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To alleviate the dilemma of drug administration in Alzheimer’s disease (AD) patients, it is of great significance to develop a new drug delivery system. In this study, a subcutaneously implanted microneedle (MN) device with a swellable gelatin methacryloyl (GelMA) needle body and a dissolvable polyvinyl alcohol (PVA) backing layer was designed. The backing layer quickly dissolved once the MN was introduced into the subcutaneous, and the hydrogel needles were implanted in the subcutaneous to enable prolonged drug release. Compared with oral administration, the MN system offers the benefits of a high administration rate, a fast onset of effect, and a longer duration of action. By detecting the concentration of acetylcholine (ACH) and Aβ 1–42, it was found that MN administration exhibited a stronger therapeutic effect. The biological safety of the MN system was also assessed, and no obvious signs of hemolysis, cytotoxicity, and inflammatory reaction were observed. Together, these findings suggested that the MN system is a convenient, efficient, and safe method of delivering donepezil hydrochloride (DPH) and may provide AD patients with a novel medicine administration option.

In this study, we reported two types of PMNs based on polylactic acid (PLA) and polyvinyl alcohol (PVA), respectively. Parafilm M® film, porcine skin, and rats' models were operated to evaluate the mechanical properties in vitro and in vivo to find optimal parameters for efficient insertion. Insertion depth was measured using Digital Force Gauge by changing insertion force and speed, respectively. Results showed that increasing the insertion force and speed used for PMNs application led to a significant increase in the depth of insertion. A force of 18 N under a speed of 330 mm/min was the optimal condition for inserting PMNs array into Parafilm M® film and porcine skin. In addition, PLA-MNs exhibited higher robustness and enhanced homogeneity in insertion depth compared with PVA-MNs, but PVA-MNs were able to reach much deeper insertion depth. Moreover, Sprague Dawley (SD) rat experiments confirmed the effectiveness of optimal insertion parameters for transdermal drug delivery. This study illustrated not only the development of novel PMNs but also the mechanical evaluation for the design of PMNs. [ABSTRACT FROM AUTHOR]

The stability of drug-loaded nanoparticles in vivo is related to the success of the drug delivery, which is investigated as a deficiency due to the limitation of traditional experimental methods. In this study, dissipative particle dynamics (DPD), a simulation method suitable for soft matter and fluids, was used to study the stability of amphiphilic nanoparticles in the blood microenvironment. By comparing the morphology alteration of nanoparticles with various molecular topologies in the shear fluid field, we have found that branch degree and geometric symmetry would be the key factors in maintaining the nanoparticle’s stability. This research could provide more theoretical guidance for drug delivery system design.

ABSTRACTA Ka-band multifunctional quadrupler with high harmonic rejection and high output power flatness has been designed, fabricated and measured using GaAs process. The quadrupler is integrated with two amplifiers, two filters, a limiter and a quadrupler in a single chip. Measurement results show that this chip achieves an output power of 16.7 dBm with an input power range from −5 to 1 dBm, in the frequency range of 34–36 GHz. A high output power flatness of ±0.8 dB is demonstrated at all working temperatures. Harmonics in the output spectrum are suppressed by more than 50 dBc. The total chip power consumption is about 130 mA with 5 V bias voltage, occupying an area of 2.26 × 3.26 mm2. The proposed MMIC is able to be effectively integrated into a multifunction module for wideband active electronically scanned array or phased array systems.

