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Objective: To investigate the characteristics of tau deposition and its impact on functional connectivity (FC) in Alzheimer’s disease (AD).Methods: Hybrid PET/MRI scans with [18F]-THK5317 and neuropsychological assessments were undertaken in 26 participants with AD and 19 healthy controls (HC). The standardized uptake value ratio (SUVR) of [18F]-THK5317 PET imaging was compared between the AD and HC groups. Significant clusters that revealed higher tau deposition in the AD group compared to the HC group were selected as regions of interest (ROI) for FC analysis. We evaluated the difference in the FC between the two groups for each ROI pair. The clinical and radiological characteristics were compared between the AD patients with negative FC and AD patients with positive FC for exploratory analysis.Results: The bilateral inferior lateral temporal lobe, dorsal prefrontal cortex, precuneus, posterior cingulate cortex, hippocampus, and occipital lobe showed significantly higher [18F]-THK5317 accumulation in AD patients. Decreased FC in regions with higher SUVR was observed in AD patients, and the FC strength was negatively correlated with regional SUVR. Patients with a positive FC exhibited older ages, better cognitive performances, and a lower SUVR than patients with a negative FC.Conclusions: An impact of tau deposition was observed on FC at the individual level in AD patients. Our findings suggested that the combination of tau-PET and rs-fMRI might help predict AD progression.

Background To summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC). Methods We performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS). Results A total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36∼0.72], p = 0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30∼0.72], p = 0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25∼0.99], p = 0.05), PFS (HR: 0.47, 95% CI [0.23∼0.96], p = 0.04) and RFS (HR: 0.60, 95% CI [0.41∼0.87], p = 0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [−2.37∼8.92], p = 0.26) and OS (HR: 1.20, 95% CI [0.44∼3.32], p = 0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29∼1.53], p = 0.34), RFS (HR: 0.90, 95% CI [0.56∼1.46], p = 0.68) and PFS (HR: 0.71, 95% CI [0.32∼1.55], p = 0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%). Conclusion The IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.

Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.

Consensus about the universality of the power law feature in complex networks is experiencing widespread challenges. In this paper, we propose a generic theoretical framework in order to examine the power law property. First, we study a class of birth-and-death networks that are more common than BA networks in the real world, and then we calculate their degree distributions; the results show that the tails of their degree distributions exhibit a distinct power law feature. Second, we suggest that in the real world two important factors—network size and node disappearance probability—will affect the analysis of power law characteristics in observation networks. Finally, we suggest that an effective way of detecting the power law property is to observe the asymptotic (limiting) behavior of the degree distribution within its effective intervals.

Background: Tumor-associated antigens (TAAs) have been investigated for many years as potential early diagnosis tools, especially for hepatocellular carcinoma (HCC). Nonetheless, very few studies have focused on the Hispanic HCC group that may be associated with distinct etiological risk factors. In the present study, we investigated novel anti-TAA autoantibodies as diagnostic biomarkers for Hispanic HCC patients. Methods: Novel TAA targets were identified by the serological proteome analysis (SERPA) and from differentially expressed HCC driver genes via bioinformatics. The autoantibody levels were validated by enzyme-linked immunosorbent assay (ELISA). Results: Among 19 potential TAA targets, 4 anti-TAA autoantibodies were investigated as potential diagnostic biomarkers with significantly high levels in Hispanic HCC sera, including DNA methyltransferase 3A (DNMT3A), p16, Hear shock protein 60 (Hsp60), and Heat shock protein A5 (HSPA5). The area under the ROC curve (AUC) value of the single autoantibodies varies from 0.7505 to 0.8885. After combining all 4 autoantibodies, the sensitivity of the autoantibody panel increased to 75% compared to the single one with the highest value of 45.8%. In a separate analysis of the Asian cohort, autoantibodies against HSPA5 and p16 showed significantly elevated levels in HCC compared to normal healthy controls, but not for DNMT3A or HSP60. Conclusion: Anti-DNMT3A, p16, HSPA5, and HSP60 autoantibodies have the potential to be diagnostic biomarkers for Hispanic HCC patients, of which DNMT3A and HSP60 might be exclusive for Hispanic HCC diagnosis.

Purpose: Prostate cancer (PCa) is characterized by high expression of prostate-specific 1membrane antigen (PSMA), a type II transmembrane protein. Prostate-specific membrane antigen positron emission tomography (PSMA PET) has high sensitivity and specificity and can therefore be potentially used to detect PCa. Exploiting the advantages of PSMA PET imaging, in this study, we aim to develop a novel radiopharmaceutical to facilitate biopsy punching of PCa. Methods: We synthesized a high-affinity radiopharmaceutical of PSMA (125I-PSMA-7). We evaluated the properties of 125I-PSMA-7, including the purity, stability, affinity, partition coefficient, and toxicity. (PSMA+) 22Rv1 and (PSMA−) PC3 cell lines were used to evaluate 125I-PSMA-7 in vitro. BALB/c nude mice bearing 22Rv1 and PC3 xenografts were used for biodistribution and imaging. The uptake of the main organs was evaluated in vivo using single photon emission computed tomography (SPECT). Results: 125I-PSMA-7 had a purity of 99.6% and remained stable for seven days and was therefore always safe to use. 125I-PSMA-7 had a Ki of 4.037 × 10−11 and a partition coefficient of −1.80. The results of in vitro cellular experiments showed a high uptake by 22Rv1 cells (ranging from 2.88 ± 0.14 IA%/106 at 5 min to 61.98 ± 3.43 IA%/106 at 24 h, where the internalization was 46.1% at 1 h and 88.06% at 24 h). However, the uptake of PC3 cells was very low (ranging from 0.34 ± 0.08 IA%/106 at 5 min to 1.60 ± 0.15 IA%/106 at 24 h). The tumors’ uptake of 125I-PSMA-7 ranged from 9.02 ± 0.30 ID%/g at 1 h to 4.11 ± 1.04 ID%/g at 7 d and the tumor/muscle ratios and tumor/blood ratios increased over time. In addition, we used γ-counter to measure cpm per milligram of tumor and muscle on days 4 and 7. The background on day 4 is 42 cpm and the tumor is 1739 cpm/mg and the muscle is 45 cpm/mg, and the background on day 7 is 74 cpm and the tumor is 1404cpm/mg and the muscle is 32 cpm/mg. At 1 h post-injection, the high uptake of 125I-PSMA-7 resulted in clear delineation of 22Rv1-derived tumors upon imaging. By comparison, 22Rv1-blocking mice took up less 125I-PSMA-7. Conclusions: These results show that 125I-PSMA-7 is a promising radiotracer that could be used to puncture the prostate. 125I-PSMA-7 could be applied to targeted biopsy, reducing the need for saturated biopsy.

