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Abstract Object Mycobacterium tuberculosis (MTB) is a bacterium that can cause zoonoses by aerosol transmission. Tuberculosis (TB) caused by MTB heavily burdens world public health security. Developing efficient, specific, convenient, and inexpensive MTB assays are essential for preventing and controlling TB. Methods In this study, we established a specific detection method for MTB using the Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) system, combined with recombinase mediated isothermal nucleic acid amplification (RAA) to improve the sensitivity of the detection system and achieve “two-level” amplification of the detection signal. The sensitivity and specificity of RAA combined with the CRISPR/Cas system were analyzed. Using BACTEC 960 culture as the gold standard for detecting MTB, we established the TB-CRISPR technique by testing 504 samples from patients with suspected TB. Results MTB H37Ra could be seen as low as 3.13 CFU/mL by the CRISPR-Cas12a system targeting IS6110. With BACTEC960 culture (120 positives and 384 negatives) as the gold standard, the sensitivity of the TB-CRISPR technique was 0.883 (0.809–0.932), and the specificity was 0.940 (0.910–0.961). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) reached 0.944 (0.914–0.975) within 95% CI. The positive likelihood ratio (PLR) was 14.747 (9.870-22.035), and the negative likelihood ratio (NLR) was 0.124 (0.076–0.203). The positive predictive value (PPV) was 0.822 (0.742–0.881), and the negative predictive value (NPV) was 0.963 (0.937–0.979). Conclusion TB-CRISPR plays an essential role in the molecular diagnosis of TB. The whole detection time is less than 1.5 h. It is easy to operate and does not need complex instruments. It is of great significance for the rapid detection of MTB and the clinical diagnosis of TB.

Abstract Background In recent years, minimally invasive and non-invasive rejuvenation methods have been welcomed. PRP has been used widely for skin rejuvenation, but there are few studies on PRP for lip rejuvenation. Objective The objective of this study was to investigate the preliminary effects of PRP for lip rejuvenation. Methods Between October 2018 and April 2023, 15 participants with lip aging (1 male, 14 females; range 27–58 years) were treated with PRP. The follow-up time was 3 to 24months. After 3 to 6 times treatments, beauty seekers and experienced physicians jointly evaluated effectiveness of treatment. The assessment included improvements in the colour, wrinkles, and skin texture of the lips before and after treatment. Results According to the beauty seekers and Surgeons ’evaluation, the aging characteristics of the lips of the 15 beauty seekers have been improved to varying degrees. The most obvious improvement was that the color of the lips which became more vivid. There was no swelling, bruising, scar hyperplasia and other complications. A participant was evaluated using the VISIA skin detector. The patient’s lip color and discoloration improved after treatment. Of the 15 participants treated. 3 participants experienced mild pain or discomfort during the injection process. There was no swelling, bruising, scar hyperplasia and other complications. Conclusion The results of this study revealed promising evidence of PRP as an effective option on lip rejuvenation. However, large, multi-center, controlled, long term, pilot studies are required to confirm the preliminary results of our study.

Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman’s syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose‐derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-β/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling.

The market value of tea is largely dependent on the tea species and cultivar. Therefore, it is important to develop efficient molecular markers covering the entire tea genome that can be used for the identification of tea varieties, marker-assisted breeding, and mapping important quantitative trait loci for beneficial traits. In this study, genome-wide molecular markers based on intron length polymorphism (ILP) were developed for tea trees. A total of 479, 1393, and 1342 tea ILP markers were identified using the PCR method in silico from the ‘Shuchazao’ scaffold genome, the chromosome-level genome of ‘Longjing 43’, and the ancient tea DASZ chromosome-level genome, respectively. A total of 230 tea ILP markers were used to amplify six tea tree species. Among these, 213 pairs of primers successfully characterize products in all six species, with 112 primer pairs exhibiting polymorphism. The polymorphism rate of primer pairs increased with the improvement in reference genome assembly quality level. The cross-species transferability analysis of 35 primer pairs of tea ILP markers showed an average amplification rate of 85.17% through 11 species in 6 families, with high transferability in Camellia reticulata and tobacco. We also used 40 pairs of tea ILP primers to evaluate the genetic diversity and population structure of C. tetracocca with 176 plants from Puan County, Guizhou Province, China. These genome-wide markers will be a valuable resource for genetic diversity analysis, marker-assisted breeding, and variety identification in tea, providing important information for the tea industry.

