Novel biomaterials capable of accelerating the healing process of skeletal tissues are urgently needed in dentistry. The present in vivo study assessed the osteoconductive and osteoinductive properties of experimental biphasic bioceramics (HA-TCP) modified or not by a nacre extract (marine organic extract, MOE) in a sheep model. Fabrication of MOE involved mixing ground nacre (0.05 g, particle sizes < 0.1 mm) with glacial ethanoic acid (5 mL, pH 7) for 72 hours using external magnetic stirring (25°C). Nonreactive carriers (sterile polythene tubes; 3/animal, radius: 2.5 mm, length: 10.0 mm) pertaining to the control (empty) or experimental groups (HA-TCP or MOE-modified HA-TCP) were implanted intramuscularly into the abdominal segment of the torso in sheep (n = 8, age: 2 years, weight: 45 kg). Euthanization of animals was performed at 3 and 6 months after surgery. Tissues harvested were subjected to macroscopic and radiographic assessments. Specimens were then stained for histological analysis. Both control and experimental animals were capable of inducing the neoformation of fibrous connective tissue at both time points where superior amounts of tissue formation and mineralization were detected for experimental groups (unaltered (at 3 and 6 mos) and MOE-modified HA-TCP (at 3 mos)). Histological results, however, revealed that mature bone formation was only observed for specimens fabricated with MOE-modified HA-TCP in a time-dependent manner. The present study has successfully demonstrated the in vivo utility of experimental biphasic bioceramics modified by MOE in an ectopic grafting sheep model. Promising osteoconductive and osteoinductive properties must be further developed and confirmed by subsequent research.

The 2017 American College of Cardiology and American Heart Association hypertension guideline updated stage 1 hypertension definition as systolic blood pressure range from 130 to 139 mmHg or diastolic blood pressure from 80 to 89 mmHg. However, the association of stage 1 hypertension with stroke and its subtypes among the older population in rural China remains unclear.

Giardia duodenalis is a zoonotic enteric parasite that can infect humans and a number of animal species including rabbits with a worldwide distribution. Infection with G. duodenalis can cause serious public health problems and significant economic losses to animal husbandry. So accurate understanding of the prevalence and genotype distribution of G. duodenalis in rabbits is necessary. In the present study, a total of 616 fecal samples were collected from rabbits in Shandong province, eastern China, and examined in G. duodenalis prevalence and genotypes by nested PCR amplification of β-giardin (bg), glutamate dehydrogenase (gdh), and triosephosphate isomerase (tpi) gene loci of G. duodenalis. Sixty-nine (11.2%) of the examined rabbit fecal samples were G. duodenalis-positive. Of them, the prevalence of G. duodenalis is 8.4% (41/490) in Rizhao city and 22.2% (28/126) in Weihai city. Breeds, region, and feeding modes were highly correlated with G. duodenalis infection in rabbits. Moreover, three genotypes (assemblages A, B, and E) were identified in rabbits at three gene loci, and the assemblage E was the dominant genotype, while the assemblage A was reported in rabbits in China for the first time. It is noticeable that two rabbits were found to be infected with two different G. duodenalis assemblages (assemblages A and E, assemblages B and E, respectively). These findings enrich the genotype distribution of G. duodenalis in rabbits and provide baseline data for preventing and controlling G. duodenalis infection in rabbits in eastern China.

The present study aimed to identify changes in decidual natural killer (dNK) cells and related cytokines in women who have undergone induced abortions (IAs). The effects of dNK cells on subsequent pregnancies remain unknown. Accordingly, we sought to investigate whether a history of early pregnancy can change dNK cells and facilitate their role in the regulation of angiogenesis and trophoblast invasion. Materials and Methods. dNK cells were obtained from primiparous women who had undergone IA(s) prior to this study and primiparous women who had never been pregnant before this IA (control). Real-time polymerase chain reaction (PCR) was used to measure the mRNA levels of IFN-γ, IP-10, VEGF, and PLGF in dNK cells. The levels of these cytokines were quantified using the enzyme-linked immunosorbent assay. HUVEC and HTR-8/SVneo cells were used to evaluate the angiogenesis, migration, and invasion activities influenced by dNK cells.

