Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined in vitro experiments such as wound healing, CCK8, and transwell assay with in vivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

Genomic landscape and distinct molecular subtypes of primary testicular lymphoma.

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.

A transcription factor WRKY36 interacts with AFP2 to break primary seed dormancy by progressively silencing DOG1 in Arabidopsis.

The phytohormones abscisic acid (ABA) and gibberellic acid (GA) antagonistically control the shift between seed dormancy and its alleviation. DELAY OF GERMINATION1 (DOG1) is a critical regulator that determines the intensity of primary seed dormancy, but its underlying regulatory mechanism is unclear. In this study, we combined physiological, biochemical, and genetic approaches to reveal that a bHLH transcriptional factor WRKY36 progressively silenced DOG1 expression to break seed dormancy through ABI5-BINDING PROTEIN 2 (AFP2) as the negative regulator of ABA signal. AFP2 interacted with WRKY36, which recognizes the W-BOX in the DOG1 promoter to suppress its expression; Overexpressing WRKY36 broke primary seed dormancy, whereas wrky36 mutants showed strong primary seed dormancy. In addition, AFP2 recruited the transcriptional corepressor TOPLESS-RELATED PROTEIN2 (TPR2) to reduce histone acetylation at the DOG1 locus, ultimately mediating WRKY36-dependent inhibition of DOG1 expression to break primary seed dormancy. Our result proposes that the WRKY36-AFP2-TPR2 module progressively silences DOG1 expression epigenetically, thereby fine-tuning primary seed dormancy.

Engineered and Durable Antimicrobial Polymer via Controllable Immobilization of Ionic Liquids onto the Poly(lactic acid) Chains.

Nowadays, the development of effective modification methods for PLA has gained significant interest because of the wide application of antimicrobial PLA materials in the medical progress. Herein, the ionic liquid (IL) 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide, has been grafted onto the PLA chains successfully in the PLA/IL blending films via electron beam (EB) radiation for the miscibility between PLA and IL. It was found that the existence of IL in the PLA matrix can significantly improve the chemical stability under EB radiation. The Mn of PLA-g-IL copolymer did not change obviously but was just decreased from 6.80 × 104 g/mol to 5.20 × 104 g/mol after radiation with 10 kGy. The obtained PLA-g-IL copolymers showed excellent filament forming property during electrospinning process. The spindle structure on the nanofibers can be completely eliminated after feeding only 0.5 wt % ILs for the improvement of ionic conductivity. Specially, the prepared PLA-g-IL nonwovens exhibited outstanding and durable antimicrobial activity for the enrichment of immobilized ILs on the nanofiber surface. This work provides a feasible strategy to realize the modification of functional ILs onto PLA chains with low EB radiation doses, which may have huge potential application in the medical and packaging industry.

Reflection of Solar Light from Surface Snow Loaded with Light-Absorbing Impurities: A Case Study of Black Carbon, Mineral Dust, and Ash.

Using a hemispherical directional reflectance factor instrument, spectral data of dirty snow containing black carbon (BC), mineral dust (MD), and ash was collected from multiple locations to investigate the impact of these light-absorbing impurities (LAIs) on snow reflectance characteristics. The findings revealed that the perturbation of snow reflectance caused by LAIs is characterized by nonlinear deceleration, indicating that the reduction in snow reflectance per unit ppm of LAIs declines as snow contamination increases. The reduction in snow reflectance caused by BC may reach saturation at elevated particle concentrations (thousands of ppm) on snow. Snowpacks loaded with MD or ash initially exhibit a significant reduction in spectral slope around 600 and 700 nm. The deposition of numerous MD or ash particles can increase snow reflectance beyond the wavelength of 1400 nm, with an increase of 0.1 for MD and 0.2 for ash. BC can darken the entire measurement range (350-2500 nm), while MD and ash can only affect up to 1200 nm (350-1200 nm). This study enhances our understanding of the multi-angle reflection characteristics of various dirty snow, which can guide future snow albedo simulations and improve the accuracy of LAIs' remote sensing retrieval algorithms.