Abstract Background A complementary feeding (CF) period is necessary for nutritional and developmental reasons. Preterm children encounter more feeding problems than their term counterparts in the CF period. The goal of this study was to develop a nutritional risk screening tool specific to preterm children (the NRSP) in outpatient settings in the CF period, with the expectation of providing a standardised process to determine feeding problems and subsequently offering targeted nutritional advice. Methods This study was a 2-phase study consisting of the development and evaluation phases. In the development phase, the items of the NRSP were initially developed based on references and the Delphi expert consultation method. Second, 329 preterm individuals with corrected ages from 5 to 36 months were enrolled. The participating preterm children were interviewed with the NRSP and anthropometric measurements, and underwent intellectual developmental tests and biochemistry detection (haemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, serum iron, vitamin D). Third, preterm children’s anthropometric parameters were remeasured 1 month (for infants whose corrected age was 5–11 months) or 3 months (for children whose corrected age was 12–36 months) after the interview. Data in the development phase were analysed via univariate and binary logistic regression analysis sequentially to assign scores for items of the NRSP and to generate the models to predict underweight, stunting, and microcephaly of the NRSP. In the evaluation phase, another 605 preterm individuals were recruited to undergo the interview, anthropometric measurements, intellectual developmental tests, and biochemistry detection as in the development phase. Interrater reliability, test-retest reliability, area under the curve (AUC), accuracy, sensitivity, specificity, the positive/negative predictive value (P/NPV), the positive/negative likelihood ratio (LR+/−), and the correlation coefficient by Spearman’s correlation analysis (rs) were used to assess the reliability and validity of the NRSP. Finally, anthropometric parameters, biochemistry levels, and intellectual development quotients (DQs) from the development and evaluation phases between the high- and low-risk groups classified by the NRSP were compared using a t-test. Results The κ coefficients of the interrater and test-retest reliability of the NRSP were all above 0.600, which meant that the reliability of the NRSP was moderate to substantial. The NRSP exhibited relatively higher efficiency in predicting underweight and stunting, with AUCs, accuracies, specificities, and NPVs near to or greater than 0.900, sensitivities above 0.600, PPVs above 0.400, LR + s near to or greater than 10, and rss above 0.400. On the other hand, the NRSP manifested a weaker ability in predicting microcephaly, with most of the values of validity indicators lower than those of underweight and stunting prediction. Z scores of body weight, body length and head circumference, as well as DQs, were all higher in the low-risk groups than in the high-risk groups. There were no significant differences with respect to biochemistry levels between the high- and low-risk groups. Conclusion The NRSP shows moderate to substantial reliability and validity in predicting underweight, stunting, and microcephaly. Health care staff should shed light on improving the feeding practices of preterm children with high nutritional risk classified by the NRSP to facilitate their physical growth and intellectual development. More research is expected to promote the NRSP models.

Posterior reversible encephalopathy syndrome is a clinical-neuroradiological syndrome with typical neuroimaging features of posterior cerebral white matter changes that are usually reversible. However, there are only few reports of burns with posterior reversible encephalopathy syndrome in the literature. Hence, it is a clinical entity that many burn medicine physicians may be unfamiliar with. We report a case of severe burns complicated by posterior reversible encephalopathy syndrome in a 14-month-old male patient. On the eighth day of hospitalization, the child had persistent fever, occasional convulsions, eyes staring to the right, and high-pitched cry. Magnetic resonance imaging on day 10 showed the diagnosis is posterior reversible encephalopathy syndrome. We used hormone therapy to reduce cerebral oedema, oxcarbazepine to control convulsions, and multiple other drugs and physical measures to treat fever. The symptoms, signs, and imaging abnormalities of his posterior reversible encephalopathy syndrome were rapidly reversed in a short period of time. At the 1-year follow-up, the patient had recovered completely with no residual neurological signs and symptoms. To our knowledge, the patient may be the youngest recorded patient with both burns and posterior reversible encephalopathy syndrome. Careful observation, computed tomography, and magnetic resonance imaging can achieve early detection, early diagnosis, and early treatment of posterior reversible encephalopathy syndrome, which facilitates the achievement of desired therapeutic results. Further investigation is required to determine whether burns can serve as an independent posterior reversible encephalopathy syndrome causative factor and clarify the underlying pathogenesis mechanism.

Abstract Age-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.