This paper investigates the problem of formation fault-tolerant control of multiple quadrotors (QRs) for a mobile sensing oriented application. The QRs subject to faults, input saturation and time-varying delays can be controlled to perform a target-enclosing and covering task while guaranteeing the state constraints will not be exceeded. A distributed formation control scheme is proposed, using a radial basis function neural network (RBFNN)-based time-delay position controller and an adaptive fault-tolerant attitude controller. The Lyapunov–Krasovskii approach is used to analyze the time-varying delay. Barrier Lyapunov function is deployed to handle the prescribed constraints, and an auxiliary system combined with a command filter is designed to resolve the saturation problem. An RBFNN and adaptive estimators are deployed to provide estimates of disturbances, fault signals and uncertainties. It is proven that all the closed-loop signals are bounded under the proposed protocol, while the prescribed constraints will not be violated, which enhances the flight safety and QR formation’s applicability. Comparative simulations based on application scenarios further verify the effectiveness of the proposed method.

High hydrostatic pressure (HHP, 600 MPa/15 min), pasteurization (72 °C/15 s) and pasteurization-HHP (72 °C/15 s + 600 MPa/15 min) processing of milk were comparatively evaluated by examining their effects on microorganisms and quality during 30 days of storage at 4 °C. The counts of total aerobic bacteria in HHP-treated milk were less than 2.22 lgCFU/mL during storage, while they exceeded 5.00 lgCFU/mL in other treated milk. Although HHP changed the color, it had more advantages in maintaining the nutrient (fat, calcium and β-lactoglobulin) properties of milk during storage. Moreover, the viscosity and particle size of HHP-treated milk were more similar to the untreated milk during storage. However, consumer habits towards heat-treated milk have led to poor acceptance of HHP-treated milk, resulting in a low sensory score. In sum, compared with pasteurization- and pasteurization-HHP-treated milk, HHP-treated milk showed longer shelf life and better nutritional quality, but lower sensory acceptance.

Three extraction methods: water extraction, lactic acid bacteria fermentation, and back-slopping fermentation were applied to extract a new type of legume starch, common vetch starch. Our results showed that the lactic acid bacteria fermented starch had the highest amylose content (35.69%), followed by the back-slopping fermented starch (32.34%), and the water-extracted starch (30.25%). Furthermore, erosion surface, lower molecular weight, smaller particle size, larger specific surface area, and a higher proportion of B1 chain were observed in the fermented starch, especially in the back-slopping fermented starch. All the extracted starches showed a type C structure, but a type CB structure was observed in the back-slopping fermented starch. In addition, the relative crystallinity of the lactic acid bacteria fermented starch (34.16%) and the back-slopping fermented starch (39.43%) was significantly higher than that of the water-extracted starch (30.22%). Moreover, the swelling power, solubility, pasting, and thermal properties of the fermented starches were also improved. In conclusion, the fermentation extraction method, especially back-slopping fermentation, could improve the quality of the extracted common vetch starch when compared with the traditional water extraction method.

A pathological voice detection system is designed to detect pathological characteristics of vocal cords from speech. Such systems are particularly susceptible to domain mismatch where the training and testing data come from the source and target domains, respectively. Due to the difference in speech disease etiology, recording environment, and device, etc., the feature distributions of source and target domain are quite different. Meanwhile, considering the high costs of annotating labels, it is hard to acquire labeled data in the target domain. This paper attempts to formulate cross-domain pathological voice detection as an unsupervised domain adaptation problem. Joint subspace transfer learning (JSTL) aims to find a projection matrix to transform source and target domain data into a common space. The maximum mean discrepancy function is used to measure the divergence across databases. Intra-class and inter-class distance act as regularization to guarantee the maximum separability between different classes. A graph matrix is constructed to help transfer knowledge from the relevant source data to the target data. Three popular pathological voice databases were selected in this paper. For six cross-database experiments, the accuracy of the method proposed increased by up to 15%. For different voice categories, the category of structural voice showed the most significant increase, nearly 20%.

The Belief Propagation (BP) algorithm has the advantages of high-speed decoding and low latency. To improve the block error rate (BLER) performance of the BP-based algorithm, the BP flipping algorithm was proposed. However, the BP flipping algorithm attempts numerous useless flippings for improving the BLER performance. To reduce the number of decoding attempts needed without any loss of BLER performance, in this paper a metric is presented to evaluate the likelihood that the bits would correct the BP flipping decoding. Based on this, a BP-Step-Flipping (BPSF) algorithm is proposed which only traces the unreliable bits in the flip set (FS) to flip and skips over the reliable ones. In addition, a threshold β is applied when the magnitude of the log–likelihood ratio (LLR) is small, and an enhanced BPSF (EBPSF) algorithm is presented to lower the BLER. With the same FS, the proposed algorithm can reduce the average number of iterations efficiently. Numerical results show the average number of iterations for EBPSF-1 decreases by 77.5% when N = 256, compared with the BP bit-flip-1 (BPF-1) algorithm at Eb/N0 = 1.5 dB.

Prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals have become some of the most promising tools for the diagnosis and therapy prostate cancer (PCa). The structure of existing PSMA-targeted PET tracers still needs to be optimized to improve their pharmacokinetic properties and tumor-to-background ratio. In this study, we modified the structure of a well-studied PSMA tracer, and six novel tracers with variable hydrophilicity and pharmacokinetics were developed and evaluated both in vitro and in vivo. All of the novel tracers showed high hydrophilicity (log p = −2.99 ± 0.33 to −3.49 ± 0.01), rapid clearance rates (elimination half-times = 15.55 to 35.97 min), and high affinity for PSMA (Ki = 8.11 ± 0.49 to 42.40 ± 2.11 nM) in vitro. Specific cell binding and micro-PET experiments showed that [68Ga]Ga-PSMA-Q displayed the highest specific PSMA+ cell uptake (3.75 ± 0.35 IA%/106 at 60 min), tumor uptake (SUVmax = 0.97 ± 0.24 at 60 min p.i.), and tumor-to-muscle ratio (59.33 ± 5.72 at 60 min p.i.), while the tumor-to-muscle ratio was much higher than that of [68Ga]Ga-PSMA-617. The results of this study validate the clinical potential of [68Ga]Ga-PSMA-Q for PET imaging and further targeted therapy of prostate cancer.

ObjectiveTo analyze the incidence and risk factors for lateral lymph node metastases (LNMs) in T1a papillary thyroid carcinoma (PTC) with a focus on tumor location and size.Materials and MethodsThe incidence of lateral LNM in 345 cases of T1a PTC was retrospectively analyzed. Univariate and multivariate analyses were performed to assess the relationships between lateral LNM and clinicopathological characteristics.ResultsThe incidence of skip metastasis to lateral LNM in T1a PTC located in the upper lobe was 12.1% (8/66). Logistic regression analysis indicated tumor size >5 mm (OR = 5.04, 95% CI = 1.79 to 14.18, P = 0.002), upper lobe location (OR = 7.68, 95% CI = 3.05–19.34, P < 0.001) and the number of central neck LNM (5 mm in size, which could be considered a risk factor for lateral LNM in the clinical management of T1a PTC.