As a special type of lung cancer, multiple primary lung cancer (MPLC) has unique biological characteristics, and its research remains limited. The aim of our research was to identify prognostic factors and construct a prognostic nomogram of dual primary lung cancer (DPLC). A population cohort study of patients with DPLC was conducted using the extracted data from the Surveillance, Epidemiology, and End Results (SEER) database. Relevant survival variables were identified using the Cox proportional hazard model. Prognostic nomogram was performed and its predictive performance was validated via the modeling and validating cohort data. Additionally, propensity score matching (PSM) was also applied to evaluate whether surgery affected the OS of this study population. 5411 eligible DPLC patients were included in this study cohort, with 41.0% of 3-year OS rate and 27.7% of 5-year OS rate. Age, sex, race, grade, stage, lymph node (LN) metastasis, histological type, primary site, and surgery were considered to be prognostic factors of OS. The C-indexes of the established nomogram were 0.70 (95% CI (0.69, 0.71)) in the modeling group and 0.70 (95% CI (0.68, 0.72)) in the validation group, which showed an ideal model discrimination ability. AUC and calibration plots of 3- and 5-year OS also proved the good performance of the established nomogram. After 1 : 1 PSM, surgery can potentially reduce the risk of OS (HR = 0.63, 95% CI: 0.56-0.72) of DPLC. The prognostic nomogram with reliable performance was developed to predict 3- and 5-year OS rates, which could assist clinicians to make more reasonable survival prediction for DPLC patients. For patients without absolute surgical contraindications, surgery should be actively considered.

Lung cancer is the most common cancer and the most common cause of cancer-related death worldwide. However, the molecular mechanism of its development is unclear. It is imperative to identify more novel biomarkers.

A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives 3(a-j) were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides 1(a-d) were reacted with N2H4 to get aromatic sulfonyl hydrazides 2(a-d). The intermediate hydrazides 2(a-d) were treated with substituted aldehydes to afford azaheterocyclic sulfonamide Schiff bases 3(a-j). The spectral data of synthesized compounds confirmed the formation of the final products. The inhibitory effects of 3(a-j) on carbonic anhydrase activity were determined, and it was found that derivative 3c exhibited the most potent activity with IC500.84 ± 0.12 μM among all other derivatives and is also more active than standard acetazolamide (IC500.91 ± 0.12). The enzyme inhibitory kinetics results determined by Lineweaver-Burk plots revealed that compound 3c inhibits the enzyme by noncompetitive mode of inhibition with K i value 8.6 μM. The molecular docking investigations of the synthesized analogues 3(a-j) were evaluated which assured that synthesized compounds bind well inside the active binding site of the target enzyme. Cytotoxicity on human keratinocyte (HaCaT) and MCF-7 cell lines was performed, and it was found that most of the synthesized analogues were nontoxic on these cell lines and the toxic effects follow the dose-dependent manner. Based on our investigations, it was suggested that analogue 3c may serve as core structure to project carbonic anhydrase inhibitors with greater potency.

Studies on the number and proportion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) patients have been controversial, which has led to a disagreement regarding the role of Tregs in the pathogenesis of AS. To clarify this debate, we conducted a meta-analysis to verify the reported changes in Tregs during AS. We systematically searched the PubMed, Foreign Medical Retrieval System (FMRS), and China National Knowledge Infrastructure (CNKI) web of knowledge databases for eligible articles. A meta-analysis of studies that examined the proportion and number of Tregs among peripheral blood mononuclear cells (PBMCs) and CD4+ T cells was performed using Stata software. Further, subgroup analysis was performed based on Treg definition markers and disease activity to identify potential sources of heterogeneity. Forty-seven studies involving a total of 4373 participants were included in the meta-analysis. The Treg/PBMC and Treg/CD4+ T cell ratios were significantly lower in AS patients than those in healthy controls (HCs). A subgroup analysis indicated that patients defined by CD4+CD25+/high, CD4+CD25+CD127low/-, and CD4+CD25+FOXP3+ had much lower Treg/PBMC and Treg/CD4+ T cell ratios than HCs. Active AS patients also had a substantially lower proportion of Tregs/PBMCs and Treg/CD4+ T cells than HCs. The proportion of Tregs among both PBMCs and CD4+ T cells was significantly decreased in AS patients. Treg definition markers and disease activity may influence the proportion of Tregs measured among the PBMC and CD4+ T cell populations. Further study of the correlation between AS disease activity and the proportion of Tregs in peripheral blood is needed to determine the physiological role of this association. This study implies that loss of Tregs may play a role in the pathogenesis of AS and helps clarify the contradictory Treg results in AS patients. This trial is registered with PROSPERO (CRD42019147064).

