Reg3A Overexpression Facilitates Hepatic Metastasis by Altering Cell Adhesion in LoVo Colon Cancer Cells.

Reg3A is upregulated in various cancers and considered a potential target for antitumor treatments. However, the effect of Reg3A in metastasis has been elusive. This study aims to disclose the role of Reg3A overexpression in hepatic metastasis of LoVo colon cancer cells. A stable cell line of LoVo cells overexpressing Reg3A (LoVo-luc-Reg3A), labeled with luc reporter gene, was constructed. Cell proliferation, apoptosis, migration, and invasion were determined using MTT, EdU, Hoechst's staining, flow cytometry, and transwell assays, respectively. Hepatic metastasis of LoVo-luc-Reg3A cells was investigated in BALB/c nude mice. Living bioluminescence imaging, histological examination, and mRNA sequencing (mRNA-seq) were performed to assess the metastatic efficiency and gene expression alteration. Reg3A content was determined by Western blotting and Enzyme-Linked Immunosorbent Assay. Cell attachment capacity was determined in the Matrigel culture. Reg3A overexpression did not promote LoVo cell proliferation or apoptosis, but facilitated cell migration and invasion. In the hepatic metastasis model, Reg3A overexpression increased the number of metastatic colonies. The result of mRNA-seq suggested 349 differentially expressed genes (DEGs) by Reg3A upregulation, many of which were related to colon adenocarcinoma tumorigenesis compared to normal colon tissue. Gene ontology enrichment assay indicated that the DEGs are mainly associated with cell adhesion, leukocyte regulation, extracellular matrix (ECM) remodeling, integrin binding, and STAT protein binding. Reg3A overexpression led to an enrichment of Reg3A protein in local tumor tissue of liver metastasis and ECM/intracellular space in ex vivo cultured cells. However, Reg3A concentration in serum and culture medium was relatively low. Reg3A overexpression also resulted in an increased number of cells that attach to Matrigel, which was attenuated by treatments of siRNA-Reg3A and single-chain variable fragment against Reg3A. Endogenous Reg3A overexpression facilitates hepatic metastasis of LoVo colon cancer cells. The prometastatic effect could be contributed by Reg3A enrichment in ECM, which alters the cell adhesion behavior.

Key points for protecting the external branch of the superior laryngeal nerve in open thyroidectomy: A possible exploration technique.

OBJECTIVE: Injury of the external branch of the superior laryngeal nerve (EBSLN) is easily overlooked in thyroidectomy, and voice changes caused by the injury have a negative effect on an increasing number of patients. This study aimed to reduce the injury rate of EBSLN by expanding the sternothyroid-laryngeal triangle and standardizing the exploration procedure. METHODS: A total of 520 patients who had undergone thyroidectomy at the First Affiliated Hospital of Nanchang University between September 2021 and April 2022 were analyzed. During the operation, the exposure rate of the EBSLN before and after sternothyroid-laryngeal triangle expansion was compared, and all EBSLNs were anatomically classified. RESULTS: The exposure rate of EBSLN after sternothyroid-laryngeal triangle expansion reached 82.7%, which is much higher than that before sternothyroid-laryngeal triangle expansion (33.7%), and voice change caused by injury of the EBSLN was reported in one case (the injury rate was 0.2%). The classification and proportion of the EBSLN were as follows: Type 1 (55.3%), the nerve ran within 1 cm above the STP, but no coincidence or crossover with blood vessels was observed in this region; Type 2 (14.7%), the nerve travelled within 1 cm above the STP and overlapped or intersected with blood vessels in this region; Type 3 (12.7%), the EBSLN ran below the level of the STP; and Type 4 (17.3%), no EBSLN was observed within 1 cm above the STP. CONCLUSION: In thyroidectomy, injury to the EBSLN can be effectively reduced by expanding the sternothyroid-laryngeal triangle and exploring the upper pole area of the thyroid as far as possible, which has great clinical significance in reducing postoperative voice box injury.

Exploring the pharmacological mechanisms of Biyan Qingdu Granula in the treatment after nasopharyngeal carcinoma radiotherapy based on UPLC/Q-TOF MS, network pharmacology and molecular docking.

