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A glioma is the most common malignant primary brain tumor in adults and is categorized according to its growth potential and aggressiveness. Within gliomas, grade 4 glioblastoma remains one of the most lethal malignant solid tumors, with a median survival time less than 18 months. By encapsulating CPT-11 and oleic acid-coated magnetic nanoparticles (OMNPs) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we first prepared PLGA@OMNP@CPT-11 nanoparticles in this study. After conjugating cetuximab (CET) with PLGA@OMNP@CPT-11, spherical PLGA@OMNP@CPT-11-CET nanoparticles with 250 nm diameter, 33% drug encapsulation efficiency, and 22% drug loading efficiency were prepared in a single emulsion/evaporation step. The nanoparticles were used for dual-targeted delivery of CPT-11 to U87 primary glioblastoma cells by actively targeting the overexpressed epidermal growth factor receptor on the surface of U87 cells, as well as by magnetic targeting. The physicochemical properties of nanoparticles were characterized in detail. CET-mediated targeting promotes intracellular uptake of nanoparticles by U87 cells, which can release four times more drug at pH 5 than at pH 7.4 to facilitate drug release in endosomes after intracellular uptake. The nanovehicle PLGA@OMNP-CET is cytocompatible and hemocompatible. After loading CPT-11, PLGA@OMNP@CPT-11-CET shows the highest cytotoxicity toward U87 compared with free CPT-11 and PLGA@OMNP@CPT-11 by providing the lowest drug concentration for half-maximal cell death (IC50) and the highest rate of cell apoptosis. In orthotopic brain tumor-bearing nude mice with U87 xenografts, intravenous injection of PLGA@OMNP@ CPT-11-CET followed by guidance with a magnetic field provided the best treatment efficacy with the lowest tumor-associated signal intensity from bioluminescence imaging.

Collisional resonances of molecules can offer a deeper understanding of interaction potentials and collision complexes, and allow control of chemical reactions. Here, we experimentally map out the spectrum of Feshbach resonances in collisions between ultracold triplet rovibrational ground-state NaLi molecules and Na atoms over a range of 1400 G. Preparation of the spin-stretched state puts the system initially into the nonreactive quartet potential. A total of 25 resonances are observed, in qualitative agreement with quantum-chemistry calculations using a coupled-channels approach. Although the theory cannot predict the positions of resonances, it can account for several experimental findings and provide unprecedented insight into the nature and couplings of ultracold, strongly interacting complexes. Previous work has addressed only weakly bound complexes. We show that the main coupling mechanism results from spin-rotation and spin-spin couplings in combination with the anisotropic atom-molecule interaction, and that the collisional complexes which support the resonances have a size of 30a_{0}–40a_{0}. This study illustrates the potential of a combined experimental and theoretical approach.

Acupuncture treatment in local areas is commonly used to treat pain or soreness; however, acupuncture around the neck or shoulder may be a risk factor for pneumothorax. Herein, we report two cases of iatrogenic pneumothorax after acupuncture. These points indicate that physicians should be aware of these risk factors through history-taking before acupuncture. Chronic pulmonary diseases, such as chronic bronchitis, emphysema, tuberculosis, lung cancer, pneumonia, and thoracic surgery, may be associated with a higher risk of iatrogenic pneumothorax after acupuncture. Even if the incidence of pneumothorax should be low under caution and fully evaluated, it is still recommended to arrange further imaging examinations to rule out the possibility of iatrogenic pneumothorax.