Optogenetic technology is to express the channel proteins that can be act on light for realizing the activity of neurons activated and inhibited. Here, inspired by optogenetics, a flexible side‐gate artificial synaptic transistor based on ion gel and graphene is demonstrated, where the long‐term remembering or forgetting could be activated by the 450 nm light stimulus. Taking advantage of in‐plane‐field tunable carrier transport in graphene and the high ionic motion of ion gels, various synaptic functions under flatting or bending conditions by electric stimuli are successfully mimicked, including inhibition postsynaptic current, excitatory postsynaptic current, and paired‐pulse facilitation. A light‐induced forgetting or remembering is demonstrated by long‐term synaptic plasticity under 20 s and 10 Hz positive or negative gate pulse stimulus in the dark and 4 min recovery with light illumination. Moreover, the light stimulus promotes the associative learning and remembering function, which is demonstrated by Pavlov's dog experiment with electrical pulses and light stimulus. Such light‐assisted learning and memory function on synaptic plasticity can be attributed to the photogenerated electrons trapping effects in our device. The authors’ results provide a feasible strategy for realizing flexible light–electrical‐stimulus synaptic transistors and developing the low‐energy flexible neuromorphic optoelectronic hardware platform.

Background: Artificial intelligence (AI) has been successfully applied to the screening tasks of fundus diseases. However, few studies focused on the potential of AI to aid medical teaching in the residency training program. This study aimed to evaluate the effectiveness of the AI-based pathologic myopia (PM) identification system in the ophthalmology residency training program and assess the residents’ feedback on this system.Materials and Methods: Ninety residents in the ophthalmology department at the Second Affiliated Hospital of Zhejiang University were randomly assigned to three groups. In group A, residents learned PM through an AI-based PM identification system. In group B and group C, residents learned PM through a traditional lecture given by two senior specialists independently. The improvement in resident performance was evaluated by comparing the pre-and post-lecture scores of a specifically designed test using a paired t-test. The difference among the three groups was evaluated by one-way ANOVA. Residents’ evaluations of the AI-based PM identification system were measured by a 17-item questionnaire.Results: The post-lecture scores were significantly higher than the pre-lecture scores in group A (p < 0.0001). However, there was no difference between pre-and post-lecture scores in group B (p = 0.628) and group C (p = 0.158). Overall, all participants were satisfied and agreed that the AI-based PM identification system was effective and helpful to acquire PM identification, myopic maculopathy (MM) classification, and “Plus” lesion localization.Conclusion: It is still difficult for ophthalmic residents to promptly grasp the knowledge of identification of PM through a single traditional lecture, while the AI-based PM identification system effectively improved residents’ performance in PM identification and received satisfactory feedback from residents. The application of the AI-based PM identification system showed advantages in promoting the efficiency of the ophthalmology residency training program.

PurposeTo apply deep learning (DL) techniques to develop an automatic intelligent classification system identifying the specific types of myopic maculopathy (MM) based on macular optical coherence tomography (OCT) images using transfer learning (TL).MethodIn this retrospective study, a total of 3,945 macular OCT images from 2,866 myopic patients were recruited from the ophthalmic outpatients of three hospitals. After culling out 545 images with poor quality, a dataset containing 3,400 macular OCT images was manually classified according to the ATN system, containing four types of MM with high OCT diagnostic values. Two DL classification algorithms were trained to identify the targeted lesion categories: Algorithm A was trained from scratch, and algorithm B using the TL approach initiated from the classification algorithm developed in our previous study. After comparing the training process, the algorithm with better performance was tested and validated. The performance of the classification algorithm in the test and validation sets was evaluated using metrics including sensitivity, specificity, accuracy, quadratic-weighted kappa score, and the area under the receiver operating characteristic curve (AUC). Moreover, the human-machine comparison was conducted. To better evaluate the algorithm and clarify the optimization direction, the dimensionality reduction analysis and heat map analysis were also used to visually analyze the algorithm.ResultsAlgorithm B showed better performance in the training process. In the test set, the algorithm B achieved relatively robust performance with macro AUC, accuracy, and quadratic-weighted kappa of 0.986, 96.04% (95% CI: 0.951, 0.969), and 0.940 (95% CI: 0.909–0.971), respectively. In the external validation set, the performance of algorithm B was slightly inferior to that in the test set. In human-machine comparison test, the algorithm indicators were inferior to the retinal specialists but were the same as the ordinary ophthalmologists. In addition, dimensionality reduction visualization and heatmap visualization analysis showed excellent performance of the algorithm.ConclusionOur macular OCT image classification algorithm developed using the TL approach exhibited excellent performance. The automatic diagnosis system for macular OCT images of MM based on DL showed potential application prospects.