BACKGROUND: Biyan Qingdu Granula (BYQD) is a traditional Chinese medicine (TCM) formula commonly used for post-radiotherapy treatment of nasopharyngeal carcinoma (NPC). Despite its extensive use, the underlying pharmacological mechanisms have yet to be fully elucidated. METHODS: UPLC/Q-TOF MS was used to comprehensively analyze the chemical composition of BYQD. Additionally, an everted gut sac model, coupled with UPLC/Q-TOF MS, was used to screen and identify the active ingredients. Subsequently, we conducted a network pharmacological analysis to delve into the potential mechanisms of these active ingredients. Molecular docking experiments were also performed to assess the interactions between active ingredients and potential core targets. RESULTS: The findings revealed the identification of 62 identical ingredients upon comparing the sample solution and intestinal absorbed solution of BYQD. We constructed a protein-protein interaction (PPI) network, which led to the identification of five core targets, namely, TP53, STAT3, MAPK1, SRC and AKT1. Through the construction of a drug-active ingredient-intersection target network, we identified Quercetin, Luteolin, Eupatilin, Magnoflorine, Acacetin and other compound as potential active ingredients. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that pathways in cancer, PI3K-Akt signaling pathway, lipid and atherosclerosis, proteoglycans in cancer, and the MAPK signaling pathway might play the key roles in the treatment of NPC after radiotherapy using BYQD. Molecular docking results corroborated strong binding activity between the putative core targets and the corresponding key active ingredients. CONCLUSION: This study provides a preliminary revelation of the active ingredients and potential pharmacological mechanisms of BYQD in the post-radiotherapy treatment of NPC. These findings establish a vital theoretical basis and serve as a scientific reference for the future investigating the pharmacological mechanisms and clinical application of BYQD.

Protective effect of Xinmai'an tablets via mediation of the AMPK/SIRT1/PGC-1α signaling pathway on myocardial ischemia-reperfusion injury in rats.

BACKGROUND: Xinmai'an tablets are a compound Chinese medicine comprising six traditional Chinese medicines that have been clinically applied to treat cardiovascular diseases such as premature ventricular contractions for many years. However, pharmacological effects and underlying mechanisms of Xinmai'an tablet in protecting against myocardial ischemia-reperfusion injury (MIRI) were barely ever studied. PURPOSE: To investigate the cardioprotective properties of Xinmai'an tablet against MIRI and the underlying molecular mechanism in rats. METHODS: We initially established the UHPLC-QTRAP-MS/MS analysis method to ensure the controllable quality of Xinmai'an tablet. We further identified the cardioprotective effects of Xinmai'an tablet against MIRI using TTC staining, hematoxylin and eosin, echocardiography, the transmission electron microscope analysis, biochemical analysis, and ELISA. We then investigated whether the safeguarding effect of Xinmai'an tablet on MIRI model rats was related to AMPK/SIRT1/PGC-1α pathway via western blotting. RESULTS: Xinmai'an tablet decreased myocardial infarct size; ameliorated cardiac function; alleviated myocardial and mitochondrial damage; and suppressed oxidative stress injury, vascular endothelial damage, and apoptosis response in MIRI model rats. Mechanistically, our results showed that Xinmai'an tablet can dramatically activate the AMPK/SIRT1/PGC-1αpathway and subsequently diminish mitochondrial oxidative stress damage. This was evidenced by increased ATP, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase levels, upregulation of GLUT4, p-AMPK, SIRT1, and PGC-1α protein levels; and reduced GLUT1 protein level. CONCLUSION: To the knowledge of the author of this article, this study is the first report of Xinmai'an tablet attenuating MIRI, potentially associated with the activation of the AMPK/SIRT1/PGC-1α pathway and subsequent reduction of mitochondrial oxidative stress damage. These findings reveal a novel pharmacological effect and mechanism of action of Xinmai'an tablet and highlight a promising therapeutic drug for ischemic cardiovascular diseases.

Graphene oxide enabled self-assembly of silver trimolybdate nanowires into robust membranes for nanosolid capture and molecular separation.