Nutritional qualities and antioxidant activity of Pleurotus floridanus grown on composted peach sawdust substrate with different composting time.

Recently, composting cultivation method is widely used in oyster mushroom production. In this study, we focused on the effects of composting processes on nutritional qualities and antioxidant activity of Pleurotus floridanus mushroom fruiting bodies. Three treatments of different composting time (2, 4, and 5 days) were performed with an atmospheric sterilization treatment as the control. The results showed that the pH value, total carbon content, and total nitrogen content of substrate were critical parameters which would significantly affect mushroom qualities and bioactivities. Fruiting bodies of the control demonstrated significantly higher crude protein content, total amino acid content, and essential amino acid content than that of composting treatments. Moreover, fruiting bodies of treatment D4 and D5 manifested significantly higher crude polysaccharide contents. Crude polysaccharide of treatment D4 represented the highest scavenging ability toward both radical 3-ethylbenzthiazoline-6-sulfonic acid (ABTS·+ ) and Hydroxyl radical (OH·). It suggests that composting processes is suitable for oyster mushroom cultivation based on nutritional and antioxidant qualities of fruiting bodies.

Insulin-like growth factor binding protein 7 promotes acute kidney injury by alleviating poly ADP ribose polymerase 1 degradation.

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.

The protective effect of rabeprazole on cisplatin-induced apoptosis and necroptosis of renal proximal tubular cells.

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.

Stratifin promotes renal dysfunction in ischemic and nephrotoxic AKI mouse models via enhancing RIPK3-mediated necroptosis.

Stratifin (SFN) is a member of the 14-3-3 family of highly conserved soluble acidic proteins, which regulates a variety of cellular activities such as cell cycle, cell growth and development, cell survival and death, and gene transcription. Acute kidney injury (AKI) is prevalent disorder characterized by inflammatory response, oxidative stress, and programmed cell death in renal tubular epithelial cells, but there is still a lack of effective therapeutic target for AKI. In this study, we investigated the role of SFN in AKI and the underlying mechanisms. We established ischemic and nephrotoxic AKI mouse models caused by ischemia-reperfusion (I/R) and cisplatin, respectively. We conducted proteomic and immunohistochemical analyses and found that SFN expression levels were significantly increased in AKI patients, cisplatin- or I/R-induced AKI mice. In cisplatin- or hypoxia/reoxygenation (H/R)-treated human proximal tubule epithelial cells (HK2), we showed that knockdown of SFN significantly reduced the expression of kidney injury marker Kim-1, attenuated programmed cell death and inflammatory response. Knockdown of SFN also significantly alleviated the decline of renal function and histological damage in cisplatin-caused AKI mice in vivo. We further revealed that SFN bound to RIPK3, a key signaling modulator in necroptosis, to induce necroptosis and the subsequent inflammation in cisplatin- or H/R-treated HK2 cells. Overexpression of SFN increased Kim-1 protein levels in cisplatin-treated MTEC cells, which was suppressed by RIPK3 knockout. Taken together, our results demonstrate that SFN that enhances cisplatin- or I/R-caused programmed cell death and inflammation via interacting with RIPK3 may serve as a promising therapeutic target for AKI treatment.

Nervous System-Driven Osseointegration.

Implants are essential therapeutic tools for treating bone fractures and joint replacements. Despite the in-depth study of osseointegration for more than fifty years, poor osseointegration caused by aseptic loosening remains one of the leading causes of late implant failures. Osseointegration is a highly sophisticated and spatiotemporal process in vivo involving the immune response, angiogenesis, and osteogenesis. It has been unraveled that the nervous system plays a pivotal role in skeletal health via manipulating neurotrophins, neuropeptides, and nerve cells. Herein, the research related to nervous system-driven osseointegration was systematically analyzed and reviewed, aiming to demonstrate the prominent role of neuromodulation in osseointegration. Additionally, it is indicated that the implant design considering the role of neuromodulation might be a promising way to prevent aseptic loosening.