Magnesium phosphate (MgP) has garnered growing interest in hard tissue replacement processes due to having similar biological characteristics to calcium phosphate (CaP). In this study, an MgP coating with the newberyite (MgHPO4·3H2O) was prepared on the surface of pure titanium (Ti) using the phosphate chemical conversion (PCC) method. The influence of reaction temperature on the phase composition, microstructure, and properties of coatings was systematically researched with the use of an X-ray diffractometer (XRD), a scanning electron microscope (SEM), a laser scanning confocal microscope (LSCM), a contact angle goniometer, and a tensile testing machine. The formation mechanism of MgP coating on Ti was also explored. In addition, the corrosion resistance of the coatings on Ti was researched by assessing the electrochemical behavior in 0.9% NaCl solution using an electrochemical workstation. The results showed that temperature did not obviously affect the phase composition of the MgP coatings, but affected the growth and nucleation of newberyite crystals. In addition, an increase in reaction temperature had a great impact on properties including surface roughness, thickness, bonding strength, and corrosion resistance. Higher reaction temperatures resulted in more continuous MgP, larger grain size, higher density, and better corrosion resistance.

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis:

Abstract Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

The effect of nano-scaled Si3N4 particles on the microstructure, mechanical and electrochemical behavior of hopeite (Zn3(PO4)2·4H2O) conversion coating on pure titanium was investigated. Different concentrations of nanoparticles were dispersed into the phosphating bath to incorporate the process of coating deposition. The XRD results demonstrated that nano-Si3N4 were doped into the coatings without any decomposition or reaction with the hopeite phase. A finer and denser microstructure of the composite coating could be obtained at the addition of 0.5 g/L Si3N4 in comparison with the pure hopeite coating. Moreover, the composite coating presented a higher bonding strength and corrosion resistance related to the refinement of microstructure and filling of the embedded nanoparticles. It is suggested that the incorporation of nano-Si3N4 particles in conversion coating is a promising approach for performance optimization.

Abstract Longitudinal trends on traumatic cataract wound dehiscence are scant. In this study, we present the characteristics of traumatic cataract wound dehiscence using 15 years of longitudinal trend in one of the largest medical centers in Taiwan for a period when cataract surgeries were gradually shifting from extracapsular cataract extraction (ECCE) to phacoemulsification. All patients with a prior cataract surgery who suffered from blunt open globe trauma between 2001 and 2015 at a tertiary referral center in Taiwan were included. The number of cases per year; type of prior cataract surgery; visual acuity (VA); mechanism and place of injury were analyzed. The risk factors associated with final VA were investigated in patients followed up for ≥ 1 month. Seventy-six eyes of 75 patients were included and all of them were traumatic cataract wound dehiscence with a prior ECCE (65 eyes) or phacoemulsification. The most common mechanism and place of injury was fall and at home in both cataract surgical types. The mean log of the minimal angle resolution (logMAR) of final VA was 2.15 ± 0.88 (ECCE) and 1.61 ± 0.83 (phacoemulsification) (P = .026). The most significant risk factors associated with worse final VA were retinal detachment at the initial visit and low ocular trauma score (both P

The number of older adults is rising rapidly in China. Various concerns such as chronic diseases, financial inadequacy, and a feeling of loneliness have adversely affected the mental health of older adults, and this has become an important public health and social issue. To realize healthy aging, the Nineteenth National People's Congress of China put forth the Healthy China strategy, speeding up the promotion activities of mental health and pension measures, carrying out public welfare pension insurance for the entire population, and contributing to the mental health of older adults. This study used data from China Family Panel Studies. This study mainly uses the random effect estimation method (random effect, RE) and the feasible generalized least squares estimation method (FGLS) to control for heterogeneity to explore the impact of social and commercial pension insurance on the mental health of older adults, the moderating effect of social capital on pension insurance, and the mental health of older adults. The results showed that social pension insurance is proportional to the mental health of older adults, whereas commercial pension insurance is inversely proportional to mental health. Social capital had a significant moderating effect on pension insurance. When a country develops an aging economy, the emphasis on social capital helps make targeted industrial development suggestions. The government's expansion of insurance coverage is crucial for improving the mental health of older adults.