A graphene oxide (GO) assisted self-assembly strategy for growing a silver trimolybdate nanowire membrane with capabilities of nanosolid capture and small molecule separation is reported. Thanks to the GO bridges and the accurate self-assembly process, the resulting membrane exhibits outstanding mechanical properties (can withstand 4300 times its weight) and impressively high porosity (97%). On the basis of the robustness and high porosity of the membrane, column-shaped filter apparatus has been fabricated, in which the membrane served as a self-standing permeation barrier to assess its permeability and practical application as a nanosolid filter and molecule filter. The permeability test of the membrane with pure water uncovers that the membrane exhibits fast permeability while driven by hydrostatic pressure only because of its significantly high porosity. The separation test of the membrane with P25 TiO2 solution, 13 nm Au solution, and yellow-emitting CdTe QDs reveals that all the tiny nanosolids are completely removed from the solution, which suggests that the membrane is an efficient nanosolid filter. Its efficiency is increased by the induction of surface collision from numerous nanowire barriers and the deposition of nanosolids on the nanowire surface. The separation test of the membrane with a mixed-dye solution reveals that sulfur containing methylene blue (MB) molecules are highly efficiently extracted under various chemical conditions, evidencing that the membrane is an ideal molecule filter too. Its high selectivity and high efficiency originated from the Ag-S bonding between the interlayered silver ions of the silver trimolybdate nanowire and the sulfur atom of MB molecules. Based on the above results, the silver trimolybdate nanowire membrane has been applied to purify drugs, which successfully removed sulbactam sodium impurity F from sulbactam sodium, demonstrating a purity increment from 98.92% to 99.93%. The present work should provide a significant step forward to bringing macroscopic 1D nanomaterial architectures much closer to real-world applications involving isolation and enrichment of catalyst reclamation, high-value chemical recovery, drug purification, and environmental remediation.

VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice.

Silicosis is a diffuse fibrotic lung disease in which excessive inflammatory responses are triggered by silica exposure. Pyroptosis, a pro-inflammatory mode of programmed cell death, is mediated by gasdermin and may play a pivotal role in the development of silicosis. The caspase-1 inhibitor, VX-765, was used in vivo and in vitro to investigate the effects of silica-induced early inflammatory injury and later lung fibrosis. Our findings show that VX-765 reduces inflammatory lung injury by inhibiting silica-induced pyroptosis of alveolar macrophages in a silicosis mouse model. VX-765 limits the infiltration of inflammatory M1 alveolar macrophages, decreasing expression of inflammatory cytokines, including IL-1ß, TNF-α, IL-6, CCL2, and CCL3, and down-regulating endogenous DAMPs and inflammatory immune-related cell pattern recognition receptors TLR4 and NLRP3. Furthermore, VX-765 alleviates fibrosis by down-regulating α-smooth muscle actin (α-SMA), collagen, and fibronectin. In this study, we illustrate that Alveolar macrophages pyroptosis occur in the early stages of silicosis, and VX-765 can alleviate the development of silicosis by inhibiting the pyroptosis signaling pathway. These results may provide new insight into the prevention and treatment of early-stage silicosis.

Nonlinear model fitting analysis of feather growth and development curves in the embryonic stages of Jilin white geese (Anser cygnoides).

Poultry is subject to varying degrees of feather loss and feather pecking during production, which seriously affects the live appearance and carcass appearance of their commercial traits and greatly reduces the production profitability of the farming enterprise. It also has an impact on down production and quality in the case of geese. In this study, mathematical models (Logistic, Gompertz, and Von Bertalanffy) were used to assess feather growth and development during the embryonic period in Jilin white geese (Anser cygnoides) predicting the weight and length of feathers from the back, chest, and belly tracts at different embryonic ages, to determine which growth model more accurately described feather growth patterns. The result first showed that the primary feather follicles of the Jilin white goose developed at E14 and secondary feather follicles at E18; primary feather follicle density increased and then decreased, whereas secondary feather follicle density increased continuously and the primary and secondary feather follicles developed independently. Secondly, the embryonic feather growth followed a slow-fast-slow pattern, with feathers growing slowly from E12 to E18, quickly from E18 to E24, and then decreasing after E24 until just before emergence (E30). In addition, before E14, feathers were concentrated in the back tracts, and no feathers were found on the head, neck, chest, abdomen, or wings. By E22, the whole body of the embryo was covered with feathers, and the back feathers were the earliest and fastest to develop. Compared to the Gompertz and von Bertalanffy models, the logistic model fit (R2 = 0.997) was the highest, while the sum of residual squares (RSS = 25661.67), Akaike's information criterion (AIC = 77.600), Bayesian information criterion (BIC = 78.191), and mean square error (MSE = 2851.296) were the lowest. Therefore, the logistic model was more suitable for describing the changes in whole-body feather growth during the embryonic period in Jilin white geese. In conclusion, using the growth curve model to explain the relationship between feather growth and embryonic age in geese will potentially speed up the process of genetic improvement in Jilin white geese (A. cygnoides) and thus provide scientific support for molecular genetic breeding.