Differential Nanoscale Topography Dedicates Osteocyte-Manipulated Osteogenesis via Regulation of the TGF-ß Signaling Pathway.

Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone formation. It is confirmative that osteocyte processes extend directly to the implant surface, but whether the surface physicochemical properties can affect the functionality of osteocytes and determine the fate of the osseointegration in the final remodeling stage remains to be determined. Titania nanotube arrays (NTAs) with distinct diameters were fabricated to investigate the relationship between the nanoscale topography and the functionality of osteocytes. In vitro results pinpointed that NTA with a diameter of 15 nm (NTA-15) significantly promote osteogenesis of osteocytes via the enhancement of spreading, proliferation, and mineralization. The osteocyte transcriptome of each group further revealed that the TGF-ß signaling pathway plays a pivotal role in osteocyte-mediated osteogenesis. The in vivo study definitely mirrored the aforementioned results, that NTA-15 significantly promotes bone formation around the implant. Consequently, nanoscaled topography-induced osteocyte functionality is important in late osseointegration. This suggests that surface designs targeting osteocytes may, therefore, be a potential approach to solving the aseptic loosening of the implant, and thus strengthen osseointegration.

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis.

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

The Optimization of Chlorella vulgaris Flocculation Harvesting by Chitosan and Calcium Hydroxide.

The high cost for microalgae harvesting still is the bottleneck of microalgae commercial production. In the present study, the effect of adjusting pH to alkaline conditions with sodium hydroxide/calcium hydroxide and the addition of chitosan together with pH adjustments on the flocculation of Chlorella vulgaris (C. vulgaris) was studied, respectively. A single-factor experiment showed a maximum flocculation efficiency of 96.7% when adjusting the pH to 12 with calcium hydroxide. There was synergistic action between chitosan and calcium hydroxide. Flocculation conditions of C. vulgaris for the combined use of calcium hydroxide and chitosan was optimized by response surface methodology (RSM) with a Box-Behnken design (BBD). Flocculation efficiency reached 97.08% under optimal flocculation conditions when adjustion of pH to 8.97 with 2 g/L calcium hydroxide, a chitosan dosage of 20 mg/L, and a flocculation time of 60 min. The current study presents one method for efficient flocculation harvesting of C. vulgaris at weak alkaline conditions and low chitosan dosage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01004-1.

Evaluation of tofacitinib citrate bioequivalence based on pharmacokinetic parameters in healthy Chinese subjects.

OBJECTIVE: To evaluate the pharmacokinetics and bioequivalence of tofacitinib citrate using pharmacokinetic parameters, a single-dose, randomized-sequence, two-way crossover study of tofacitinib citrate test (T) and reference (R) formulations, with a 4-day washout period, was performed. MATERIALS AND METHODS: 72 healthy Chinese subjects were randomly divided into 4 groups: sequence A (TR) and B (RT) in a fasted state and sequence C (TR) and D (RT) in a fed state. Plasma tofacitinib citrate levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameter maximum concentration (Cmax) and area under the concentration-time curve (AUC0-t and AUC0-∞) were used to evaluate bioequivalence. RESULTS: The geometric least-squares mean (GLSM) ratio and 90% confidence intervals for fasted state Cmax, AUC0-t, and AUC0-∞ were 93.90 - 108.17%, 100.41 - 103.95%, and 100.48 - 104.02% and at fed state were 99.45 - 119.52%, 100.05 - 104.23%, and 100.00 - 104.20%, respectively. The 90% CI of the two preparations, Cmax, AUC0-t, and AUC0-∞, all fell within the equivalent range of 80 - 125%. tmax was ~ 0.6 hours later, and Cmax was ~ 27% lower after a high-fat diet in the fasted state. CONCLUSION: Two types of tofacitinib citrate tablets were bioequivalent under both fasted and fed conditions, and both were generally well tolerated; moreover, food-drug interaction may affect drug pharmacokinetics.

Eleutheroside B-loaded poly (lactic-co-glycolic acid) nanoparticles protect against renal fibrosis via Smad3-dependent mechanism.