The aim of the study was to describe the changes in kidney parameters induced by 10 days of tapering (TP) during a training camp (TC), where the players were preparing for a group competition, in 15 female handball team members of a Division 1 Amateur of Benin, in the sub-Saharan environment. Measures were taken in all the players before and after the intensive training (IT) and tapering (TP) phases in an intervention study. The estimated glomerular filtration rate (eGFR) with the CKD-EPI 4-level race formula, the fractional excretions of sodium (FeNa) and potassium (FeK), the urine potassium-to-sodium ratio (Na/K urine), and the hemoglobin rate [Hb] were determined for all participants. At the end of IT, eGFR and FeNa increased, respectively, by 22.39% (P < 0.01) and 143.85% (P < 0.01), but the variation of FeK is not significant (P > 0.05). The number of abnormally low eGFR values (<90 mL/min/1.73 m2) was reduced from 11 to 5 (P < 0.05). At the end of TP, the eGFR and urine Na-to-K ratio remained on average constant (P > 0.05) but FeNa decreased by 96.32% (P < 0.001) and FeK increased by 144.41% (P < 0.001). The [Hb] rate increased by 9.80% (P < 0.001), and players had inadequate hydration practice. The results suggested that in addition to its already known effects, TP preserves the positive effects of IT on glomerular function in athletes preparing for a competition that presents a major challenge.

Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4+/CD8+ ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.

To explore effects of Epstein-Barr virus (EBV) infection on CD19+ B lymphocytes in patients with immunorelated pancytopenia (IRP).

Super-resolution fluorescence microscopy techniques allow imaging fluorescently labelled structures with a resolution that surpasses the diffraction limit of light (approx. 200nm). The quality and, thus, reliability of each of these techniques is strongly dependent on (1) the quality of the optics, (2) the fitness of the specific fluorescent label for the given technique and (3) the algorithms being used. Of these, the fitness of the labels is most subjective, as fitness metrics are scarce, and generating samples with different labels and imaging them is laborious. This prevent rigorous fitness assessment of fluorescent labels. We have developed a mathematical framework for assessing the quality of SOFI data [1], [2], which we used to assess the fitness of 20 different fluorescent protein labels for SOFI imaging. Here, we report this dataset of 2240 image sequences, representing 10 fields of view each of transfected Cos7 cells expressing each of the 20 different fluorescent proteins under 4-12 imaging conditions. The labels span the visible spectrum and include non-photo-transforming and photo-transforming fluorescent proteins. The imaging conditions consist of 4 different excitation powers, each with three different powers of 405 nm light added (except for the blue labels that are excited with 405 nm light). Though this data was in essence generated to assess which labels are best suited for SOFI imaging, it can be used as a benchmark for further development of the SOFI algorithm, or for the development of other super-resolution imaging modalities that benefit from similar input data.

Inadvertent inhalation of various volatile organic compounds during industrial processes, such as coal and metal mining, metal manufacturing, paper and pulp industry, food processing, petroleum refining, and concrete and chemical industries, has caused an adverse effect on human health. In particular, exposure to trimethylamine (TMA), a fishy odor poisonous gas, resulted in numerous health hazards such as neurotoxicity, irritation in eyes, nose, skin, and throat, blurred vision, and many more. According to the environmental protection agency, TMA in the level of 0.10 ppm is generally considered as safe, and excess dose results in "trimethylaminuria" or "fish odor syndrome." In order to avoid the health hazards associated with the inhalation of TMA, there is an urge to design a sensor for TMA detection even at low levels for use in food-processing industries, medical diagnosis, and environment. In this report, for the first time, we have developed a TMA sensor fabric using a sequential self-assembly process from silver-incorporated glycolipids. Formation of self-assembled supramolecular architecture, interaction of the assembled structure with the cotton fabric, and sensing mechanism were completely investigated with the help of various instrumental methods. To our surprise, the developed fabric displayed a transient response for 1-500 ppm of TMA and a stable response toward 100 ppm of TMA for 15 days. We believe that the reported flexible TMA sensor fabrics developed via the sequential self-assembly process hold great promise for various innovative applications in environment, healthcare, medicine, and biology.