Feathers are an important external feature of poultry, and feather follicles are important appendages to the skin. Especially for geese, feather follicle development largely determines feather length and quality, which in turn affects feather-related economic traits. The growth curve is to use mathematical equations to fit the growth and development curve and analyze the growth and development laws of livestock and poultry. Therefore, whether the establishment of a growth curve model can be used to describe the growth process between the embryonic feather weight, length, and embryo age of the Jilin white goose will be worth further study.

C-X-C-Chemokine-Receptor-Type-4 Inhibitor AMD3100 Attenuates Pulmonary Inflammation and Fibrosis in Silicotic Mice.

Background: Silicosis is a severe pulmonary disease caused by inhaling dust containing crystalline silica. The progression of silicosis to pulmonary fibrosis is usually unavoidable. Recent studies have revealed positivity for the overexpression of C-X-C chemokine receptor type 4 (CXCR4) in pulmonary fibrosis and shown that the CXCR4 inhibitor AMD3100 attenuated pulmonary fibrosis after bleomycin challenge and paraquat exposure. However, it is unclear whether AMD3100 reduces crystalline silica-induced pulmonary fibrosis. Methods: C57BL/6 male mice were instilled intranasally with a single dose of crystalline silica (12 mg/60 µL) to establish an acute silicosis mouse model. Twelve hours later, the mice were injected intraperitoneally with 5 mg/kg AMD3100 or control solution. Then, the mice were weighed daily and sacrificed on day 7, 14, or 28 to collect lung tissue and peripheral blood. Western blotting was also applied to determine the level of CXCR4, while different histological techniques were used to assess pulmonary inflammation and fibrosis. In addition, the level of B cells in peripheral blood was measured by flow cytometry. Results: CXCR4 and its ligand CXCL12 were upregulated in the lung tissues of crystalline silica-exposed mice. Blocking CXCR4 with AMD3100 suppressed the upregulation of CXCR4/CXCL12, reduced the severity of lung injury, and prevented weight loss. It also inhibited neutrophil infiltration at inflammatory sites and neutrophil extracellular trap formation, as well as reduced B-lymphocyte aggregates in the lung. Additionally, it decreased the recruitment of circulating fibrocytes (CD45+collagen I+CXCR4+) to the lung and the deposition of collagen I and α-smooth muscle actin in lung tissue. AMD3100 also increased the level of B cells in peripheral blood, preventing circulating B cells from migrating to the injured lungs. Conclusion: Blocking CXCR4 with AMD3100 delays pulmonary inflammation and fibrosis in a silicosis mouse model, suggesting the potential of AMD3100 as a drug for treating silicosis.

Clinical application of transoral and submental thyroidectomy (TOaST): a series of 54 human cases.

OBJECTIVE: A new endoscopic thyroidectomy approach-transoral and submental endoscopic thyroidectomy (TOaST)-was applied in clinical practice and considered an improved approach for endoscopic thyroid surgery via the oral approach. This paper discusses the feasibility and effectiveness of this surgical method. METHODS: A retrospective analysis was performed on the clinical data of 54 patients who had undergone TOaST in the thyroid disease center of the First Affiliated Hospital of Nanchang University between December 2020 and December 2021. The surgical data and techniques, complications, and cosmetic outcomes of these patients were studied. RESULTS: Among the total 54 patients, 23 underwent unilateral subtotal thyroidectomy, 3 patients underwent bilateral subtotal thyroidectomy, 27 with unilateral thyroid cancer underwent affected thyroid + isthmus + central lymph node resection, and only 1 patient underwent total thyroidectomy. The mean operative time was 88.06 ± 12.03 min (range: 65-135 min), the mean intraoperative blood loss was 8.61 ± 4.60 ml (range: 5-20 ml), the mean postoperative drainage volume was 49.96 ± 9.88 ml (range: 30-60 ml), the mean drainage time was 36.61 ± 2.65 h (range: 32-50 h), and the mean length of hospital stay was 46.63 ± 3.28 h (range 45-70 h). One patient experienced transient recurrent laryngeal nerve injury, and another patient experienced transient parathyroid dysfunction; there was no superior laryngeal nerve injury and other complications, such as postoperative subcutaneous hematoma, hypercapnia, mental nerve injury, tracheoesophageal injury, infection, or lymphatic leakage. CONCLUSION: TOaST cannot only achieve a good therapeutic effect but also avoid mental nerve injury, reduce the discomfort of the patient's jaw, obtain a good cosmetic effect, and facilitate the operation of the operator. It is an endoscopic thyroidectomy technique with a certain clinical value.