Although renal fibrosis is a common complication of chronic kidney disease (CKD), effective options for its treatment are currently limited. In this study, we evaluated the renal protective effect and possible mechanism of eleutheroside B. In order to solve the allergic reactions, side effects, and low oral bioavailability of eleutheroside B, we successfully prepared PLGA (poly [lactic-co-glycolic acid])-eleutheroside B nanoparticles (NPs) with the diameter of about 128 nm. In vitro and in vivo results showed that eleutheroside B could inhibit expression levels of α-smooth muscle actin (α-SMA) and collagen I. Molecular docking results showed that eleutheroside B bound to Smad3 and significantly decreased the expression of phospho-Smad3 (p-Smad3). Silencing Smad3 reversed the fibrotic protective effect of eleutheroside B in HK2 cells. Furthermore, small animal imaging showed that NPs can selectively accumulate in the UUO kidneys of mice, and retention time reached as long as 7 days. In conclusion, our results suggested that eleutheroside B is a potential drug to protect renal fibrosis and PLGA-eleutheroside B NPs could facilitate specific targeted therapy for renal fibrosis.

Pharmacokinetics and bioequivalence of two oral formulations of canagliflozin after single-dose administration in healthy Chinese subjects
.

OBJECTIVE: This study was conducted to evaluate the pharmacokinetic properties and bioequivalence of two oral formulations of canagliflozin: a newly developed generic formulation (test) and a branded formulation (reference). MATERIALS AND METHODS: A randomized, open-label, two-way crossover study was conducted in 55 healthy Chinese subjects. They were randomized to receive a single oral dose of 100 mg of test or reference canagliflozin tablets according to an open crossover design under fasting and fed states. Plasma canagliflozin concentrations were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters maximum concentration (Cmax) and area under the concentration-time curve (AUC0-t and AUC0-∞) were used to evaluate bioequivalence. RESULTS: The geometric mean ratio 90% confidence intervals for fasting Cmax, AUC0-t, and AUC0-∞ were 85.14 - 114.40%, 102.14 - 106.51%, and 102.21 - 106.85%, respectively, and fed Cmax, AUC0-t, and AUC0-∞ were 90.15 - 107.17%, 97.38 - 102.19%, and 96.78 - 101.92%, respectively. The mean values of tmax were prolonged in the test compared with the reference formulations. In addition, the mean values of tmax and Cmax for both formulations were significantly different under fed compared with fasting conditions, while there was no significant difference in AUC0-t or AUC0-∞. CONCLUSION: The two types of canagliflozin tablets were bioequivalent under both fasting and fed states, and both were generally well tolerated.

Two Natural Alkaloids Synergistically Induce Apoptosis in Breast Cancer Cells by Inhibiting STAT3 Activation.

Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a new strategy against breast cancer due to their reliable anticancer potential. In the present study, cell viability, flow cytometry, and Western blot assays were performed to evaluate the suppression effect of PP and PL, alone or in combination. Data showed that PP and PL synergistically inhibited breast cancer cells proliferation at lower doses, while only weak killing effect was observed in normal breast cells, indicating a good selectivity. Furthermore, apoptosis and STAT3 signaling pathway-associated protein levels were analyzed. We demonstrated that PP and PL in combination inhibit STAT3 phosphorylation and regulate downstream molecules to induce apoptosis in breast cancer cells. Taken together, these results revealed that inactivation of STAT3 was a novel mechanism with treatment of PP and PL, suggesting that combination application of natural alkaloids may be a potential strategy for prevention and therapy of breast cancer.

An ultrasensitive electrochemiluminescence immunosensor for alpha-fetoprotein based on a poly(aniline-luminol)/graphene oxide nanocomposite.