The quantitative structure-property relationship (QSPR) models for predicting the octane number (ON) of toluene primary reference fuel (TPRF; blends of n-heptane, isooctane, and toluene) was investigated. The electrotopological state (E-state) index of TPRF components was computed and weight-summed to generate the quantitative descriptor of TPRF samples. The partial least squares (PLS) technique was used to build up the regression model between the ON and weight-summed E-state index of the investigated samples. The QSPR models for the research octane number (RON) and motor octane number (MON) of TPRF were built. The prediction performance of the obtained PLS models was assessed by the external test set validation and leave-one-out cross-validation. The validation results demonstrate that the proposed PLS models are feasible for predicting the ON, both RON and MON, of TPRF. In addition, several other QSPR models for the ON of TPRF were developed by employing the stepwise regression and Scheffé polynomials methods, and the prediction performance of these models were compared with that of the PLS models. The comparison result shows that the proposed PLS models are slightly better than multiple linear regression models and Scheffé models. It is demonstrated that the combination of the E-state index and PLS is an easy-to-use and promising method for studying and forecasting the ON of TPRF.

Currently, there is a growing concern regarding water remediation from agricultural and domestic wastewaters. Among water treatment methods, flocculation is a widely used approach. In this study, the bioflocculation of wastewaters from Sinaloa (Mexico) was examined using two bioflocculants: chitosan and bean straw flour (BSF). The jar-test results showed that chitosan exhibited high effectiveness in pollutant removal from different sampling zones (agricultural wastewater and river water). Additionally, this bioflocculant reduced remarkably the concentration of Mn and Fe. On the other hand, BSF showed high effectiveness in pollutant removal for a specific type of wastewater, being highly competitive as compared to chitosan. Besides, BSF led to 40% of Mn removal from highly contaminated river water samples. For both biomaterials, bioflocculation was driven by charge neutralization and sweep flocculation mechanisms. For a given agricultural wastewater sample, both bioflocculants performed better than the commercial poly(aluminum chloride) for pH regulation and Fe removal.

An ecofriendly, magnetically retrievable amine-functionalized SiO2@Fe3O4 catalyst was successfully synthesized and affirmed by several physicochemical characterization tools, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), energy-dispersive X-ray spectroscopy (EDX), and powder X-ray diffraction. Thereafter, the catalytic performance of this environmentally benign NH2@SiO2@Fe3O4 catalyst was investigated in the one-pot multicomponent synthesis of 2-amino-4H-benzo[b]pyran derivatives. The reaction was simply achieved by grinding of various substituted aromatic aldehydes, dimedone, and malononitrile at room temperature under solvent and waste-free conditions with excellent yields and high purity. Moreover, the developed catalyst not only possesses immense potential to accelerate the synthesis of bioactive pyran derivatives but also exhibits several remarkable attributes like broad functional group tolerance, durability, improved yield, reusability, and recyclability. Besides, various other fascinating advantages of this protocol are milder reaction conditions, cost effectiveness, short reaction time, and simple work up procedures.

