficacy as compared to CH-MnO2 NPs might be attributed to the synergistic effect of the VBLE-MnO2 NPs' physical properties and the adsorbed biologically active phytomolecules from the leaves extract of V. betonicifolia on their surface. Thus, our study establishes a novel ecologically acceptable route for nanomaterials' fabrication with increased and/or extra medicinal functions derived from their herbal origins.

Co-adsorption performance and mechanism of nitrogen and phosphorus onto eupatorium adenophorum biochar in water.

To reduce the eutrophication caused by nitrogen and phosphorus in water, invasive plant Eupatorium adenophorum was used to prepare biochar under different pyrolysis temperatures for the co-adsorption of nitrogen and phosphorus. The influencing factors of the co-adsorption of ammonium and phosphate onto EBC and its adsorption mechanism were systematically studied. The results show that Eupatorium adenophorum biochar (EBC) has rich functional groups and high specific surface area. Low pyrolysis temperature (300 °C) and alkaline conditions are beneficial for the co-adsorption. The adsorption of ammonium and phosphate by EBC is more in line with the pseudo-second-order kinetics and Langmuir-Freundlich model (Qmax is 2.32 mg P/g and 1.909 mg N/g). Site energy analysis further confirms that electrostatic attraction is the main mechanism. This study shows that EBC could be used as a low-cost and effective adsorbent to simultaneously remove ammonium and phosphate from water, providing a method for resource utilization of invasive plants.

Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections.

Enterovirus D68 (EV-D68) is an emerging pathogen associated with respiratory diseases and/or acute flaccid myelitis. Here, two MAbs, 2H12 and 8F12, raised against EV-D68 virus-like particle (VLP), show distinct preference in binding VLP and virion and in neutralizing different EV-D68 strains. A combination of 2H12 and 8F12 exhibits balanced and potent neutralization effects and confers broader protection in mice than single MAbs when given at onset of symptoms. Cryo-EM structures of EV-D68 virion complexed with 2H12 or 8F12 show that both antibodies bind to the canyon region of the virion, creating steric hindrance for sialic acid receptor binding. Additionally, 2H12 binding can impair virion integrity and trigger premature viral uncoating. We also capture an uncoating intermediate induced by 2H12 binding, not previously described for picornaviruses. Our study elucidates the structural basis and neutralizing mechanisms of the 2H12 and 8F12 MAbs and supports further development of the 2H12/8F12 cocktail as a broad-spectrum therapeutic agent against EV-D68 infections in humans.

Enhanced Proinflammatory Cytokine Production and Immunometabolic Impairment of NK Cells Exposed to Mycobacterium tuberculosis and Cigarette Smoke.

Aim: Smoker COPD patients with chest radiological signs of prior tuberculosis (TB) showed more severe lung damage, but the mechanisms remain unclear. Emerging evidence has implicated NK cells in the pathogenesis of both COPD and TB. The purpose of this study was to delineate the profile and cytokine production of NK-cell subpopulations and their immunometabolic changes after exposure to both cigarette smoke (CS) and Mycobacterium tuberculosis(MTB). Methods: We profiled NK-cell subpopulations in terms of percentage and cytokine production by flow cytometry in smoker patients with pulmonary TB (PTB). In an in vitro coexposure model, we investigated proinflammatory cytokine production, glycolytic influx, and oxidative phosphorylation of NK cells under CS extract (CSE) and PPD costimulation. Results: Peripheral blood NK cells in smoker patients with active PTB (CS+PTB group) showed altered proportion of subpopulations and excessive proinflammatory cytokine expressions. In vitro, CSE- and PPD-coexposed NK-92 cells displayed enhanced proinflammatory cytokine production, concurrent with decreased glycolytic influx and oxidative phosphorylation. Conclusion: Smoker patients with active PTB showed enhanced proinflammatory cytokine expression within altered NK cell subpopulations. CSE and PPD coexposure induced heightened cytokine production concurrent with impaired cell metabolism in NK cells. These novel data suggest a potential role of NK cells in the pathogenesis of lung injury in subjects with coexposure to CS and TB.

[Analysis of clinical aesthetic effect of buccal alveolar ridge preservation and connective tissue transplantation with single implant].

PURPOSE: To evaluate the clinical aesthetic effect of buccal alveolar ridge preservation (ARP) and connective tissue transplantation (CTG) in patients who received a single implant. METHODS: Forty-three patients with tooth loss admitted to the Department of Stomatology of Shunde Hospital of Southern Medical University from May 2014 to May 2016 were included in the study. Tooth extraction, ARP, implant implantation, CTG and permanent repair were performed respectively. The incidence of bleeding, depth of probing, marginal bone resorption, and red-white aesthetic effect of implants were evaluated 1 year and 3 years after surgery. The buccal mucosa thickness of implants before, immediately after CTG, 1 year and 3 years after surgery were measured. The patient satisfaction was evaluated by visual analogue scale (VAS) from masticatory function, overall aesthetics, attachment height, and color, respectively. The implant conditions at the third year after surgery were observed, and complications during follow-up were recorded. SPSS 20.0 software package was used for statistical analysis of the data. RESULTS: The follow-up rate in the first year after surgery was 100%, and that in the third year after surgery was 90.70%. One year and 3 years after operation, the aesthetic effect of the implant was satisfactory. At the 3rd year after operation, the scores of the near middle gingival papillary were significantly higher than that at the 1st year after operation (P<0.05). The buccal mucosal thickness of the implant immediately after CTG and 1 year and 3 years after surgery increased significantly compared with that before CTG (P<0.05). The buccal mucosal thickness of the implant increased 1.02 mm (relative stability: 90.12%) 1 year after operation and 1.01 mm (relative stability: 84.31%) 3 years after operation, respectively. The satisfaction scores of the patients on chewing function, overall aesthetics, attachment height and color of the implant immediately after CTG, one year after surgery and 3 years after surgery were all > 8. The 3-year survival rate of the implants was 100%, and the 3-year success rate of the implants was 97.44%. During the follow-up, two patients developed peri-implant mucositis, which was relieved after tooth cleaning, but no complications such as tissue flap necrosis, limited opening and tongue movement disorder occurred. CONCLUSIONS: ARP and CTG have good clinical and aesthetic effects on patients with tooth loss. In three years, the buccal mucosal thickness of the implant can be increased and relatively stable, which is worthy of clinical promotion and application.