Thinopyrum intermedium (2n = 6x = 42, JJJSJSStSt) is one of the important resources for the wheat improvement. So far, a few Th. intermedium (Thi)-specific molecular markers have been reported, but the number is far from enough to meet the need of identifying alien fragments in wheat-Th. intermedium hybrids. In this study, 5,877,409 contigs were assembled using the Th. intermedium genotyping-by-sequencing (GBS) data. We obtained 5,452 non-redundant contigs containing mapped Thi-GBS markers with less than 20% similarity to the wheat genome and developed 2,019 sequence-tagged site (STS) molecular markers. Among the markers designed, 745 Thi-specific markers with amplification products in Th. intermedium but not in eight wheat landraces were further selected. The distribution of these markers in different homologous groups of Th. intermedium varied from 47 (7/12/28 on 6J/6St/6JS) to 183 (54/62/67 on 7J/7St/7JS). Furthermore, the effectiveness of these Thi-specific markers was verified using wheat-Th. intermedium partial amphidiploids, addition lines, substitution lines, and translocation lines. Markers developed in this study provide a convenient, rapid, reliable, and economical method for identifying Th. intermedium chromosomes in wheat. In addition, this set of Thi-specific markers can also be used to estimate genetic and physical locations of Th. intermedium chromatin in the introgression lines, thus providing valuable information for follow-up studies such as alien gene mining.

Postoperative neurocognitive disorder (PND) is one of the most common postoperative neurological complications in aged patients, characterized by mental disorder, anxiety, personality changes, and impaired memory. At present, the molecular mechanism of PND remains largely unclear, and the ideal biomarker for clinical diagnosis and prognosis are lacking. Circular RNA (circRNA) and microRNA (miRNA), as unique non-coding RNAs, affecting the regulation of miRNAs on genes and further intervening in the progression of diseases through the sponge action between the two. Besides, it could be served as novel biomarkers in various diseases. In order to detect the differential expression profiles of genes caused by PND, a total of 26 18-month-old male C57BL/6 mice were randomly assigned to control group and PND group. Behavioral tests showed that mice in the PND group had impaired cognitive function compared with the control group. Three mice in each group were randomly selected to harvest the brain for analysis the expressions of circRNAs, miRNAs, and mRNAs in the prefrontal cortex by next-generation sequencing (NGS) technology. Differentially expressed genes, including 1192 circRNAs, 27 miRNAs, and 266 mRNAs were identified, and its accuracy was further confirmed by qRT-PCR. Bioinformatics analysis results suggested that neuroinflammation was the main pathological mechanism of PND. The construction of competitive endogenous RNA (ceRNA) networks and the identification of hub genes provided possible therapeutic targets for PND. Cinnarizine and Clemastine were predicted to have the potential therapeutic effects on PND. This is the first study to explore the differential expression profiles of genes and their regulation mechanisms in PND, our results provided new clues and targets for the treatment of this refractory disease.

Glycogen synthase kinase 3 (GSK3) is a vital multifunctional molecule that is widely distributed in invertebrates and vertebrates. GSK3 is a highly conserved serine/threonine (Ser/Thr) protein kinase, which plays an important role in insulin, Wnt, and various signaling pathways. In this study, a GSK3 gene were identified in the genome of the Pacific white shrimp, Litopenaeus vannamei, and analyzed its gene structure, phylogeny, and expression profiles. The deduced LvGSK3 protein contains a highly conserved Ser/Thr protein kinase catalytic (S_TKc) domain, the LvGSK3 gene exhibited high expression in different early developmental stages, most adult tissues, and premolting stages. RNA interference of LvGSK3 significantly retarded the increment of body weight and affected the expressions of molting-related genes compared with control groups. These results will improve our understanding of the conserved structure and functions of the LvGSK3 gene and show potential applications of shrimp growth.

Deltamethrin (DM) is a synthetic pyrethroid used for agricultural purposes to control insects. However, its extensive use contaminates the aquatic environment and results in serious health problems in aquatic organisms. Knowledge about the toxic effect of DM in freshwater prawns is limited; therefore, this study aims to assess the toxicity of DM in Macrobrachium rosenbergii based on multiple biomarkers. Four-day acute toxicity tests showed that DM was highly toxic to M. rosenbergii with the 24 h, 48 h, 72 h and 96 h LC50 values to be 1.919, 0.603, 0.539, and 0.449 μg/L, respectively. According to 96 h LC50, prawns were exposed to DM at three concentrations (0.02, 0.08, and 0.32 μg/L) for 4 days, and then moved into fresh water for decontamination to investigate the toxic effect of DM in M. rosenbergii. At low concentration (0.02 μg/L and 0.08 μg/L), DM did not cause obvious histopathological damage to hepatopancreas and gill tissue, while at high concentration (0.32 μg/L), the histopathological harm was serious and the damage did not recover to the initial level after 7-day decontamination. 0.02 μg/L DM exposure did not induce significant changes in most of the biomarkers except the increased lactate dehydrogenase (LDH) activity, lactic acid (LD) level, and the first increased then decreased mRNA expression of immune-related genes, indicating the stimulation of DM on energy production and immunity. 0.08 μg/L and 0.32 μg/L DM exposure resulted in varying degrees of damage on prawns, but overall, their toxic effects showed similar trends based on the biomarkers. Increase in malonaldehyde (MDA) and hydrogen peroxide (H2O2) content and decrease in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity after DM exposure demonstrated the oxidative stress caused by DM. The significantly increased acid phosphatase (ACP), alkaline phosphatase (AKP), LDH activity and LD level indicated hepatopancreatic dysfunction and respiration disruption. The first increased and then decreased expression pattern of immune-related genes indicated the immunosuppression caused by DM. After 7-day decontamination in freshwater, the activity/level of the biomarkers partly recovered. This study revealed the severe toxic effect of DM on Macrobrachium rosenbergii based on multiple biomarkers, providing fundamental knowledge for the establishment of DM toxicity assessment system with proper parameters in freshwater crustaceans.

Penaeid shrimp (family Penaeidae) represents one of the most economically and ecologically important groups of crustaceans. However, their genome sequencing and assembly have encountered extreme difficulties during the last 20 years. In this study, based on our previous genomic data, we investigated the genomic characteristics of four penaeid shrimp species and identified potential factors that result in their poor genome assembly, including heterozygosity, polyploidization, and repeats. Genome sequencing and comparison of somatic cells (diploid) of the four shrimp species and a single sperm cell (haploid) of Litopenaeus vannamei identified a common bimodal distribution of K-mer depths, suggesting either high heterozygosity or abundant homo-duplicated sequences present in their genomes. However, penaeids have not undergone whole-genome duplication as indicated by a series of approaches. Besides, the remarkable expansion of simple sequence repeats was another outstanding character of penaeid genomes, which also made the genome assembly highly fragmented. Due to this situation, we tried to assemble the genome of penaeid shrimp using various genome sequencing and assembly strategies and compared the quality. Therefore, this study provides new insights about the genomic characteristics of penaeid shrimps while improving their genome assemblies.