Necroptosis in pulmonary macrophages promotes silica-induced inflammation and interstitial fibrosis in mice.

Silicosis is a disease characterized by extensive lung nodules and fibrosis caused by the prolonged inhalation of silica in occupational settings. However, the molecular mechanism of silicosis development is complex and not fully understood. Furthermore, the role of necroptosis, a death receptor-mediated and caspase-independent mode of inflammatory cell death, is not well understood in silicosis. Here, we demonstrate that the necroptotic signaling pathway of macrophages is significantly activated in the lungs of silicosis mouse models. Meanwhile, increased M1 macrophage infiltration and up-regulation of pro-inflammatory cytokines (TNF-α, IL-6) were observed in our silicosis model. Notably, the expression of the pro-fibrotic factor, TGF-ß1, and fibrosis biomarkers α-SMA and collagen I were also unregulated; however, these phenomena were recovered by Nec-1, an inhibitor specific for RIP1 kinase-dependent necroptosis. We conclude that macrophage-mediated necroptosis promotes the progression of silicosis by enhancing lung inflammatory responses and fibrogenesis in a mouse model of silicosis. These findings provide new insights for drug discovery and clinical treatment of silicosis.

A suitable silicosis mouse model was constructed by repeated inhalation of silica dust via nose.

Silicosis as the serious occupational disease is highly necessary to construct a suitable mouse model for disclosing mechanism of occurrence and development in this disease. Here, the volume-effect relationship and volume-based survival curves in mice who inhaled silica suspension intranasally were analyzed. Notable, the optimal volume 80 µl repeated-inhalation by nose to silica suspension in the inbred mouse C57BL/6 J with the highest susceptibility to silicosis led to a great entrance into the lung and a high survival rate after instillation. After repeated-exposure to 20 mg/mL, 80 µl silica for 16 days and then fed without silica exposure until 31 days, weight of mice showed a trend of first decrease and then recover. Moreover, the degree of pulmonary inflammation and fibrosis in mice were analyzed by pathological and immunohistochemistry staining. Transforming growth factor-beta (TGF-ß), smooth muscle alpha-actin (α-SMA) and collagen type-I (collagen I, Col-I) were significantly increased in the silica-exposed mouse lung at post-exposure day 16 compared with the controls. Sirius red stain and Micro-CT analysis showed that lung fibrosis formed at post-exposure day 31. This study highlights the critical importance of perfusion volume and repeated nasal drops in inducing inflammatory response and pulmonary fibrosis in silicosis.

Preventive and therapeutic effects of Lactobacillus rhamnosus SHA113 and its culture supernatant on alcoholic gastric ulcers.

BACKGROUND: Alcoholic gastric ulcers are currently a common upper gastrointestinal disease with a high recurrence rate, causing gastric perforation or even gastric cancer in severe cases. Lactobacillus rhamnosus was previously found to prevent alcoholic gastric ulcers, but its therapeutic effects were not illustrated. AIMS: This study aims to illustrate the preventive and therapeutic effects of L. rhamnosus SHA113 cells and their culture supernatant on alcoholic gastric ulcers and explore the related mechanisms. METHODS: An alcoholic gastric ulcer model was established by feeding mice with 75% ethanol once at a dosage of 10 ml per kg body weight. The L. rhamnosus SHA113 cells (SHA) and their culture supernatant (SHA-FS) were separately used to feed mice for 2 weeks before ethanol injury in preventive experiments and for 2 days after ethanol injury in therapeutic experiments. The mechanisms were analyzed in view of anti-oxidant and anti-inflammatory activities and intestinal barrier functions. RESULTS: The preventive effects of SHA-FS were much better than those of SHA via similar mechanisms, such as promoting the secretion of mucus, improving the antioxidant capacity of the gastric mucosa, and inhibiting inflammation. In terms of the therapeutic effects, SHA-FS and SHA could accelerate the healing of damaged ulcers by improving the secretion of tight junction proteins and mucus proteins, increasing angiogenesis, and inhibiting the apoptosis of gastric epithelial cells. CONCLUSION: L. rhamnosus SHA113 and its culture supernatant had preventive and therapeutic effects on alcoholic gastric ulcers via anti-oxidant and anti-inflammatory pathways and the promotion of healing of damaged ulcers by enhancing intestinal barrier functions, respectively.