Objective: Dyslipidemia is associated with an increased risk of cardiovascular disease, the major cause of death in an aging population. This study aimed to estimate the prevalence of dyslipidemia for the past decade among adults in Wuhan, China. Methods: We performed a serial cross-sectional study that recruited 705 219 adults from the Health Management Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2010 to 2019. The diagnosis of dyslipidemia was based on the 2016 Chinese Guidelines for the Management of Dyslipidemia in Adults. Fixed effects and random effects models were applied to adjust the confounding variables (gender and age). Results: The overall prevalence of dyslipidemia was 33.1% (46.2% in men and 14.7% in women) in 2019. The prevalence of dyslipidemia was significantly increased over 10 years [from 28.6% (95% CI: 28.2%–29.1%) in 2010 to 32.8 % (95% CI:32.6%–33.1%) in 2019;. P–0.001], especially for hypo-high-density lipoprotein cholesterolemia [from 18.4% (95% CI: 18.0%–18.8%) in 2010 to 24.5% (95% CI: 24.3%–24.7%) in 2019; P–0.001]. In 2019, the prevalence of dyslipidemia was higher in participants with comorbidities, including overweight/obesity, hypertension, diabetes, hyperuricemia, or chronic kidney disease, and dyslipidemia was the most significant among participants aged 30–39 years. Conclusion: This study demonstrated that dyslipidemia is on the rise in men, and more emphasis should be provided for the screening of dyslipidemia in young males for the primary prevention of cardiovascular and renal diseases.

The drug diffusion issue in microneedles is the focus of its medical application. It will not only affect the distribution of drugs in the needle body but will also have an impact on the drug release performance of the microneedle. The utilization of cross-linked polymer materials to obtain the drug diffusion control has been experimentally verified as a feasible method. However, the mechanism research on the molecular level is still incomplete. In this study, the dissipative particle dynamics (DPD) simulation has been applied to study the effect of the cross-linking reaction on drug diffusion in hyaluronic acid microneedles. We have discovered that when the cross-linking degree reaches 90%, the diffusion coefficient of the drug is 6.45 times lower than that of the uncross-linked system. The main reason for the decline in drug diffusion ability is that the cross-linking reaction varies the conformation of the polymer. The amplification in the cross-linking degree makes the polymer coils more compact and approach each other, finally forming a continuously distributed cross-linked network, which reduces its degradation rate in the body. Simultaneously, these cross-linked networks can also hinder the interaction of soluble drugs with water, thereby preventing the premature release of drugs. The simulation results are consistent with the data collected in the previous microneedle experiment. This work will be an extension of DPD simulation in the application of biological materials.

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker‐guided trial investigated whether in low immunological‐risk kidney transplants without pretransplant DSA and donor‐specific T cells assessed by a standardized IFN‐γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non‐inferior regarding 6‐month BPAR than tacrolimus‐based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E−) were randomized to LI (n= 48) or SOC (n= 53), E+ received the same SOC. Six‐ and 12‐month BPAR rates were higher among LI than SOC/E− (4/35 [13%] vs. 1/43 [2%], p= .15 and 12/48 [25%] vs. 6/53 [11.3%], p= .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per‐protocolanalyses. Post‐hoc analysis revealed that poor class‐II eplet matching, especially DQ, discriminated E− patients, notably E−/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p= .043). Eplet mismatch also predicted anti‐class‐I (p= .05) and anti‐DQ (p< .001) de novoDSA. Adverse events were similar, but E−/LI developed fewer viral infections, particularly polyoma‐virus‐associated nephropathy (p= .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune‐risk stratification and guide immunosuppression decision‐making in kidney transplantation. In a multicenter, randomized, biomarker‐guided trial assessing pretransplant donor‐reactive memory T cells for immunosuppression minimization in kidney transplant recipients, both absence of preformed cellular alloreactivity and optimal HLA class II molecular matching identified patients who could be maintained on tacrolimus monotherapy at 1 year after transplantation.

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E–) were randomized to LI (n= 48) or SOC (n= 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E– (4/35 [13%] vs. 1/43 [2%], p= .15 and 12/48 [25%] vs. 6/53 [11.3%], p= .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocolanalyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E– patients, notably E–/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p= .043). Eplet mismatch also predicted anti-class-I (p= .05) and anti-DQ (p< .001) de novoDSA. Adverse events were similar, but E–/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p= .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.