Carbonic anhydrase IX (CAIX) is a membrane-bound enzyme associated with tumor hypoxia and found to be over expressed in various tumor conditions. Targeting CAIX catalytic activity is proven to be efficient modality in modulating pH homeostasis in cancer cells. Proteoglycan-like (PG) region is unique to CAIX and is proposed to serve as an antenna enhancing the export of protons in conjunction with facilitated efflux of lactate ions via monocarboxylate transporters. Moreover, the PG region is also reported to contribute to the assembly and maturation of focal adhesion links during cellular attachment and dispersion on solid supports. Thus, drug targeting of this region shall efficiently modulate pH homeostasis and cell adhesion in cancer cells. As the PG region is intrinsically disordered, the complete crystal structure is not elucidated. Hence, in this study, we intend to sample the conformational landscape of the PG region at microsecond scale simulation in order to sample the most probable conformations that shall be utilized for structure-based drug design. In addition, the sampled conformations were subjected to high-throughput virtual screening against NCI and Maybridge datasets to identify potential hits based on consensus scoring and validation by molecular dynamics simulation. Further, the identified hits were experimentally validated for efficacy by in vitro and direct enzymatic assays. The results reveal 5-(2-aminoethyl)-1,2,3-benzenetriol to be the most promising hit as it showed significant CAIX inhibition at all levels of in silico and experimental validation.

X inactivate-specific transcript (XIST) is an attractive long noncoding RNA (lncRNA) functioning as an indicator of various human tumors, including laryngeal squamous cell carcinoma (LSCC). The present study was conducted to explore a novel regulatory network of lncRNA XIST in LSCC cells.

Vaspin, visceral-adipose-tissue-derived serine protease inhibitor, is involved in the development of obesity, insulin resistance, inflammation, and energy metabolism. Our previous study showed vaspin expression and its regulation in the ovary; however, the role of this adipokine in ovarian cells has never been studied. Here, we studied the in vitro effect of vaspin on various kinase-signaling pathways: mitogen-activated kinase (MAP3/1), serine/threonine kinase (AKT), signal transducer and activator of transcription 3 (STAT3) protein kinase AMP (PRKAA1), protein kinase A (PKA), and on expression of nuclear factor kappa B (NFKB2) as well as on steroid synthesis by porcine ovarian cells. By using western blot, we found that vaspin (1 ng/ml), in a time-dependent manner, increased phosphorylation of MAP3/1, AKT, STAT3, PRKAA1, and PKA, while it decreased the expression of NFKB2. We observed that vaspin, in a dose-dependent manner, increased the basal steroid hormone secretion (progesterone and estradiol), mRNA and protein expression of steroid enzymes using real-time PCR and western blot, respectively, and the mRNA of gonadotropins (FSHR, LHCGR) and steroids (PGR, ESR2) receptors. The stimulatory effect of vaspin on basal steroidogenesis was reversed when ovarian cells were cultured in the presence of a PKA pharmacological inhibitor (KT5720) and when GRP78 receptor was knocked down (siRNA). However, in the presence of insulin-like growth factor type 1 and gonadotropins, vaspin reduced steroidogenesis. Thus, vaspin, by activation of various signaling pathways and stimulation of basal steroid production via GRP78 receptor and PKA, could be a new regulator of porcine ovarian function.

Itacitinib is a novel, selective, Janus kinase 1 inhibitor in development for treatment of graft-versus-host disease. The objective of this study was to assess pharmacokinetics and safety of 300-mg itacitinib dosed in participants with normal renal function (n = 10), severe renal impairment (n = 8), and end-stage renal disease (ESRD) on hemodialysis (n = 8). Serial plasma and urine samples (urine from normal and severe groups only) were collected before dosing until 72 hours after dosing. In the ESRD group, itacitinib was evaluated in 2 periods, when dosed before (period 1) and after (period 2) a hemodialysis session. Geometric mean ratios (90% confidence interval) in participants with severe renal impairment, ESRD period 1 and ESRD period 2 relative to participants with normal renal function were 1.65 (1.13-2.39), 0.71 (0.49-1.03), and 0.83 (0.57-1.20) for maximum plasma drug concentration and 2.23 (1.56-3.18), 0.81 (0.57-1.16), and 0.95 (0.66-1.35) for area under the plasma concentration-time curve from time zero to infinity. Itacitinib was well tolerated, and 3 grade 1 treatment-emergent adverse events were reported over the course of the study. Given the magnitude of exposure changes in participants with severe renal impairment or ESRD and the historic risk-benefit profile, no dose adjustment is recommended for itacitinib in patients with impaired renal function, although the final dosage recommendation will be based on cumulative pharmacokinetics and safety from this study and from the pivotal graft-versus-host disease trial. Additionally, itacitinib may be administered to patients undergoing dialysis regardless of the time of dialysis.