Maternal Nicotine Exposure Alters Hippocampal Microglia Polarization and Promotes Anti-inflammatory Signaling in Juvenile Offspring in Mice.

Accumulating evidence reveal that maternal smoking or perinatal nicotine replacement therapy impairs hippocampal neurogenesis, neural development, and cognitive behaviors in the offspring. Microglia is a source of non-neural regulation of neuronal development and postnatal neurogenesis. In this study, we explored the impact of nicotine on the microglia during the development of hippocampus. Developmental nicotine exposure in a mouse model was conducted by supplementing nicotine in the drinking water to mother mice during gestation and lactation period. We found that juvenile offspring with maternal nicotine exposure presented physical and neurobehavioral development delay and an increase in anxiety-like behavior in the open field test on postnatal day (PND) 20. To further detect possible developmental neurotoxic effects of nicotine in offspring and underlying mechanism, whole genome microarray analysis of the expression profile of the hippocampus was performed on postnatal day 20. Significant alterations in the expression of genes related to inflammatory, neurotransmitter, and synapsis were observed in the hippocampus after maternal nicotine exposure, as compared to the vehicle control. Concurrently, an increase in microglial markers and the presence of M2 polarity state in the hippocampus of the nicotine offspring were observed by histological analysis and confocal z-stacking scanning. The M2 microglial polarization state was further confirmed with in vitro primary microglia culture by cytokine array, and double-positive expression of BDNF/Iba1 in microglia by immunohistochemical staining in the juvenile offspring hippocampus was visualized. We also found that nicotine offspring showed an increase of neurite length in the molecular layer and CA1 by Tuj1 staining, as well as an increase in the expression of synapse associated protein, PSD95, but the expression of NeuroD1 in CA1 and CA3 reduced. In summary, maternal nicotine exposure dysregulates immune-related genes expression by skewing the polarity of M2 microglia in the hippocampus, which may cause abnormal cognitive and behavioral performance in the offspring.

Determination of the zeta potential of planar solids in nonpolar liquids.

ZetaSpin determines zeta potential by measuring the streaming potential generated by rotating a disk-shaped sample about its axis while submerged in the liquid. The apparatus and procedure developed for ZetaSpin in aqueous solutions was adapted for use in highly nonpolar fluids like surfactant-doped alkanes. Perhaps most unexpected is the need for up to 10 min (instead of a fraction of one second for aqueous solutions) for the electrometer to display changes in streaming potential in response to changes in rotation speed. Four tests (suggested by theory) confirm that the potential finally reported by the electrometer was indeed the streaming potential. Compared to electrophoresis, ZetaSpin does not require a value for the Debye length, avoids the complication caused by the electric-field-dependence of electrophoretic mobility and can be used with planar samples as well as colloidal particles.

Capability of Bacillus Subtilis to remove Pb2+ via producing lipopeptides.

Lead contamination is widely found in soil and waters, which makes great threat to animal and human health. Environmentally friendly, efficient, and economical methods for the removal of Pb2+ pose significant challenges for environmental protection. Bacillus subtilis lipopeptide was firstly used to remove Pb2+ from water. In mechanisms, the lipopeptides formed complexes and chelated with Pb2+ via OH, CO, OCO, and NH. In kinetics, the Pb2+ removal process closely followed a pseudo-first-order model, and the equilibrium Pb2+ adsorption capacity ranged from 112.6 to 113.7 mg/g within a temperature range of 293.13-313.13 K. The Pb2+ removal process could be well described by a Langmuir isotherm. The maximum Pb2+ removal capability of lipopeptides was 164.4 mg/g in manually metal contaminated water and 130.4 mg/g in actual wastewater. Furthermore, the lipopeptides can not only decrease the amount of lead in oats grown, but also promote oat growth under Pb2+ stress. The results showed that lipopeptides can be used as a highly efficient adsorbent to remove Pb2+ from water, which means the great potential of lipopeptides in practical environments.