The metabolic difference in caecal digesta between Jinhua pig and Landrace pig was compared. Twenty weaned piglets at 28 days of age, including ten Landrace pigs (a Western pig breed) and ten Jinhua pigs (a Chinese native pig breed), were randomly selected and allocated into two groups. The pigs were fed the same corn-soybean diet on the same pig farm. At the age of 240 days, all pigs of each group were slaughtered, the digesta in the caecum of the twenty pigs were collected for metabolomic analysis and determination of short-chain fatty acids (SCFAs). The results showed that a total of 56 different metabolites (22 metabolites named and 34 metabolites without identification) were detected in caecal digesta using a gas chromatography time-of-flight/mass spectrometry (GC-TOF-MS)-based metabolomic approach. Forty-six of the 56 metabolites were upregulated significantly (P < 0.05) in Landrace group compared with Jinhua group. The metabolic pathways with different impact value in which different metabolites were mainly involved were tyrosine metabolism, citrate cycle and steroid biosynthesis. In addition, we found that Landrace accumulated more SCFAs in caecal digesta, while the concentrations of acetic acid (P < 0.01) and butyric acid (P < 0.05) in caecal digesta of Jinhua pig were markedly lower than those of Landrace pig. Collectively, our study was the first to compare the metabolic difference in caecal digesta between Jinhua pig and Landrace pig using a metabolomics approach, which might be used as a potential metabolomics mechanism to research different breeds of pigs.

Abstract This paper is concerned with the stability criteria for a discrete-time linear system with interval time-varying delays. By using the time delay division we construct an augmented Lyapunov–Krasovskii functional for two delay subintervals. Moreover, we use a new summation inequality to estimate the derivatives of LKFs more accurately and derive less conservative criteria. Finally, we present two numerical examples to demonstrate that the obtained results are less conservative.

This paper is concerned with the stability criteria of discrete neural networks with two additive input time-varying delays. By using the time delay division and a new summation inequality, a less conservative criterion is derived. Moreover, to compare the obtained criterion more directly with the existing results, a corollary is proposed accordingly. Finally, some numerical examples are presented to demonstrate that the obtained criteria are less conservative.

In multiple-input multiple-output wireless communication system, artificial noise (AN) is designed to be aligned into the null space of the legitimate channel so that it has no effect on the legitimate channel. Meanwhile, AN will reduce the secrecy capacity of the eavesdropping channel so that AN increase the secrecy capacity of the wireless communication system. Nevertheless, AN technology only pays attention to the CSI of the legitimate channel but does not pay attention to the CSI of the eavesdropping channel so that the secrecy capacity of the system can be further improved. In this paper, we analyze the performance of traditional AN. A secrecy capacity optimization artificial noise for the whole communication system to further improve the system's secrecy capacity is proposed. The secrecy capacity optimization artificial noise is considered as a kind of artificial noise which is disadvantageous to the legitimate receiver but more disadvantageous to the eavesdropper. Furthermore, we further analyzed the technical details of AN technology and found the key factor affecting the secrecy capacity. Meanwhile, the secrecy capacity optimization artificial noise is effectively designed by applying these conclusions and the key factors of secrecy capacity optimization artificial noise affecting the secrecy capacity of the wireless communication system are described. The analysis and simulation results in practical environments show that the proposed method has a good performance on improving the secrecy capacity.

The Pacific white shrimp Litopenaeus vannamei is an important aquaculture species and a promising model for crustacean biology. Here, the authors provide a reference genome assembly, and show that gene expansion is involved in the regulation of frequent molting as well as benthic adaptation of the shrimp.

The Pacific white shrimp (Litopenaeus vannamei) is the most widely cultured shrimp in the world. A great attention has been paid to improve its body weight (BW) at harvest through genetic selection for decades. Genome-wide association study (GWAS) is a tool to dissect the genetic basis of the traits. In this study, a GWAS approach was conducted to find genes related to BW through genotyping 94,113 single nucleotide polymorphisms (SNPs) in 200 individuals from a breeding population. Four BW-related SNPs located in LG19 and LG39 were identified. Through further candidate gene association analysis, the SNPs in two candidate genes, deoxycytidylate deaminase and non-receptor protein tyrosine kinase, were found to be related with the body weight of the shrimp. Marker-assisted best linear unbiased prediction (MA-BLUP) based on the SNPs in these two genes was used to estimate the breeding values, and the result showed that the highest prediction accuracy of MA-BLUP was increased by 9.4% than traditional BLUP. These results will provide useful information for the marker-assisted breeding in L. vannamei.

Abstract Fusarium wilt (FW) disease of cotton, caused by the fungus Fusarium oxysporum f. sp. vasinfectum (Fov), causes severe losses in cotton production worldwide. Though significant advancements have been made in development of FW‐resistant Upland cotton (Gossypium hirsutum) in resistance screening programs, the precise resistance genes and the corresponding molecular mechanisms for resistance to Fov remain unclear. Herein it is reported that Fov7, a gene unlike canonical plant disease‐resistance (R) genes, putatively encoding a GLUTAMATE RECEPTOR‐LIKE (GLR) protein, confers resistance to Fov race 7 in Upland cotton. A single nucleotide polymorphism (SNP) (C/A) in GhGLR4.8, resulting in an amino acid change (L/I), is associated with Fov resistance. A PCR‐based DNA marker (GhGLR4.8SNP(A/C)) is developed and shown to cosegregate with the Fov resistance. CRISPR/Cas9‐mediated knockout of Fov7 results in cotton lines extremely susceptible to Fov race 7 with a loss of the ability to induce calcium influx in response to total secreted proteins (SEPs) of Fov. Furthermore, coinfiltration of SEPs with GhGLR4.8A results in a hypersensitive response. This first report of a GLR‐encoding gene that functions as an R gene provides a new insight into plant–pathogen interactions and a new handle to develop cotton cultivars with resistance to Fov race 7.

ObjectivesTo analyze the diagnostic benefit of fine needle aspiration biopsy cytology (FNAB-C) and core needle biopsy tissue (CNB-T) with the addition of thyroglobulin (Tg) in the washout of the needle or BRAF V600E mutation assessment in assessing cervical lymph node metastasis (LNM) in papillary thyroid carcinoma.Materials and MethodsA total of 186 lymph nodes were punctured by fine or core needle. The diagnostic performance of FNAB-C and CNB-T with Tg in the washout or BRAF V600E mutation assessment was compared.ResultsThe optimal cutoff value of FNAB-Tg was 1.0 ng/ml, with an AUC of 0.976. The sensitivity and specificity of FNAB-C in predicting cervical LNM were 97.4% and 71.4%, respectively, and the addition of FNAB-Tg could contribute to a sensitivity of 100% and a specificity of 95%, but the introduction of BRAF V600E mutation assessment was associated with a decreased sensitivity of 96.3% and a decreased specificity of 50.0%. The FNAB-Tg level showed a comparable distribution in malignant lymph nodes with different TgAb statuses, serum TSH levels, and serum Tg levels. The sensitivity and specificity of CNB-T in predicting cervical LNM were 98.9% and 100%, respectively. The addition of CNB-Tg did not alter the diagnostic ability, but the introduction of BRAF V600E mutation assessment obtained the best performance, with a sensitivity of 100% and specificity of 100%.ConclusionThe sensitivity and specificity of FNAB-C could be increased if combined with FNAB-Tg. CNB-T alone could provide satisfactory diagnostic reliability.