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

We report both experimentally and numerically that near-perfect absorption of low-frequency sound is realized in an open tunnel embedded with two deep sub-wavelength (0.085 λ) Mie resonators. The resonators are composed of a multiple-cavity structure and an outer frame on three sides. In the eigenmode analysis, we obtain two types of monopolar Mie resonance modes (MMR I&II) in a single resonator around 250 Hz. The eigenfrequency of MMR I is mainly determined by the Helmholtz resonance of each cavity in the multiple-cavity structure, while that of MMR II is closely related to the coupling between the multiple-cavity structure and its outer frame, showing high performances of coupling and sound absorption. Based on the thermal viscous loss of sound energy in the channels created by the mutual coupling of MMR II of both Mie resonators with different diameters, the near-perfect sound absorption through the open tunnel is realized around 283 Hz. More interestingly, by increasing the number of Mie resonators in the tunnel, a broadband near-perfect sound absorption is observed, and the fractional bandwidth can reach about 0.25 and 0.46 for the tunnels with 6 and 13 resonators, The proposed deep sub-wavelength Mie resonator and its associated near-perfect sound absorptions have great potential applications in architectural acoustics and mechanical engineering.

Objective: Fatigue, a painful and unpleasant subjective experience, is common in perimenopausal women. Therefore, an effective tool to evaluate the fatigue-precipitating factor is important for perimenopausal women prone to fatigue syndrome. Materials and methods: This study was surveyed by short-term perimenopausal fatigue scale. The enrollment period was from November 2019 to January 2020. The subjects were perimenopausal women prone to perimenopausal fatigue. The differences between the fatigue-precipitating factors and the degrees of fatigue and disturbance were determined by one-way ANOVA and t test. Results: A total of 220 perimenopausal women with mean age of 51.3 years were included. Among these, 64.1% did not have a habit of regular exercise and 55.5% had chronic diseases. Fatigue syndrome was found in 64.1% of subjects, who were mainly presented by shoulder and neck pain and sleep problems. There were significant differences between “perimenopausal fatigue” and “duration” (p

Abstract Erectile dysfunction (ED) is mostly due to the lack of blood flow into the penis. In the past 20 years, near-infrared spectroscopy (NIRS) was used in measuring the concentrations and temporal dynamics of different hemoglobin types. However, the dynamics of the light absorption (photoplethysmography; PPG) have not been applied to survey penile hemodynamics and erection quality. This paper compared the use of photoplethysmography (PPG) to study vascular ED with standard penile Doppler ultrasonography. Men diagnosed with vascular ED for at least 6 months and nominated for penile ultrasonography were included. PPG signals were collected during the ultrasound examination. All beat-to-beat PPG waveforms were aligned with the peak and averaged to one representative template waveform for feature analysis, including amplitude differences (APD) index, reflection time index (RTI), augmentation index (AI), and perfusion index (PI). An inverse correlation was found between end-erection amplitude and both erection hardness score (EHS) and resistive index (RI). APD index and EHS as well as the international index of erectile function-5 (IIEF) and RI were positively correlated. RTI and AI were inversely correlated to IIEF and RI. PI was positively correlated to RI. PPG may therefore be useful as a noninvasive, convenient, technique for sexual function evaluation.

Climate change, which is mainly caused by carbon emissions, has attracted attention worldwide. With the continuous increase in temperature, the urban heat island effect, extreme weather, and water shortages have seriously affected the urbanization process. Through an empirical analysis of panel data from 28 provinces in China from 2006 to 2018, this study examines the impact of climate change-induced temperature changes on the urbanization of China’s population. The results show that the urbanization level has a significant double-threshold effect on the impact of temperature on urbanization. When the urbanization level crosses the corresponding threshold value, the negative impact of temperature on urbanization is relatively weak. Understanding the impact of climate change on urbanization has become increasingly important as climate warming increases. On the one hand, the climate issue has always been a topic of common concern around the world. On the other hand, studying how climate change affects population urbanization is conducive to identifying the human factors that affect climate change and proposing corresponding solutions. Simultaneously, it also provides a reference for optimizing the distribution of urban and rural populations, and can comprehensively consider the relationship between climate change and urbanization in the formulation and implementation of policies. On this basis, the Chinese government should strengthen financial support for climate change, play a leading role in policies, improve the urban layout and structure, and increase the resilience of cities to climate change.