Brassica juncea has adapted to diverse climate zones and latitudes, especially in the Yunnan-Guizhou Plateau with the complexity and diversity of the ecological types of western China. However, the genetic variations underlying the diversity of these ecotypes are poorly known. In this study, we resequenced the genome of 193 indigenous B. juncea accessions and obtained 1.04 million high-quality SNPs and 3.23 million InDels by mapping reads to the reference genomes of B. juncea var. timuda. Phenotype, population genetic, phylogenetic and principal component analyses showed considerable genetic variation including four distinct genetic groups. Selective sweep analysis and a genome-wide association study revealed the candidate genes for seed color and fatty acid biosynthesis. The results provide a comprehensive insight into the spread and improvement of B. juncea and laya foundation for accelerating rapeseed breeding by facilitating screenings of molecular markers.

Immune cells infiltrating the tumour microenvironment play critical roles in disease pathogenesis and the immune response. Here the authors present the characterisation of infiltrating B cells in breast tumours by the formation of an atlas created from paired RNA sequence and antigen receptor profiling.

Abstract Background Antenatal corticosteroids (ACS) treatment is critical to support survival and lung maturation in preterm infants, however, its effect on feeding and growth is unclear. Prior preterm delivery, it remains uncertain whether ACS treatment should be continued if possible (repeated course ACS), until a certain gestational age is reached. We hypothesized that the association of single-course ACS with feeding competence and postnatal growth outcomes might be different from that of repeated course ACS in very-low-birth-weight preterm infants. Methods A multicenter retrospective cohort study was conducted in very-low-birth-weight preterm infants born at 23–37 weeks’ gestation in South China from 2011 to 2014. Data on growth, nutritional and clinical outcomes were collected. Repeated course ACS was defined in this study as two or more courses ACS (more than single-course). Infants were stratified by gestational age (GA), including GA

Abstract Studies have shown that the use of artificial intelligence can reduce errors in medical image assessment. The diagnosis of breast cancer is an essential task; however, diagnosis can include ‘detection’ and ‘interpretation’ errors. Studies to reduce these errors have shown the feasibility of using convolution neural networks (CNNs). This narrative review presents recent studies in diagnosing mammographic malignancy investigating the accuracy and reliability of these CNNs. Databases including ScienceDirect, PubMed, MEDLINE, British Medical Journal and Medscape were searched using the terms ‘convolutional neural network or artificial intelligence’, ‘breast neoplasms [MeSH] or breast cancer or breast carcinoma’ and ‘mammography [MeSH Terms]’. Articles collected were screened under the inclusion and exclusion criteria, accounting for the publication date and exclusive use of mammography images, and included only literature in English. After extracting data, results were compared and discussed. This review included 33 studies and identified four recurring categories of studies: the differentiation of benign and malignant masses, the localisation of masses, cancer‐containing and cancer‐free breast tissue differentiation and breast classification based on breast density. CNN's application in detecting malignancy in mammography appears promising but requires further standardised investigations before potentially becoming an integral part of the diagnostic routine in mammography.

In order to reduce the fluctuations of traffic flow and the impacts of traffic flow fluctuations, thereby increasing the level of service of roads and constructing the Internet of Things-based traffic system, based on the various causes of traffic flow fluctuations, the countermeasures were taken, such as the optimization of lanes, the management of intersections, the improvement and perfection of slow-vehicle lanes and bus stops, the timely renewal of traffic signs and marks, the rational arrangements of road operations, and the removal of visual obstacles, etc. The research results showed that these countermeasures could effectively reduce the hidden peril of accidents and improve the road capacity, thereby improving the level of service of roads, which provided a theoretical foundation and basis for road engineering design and traffic management. It can be seen that improving urban traffic through rational management and control measures can effectively improve the level of service of urban traffic.

Anemia is associated with neurodevelopmental delays and brain injury in infants and toddlers, but whether early anemia has a similar effect in neonatal preterm infants is largely unknown. Thus, this study aimed to determine the relationship of early anemia with neurodevelopment and brain injury in very-low-birth-weight (VLBW) preterm infants within the neonatal period. A prospective cohort study including 110 VLBW preterm infants was conducted in Southern China from 2016 to 2018. All participants were followed from birth to 1 month corrected age. Early anemia is defined as hemoglobin of ≤145 g/L within the first week after birth. The non-anemic group (control group, N = 55) was 1:1 matched with the early anemia group (N = 55) according to birth weight and gestational age. Neurodevelopment at 1 month corrected age and brain injury within 1 month corrected age were measured by neonatal behavioral neurological assessments (NBNA) and cranial ultrasound, respectively. Compared to the control group, the early anemia group had a lower score in behavioral ability in the NBNA test [11 (10–12) vs. 10 (9.5–11), p = 0.033]. Early anemia was negatively associated with the NBNA total score (β= −0.680, 95% CI: −1.300, −0.059), especially with the behavioral ability score (β= −0.504, 95% CI: −0.941, −0.067) after adjusting for the confounders. However, no association between early anemia and brain injury was observed. In conclusion, in VLBW preterm infants, early anemia is negatively correlated with neurodevelopment, especially with behavioral ability.

Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.

Coronavirus disease 2019 (COVID-19) has become a global public health concern. We aimed to study the cytokine profile during the convalescent phase and its association with liver functions. We performed a retrospective study to investigate the longitudinal dynamic serum cytokine, liver function, and metabolomic profiles, as well as their potential correlations, from the viral replication phase to early convalescence. Our results demonstrated that liver injury was common. Liver injury was significantly associated with higher levels of interleukin (IL)-6 and IL-10 (p < 0.05). However, alanine aminotransferase levels decreased during the first week after hospital discharge (p < 0.01). In parallel, T-cell and B-cell immune response-stimulating cytokine IL-4, but not IL-2, was significantly elevated (p < 0.05). Furthermore, interferon-γ (IFN-γ) and tumor necrosis factor-α (TFN-α) levels increased, in contrast to the decrease in IL-6 and IL-10 levels; liver function returned to normal. The metabolomic analysis supported active recovery during early convalescence of COVID-19 patients that had distinct metabolic profiles associated with the hepatic tricarboxylic acid cycle, amino acid metabolism, and lipid metabolism. In addition, we identified a metabolomic association of IL-4 with liver repair. Our findings suggest that discharged patients continue to recover from the physiological effects of COVID-19, and the association of IL-4, IL-6, and IL-10 levels with metabolic changes and liver function repair may have important implications for clinical manifestations and treatment of COVID-19.

Humic acid (HA) is a kind of organic substance that has shown good effects in regard to promoting crop growth. In the current study, the influences of three kinds of fertilizers mainly containing humic/fulvic acids, including water-soluble fertilizer containing humic acid (WHA), fulvic acid potassium (FAP), and fulvic acid distillate (FAD), on the qualities of ‘Eureka’ lemon fruits were investigated systematically at their different harvest times. As demonstrated by the results, the indexes used to assess the quality of lemon fruit showed that all lemons treated with those three humic/fulvic acid fertilizers at different harvest times improved in quality. Notably, the single fruit weight, edible rate, and juice yield of lemon fruit in the WHA- and FAP-treated groups, as well as the contents of vitamin C, total acid, total sugar, and total soluble solid, were higher than those in the blank control (CK) group (p < 0.05). Furthermore, the contents of total flavonoids and phenols in the peels, pulps, and seeds of lemons in humic/fulvic acid fertilizer–treated groups were all higher than those in the CK group at the three harvest times (p < 0.05). This result indicated that humic/fulvic acid fertilizers produced positive effects on the quality of lemon fruits and could be used in lemon planting to improve the quality and added value of lemons.

Graphene and hBN as two-dimensional materials with excellent optical properties can be combined with other materials. In this paper, graphene and hBN is sequentially deposited on the surface of the silicon-core fiber to serve as transverse magnetic (TM) or transverse electric (TE) mode polarizer alternatively depending on the input wavelength and the diameter of the silicon-core. The Gr/hBN stack structure on the surface silicon-core microfiber is used not only for enlarging the wavelength bandwidth, such as from 350 nm (TM) and 670 nm (TE) for double Gr/hBN stack to 300 nm (TM) and 550 nm (TE) for single Gr/hBN stack, but also enhancing the light-graphene interaction to multiply the polarization extinction ratio, as compared with that of monolayer graphene. Small radius silicon core could provide large light-graphene interaction for flat extinction ratio with different thickness of the hBN.

The 4.2% mismatch at the Si/Ge interface has a significant impact on Si/Ge photodetectors. However, few researchers have attempted to determine the major noise source or study the effects of the Si/Ge interface on the dark current, the responsivity and the 3-dB bandwidth of these devices. In this letter, we found that the dark current was dominated by generation-recombination processes that were enhanced by trap-assisted-tunneling around the interface below 220 K, with a characteristic tunneling energy of E00 = 14 meV corresponding to an effective mass of m* = 18m0. This behavior can be explained by the rise in the heavy-hole band caused by the compressive strain on the Ge layer. When the temperature increased above 240 K, Shockley-Read-Hall recombination was clearly observed and believed to be dominant. The responsivity, the collection efficiency and the absorption efficiency were all extracted at 850 nm, 1310 nm, and 1550 nm. The absorption coefficient around the interface was found to be lower than that of the bulk material. In addition, comparison of the measured 3-dB frequency (~20.6 GHz @ -0.5 V) with the theoretical value (~29.37 GHz) indicated that defects have little effect on the bandwidth at high frequencies.