Gut microbiota is recognized as a strong determinant of host physiology including fat metabolism and can transfer obesity-associated phenotypes from donors to recipients. However, the relationship between gut microbiota and intramuscular fat (IMF) is still largely unknown. Obese Jinhua pigs (JP) have better meat quality that is associated with higher IMF content than lean Landrace pigs (LP). The present study was conducted to test the contribution of gut microbiota to IMF properties by transplanting fecal microbiota of adult JP and LP to antibiotics-treated mice. Similar to JP donors, the mice receiving JP's microbiota (JM) had elevated lipid and triglyceride levels and the lipoprotein lipase activity, as well as reduced mRNA level of angiopoietin-like 4 (ANGPTL4) in the gastrocnemius muscles, compared to those in mice receiving LP's microbiota (LM). High-throughput 16S rRNA sequencing confirmed that transplantation of JP and LP feces differently reconstructed the gut microbiota in both jejunum and colon of mouse recipients. In colonic samples, we observed an elevated ratio of Firmicutes to Bacteroidetes and increased abundance of genus Romboutsia in JM, which were positively correlated with obesity. Furthermore, the abundance of Akkermansia decreased in JM, which is positively correlated with lean. Colonic concentrations of acetate (P = 0.047) and butyrate (P = 0.014) were significantly lower in JM than in LM, and consistently, the terminal genes for butyrate synthesis, butyryl CoA: acetate CoA transferase were less abundant in colonic microbiota of JM. Taken together, these gut microbiota of obese JP intrinsically promotes IMF accumulation and can transfer the properties to mouse recipients. Manipulation of intestinal microbiota will, therefore, have the potential to improve the meat quality and flavor of pigs and even to ameliorate the metabolic syndrome in human.

Summary: Histones are main components of chromatin, and the protein levels of histones significantly affect chromatin assembly. However, how histone protein levels are regulated, especially whether and how histones are degraded, is largely unclear. Here, we found that histone H2B is mainly degraded through the proteasome-mediated pathway, and the lysine-120 site of H2B is essential for its K48-linked polyubiquitination and degradation. Moreover, the degradation-impaired H2BK120R mutant shows an increased nucleolus localization, and inhibition of the proteasome results in an elevated nucleolus distribution of wild-type H2B, which is similar to that of H2BK120R mutants. More importantly, the nucleolus fractions can ubiquitinate and degrade the purified H2B in vitro, suggesting that the nucleolus, in addition to its canonical roles regulating ribosome genesis and protein translation, likely associates with H2B degradation. Therefore, these findings revealed a novel mechanism for the regulation of H2B degradation in which a nucleolus-associated proteasome pathway is involved.

Non-O1 Vibrio cholerae is a highly virulent pathogen which has seriously threatened the development of Macrobrachium nipponense in various farms. However, little information is available in relation to underlying mechanisms of host-bacteria interaction in M. nipponense. In this study, we performed transcriptome analysis of M. nipponense at 6 and 12 h post-infection (hpi), and differentially expressed genes (DEGs) (P

ObjectivesThe purpose of this study was to evaluate the feasibility and diagnostic performance of prostate-specific membrane antigen (PSMA) based 18F-DCFPyL PET/CT-ultrasound (PET/CT-US) or PET/MRI-ultrasound (PET/MRI-US) fusion targeted biopsy for intra-prostatic PET-positive lesions.MethodsFrom April 2018 to November 2019, we prospectively enrolled 55 candidates to perform PET/CT-US or PET/MRI-US fusion targeted biopsies for solitary PET-positive prostate lesions (two to four cores/lesion). The positive rates of prostate cancer based on patients and biopsy cores were calculated respectively. With reference to the pathological results of biopsy cores, the MR signal characteristics in the area of the PET-positive lesion were analyzed for the patients who underwent PET/MRI.ResultsA total of 178 biopsy cores were taken on the 55 patients. One hundred forty-six biopsy cores (82.0%, 146/178) from 51 (92.7%, 51/55) patients were positive for prostate cancer; 47 (85.5%, 47/55) were clinically significant prostate cancer. It is noteworthy that nine patients underwent both 18F-DCFPyL PET/CT and PET/MRI examinations; the seven patients with prostate cancer showed abnormal MR signal in the area of the PET-positive lesion while the other two patients with prostatic hyperplasia and prostatitis showed normal MR signal in the area of the PET-positive lesion.ConclusionThis study indicated that 18F-DCFPyL PET/CT-US or PET/MRI-US fusion targeted prostate biopsies may be valuable for prostate cancer diagnosis and have a high detection rate of clinically significant prostate cancer for PET-positive lesions. PET/MR can rule out some false PET-positive lesions, which may potentially reduce unnecessary prostate biopsies.

Summary: Zinc finger protein 521 (Zfp521), a quiescent hematopoietic stem cell (HSC)-enriched transcription factor, is involved in the self-renewal and differentiation of fetal liver HSC. However, its role in adult hematopoiesis remains elusive. Here, we found that Zfp521 deletion did not inhibit adult hematopoiesis under homeostatic conditions. In contrast, Zfp521-null chimeric mice showed significantly reduced pool size of HSC and hematopoietic progenitor cells associated with increased apoptosis and loss of quiescence. Competitive serial transplantation assays revealed that Zfp521 regulates HSC self-renewal and differentiation under regenerative stress. Mechanistically, Zfp521 transcriptionally repressed Rela expression by increasing H3K9ac and decreasing H3K9me3 levels in its promoter. Knockdown of Rela inhibited the hyper-activated NF-κB pathway and reversed the loss of quiescence in Zfp521-null HSC under stress. Thus, our results reveal a previously unrecognized role for Zfp521 as critical regulator of quiescence and self-renewal of HSC in adult hematopoiesis mediated at least partly by controlling Rela expression.

In the field of mine blasting practice, accurate prediction of blasting vibration is considered as a critical task. In accordance with the theory of elastic wave, the reflection of blasting vibration wave at the interface of negative elevation is analyzed in this paper. The negative elevation effect exerted by blasting vibration is interpreted considering the mechanism, and the formula of the blasting vibration prediction step (negative) V=KQ1/3/Rα⋅1/Hβ is derived, reflecting the negative elevation effect. Besides, the formula accuracy is verified by the measured vibration velocity of the mass in the Jinou coal mine. The step (negative) formula acts as a more feasible candidate for the prediction of step blasting vibration.

Sulcus vocalis is an indentation parallel to the edge of vocal fold, which may extend into the cover and ligament layer of the vocal fold or deeper. The effects of sulcus vocalis depth d on phonation and the vocal cord vibrations are investigated in this study. The three-dimensional laryngeal models were established for healthy vocal folds (0 mm) and different types of sulcus vocalis with the typical depth of 1 mm, 2 mm, and 3 mm. These models with fluid-structure interaction (FSI) are computed numerically by sequential coupling method, which includes an immersed boundary method (IBM) for modelling the glottal airflow, a finite-element method (FEM) for modelling vocal fold tissue. The results show that a deeper sulcus vocalis in the cover layer decreases the vibrating frequency of vocal folds and expands the prephonatory glottal half-width which increases the phonation threshold pressure. The larger sulcus vocalis depth makes vocal folds difficult to vibrate and phonate. The effects of sulcus vocalis depth suggest that the feature such as phonation threshold pressure could assist in the detection of healthy vocal folds and different types of sulcus vocalis.