Killer-cell immunoglobulin-like receptors associate with HIV-1 infection in a narrow-source Han Chinese cohort.

BACKGROUND: The HIV pandemic remains the most serious challenge to public health worldwide. The hallmark characteristics of the disease is the eventual failure of the immune system to control opportunistic infections and death. However not everyone who has HIV develops the disease at the same rate and so we are studying how the immune system works to control the virus in those who have been infected for decades and remain relatively healthy without the need of anti-retroviral therapy (ART). METHODS: Genomic DNA samples from 513 Chinese Han individuals from Henan province were typed for 15 KIR and 3 HLA class I genes. Genotype frequencies were compared between a village cohort of 261 former plasma donors (SM cohort) infected with HIV-1 through an illegal plasma donor scheme who survived more than 10 years of infection without ART and 252 ethnically-matched healthy controls from a nearby village. KIR and HLA were molecularly typed using a combination of polymerase chain reaction (PCR) with sequence-specific primers (PCR-SSP) and sequence based techniques. RESULTS: All 15 KIR genes were observed in the study population at various frequencies. KIR2DL3 was significantly less common in the HIV-1 infected group (95.8% vs 99.2%, p = 0.021). The combination of KIR3DS1 with homozygosity for HLA-Bw4 alleles (the putative ligand for KIR3DS1) was significantly less frequent in the HIV-1 infected group than in the control group (6.0% vs 12.0% respectively, p = 0.023). CONCLUSION: Specific KIR-HLA compound genotypes associate with differential outcomes to infection and disease progression following exposure to a narrow-source HIV-1.

A Comprehensive Analysis of the Impact of HIV on HCV Immune Responses and Its Association with Liver Disease Progression in a Unique Plasma Donor Cohort.

OBJECTIVE: Human Immunodeficiency Virus (HIV) and Hepatitis C virus (HCV) co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected patients. Our understanding of the impact of HIV infection on HCV specific immune responses and liver disease outcome is limited by the heterogeneous study populations with genetically diverse infecting viruses, varying duration of infection and anti-viral treatment. METHODS: Viral-specific immune responses in a cohort of 151 HCV mono- and HIV co-infected former plasma donors infected with a narrow source of virus were studied. HCV and HIV specific T cell responses were correlated with clinical data. RESULTS: HIV-1 accelerated liver disease progression and decreased HCV specific T cell immunity. The magnitude of HCV specific T cell responses inversely correlated with lower HCV RNA load and reduced liver injury as assessed by non-invasive markers of liver fibrosis. HIV co-infection reduced the frequency of HCV specific CD4+ T cells with no detectable effect on CD8+ T cells or neutralizing antibody levels. CONCLUSION: Our study highlights the impact of HIV co-infection on HCV specific CD4+ T cell responses in a unique cohort of patients for both HCV and HIV and suggests a crucial role for these cells in controlling chronic HCV replication and liver disease progression.

Improving Adherence to Antiretroviral Therapy With Triggered Real-time Text Message Reminders: The China Adherence Through Technology Study.