Human mitochondrial peptide deformylase (HsPDF) is responsible for removing the formyl group from N-terminal formylmethionines of newly synthesized mitochondrial proteins and plays important roles in maintaining mitochondria function. It is overexpressed in various cancers and has been proposed as a novel therapeutic target. Actinonin, a naturally occurring peptidomimetic HsPDF inhibitor, was reported to inhibit the proliferation of a broad spectrum of human cancer cells in vitro. However, its efficacy and pharmacokinetic profile requires significant improvement for therapeutic purposes. To obtain HsPDF inhibitors as anticancer therapeutics, we screened an in-house collection of actinonin derivatives and found two initial hits with antiproliferation activity. Further optimization along the peptidomimetic backbone lead to two series of compounds containing substituted phenyl moieties. They are potent HsPDF inhibitors and exhibited greatly improved antiproliferation activity in selected cancer cell lines. Finally, compound 15msignificantly inhibited the growth of human colon cancer in xenograft animal models.

Developing an efficient antimicrobial surface has important significance in the field of advanced biomaterials. A novel water-soluble benzophenone tetracarboxylamine derivative containing two quaternary ammonium groups, 3,3′-[4,4′-carbonyl-diphthalimide-]-bis(N-benzyl-N,N-dimethyl-N-propyl-1-aminium)dichloride (BPTCA-N), as a photoactive antibacterial agent was designed and synthesized. The ability of BPTCA-N to generate reactive oxygen species (ROS) in solution was investigated by light-induced activity. Its antibacterial activity in a dark environment or UV exposure was tested on Staphylococcus aureusand Escherichia coli. The influences of different solvents and the pH values on the ability of BPTCA-N to generate ROS were also discussed. BPTCA-N possessed high photoactivity and efficient ROS generation ability. The generation of hydroxyl radicals could be greatly affected by addition of other solvents and H+or OH–. For the BPTCA-N solution at a concentration of 0.2 mmol/L, the reduction of S. aureusand E. colicould all reach 99.99%. The BPTCA-N compound was assembled onto wool protein fibers. The modified protein fabrics also showed excellent photoactivity and antibacterial property against S. aureusand E. coli. For the wool fabric modified with 30 g/L of BPTCA-N, the reduction of S. aureuscould reach 99.91% and that of E. coliwas 91.23%. BPTCA-N had the synergistic antibacterial effect of quaternary ammonium salt and benzophenones. It has potential application in the biomedical field as highly effective antimicrobial agent or antimicrobial biomaterial.

Epidemiological studies demonstrated that Helicobacter pylori(H. pylori) infection was associated with cardiovascular disease and its risk factors. However, the association between H. pyloriinfection and hypertension remained unclear. The aim of this study was to investigate the association between H. pyloriinfection and prevalence of hypertension among Chinese adults. We performed a cross-sectional study of 5246 adult participants who were recruited from a health manage center. All participants underwent a 13C-urea breath test and a routine health check-up. Logistic and liner regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for hypertension in relation to H. pyloriinfection. Of the 5168 study participants aged 18–70 years, 2034 (39.4%) were females and 955 (18.5%) had hypertension. After adjustment for potential confounders, H. pyloriinfection was associated with an increased prevalence of hypertension (OR, 1.23; 95% CI, 1.04, 1.46). In addition, compared with participants not infected with H. pylori, those with H. pyloriinfection had an increase of 0.735 mmHg (95% CI, 0.101, 1.369) for diastolic blood pressure and 0.723 mmHg (95% CI, 0.034, 1.413) for mean arterial pressure. There was no significant interaction between H. pyloriinfection and age, sex, and body mass index on the prevalence of hypertension (all Pvalues for interaction >0.05). Findings from this study demonstrate that H. pyloriinfection was positively associated with prevalence of hypertension among Chinese adults. More well-designed studies are warranted to confirm our findings.