ObjectivesOur goal was to analyze the possibility of using metabolic tumor volume (MTV) to predict occult cervical metastasis and survival in cT1-2N0 squamous cell carcinoma (SCC) of the tongue.MethodsData on the primary tumor MTV and cervical node status as determined by the maximum standardized uptake value were retrieved. The sensitivity and specificity in predicting occult metastasis were calculated with a fourfold table. Associations between occult metastasis and clinicopathological variables were evaluated by univariate and multivariate analyses. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS).ResultsA total of 24 (20.3%) of 118 patients had occult metastasis. An MTV cutoff value of 4.3 cm3 showed a sensitivity of 50.0% and a specificity of 76.6% in predicting occult metastasis. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT1 tumors were 66.6 and 89.8%, respectively, with values of 83.3 and 67.3%, respectively, when combined with the MTV. The sensitivity and specificity of PET-CT in predicting occult metastasis in cT2 tumors were 72.2 and 82.2%, respectively, with values of 88.9 and 57.8%, respectively, when combined with the MTV. Patients with MTV ≥4.3 cm3 had a higher occult metastasis rate than patients with MTV

In the process of geotechnical engineering excavation, wet and water-filled rock masses are inevitable. To obtain the mechanical properties of these rocks, indoor tests are required, and most of the rock tests rock tests are dry or nearly dry. They cannot really reflect the true nature of the rock, let alone its nature under a dynamic load. The rock was repeatedly impacted during the blasting excavation process. To determine the mechanical response characteristics and damage evolution of rocks with different moisture states under cyclic dynamic loads, rock samples with three saturation levels were prepared. In the experiment, the Hopkinson pressure bar equipment was utilized to perform five cycles of impact with the same incident energy, and the dynamic response of rocks with different impact times was recorded. Nuclear magnetic resonance technology was employed to obtain the change law of the pores of rock specimens after impact, and the cumulative damage rules of rock were combined with the fractal theory. From the experiments, it can be observed that the stress-strain curves of all rock samples are similar, in that they all have stress addition and unloading stages. The peak stress is proportional to the impact time and moisture content, whereas the opposite is true for the peak strain. After the impact, the small and large pores closed and increased, respectively. The porosity and porosity change rate increased with an increase in the impact time. With an increase in moisture content, this trend is more obvious. It can be observed via magnetic resonance imaging that the internal fractures of the water-bearing rock are obvious after multiple impacts. In particular, the saturated rock specimens exhibited severe damage. Fractal analysis of the NMR figures revealed that after three impact times, the fractal dimension change in the water-bearing rock samples was not obvious. This phenomenon indicated that a macro gap appeared. The fractal dimensions of the dry rock samples continued to increase, and the internal damage was less obvious.

Purpose: With the increasing detection rate of early prostate cancer (PCa), the proportion of surgical treatment is increasing. Surgery is the most effective treatment for PCa. Precise targeting of tumors during surgery can reduce the incidence of positive surgical margins (PSMs) and preserve the neurovascular bundles (NVBs) as much as possible. The objective of this study was to synthesize a PSMA fluorescent probe (PSMA-Cy5) and verify the targeting specificity of the probe for prostate cancer, thereby providing a theoretical basis for the development of PSMA fluorescent probes for clinical application in the future. Methods: In this study, a novel water-soluble 3H-indocyanine-type bioluminescent dye-Cy5-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-Cy5) was synthesized by liquid phase synthesis. The PSMA ligand was developed based on the glutamine-urea-lysine (Glu-urea-Lys) structure. The new fluorescent probe was evaluated in vitro and in vivo, and its safety was evaluated. Confocal microscopy was used to observe the binding uptake of PSMA-Cy5 with PSMA (+) LNCaP cells, PSMA (-) PC3 cells and blocked LNCaP cells. In in vivo optical imaging studies, the targeting specificity of PSMA (+) 22Rv1 tumors to probe binding was validated by tail vein injection of PSMA-Cy5. The safety of the PSMA-Cy5 probe was evaluated by histopathological analysis of mouse organs by a single high-dose tail vein injection of PSMA-Cy5. Results: In vitro fluorescence cell uptake experiments showed that the binding of PSMA-Cy5 to LNCaP cells has targeting specificity. PC3 cells and blocked LNCaP cells showed almost no uptake. The results of in vivo optical imaging studies showed that the tumor-to-background ratio in the 22Rv1 group was 3.39 ± 0.47; in the 22Rv1 blocking group it was 0.78 ± 0.15, and in the PC3 group it was 0.94 ± 0.09, consistent with the in vitro results. After a high-dose injection of PSMA-Cy5, there were no abnormalities in the tissues or organs of the mice. The probe showed good safety. Conclusions: PSMA-Cy5 is a probe with good targeting specificity and low toxicity that can accurately visualize tumors in vivo. This study has an important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to precise tumor imaging during radical prostatectomy to reduce the incidence of postoperative PSM.

Insulin-like peptide (ILP) has been identified in various crustaceans, but whether it has a similar function in regulating hemolymph glucose as vertebrate insulin is unclear. We analyzed the components of hemolymph sugar in the Pacific white shrimp, Litopenaeus vannamei, and investigated the changes of hemolymph glucose concentration and the expressions of ILP and glucose metabolism genes under different treatments. We found glucose was a major component of hemolymph sugar in shrimp. Starvation caused hemolymph glucose to rise first and then decline, and the raised hemolymph glucose after exogenous glucose injection returned to basal levels within a short time, indicating that shrimp have a regulatory mechanism to maintain hemolymph glucose homeostasis. In addition, injections of bovine insulin and recombinant LvILP protein both resulted in a fast decline in hemolymph glucose. Notably, RNA interference of LvILP did not significantly affect hemolymph glucose levels, but it inhibited exogenous glucose clearance. Based on the detection of glucose metabolism genes, we found LvILP might maintain hemolymph glucose stability by regulating the expression of these genes. These results suggest that ILP has a conserved function in shrimp similar to insulin in vertebrates and plays an important role in maintaining hemolymph glucose homeostasis.

To solve the problems that the theoretical analysis of Halbach array magnetic circuit is insufficient and that calculating the magnetic adsorption force of a permanent magnet by using the magnetic node method is complex, the magnetic flux density of a Halbach array magnetic circuit composed of multiple permanent magnets with perpendicular magnetization directions is calculated. On the basis of the concentrated magnetic phenomenon of the ferromagnetic material and the end effect of the permanent magnet, a method for calculating the magnetic adsorption force of the Halbach array magnetic circuit by using the equivalent magnetic flux density is proposed, and the variation trend of magnetic adsorption force after changing the parameters of the magnetic circuit is obtained. ANSYS software is used to analyze several magnetic circuits that produce large magnetic adsorption force, a magnetic circuit structure that produces the largest magnetic adsorption force is determined, and the permanent magnetic adsorption device of the wall-climbing robot is improved. The magnetic adsorption force of the wall-climbing robot before and after the improvement of the permanent magnetic adsorption device is measured through experiments. The experimental results show that the magnetic adsorption force after the improvement is increased by 24.63% compared to before the improvement.