While the Ganong lexicality effect has been observed for phonemic and tonal categorization, the effects of frequency and markedness are less clear, especially in terms of tonal categorization. In this study, we use Mandarin Chinese to investigate the effects of lexicality, tone frequency and markedness. We examined Mandarin speakers’ tonal categorization of tokens on all possible tonal continua with one end being a word and the other being a tonotactic gap (i.e., an unattested syllable-tone combination). The results of a forced-choice identification experiment showed a general bias against the gap endpoints, with the noted exception of continua involving T4 (X51), the most frequent lexical tone. Specifically, when T4 served as the gap endpoint, no obvious bias against it was observed regardless of its lexical status. Moreover, on the T3–T4 continua, there was an apparent bias against T3 (X214), the tone with the most complex contour, again, regardless of lexicality, suggesting a strong markedness effect. Taken together, the results of this study show the individual effects of lexicality, tone frequency and markedness, as well as their interactions, which contribute to our understanding of tonal categorization in relation to lexical statistics (tone frequency) and phonology (markedness).

Prophages have long been regarded as an important contributor to the evolution of Salmonella and Verotoxin-producing E. coli (VTEC), members of the Enterobacteriaceae that cause millions of cases of foodborne illness in North America. In S. Typhimurium, prophages provide many of the genes required for invasion; similarly, in VTEC, the Verotoxin-encoding genes are located in cryptic prophages. The ability of prophages to quickly acquire and lose genes have driven their rapid evolution, leading to highly diversified populations of phages that can infect distantly-related bacterial hosts. To defend against foreign genetic materials (i.e., phages), bacteria have evolved Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) immunity, consisting of variable spacer regions that match short nucleic acid sequences of invaders previously encountered. The number of spacer regions varies widely amongst Enterobacteriaceae, and there is currently no clear consensus if the accumulation of spacers is linked to genomic prophage abundance. Given the immense prophage diversity and contribution to bacterial host phenotypes, we analyzed the prophage sequences within 118 strains of Salmonella and VTEC, 117 of which are of agricultural origin. Overall, 130 unique prophage sequences were identified and they were found to be remarkably diverse with

Nitrate in plants is preferentially stored in vacuoles; however, how vacuolar nitrate is reallocated and to which biological process(es) it might contribute remain largely elusive. In this study, we functionally characterized three nitrate transporters NPF5.10, NPF5.14, and NPF8.5 that are tonoplast-localized. Ectopic expression in Xenopus laevis oocytes revealed that they mediate low-affinity nitrate transport. Histochemical analysis showed that these transporters were expressed preferentially in pericycle and xylem parenchyma cells. NPF5.10, NPF5.14, and NPF8.5 overexpression significantly decreased vacuolar nitrate contents and nitrate accumulation in Arabidopsis shoots. Further analysis showed that the sextuple mutant (npf5.10 npf5.14 npf8.5 npf5.11 npf5.12 npf5.16) had a higher 15NO3-uptake rate than the wild-type Col-0, but no significant difference was observed for nitrate accumulation between them. The septuple mutant (npf5.11 npf5.12 npf5.16 npf5.10 npf5.14 npf8.5 clca) generated by using CRISPR/Cas9 showed essentially decreased nitrate reallocation compared to wild type when exposed to nitrate starvation, though no further decrease was observed when compared to clca. Notably, NPF5.10, NPF5.14, and NPF8.5 as well as NPF5.11, NPF5.12, and NPF5.16 were consistently induced by mannitol, and more nitrate was detected in the sextuple mutant than in the wild type after mannitol treatment. These observations suggest that vacuolar nitrate efflux is regulated by several functional redundant nitrate transporters, and the reallocation might contribute to osmotic stress response other than mineral nutrition.