BACKGROUND: Real-time adherence monitoring is now possible through medication storage devices equipped with cellular technology. We assessed the effect of triggered cell phone reminders and counseling using objective adherence data on antiretroviral therapy (ART) adherence among Chinese HIV-infected patients. METHODS: We provided ART patients in Nanning, China, with a medication device (Wisepill) to monitor their ART adherence electronically. After 3 months, we randomized subjects within optimal (≥95%) and suboptimal (<95%) adherence strata to intervention vs. control arms. In months 4-9, intervention subjects received individualized reminders triggered by late dose taking (no device opening by 30 minutes past dose time) and counseling using device-generated data. Controls received no reminders or data-informed counseling. We compared postintervention proportions achieving optimal adherence, mean adherence, and clinical outcomes. RESULTS: Of 120 subjects enrolled, 116 (96.7%) completed the trial. Preintervention optimal adherence was similar in intervention vs. control arms (63.5% vs. 58.9%, respectively; P = 0.60). In the last intervention month, 87.3% vs. 51.8% achieved optimal adherence [risk ratio (RR): 1.7, 95% confidence interval (CI): 1.3 to 2.2] and mean adherence was 96.2% vs. 89.1% (P = 0.003). Among preintervention suboptimal adherers, 78.3% vs. 33.3% (RR: 2.4, CI: 1.2 to 4.5) achieved optimal adherence and mean adherence was 93.3% vs. 84.7% (P = 0.039). Proportions were 92.5% and 62.9% among optimal adherers, respectively (RR: 1.5, CI: 1.1 to 1.9) and mean adherence was 97.8% vs. 91.7% (P = 0.028). Postintervention clinical outcomes were not significant. CONCLUSIONS: Real-time reminders significantly improved ART adherence in this population. This approach seems promising for managing HIV and other chronic diseases and warrants further investigation and adaptation in other settings.

Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer.

Previous studies have suggested that interleukin-17 (IL-17), an inflammatory cytokine expressed predominantly by Th17 cells, is highly expressed in tumor tissue and may help tumors to evade immune surveillance. In this study, the significance of IL-17 expression in the tumors of murine models of breast cancer was explored. BALB/c mice were injected with MA782/5S28102 or 4T1 breast cancer cell lines to establish breast tumors. The expression of IL-17 in tumor tissue was detected by western blotting 1 and 4 weeks later, which revealed that it increased with tumor progression (P<0.05). Additionally, tumor cells and tumor-infiltrating lymphocytes were isolated from tumor tissues and cultured for 5 days with stimulation by phorbol-12-myristate-13-acetate (PMA), anti­CD3 antibody and anti-CD28 antibody. Culture media from stimulated tumor cells or tumor-infiltrating lymphocytes were harvested and their concentrations of IL-17 were tested by ELISA. Tumor cells secreted low levels of IL-17 into the media; however, lymphocytes from tumor tissues secreted high levels of IL-17, with 4T1 tumors secreting higher levels of IL-17 than MA782 tumors (P<0.05). To evaluate the effect of IL-17 on the proliferation of tumor cells, 4T1 cells were cultured in the presence or absence of recombinant IL-17 and cell numbers were counted on day 5 of culturing. Ectopic IL-17 did not promote the proliferation of tumor cells in vitro. To further understand the effect of IL-17 expression within tumors, 4T1 tumor-bearing mice were injected with recombinant IL-17 or saline via the tail vein. Tumor size was measured up to 21 days following the initial infusion of IL-17. IL-17 infusion resulted in an increased tumor volume and microvascular density (as measured by the immunohistochemical detection of CD34 expression in microvessels; P<0.05). Therefore, IL-17 expression within tumor tissues appears to originate from tumor-infiltrating lymphocytes and is likely to promote tumor growth by enhancing angiogenesis.

High frequency of HIV mutations associated with HLA-C suggests enhanced HLA-C-restricted CTL selective pressure associated with an AIDS-protective polymorphism.

Delayed HIV-1 disease progression is associated with a single nucleotide polymorphism upstream of the HLA-C gene that correlates with differential expression of the HLA-C Ag. This polymorphism was recently shown to be a marker for a protective variant in the 3'UTR of HLA-C that disrupts a microRNA binding site, resulting in enhanced HLA-C expression at the cell surface. Whether individuals with "high" HLA-C expression show a stronger HLA-C-restricted immune response exerting better viral control than that of their counterparts has not been established. We hypothesized that the magnitude of the HLA-C-restricted immune pressure on HIV would be greater in subjects with highly expressed HLA-C alleles. Using a cohort derived from a unique narrow source epidemic in China, we identified mutations in HIV proviral DNA exclusively associated with HLA-C, which were used as markers for the intensity of the immune pressure exerted on the virus. We found an increased frequency of mutations in individuals with highly expressed HLA-C alleles, which also correlated with IFN-γ production by HLA-C-restricted CD8(+) T cells. These findings show that immune pressure on HIV is stronger in subjects with the protective genotype and highlight the potential role of HLA-C-restricted responses in HIV control. This is, to our knowledge, the first in vivo evidence supporting the protective role of HLA-C-restricted responses in nonwhites during HIV infection.