Zebrafish fatty acids receptor Gpr84 enhances macrophage phagocytosis.

GPR84 was identified as a receptor for medium-chain fatty acids with carbon chain lengths of 9-14. It has previously been reported that lipopolysaccharide (LPS) induces significantly up-regulation of zebrafish gpr84, and zebrafish gpr84 overexpression markedly increased the LPS-stimulated production of the cytokine IL-12. Here we expanded on these studies to further investigate the roles of zebrafish Gpr84 in immune reaction. Flow cytometric assay was used to assess the effects of zebrafish Gpr84 on the phagocytosis of bacteria by macrophages. It was found that overexpression of zebrafish gpr84 significantly increased both the phagocytic ability (PA) and phagocytic index (PI) values of the macrophages engulfing the bacteria, suggesting that zebrafish Gpr84 was able to promote the phagocytosis of bacteria by the macrophages. The data proves the direct effect of Gpr84 in immune reaction.

Efficacy and safety of sitagliptin added to metformin and insulin compared with voglibose in patients with newly diagnosed type 2 diabetes

OBJECTIVE: To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM). METHODS: In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint. RESULTS: The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia. CONCLUSIONS: Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.

Cellulose Synthase Stoichiometry in Aspen Differs from Arabidopsis and Norway Spruce.

Cellulose is synthesized at the plasma membrane by cellulose synthase complexes (CSCs) containing cellulose synthases (CESAs). Genetic analysis and CESA isoform quantification indicate that cellulose in the secondary cell walls of Arabidopsis (Arabidopsis thaliana) is synthesized by isoforms CESA4, CESA7, and CESA8 in equimolar amounts. Here, we used quantitative proteomics to investigate whether the CSC model based on Arabidopsis secondary cell wall CESA stoichiometry can be applied to the angiosperm tree aspen (Populus tremula) and the gymnosperm tree Norway spruce (Picea abies). In the developing xylem of aspen, the secondary cell wall CESA stoichiometry was 3:2:1 for PtCESA8a/b:PtCESA4:PtCESA7a/b, while in Norway spruce, the stoichiometry was 1:1:1, as observed previously in Arabidopsis. Furthermore, in aspen tension wood, the secondary cell wall CESA stoichiometry changed to 8:3:1 for PtCESA8a/b:PtCESA4:PtCESA7a/b. PtCESA8b represented 73% of the total secondary cell wall CESA pool, and quantitative polymerase chain reaction analysis of CESA transcripts in cryosectioned tension wood revealed increased PtCESA8b expression during the formation of the cellulose-enriched gelatinous layer, while the transcripts of PtCESA4, PtCESA7a/b, and PtCESA8a decreased. A wide-angle x-ray scattering analysis showed that the shift in CESA stoichiometry in tension wood coincided with an increase in crystalline cellulose microfibril diameter, suggesting that the CSC CESA composition influences microfibril properties. The aspen CESA stoichiometry results raise the possibility of alternative CSC models and suggest that homomeric PtCESA8b complexes are responsible for cellulose biosynthesis in the gelatinous layer in tension wood.

Insect cell-produced recombinant protein subunit vaccines protect against Zika virus infection.

Infection with Zika virus (ZIKV) may lead to severe neurologic disorders. It is of significant importance and urgency to develop safe and effective vaccines to prevent ZIKV infection. Here we report the development of ZIKV subunit vaccines based on insect cell-produced recombinant proteins. The N-terminal approximately 80% region (designated as E80) and the domain III (designated as EDIII) of ZIKV envelope (E) protein were efficiently produced as secreted proteins in a Drosophila S2 cell expression system. Both E80 and EDIII could inhibit ZIKV infection in vitro, suggesting that they may have folded properly to display native conformations. Immunization studies demonstrated that both E80 and EDIII vaccines were able to trigger antigen-specific antibody and T-cell responses in mice. The resulting anti-E80 and anti-EDIII sera could potently neutralize ZIKV infection in vitro. More importantly, passive transfer of either anti-E80 or anti-EDIII sera protected recipient mice against lethal ZIKV challenge. It is worth noting that the anti-EDIII sera possessed higher neutralizing titers and conferred more complete protection than the anti-E80 sera, indicating that the S2 cell-produced EDIII is a superior ZIKV vaccine candidate compared with the E80. These data support further preclinical and clinical development of a ZIKV subunit vaccine based on S2 cell-produced EDIII.