Plastic shed film used in ginseng cultivation could increase phthalate acid esters (PAEs) residues in ginseng and its planting soil. This study recorded the situation of 19 PAEs in ginseng, soil, and plastic shed film samples from eight ginseng cultivation bases in Jilin Province, China. The results showed that 6 PAEs are omnipresent contaminants in ginseng cultivation bases. The Σ19 PAEs residue ranged from 0.69 to 3.30 mg kg−1 in the soil and from 32.40 to 96.20 mg kg−1 in the plastic shed film. Plastic shed film is possibly one source of PAEs in ginseng bases. In addition, PAEs concentrations in different ginseng tissues (roots, stems, and leaves) showed significant differences (p < 0.05). The residues of Σ19 PAEs in ginseng roots and stems were 0.71–2.10 mg kg−1 [dry weight (dw)] and 1.56–4.69 mg kg−1 (dw), respectively, lower than 2.37–6.82 mg kg−1 (dw) in leaves (p < 0.05). PAEs more readily accumulated in ginseng leaves than in roots and stems. Cultivation age also influenced PAEs accumulation in ginseng. PAEs residues in 3-year-old ginseng plants were higher than those in annual and biennial ginseng (p < 0.05). The noncancer and carcinogenic risk assessments of the target PAEs in ginseng indicated acceptable levels for adult intake. This study provides data for understanding the concentration, distribution, and potential risk of PAEs in ginseng and its cultivated soil.

Abstract The Neural Decision Tree (NDT) is a hybrid supervised machine‐learning algorithm that combines the self‐limiting property of a decision tree (Classification and Regression Tree [CART]) algorithm with the artificial neural network. We demonstrate the use of NDT for a regression problem of building a prediction model for the plasmasphere electron density with solar and geomagnetic measurements as inputs. Our work replicates the work by Zhelavskaya et al. reported in their 2017 article (I. S. Zhelavskaya et al., 2017, https://doi.org/10.1002/2017JA024406) to show that NDT makes available sophisticated network layout for building a predictive model, thus taking advantage of deep‐learning potential of the neural network. We also demonstrate that with the ability to automatically select an appropriate network layout, as well as, effective initialization, the NDT algorithm allows research scientists in space weather to focus more of their attention on physically and statistically relevant aspects of using machine‐learning techniques. In fact, our example highlights the fact that the basic assumptions of standard supervise machine‐learning problems are often unsatisfied in real‐world space weather applications. Greater attention to these fundamental issues may create significantly different solutions to space weather forecast problems.

Many perception and processing effects of the lexical status of tone have been found in behavioral, psycholinguistic, and neuroscientific research, often pitting varieties of tonal Chinese against non-tonal Germanic languages. While the linguistic and cognitive evidence for lexical tone is therefore beyond dispute, the word prosodic systems of many languages continue to escape the categorizations of typologists. One controversy concerns the existence of a typological class of “pitch accent languages,” another the underlying phonological nature of surface tone contrasts, which in some cases have been claimed to be metrical rather than tonal. We address the question whether the Sequence Recall Task (SRT), which has been shown to discriminate between languages with and without word stress, can distinguish languages with and without lexical tone. Using participants from non-tonal Indonesian, semi-tonal Swedish, and two varieties of tonal Mandarin, we ran SRTs with monosyllabic tonal contrasts to test the hypothesis that high performance in a tonal SRT indicates the lexical status of tone. An additional question concerned the extent to which accuracy scores depended on phonological and phonetic properties of a language’s tone system, like its complexity, the existence of an experimental contrast in a language’s phonology, and the phonetic salience of a contrast. The results suggest that a tonal SRT is not likely to discriminate between tonal and non-tonal languages within a typologically varied group, because of the effects of specific properties of their tone systems. Future research should therefore address the first hypothesis with participants from otherwise similar tonal and non-tonal varieties of the same language, where results from a tonal SRT may make a useful contribution to the typological debate on word prosody.

ObjectiveProstate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer.Materials and MethodsWe retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis.ResultsIn total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate.ConclusionsThe post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.