An ultrasensitive electrochemiluminescence (ECL) immunosensor for alpha-fetoprotein (AFP) detection based on a poly(aniline-luminol)/graphene oxide nanocomposite was developed. The nanocomposite, which was prepared using a fast and simple chemical oxidation strategy for the first time, showed excellent ECL performance. This outstanding ECL performance is due to the formation of poly(aniline-luminol) on the graphene oxide (GO) surface and the excellent electron-transfer properties of GO. Moreover, the poly(aniline-luminol)/graphene oxide nanocomposite has abundant amino groups at its surface, making it a good platform for biomacromolecule labeling. Using the nanocomposite, a novel ECL immunosensor for the determination of AFP was successfully developed. Anti-AFP was immobilized on the surface of a poly(aniline-luminol)/graphene oxide nanocomposite-modified electrode using a glutaraldehyde crosslinking method to form the ECL immunosensor. The AFP was then captured at the modified electrode surface through an antigen-antibody immunoreaction. When the AFP was captured by its antibody, the ECL intensity decreased. This ECL immunosensor for the detection of AFP exhibited a linear range of 1.7 × 10-12 to 1.7 × 10-8 mg mL-1 and a detection limit of 5 × 10-13 mg mL-1, indicating high sensitivity and linearity across a wide concentration range. Furthermore, the immunosensor was successfully applied to determine AFP in a real-world human serum sample. Graphical abstract A new poly(aniline-luminol)/graphene oxide nanocomposite was prepared using a fast and simple strategy for the first time, and an ultrasensitive electrochemiluminescence (ECL) immunosensor for alpha-fetoprotein (AFP) detection based on this nanocomposite was developed.

Pharmacokinetic and bioequivalence study of emtricitabine/tenofovir disoproxil fumarate tablets in healthy Chinese subjects
.

OBJECTIVE: This study was conducted to evaluate the pharmacokinetics and bioequivalence of two emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) tablets: a newly developed generic formulation (test) and a branded formulation (reference) in healthy Chinese subjects under fasting and fed states. MATERIALS AND METHODS: A randomized, open-label, two-way crossover study was conducted in 64 healthy Chinese subjects. Subjects were randomized to receive a single oral dose of FTC 200 mg/TDF 300 mg of test or reference tablets according to an open crossover design under fasting and fed states. Plasma canagliflozin levels of FTC/TDF were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC0-t and AUC0-∞) were used to evaluate bioequivalence. RESULTS: The geometric mean ratio 90% confidence intervals for fasting Cmax, AUC0-t, and AUC0-∞ were 89.03 - 101.98%, 94.90 - 101.36%, and 94.94 - 101.56%, respectively, and fed Cmax, AUC0-t, and AUC0-∞ were 94.12 - 108.87%, 96.89 - 104.05%, and 96.69 - 104.28%, respectively. CONCLUSION: The two types of FTC/TDF tablets were bioequivalent under both fasting and fed condition, and both were generally well tolerated.

Responses of duckweed (Lemna minor L.) to aluminum stress: Physiological and proteomics analyses.

Aluminum (Al) is commonly considered an abiotic stress factor under acidic conditions. Duckweed (Lemna minor L.) has wide application in ecotoxicological research as a model organism and, in this study, its response to Al bioaccumulation was evaluated at morphological, physiological and proteomic levels. The Al accumulation in L. minor was accompanied by chlorosis and growth inhibition. Overproduction of superoxide and hydrogen peroxide, and decreased chlorophyll and protein contents, suggested that Al exposure induced oxidative stress. Inhibition of photosynthesis was evident in a significant decrease in maximum photosystem II quantum yield. There were 261 proteins, with significant changes in expression, successfully identified and quantified through isobaric tags for relative and absolute quantification (iTRAQ) analysis. Among the KEGG pathway enrichment proteins, those related to the citrate cycle and amino acid metabolism were predominantly up-regulated, whereas those associated with energy metabolism and glyoxylate and dicarboxylate metabolism were predominantly down-regulated. In addition, antioxidant enzyme related proteins played an important role in the response of L. minor to Al. The western blot analysis further validated the changes in photosynthetic related proteins. These results provide comprehensive insights into the physiological and molecular mechanisms of Al toxicity and tolerance in L. minor.