This article demonstrates a compact prism imaging spectrometer method. A catadioptric curved prism is located at the secondary mirror position of the spectrometer and used to balance the aberrations, enlarge the dispersion width, and decrease the volume. A mathematical model of the prism and spectrometer is derived, which provides an optimal initial structure for a non-coaxial spectrometer, simplifying the optical design process and reducing the system volume. Using this method, a compact shortwave infrared imaging spectrometer with a 16° field of view is designed with an F-number/3, and the measured spectrum ranges from 0.95 to 2.5 μm. The performance is analyzed and evaluated. Laboratory testing results prove the excellent optical performance, and under the same specifications, the spectrometer length decreases by 40%.

The clinical pharmacodynamics of tacrolimus in renal transplant patients has significant interindividual variability. T lymphocytes were selected to study the pharmacodynamic response of tacrolimus, which was significantly correlated with renal function and the outcome of renal transplant patients. Ultra-performance liquid chromatography–quadrupole time-of-flight mass spectroscopy (UPLC/Q-TOF-MS) was performed to obtain the metabolic profiles of 109 renal transplant patients. A partial least squares (PLS) model was constructed to screen potential biomarkers that could predict the efficacy of tacrolimus. Multinomial logistic regression analysis established a bridge that could quantify the relationship between the efficacy of tacrolimus and biomarkers. The results showed a good correlation between endogenous molecules and the efficacy of tacrolimus. Metabolites such as serum creatinine, mesobilirubinogen, L-isoleucine, 5-methoxyindoleacetate, eicosapentaenoic acid, N2-succinoylarginine, tryptophyl-arginine, and butyric acid were indicated as candidate biomarkers. In addition, the key biomarkers could correctly predict the efficacy of tacrolimus with an accuracy of 82.5%. Finally, we explored the mechanism of individual variation by pathway analysis, which showed that amino acid metabolism was significantly related to the efficacy of tacrolimus. Moreover, orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there was no difference in key metabolites among different pharmacodynamic groups at 1 month and 3 months after dose adjustment, suggesting that pharmacometabonomics is a useful tool to predict individual differences in pharmacodynamics and thus to facilitate individualized drug therapy.

Abstract Background It has been reported that CBP/p300-Interacting Transactivator with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain 1 (CITED1) is overexpressed in papillary thyroid cancer (PTC). However, the functional significance and underlying mechanisms of CITED1 in PTC are largely unknown. Methods The Cancer Genome Atlas dataset and real-time PCR were used to determine the expression of CITED1 in PTC. The role of CITED1 in PTC cell proliferation was determined conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, 5-ethynyl-2′-deoxyuridine (EdU) incorporation, and flow cytometry assays in vitro, and a subcutaneous xenotransplantation tumor model in nude mice was established to analyze tumor growth in vivo. We studied the potential mechanisms underlying the contribution of CITED1 to PTC proliferation using western blotting and luciferase assays. Results We found that CITED1 was highly expressed in PTC. In vitro and in vivo experiments demonstrated that CITED1 was involved in PTC cell proliferation and tumorigenesis. Then, gain- and loss-of-function experiments revealed that CITED1 decreased the expression of p21 and p27, and thereby increased the phosphorylation of pRb as well as E2F1 transcriptional activity. Conclusions Our results suggest that CITED1 is overexpressed in PTC and that CITED1 promotes the proliferation of PTC cells via the regulation of p21 and p27, which indicates that CITED1 might be a potential therapeutic target in the treatment of PTC.

Our understanding of debris-flow initiation by slope failure is restricted by the challenge of acquiring accurate geomorphic features of debris flows and the structural setting of the rock mass in the remote mountainous terrain. Point cloud data of debris flows in Sabino Canyon, Tucson, Arizona, July 2006, with initiation by joint-controlled rock slope were obtained using multitemporal LiDAR scanning. Topographic changes were detected by comparing historical LiDAR scanning data of this area since 2005 by adopting open-source CloudCompare software. The results showed persistent scour and erosion in the debris flows after 2006. Point cloud data of joint-controlled rock in the initiation zone were generated by the means of photogrammetry using Pix4D software. The joint planes, the dip direction and the dip value of the joint plane, the joint spacing, and the joint roughness were therefore acquired by point cloud processing. Our study contributes a foundation for analyzing the relationship between the rock features, the generation of slope failure, and the initiation of debris flows.