Icariside I, the glycosylation product of icaritin, is a novel effective anti-cancer agent with immunological anti-tumor activity. However, very limited natural icariside I content hinders its direct extraction from plants. Therefore, we employed a computer-aided protein design strategy to improve the catalytic efficiency and substrate specificity of the α-L-rhamnosidase from Thermotoga petrophila DSM 13995, to provide a highly-efficient preparation method. Several beneficial mutants were obtained by expanding the active cavity. The catalytic efficiencies of all mutants were improved 16–200-fold compared with the wild-type TpeRha. The double-point mutant DH was the best mutant and showed the highest catalytic efficiency (kcat/KM: 193.52 s−1 M−1) against icariin, which was a 209.76-fold increase compared with the wild-type TpeRha. Besides, the single-point mutant H570A showed higher substrate specificity than that of the wild-type TpeRha in hydrolysis of different substrates. This study provides enzyme design strategies and principles for the hydrolysis of rhamnosyl natural products.

BackgroundTo evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during follow-up.MethodsThyroid cancer patients registered in Chang Gung Memorial Hospital thyroid cancer database between January 1979 and December 2019 were assessed.ResultsAmong 1053 DTC patients with excellent response to initial therapy, 14 (1.3%) patients developed metastatic disease during follow-up, including 6 males and 8 females with median age of 50.2 years [interquartile range (IQR), 39.9-53.7]. Nine (64.3%) patients had papillary cancer, four (28.6%) had follicular cancer, and one (7.1%) had Hürthle cell cancer. Most patients (92.9%) had stage I disease at diagnosis. The sites of metastasis were lung (71.4%), bone (7.1%), mediastinum (7.1%) and multiple sites (14.3%). With a median follow-up of 18.3 years (IQR, 14.8-23.8), 2 patients had disease-specific mortality. The 5- and 10-year disease-specific survival after the diagnosis of distant metastasis was 92% and 74%, respectively. Multiple sites of metastasis was associated with increased risk of mortality (P = 0.022).ConclusionsA small proportion of DTC patients with an excellence response to initial therapy developed distant metastasis during follow-up. Multiple organ distant metastases conferred a worse disease-specific survival.

Tripterygium glycosides tablets (TGT) are widely used for treating nephrotic syndrome (NS), but hepatotoxicity is frequently reported. The presence of underlying disease(s) can alter the disposition of drugs and affect their efficacy and toxicity. However, no studies have reported the impact of NS on the ADME profiles of TGT or its subsequent impact on the efficacy and toxicity. Thus, the efficacy and hepatotoxicity of TGT were evaluated in normal and NS rats after oral administration of TGT (10 mg/kg/day) for 4 weeks. The corresponding ADME profiles of the six key TGT components (triptolide (TPL), wilforlide A (WA), wilforgine (WFG), wilfortrine (WFT), wilfordine (WFD), and wilforine (WFR)) were also measured and compared in normal and NS rats after a single oral gavage of 10 mg/kg TGT. Canonical correlation analysis (CCA) of the severity of NS and the in vivo exposure of the six key TGT components was performed to screen the anti–NS and hepatotoxic material bases of TGT. Finally, the efficacy and hepatotoxicity of the target compounds were evaluated in vitro. The results showed that TGT decreased the NS symptoms in rats, but caused worse hepatotoxicity under the NS state. Significant differences in the ADME profiles of the six key TGT components between the normal and NS rats were as follows: higher plasma and tissue exposure, lower urinary and biliary excretion, and higher fecal excretion for NS rats. Based on CCA and in vitro verification, TPL, WA, WFG, WFT, WFD, and WFR were identified as the anti–NS material bases of TGT, whereas TPL, WFG, WFT, and WFD were recognized as the hepatotoxic material bases. In conclusion, NS significantly altered the ADME profiles of the six key TGT components detected in rats, which were related to the anti–NS and hepatotoxic effects of TGT. These results are useful for the rational clinical applications of TGT.