Objective This study aimed to investigate the relationship between birth order and stereoacuity among Chinese children aged 60–72 months.Design Cross-sectional.Participants 1342 children with complete data on the questionnaire, stereoacuity and refraction were included.Results The mean stereoacuity was 53.2±1.7, 56.9±1.9 and 60.9±1.5 s of arc in the first-born group, second-born group and third-born group, respectively. Lower birth order was significantly correlated with better stereoacuity (p=0.036). Third-borns (OR=3.02, p=0.027) were at higher risk of having subnormal stereoacuity compared with first-borns in the multivariate analysis.Conclusion Later-borns had poorer stereoacuity than first-borns.

BackgroundPositron emission tomography (PET) images are being applied for defining radiotherapy targets. However, a recognized method for defining radiotherapy targets is lacking. We investigate the threshold to outline the radiotherapy target of a tumor on PET images and its influencing factors, and then expressed it by formula.MethodsPET imaging for spherical tumors with a different tumor diameter (D), under different system resolutions [full width at half maximum (FWHM)], in different backgrounds with different pixel sizes, was simulated. PET images were analyzed to determine the relationship between the threshold and the factors mentioned above. Finally, the simulation results were verified by phantom experiments.ResultsThe threshold decreased sharply with D for D < 2 FWHM, reached the minimum of 31% at D = 2 FWHM and then increased slowly, and it tended to constant for D > 8 FWHM. The threshold decreased with FWHM for FWHM < D/2, reached a minimum at FWHM = D/2, and then increased. The threshold increased with pixel size for D ≤ FWHM and decreased for D > FWHM. The threshold was independent of the background. The relationship between the threshold and its influencing factors was expressed as a formula. The results of the phantom verification indicated that the error of the target volume delineation that was calculated by the formula was less than 9%.ConclusionsThe threshold changes with tumor size, resolution of the PET system and pixel size according to certain rules. The formula to calculate the threshold could provide a method to estimate threshold to outline the radiotherapy target (tumor).

PurposeTo summarize and analyze the current evidence about surgical, oncological, and functional outcomes between laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN).Materials and MethodsThrough a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis. Meanwhile, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions.ResultsA total of 26 studies with 8095 patients were included. There was no statistical difference between the LPN and OPN in the terms of operation time (p=0.13), intraoperative complications (p=0.94), recurrence (p=0.56), cancer-specific survival (p=0.72), disease-free survival (p=0.72), and variations of estimated glomerular filtration rate (p=0.31). The LPN group had significantly less estimated blood loss (P

Carotenoids are almost universally distributed in living organisms. The oxidative metabolism by carotene oxygenase contributes to the metabolic processes of carotenoids. 15,15ʹ-beta-carotene oxygenase (BCO1) and 9ʹ,10ʹ-beta-carotene oxygenase (BCO2) are two important carotenoid oxygenases. In order to understand the function of carotenoid oxygenases in crustaceans, seven genes encoding carotenoid oxygenases (named EcBCO-like) were isolated from the transcriptome database of Exopalaemon carinicauda. After phylogenetic analysis with carotenoid oxygenases reported in other species, EcBCO-like1, EcBCO-like3, and EcBCO-like6 were chosen for further functional study. The prawns after EcBCO-like1 knockdown suffered continuous death, which suggested its important role for the survival of the animals. For the prawns after EcBCO-like3 knockdown, no phenotype change was observed. The prawns after EcBCO-like6 knockdown showed color changes in their hepatopancreas when they were fed with carotenoids-containing diet, and the content of carotenoid in their hepatopancreas was much higher than that in the control prawns. The present study will pave the way for further understanding the carotenoids metabolism in the prawns.

Pulmonary hypertension (PH) comprises a group of pathophysiological syndromes characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, which lead to right ventricular overload, and even right heart failure. PH has a poor prognosis and severely leads to a decline in quality of life. Historically, patients with PH were advised to limit their physical activity. However, an increasing number of studies have reported the safety and efficacy of exercise rehabilitation training in PH. This review briefly examined and summarized the effects of exercise rehabilitation training on PH patients reported in the recent literature. The findings of the reviewed studies indicate that exercise rehabilitation training in PH patients has beneficial effects in terms of exercise capacity and quality of life, vascular and right ventricle remodelling, inflammatory response, muscular function and oxidative stress. However, the underlying mechanisms and appropriate exercise strategies (e.g. the duration and intensity of exercise) still need to be explored. In conclusion, exercise rehabilitation training of the appropriate intensity and frequency can improve the prognosis and quality of life of PH patients. The training should be monitored by professional staff and be provided as an adjunct to pharmacological treatment. Larger clinical trials are required to confirm the safety and efficacy of exercise rehabilitation training in PH.

Results from the epidemiologic studies on the relationship between hormone replacement therapy (HRT) and the risk of kidney cancer in women were not completely consistent. This meta-analysis aimed to evaluate the relationship between HRT and risk of kidney cancer in women. We performed a meta-analysis of observational studies to assess this association. The PubMed and Embase databases were searched from their inception to January 29, 2020, to identify relevant studies that fit the pre-stated inclusion criteria; reference lists from the retrieved articles were also been reviewed. Relative risks (RRs) with corresponding 95% CIs were extracted and combined using random effects models. Furthermore, dose–response, sensitivity analyses, publication bias, and subgroup analysis by study design, regional location, and exposure assessment method were conducted. Thirteen articles involving 6 cohort studies and 8 case–control studies were included in our meta-analysis. Overall, 4194 women were diagnosed with kidney cancer among 648 107 participants. The pooled RR for kidney cancer was 1.08 (95% CI: 0.96-1.22) in those who were administered HRT compared to those who had not. Subgroup analysis indicated the overall result was not influenced by study type, regional location, or adjusted variables. Dose–response analysis showed a nonlinear relationship between HRT and kidney cancer ( P = .0021) and the risk of kidney cancer decreased by 15% to 28% with 12 to 18 years of HRT use. No evidence of publication bias was found ( P for Egger =.111). Our meta-analysis showed that HRT use is inversely associated with kidney cancer risk in a dose–dependent fashion.