Objectives: The interaction between the components of traditional Chinese medicine (TCM) is an important basis for their synergy. Rhein and curcumin exert various pharmacological activities, including anti-tumour, anti-inflammatory, antioxidant, anti-fibrosis and renoprotective effects. However, no investigation has reported the synergistic anti-fibrosis effect yet. This study aims at determine the pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment for chronic kidney disease in rats.Design: Fifty two male Sprague-Dawley (SD) rats were randomly divided into rhein group, curcumin group and their combination group for pharmacodynamics studies. HE and Masson staining was conducted to observe the changes of renal morphology. Kits were used to detect the level of urea nitrogen (BUN) and creatinine (Scr). For pharmacokinetic study, 36 SD rats were randomly divided into rhein group, curcumin group and a combination group, the content of rhein and curcumin in plasma and renal tissue was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In additon, molecular docking method and cell experiments was used to disclose the interaction mechanism between curcumin and rhein.Results: The pharmacodynamic results showed that the degree of renal fibrosis was improved obviously by co-administration rhein and curcumin. Meanwhile, compared to single administration, the Cmax and AUC of rhein and curcumin in plasma and renal tissue were enhanced significantly after co-administration. Moreover, the result of molecular docking and cell experiments showed that both two compounds could interact with P-gp, CYP2C9 and CYP2C19.Conclusion: Together, these findings demonstrated that rhein and curcumin had a synergistic effect in ameliorateing chonic kidney disease, providing an important explanation on the synergistic mechanism of curcumin and rhein from a pharmacokinetic viewpoint.

Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25–8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

A new species Leptopulvinaria sapinda sp. n. is described and illustrated based on adult females collected on Sapindus saponaria (Sapindaceae) from Shanghai and Jiangsu. This is the first report of Leptopulvinaria species in China. A key to the species of Leptopulvinaria Kanda is provided.

Silicon PIN photodiodes in the visible wavelength range have been widely applied in aerospace, defense, security, medical, and scientific instruments because of their high sensitivity and low cost. In this paper, the phenomena of the current kink and the capacitance frequency dispersion are observed. Contamination at the p-type Ohmic contact interface is proposed to explain the current kink effect and capacitance frequency dispersion, according to the temperature-dependent I-V measurement results in which trap-assisted tunneling process demonstrated.

Alpinetin, a bioactive flavonoid, has been known to have a diverse therapeutic effect, with namely anti-inflammatory, anticancer and antioxidant effects with low systemic toxicity. This study aimed to obtain metabolic profiles of alpinetin in orally administrated rats. The metabolites of alpinetin were systematically analyzed and identified by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The chromatographic separation was achieved on a High Strength Silica (HSS) T3 (1.8 μm, 2.1 × 100 mm) column with the mobile phase consisting of water containing 0.1% formic acid and acetonitrile with 0.1% formic acid via gradient elution. An extracted ion chromatogram strategy based on multiple prototype/metabolite intermediate templates and 71 typical metabolic reactions was proposed to comprehensively profile the metabolites of alpinetin. With the metabolite profiling strategy, altogether 15 compounds were recognized from urine, plasma, bile and feces of rats after intragastric administration of alpinetin for the first time. The prototype, glucuronide conjugates and phenolic acids metabolites were the probable predominant form of alpinetin in rats. This work showed a comprehensive study of the probable metabolic pathways of alpinetin in vivo, which could provide meaningful information for future pharmacological studies.

Purpose. This study aimed to explore the relationship among insulin sensitivity and ectopic fat depots in participants with different glucose status. Methods. Fifty-nine men and women were enrolled in this study: 29 with normal glucose tolerance (NGT), 17 with impaired glucose tolerance (IGT), and 13 with type 2 diabetes mellitus (T2DM). All participants underwent a hyperinsulinemic-euglycemic clamp to assess the insulin sensitivity index (M value) and magnetic resonance imaging to measure the hepatocellular lipid content (HCL), skeletal muscle fat content including intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) of tibialis anterior (ta), and soleus muscle (sol). Results. The M value of NGT group was higher than those of IGT and T2DM groups (P=0.001). Participants with T2DM had the highest HCL and IMCL (ta) compared with those in NGT and IGT groups (P=0.001). The M value had an inverse relationship with HCL (r=-0.789, P=0.001), IMCL (sol) (r=-0.427, P=0.002), and IMCL (ta) (r=-0.419, P=0.002). Stepwise linear regression analysis showed that HCL (standardized β=-0.416; P=0.001) had an independent relationship with M value. Conclusions. Hepatocellular lipid content deposition happens earlier than skeletal muscle fat deposition. HCL is an independent risk factor for insulin resistance and may be used to evaluate the risk of developing T2DM as a noninvasive marker of insulin sensitivity index.