Microdrills are specific cutting tools widely used to drill microholes and microvias. For certain microdrill manufacturers, a conventional sampling inspection procedure is still manually operated for carrying out the destructive and visual measurements of two essential cross-sectional geometric parameters (CSGPs), called the cross-sectional web thickness (CSWT) and the cross-sectional outer diameter (CSOD), of their straight (ST) and undercut (UC) type microdrill products. In order to comprehensively automate the conventional sampling inspection procedure, a destructive and visual measuring system improved from an existing vision-aided automation system, for both the hardware and the automated measuring process (AMP), is presented in this paper. The major improvement of the hardware is characterized by a machine vision module consisting of several conventional machine vision components in combination with an innovative and lower cost optical subset formed by a set of plano-concave achromatic (PCA) lenses and a reflection mirror, so that the essential functions of visually positioning the drilltip and visually measuring the CSGPs can both be achieved via the use of merely one machine vision module. The major improvement of the AMP is characterized by the establishment of specific image processing operations for an auto-focusing (AF) sub-process based on two-dimensional discrete Fourier transform (2D-DFT), for a web thickness measuring (WTM) sub-process based on an iterative least-square (LS) circle-fitting approach, and for an outer diameter measuring (ODM) sub-process based on integrated applications of an iterative LS circle-fitting approach and an LS line-fitting-based group-dividing approach, respectively. Experiments for measuring the CSGPs of microdrill samples were conducted to evaluate the actual effectiveness of the developed system. It showed that the developed system could achieve good repeatability and accuracy for the measurements of the CSWTs and CSODs of both ST and UC type microdrills. Therefore, the developed system could effectively and comprehensively automate the conventional sampling inspection procedure.

Surface plasmon resonance (SPR) sensing is a real-time detection technique for measuring biomolecular interactions on gold surfaces. This study presents a novel approach using nano-diamonds (NDs) on a gold nano-slit array to obtain an extraordinary transmission (EOT) spectrum for SPR biosensing. We used anti-bovine serum albumin (anti-BSA) to bind NDs for chemical attachment to a gold nano-slit array. The covalently bound NDs shifted the EOT response depending on their concentration. The number of ND-labeled molecules attached to the gold nano-slit array was quantified from the change in the EOT spectrum. The concentration of anti-BSA in the 35 nm ND solution sample was much lower than that in the anti-BSA-only sample (approximately 1/100). With the help of 35 nm NDs, we were able to use a lower concentration of analyte in this system and obtained better signal responses. The responses of anti-BSA-linked NDs had approximately a 10-fold signal enhancement compared to anti-BSA alone. This approach has the advantage of a simple setup and microscale detection area, which makes it suitable for applications in biochip technology.

The structure used in this study is as follows: substrate/PMMA/ZnS/Ag/MoO3/NPB/Alq3/LiF/Al. Here, PMMA serves as the surface flattening layer, ZnS/Ag/MoO3 as the anode, NPB as the hole injection layer, Alq3 as the emitting layer, LiF as the electron injection layer, and aluminum as the cathode. The properties of the devices with different substrates were investigated using P4 and glass, developed in the laboratory, as well as commercially available PET. After film formation, P4 creates holes on the surface. The light field distribution of the device was calculated at wavelengths of 480 nm, 550 nm, and 620 nm using optical simulation. It was found that this microstructure contributes to light extraction. The maximum brightness, external quantum efficiency, and current efficiency of the device at a P4 thickness of 2.6 μm were 72,500 cd/m2, 1.69%, and 5.68 cd/A, respectively. However, the maximum brightness of the same structure with PET (130 μm) was 9500 cd/m2. The microstructure of the P4 substrate was found to contribute to the excellent device performance through analysis of the AFM surface morphology, film resistance, and optical simulation results. The holes formed by the P4 substrate were created solely by spin-coating the material and then placing it on a heating plate to dry, without any special processing. To confirm the reproducibility of the naturally formed holes, devices were fabricated again with three different emitting layer thicknesses. The maximum brightness, external quantum efficiency, and current efficiency of the device at an Alq3 thickness of 55 nm were 93,400 cd/m2, 1.7%, and 5.6 cd/A, respectively.

Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment.

Aromatic polyimide has good mechanical properties and high-temperature resistance. Based on this, benzimidazole is introduced into the main chain, and its intermolecular (internal) hydrogen bond can increase mechanical and thermal properties and electrolyte wettability. Aromatic dianhydride 4,4′-oxydiphthalic anhydride (ODPA) and benzimidazole-containing diamine 6,6′-bis [2-(4-aminophenyl)benzimidazole] (BAPBI) were synthesized by means of a two-step method. Imidazole polyimide (BI-PI) was used to make a nanofiber membrane separator (NFMS) by electrospinning process, using its high porosity and continuous pore characteristics to reduce the ion diffusion resistance of the NFMS, enhancing the rapid charge and discharge performance. BI-PI has good thermal properties, with a Td5% of 527 °C and a dynamic mechanical analysis Tg of 395 °C. The tensile strength of the NFMS increased from 10.92MPa to 51.15MPa after being hot-pressed. BI-PI has good miscibility with LIB electrolyte, the porosity of the film is 73%, and the electrolyte absorption rate reaches 1454%. That explains the higher ion conductivity (2.02 mS cm−1) of NFMS than commercial one (0.105 mS cm−1). When applied to LIB, it is found that it has high cyclic stability and excellent rate performance at high current density (2 C). BI-PI (120 Ω) has a lower charge transfer resistance than the commercial separator Celgard H1612 (143 Ω).

Proton pump inhibitors (PPIs) are widely prescribed in medical practice for the treatment of several gastrointestinal disorders. Previous epidemiology studies have reported the association between PPI use and the risk of AKI, although the magnitude of the association between PPIs and the risk of acute kidney injury (AKI) remains uncertain. Therefore, we conducted a meta-analysis to determine the relationship between PPI therapy and the risk of AKI. We systematically searched for relevant articles published before January 2023 on PubMed, Scopus, and Web of Science. In addition, we conducted a manual search of the bibliographies of potential articles. Two independent reviewers examined the appropriateness of all studies for inclusion. We pooled studies that compared the risk of AKI with PPI against their control using a random effect model. The search criteria based on PRISMA guidelines yielded 568 articles. Twelve observational studies included 2,492,125 individuals. The pooled adjusted RR demonstrated a significant positive association between PPI therapy and the risk of AKI (adjusted RR 1.75, 95% CI: 1.40–2.19, p < 0.001), and it was consistent across subgroups. A visual presentation of the funnel plot and Egger’s regression test showed no evidence of publication bias. Our meta-analysis indicated that persons using PPIs exhibited an increased risk of AKI. North American individuals had a higher risk of AKI compared to Asian and European individuals. However, the pooled effect from observational studies cannot clarify whether the observed association is a causal effect or the result of some unmeasured confounding factors. Hence, the biological mechanisms underlying this association are still unclear and require further research.

Abstract Background Limited data were available on the current trends in optimal medical therapy (OMT) after PCI and its influence on clinical outcomes in China. We aimed to evaluate the utilization and impact of OMT on the main adverse cardiovascular and cerebrovascular events (MACCEs) in post-PCI patients and analyzed the factors predictive of OMT after discharge. Methods We collected data from 3812 individuals from 2016.10 to 2017.09 at TEDA International Cardiovascular Hospital. They were classified into an OMT group and a non-OMT group according to their OMT status, which was defined as the combination of dual antiplatelet therapy, statins, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers after PCI. Multivariable Cox regression models were developed to assess the association between OMT and MACCEs, defined as all-cause mortality, nonfatal myocardial infarction, stroke, and target vessel revascularization. A logistic regression model was established to analyze the factors predictive of OMT. Results Our results revealed that the proportion of patients receiving OMT and its component drugs decreased over time. A total of 36.0% of patients were still adherent to OMT at the end of follow-up. Binary logistic regression analysis revealed that baseline OMT (P