Currently, the limited efficacy of antithrombotic treatments is attributed to the inadequacy of pure drugs and the low ability of drugs to target the thrombus site. More importantly, timely thrombolysis is essential to reduce the sequelae of cardiovascular disease, but ischemia–reperfusion injury (IRI) remains a major challenge that must be solved after blood flow recovery. Herein, a multifunctional therapeutic nanoparticle (NP) based on Fe3O4and strontium ions encapsulated in mesoporous polydopamine was successfully constructed and then loaded with TNK-tPA (FeM@Sr-TNK NPs). The NPs (59.9 min) significantly prolonged the half-life of thrombolytic drugs, which was 3.04 times that of TNK (19.7 min), and they had good biological safety. The NPs were shown to pass through vascular models with different inner diameters, curvatures, and stenosis under magnetic targeting and to enable accurate diagnosis of thrombi by photoacoustic imaging. NPs combined with the magnetic hyperthermia technique were used to accelerate thrombolysis and quickly open blocked blood vessels. Then, renal IRI-induced functional metabolic disorder and tissue damage were evidently attenuated by scavenging toxic reactive oxygen and nitrogen species and through the protective effects of bioactive ion therapy, including reduced apoptosis, increased angiogenesis, and inhibited fibrosis. In brief, we constructed a multifunctional nanoplatform for integrating a “diagnosis-therapy-protection” approach to achieve comprehensive management from thrombus to renal IRI, promoting the advancement of related technologies.

Small non-coding RNA genes have been concerned as an important field of life sciences in recent years. It plays important regulatory roles in cellular processes. However, the prediction of noncoding RNA genes is a great challenge, because non-coding RNAs have a small size, are not translated into proteins and show variable stability. In this paper, we propose an improved inter-nucleotide distances model as sequence characteristics, and combine with support vector machines (SVM) to predict small non-coding RNA in bacterial genomes. The prediction result of the mixed bacterial ncRNA is 95.38%, which shows that our method can effectively predict bacterial ncRNAs.

At present, microneedles have been widely used in transdermal drug delivery and detection due to their painless and non-invasive advantages, among which porous microneedles have great potential in dry or liquid drug delivery and disease monitoring due to their interoperable pore structure. However, previous literature paid little attention to the porous microneedles, and worse, most of them focused on the preparation methods of the porous microneedles used for drug delivery, while the matrix materials of porous microneedles and the potential for biomarker detection were rarely mentioned. The purpose of this review is to summarize the commonly used matrix materials for porous microneedles and highlight the ongoing challenges and prospects of their application in transdermal drug delivery and disease detection.

The article discusses the importance of modeling to ensure the stability of drilling horizontal coalbed methane (CBM) wells. Among the factors that affect wellbore stability are coal-seam thickness, seam depth, and overburden stress. It examines a CBM well in the Qinshui basin in China, particularly its water absorption rates, stresses, and mechanical properties.

MiR-145 has been implicated in the progression of non-small cell lung cancer (NSCLC); however, its exact mechanism is not well established. Here, we report that miR-145 expression is decreased in NSCLC cell lines and tumor tissues and that this low level of expression is associated with DNA methylation. MiR-145 methylation in NSCLC was correlated with a more aggressive tumor phenotype and was associated with poor survival time, as shown by Kaplan-Meier analysis. Additional multivariate Cox regression analysis indicated that miR-145 methylation was an independent prognostic factor for poor survival in patients with NSCLC. Furthermore, we found that restoration of miR-145 expression inhibited proliferation, migration and invasion of NSCLC by the direct targeting of mucin 1 by miR-145. Our results indicate that low miR-145 expression, due to methylation, promotes NSCLC cell proliferation, migration and invasion by targeting mucin 1. Therefore, miR-145 may be a valuable therapeutic target for NSCLC.

The results indicated that the amount of NO released by the furoxan-based derivatives (11a–b) of BA is generally higher than that of nitrate-based derivatives (4a–d), which is consistent with the anti-tumor activity of the corresponding derivatives. Especially, compounds 11aand 11bdisplayed the most promising potency against B16 cell lines and HepG2 cell lines (IC50<1μmol/L).