It was proposed that arresting nuclear donor cells in G0/G1 phase facilitates the development of embryos that are derived from somatic cell nuclear transfer (SCNT). Full confluency or serum starvation is commonly used to arrest in vitro cultured somatic cells in G0/G1 phase. However, it is controversial as to whether these two methods have the same efficiency in arresting somatic cells in G0/G1 phase. Moreover, it is unclear whether the cloned embryos have comparable developmental ability after somatic cells are subjected to one of these methods and then used as nuclear donors in SCNT. In the present study, in vitro cultured sheep skin fibroblasts were divided into four groups: (1) cultured to 70-80% confluency (control group), (2) cultured to full confluency, (3) starved in low serum medium for 4 d, or (4) cultured to full confluency and then further starved for 4 d. Flow cytometry was used to assay the percentage of fibroblasts in G0/G1 phase, and cell counting was used to assay the viability of the fibroblasts. Then, real-time reverse transcription PCR was used to determine the levels of expression of several cell cycle-related genes. Subsequently, the four groups of fibroblasts were separately used as nuclear donors in SCNT, and the developmental ability and the quality of the cloned embryos were compared. The results showed that the percentage of fibroblasts in G0/G1 phase, the viability of fibroblasts, and the expression levels of cell cycle-related genes was different among the four groups of fibroblasts. Moreover, the quality of the cloned embryos was comparable after these four groups of fibroblasts were separately used as nuclear donors in SCNT. However, cloned embryos derived from fibroblasts that were cultured to full confluency combined with serum starvation had the highest developmental ability. The results of the present study indicate that there are synergistic effects of full confluency and serum starvation on arresting fibroblasts in G0/G1 phase, and the short-term treatment of nuclear donor cells with these two methods could improve the efficiency of SCNT.

Recent data support a role for SHARP1, a basic helix-loop-helix transcription repressor, in the regulation of malignant cell behavior in several human cancers. However, the expression and role of SHARP1 during the development of endometrial cancer (EC) remain unclear. Here we show that upregulation of SHARP1 suppressed tumor angiogenesis by decreasing hypoxia-inducible factor-1α (HIF-1α), inhibited cell viability and tumor growth in EC. Immunohistochemical staining showed that the expression of SHARP1 was negatively correlated with tumor stage, histological grade, myometrial invasion, lymph node metastasis, blood vessel permeation in the myometrium and HIF-1α expression. Mechanistic studies showed that SHARP1 interacted with HIF-1α physically, and the protein level of HIF-1α and the mRNA level of its target genes (VEGFA, ANGPTL4 and CA9) were decreased by SHARP1 under hypoxia. Upregulation of SHARP1 in EC impeded hypoxia-induced angiogenesis by reducing VEGF secretion. Immunohistochemical analysis verified a correlation between decreased SHARP1 expression and increased microvessel density in EC tissues. Additionally, SHARP1 inhibited cell viability in EC cell lines. Overexpression of SHARP1 in vivo inhibited tumor growth and angiogenesis, and decreased HIF-1α expression. In this study, we established SHARP1 as a novel tumor suppressor of EC and shed light on the mechanisms by how SHARP1 inhibited EC progression. Therefore, SHARP1 may be a valuable prognostic biomarker for EC progression and shows promise as a new potential target for antiangiogenic therapeutics in human EC.

Vertical-cavity surface-emitting lasers (VCSELs) have been widely used in short-reach optical communication links and interconnects because of their high modulation speed and low energy consumption. In this paper, the effect of heat dissipation on the modulation bandwidth of highspeed 850-nm VCSELs has been investigated. With increasing bottom distributed Bragg reflector (DBR) diameter from 34 μm to 46 μm, optical output power increased as well as the -3 dB modulation bandwidth. The maximum small-signal modulation bandwidth of 16.2 GHz was achieved with an aperture of 5 μm. Thermal analysis showed that the heat dissipation of the bottom DBR diameter, which determined the differential gain of the quantum wells, has a strong effect on the modulation bandwidth. [ABSTRACT FROM AUTHOR]