ABSTRACT The complex bacterial community in a quinoline-degrading denitrifying bioreactor is predominated by several taxa, such as Thauera and Rhodococcus. However, it remains unclear how the interactions between the different bacteria mediate quinoline metabolism under denitrifying conditions. In this study, we designed a sequence-specific amplification strategy to isolate the most predominant bacteria and obtained four strains of Thauera aminoaromatica, a representative of a key member in the bioreactor. Tests on these isolates demonstrated that all were unable to degrade quinoline but efficiently degraded 2-hydroxyquinoline, the hypothesized primary intermediate of quinoline catabolism, under nitrate-reducing conditions. However, another isolate, Rhodococcus sp. YF3, corresponding to the second most abundant taxon in the same bioreactor, was found to degrade quinoline via 2-hydroxyquinoline. The end products and removal rate of quinoline by isolate YF3 largely varied according to the quantity of available oxygen. Specifically, quinoline could be converted only to 2-hydroxyquinoline without further transformation under insufficient oxygen conditions, e.g., less than 0.5% initial oxygen in the vials. However, resting YF3 cells aerobically precultured in medium with quinoline could anaerobically convert quinoline to 2-hydroxyquinoline. A two-strain consortium constructed with isolates from Thauera (R2) and Rhodococcus (YF3) demonstrated efficient denitrifying degradation of quinoline. Thus, we experimentally verified that the metabolic interaction based on 2-hydroxyquinoline cross-feeding between two predominant bacteria constitutes the main quinoline degradation mechanism. This work uncovers the mechanism of quinoline removal by two cooperative bacterial species existing in denitrifying bioreactors. IMPORTANCE We experimentally verified that the second most abundant taxon, Rhodococcus, played a role in degrading quinoline to 2-hydroxyquinoline, while the most abundant taxon, Thauera, degraded 2-hydroxyquinoline. Metabolites from Thauera further served to provide metabolites for Rhodococcus. Hence, an ecological guild composed of two isolates was assembled, revealing the different roles that keystone organisms play in the microbial community. This report, to the best of our knowledge, is the first on cross-feeding between the initial quinoline degrader and a second bacterium. Specifically, the quinoline degrader (Rhodococcus) did not benefit metabolically from quinoline degradation to 2-hydroxyquinoline but instead benefited from the metabolites produced by the second bacterium (Thauera) when Thauera degraded the 2-hydroxyquinoline. These results could be a significant step forward in the elucidation of the microbial mechanism underlying quinoline-denitrifying degradation.

ABSTRACT Vibrio parahaemolyticus is an important foodborne pathogen and has recently gained particular notoriety because it causes acute hepatopancreatic necrosis disease (AHPND) in shrimp, which has caused significant economic loss in the shrimp industry. Here, we report a whole-genome analysis of 233 V. parahaemolyticus strains isolated from humans, diseased shrimp, and environmental samples collected between 2008 and 2017, providing unprecedented insight into the historical spread of AHPND. The results show that V. parahaemolyticus is genetically diverse and can be divided into 84 sequence types (STs). However, genomic analysis of three STs of V. parahaemolyticus identified seven transmission routes in Asia since 1996, which promoted the transfer of an AHPND-associated plasmid. Notably, the insertion sequence (ISVal1) from the plasmid subsequently mediated the genetic exchange among V. parahaemolyticus STs and resulted in the deletion of an 11-kb region regulating cell mobility and the production of capsular polysaccharides. Phenotype assays confirmed that this deletion enhanced biofilm formation, providing a novel mechanism for environmental adaptation. We conclude that the transmission mode of AHPND consists of two steps, the transmission of V. parahaemolyticus and the subsequent horizontal transfer of the AHPND-associated plasmid. This plasmid allows ISVal1 to mediate genetic exchange and improve pathogen fitness in shrimp ponds. Current shrimp farming practices promoted such genetic exchanges, which highlighted a risk of the emergence of new virulent populations, with potentially devastating consequences for both aquaculture and human health. This study addressed the basic questions regarding the transmission mechanism of AHPND and provided novel insights into shrimp and human disease management. IMPORTANCE Global outbreaks of shrimp acute hepatopancreatic necrosis disease (AHPND) caused by V. parahaemolyticus represent an urgent issue for the shrimp industry. This study revealed that the transmission mode of AHPND consists of two steps, the transregional dissemination of V. parahaemolyticus and the horizontal transfer of an AHPND-associated plasmid. Surprisingly, the introduction of the AHPND-associated plasmid also offers a novel mechanism of genetic exchange mediated by insertion sequences, and it improved the fitness of V. parahaemolyticus in a harsh environment. The results presented herein suggest that current shrimp farming practices promote genetic mixture between endemic and oceanic V. parahaemolyticus populations, which introduced the plasmid and accelerated bacterial adaptation by the acquisition of ecologically important functions. This entails a risk of the emergence of new virulent populations both for shrimp and humans. This study improves our understanding of the global dissemination of the AHPND-associated plasmid and highlights the urgent need to improve biosecurity for shrimp farming. Author Video: An author video summary of this article is available.

ABSTRACT Gut microbiota-derived endotoxin has been linked to human nonalcoholic fatty liver disease (NAFLD), but the specific causative agents and their molecular mechanisms remain elusive. In this study, we investigated whether bacterial strains of endotoxin-producing pathogenic species overgrowing in obese human gut can work as causative agents for NAFLD. We further assessed the role of lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4) cross talk in this pathogenicity. Nonvirulent strains of Gram-negative pathobionts were isolated from obese human gut and monoassociated with C57BL/6J germfree (GF) mice fed a high-fat diet (HFD). Deletion of waaG in the bacterial endotoxin synthetic pathway and knockout of TLR4 in GF mice were used to further study the underlying mechanism for a causal relationship between these strains and the development of NAFLD. Three endotoxin-producing strains, Enterobacter cloacae B29, Escherichia coli PY102, and Klebsiella pneumoniae A7, overgrowing in the gut of morbidly obese volunteers with severe fatty liver, induced NAFLD when monoassociated with GF mice on HFD, while HFD alone did not induce the disease in GF mice. The commensal Bacteroides thetaiotaomicron (ATCC 29148), whose endotoxin activity was markedly lower than that of Enterobacteriaceae strains, did not induce NAFLD in GF mice. B29 lost its proinflammatory properties and NAFLD-inducing capacity upon deletion of the waaG gene. Moreover, E. cloacae B29 did not induce NAFLD in TLR4-deficient GF mice. These nonvirulent endotoxin-producing strains in pathobiont species overgrowing in human gut may work as causative agents, with LPS-TLR4 cross talk as the most upstream and essential molecular event for NAFLD. IMPORTANCE Recent studies have reported a link between gut microbiota and nonalcoholic fatty liver disease (NAFLD), showing that germfree (GF) mice do not develop metabolic syndromes, including NAFLD. However, the specific bacterial species causing NAFLD, as well as their molecular cross talk with the host for driving liver disease, remain elusive. Here, we found that nonvirulent endotoxin-producing strains of pathogenic species overgrowing in obese human gut can act as causative agents for induction of NAFLD and related metabolic disorders. The cross talk between endotoxin from these specific producers and the host’s TLR4 receptor is the most upstream and essential molecular event for inducing all phenotypes in NAFLD and related metabolic disorders. These nonvirulent endotoxin-producing strains of gut pathogenic species overgrowing in human gut may collectively become a predictive biomarker or serve as a novel therapeutic target for NAFLD and related metabolic disorders.

Although neural stem cells (NSCs) could migrate towards lesions after central nervous system (CNS) injury, the migration ability always is restricted due to the disturbed composition and density of the adhesion ligands and extracellular matrix (ECM) gradient after CNS injury. To date, various methods have been developed to enhance NSC migration and a number of factors, which are affecting NSC migration potential, have been identified. Here, primary NSCs were cultured and the expression of actin alpha 2 (ACTA2) in NSCs was determined using reverse transcription polymerase chain reaction (RT-PCR) and immunostaining. Next, the role of ACTA2 in regulating NSC migration and the potential mechanism was explored. Our results demonstrated that ACTA2 expressed in NSCs. Meanwhile, downregulated ACTA2 using siRNA inhibited NSC migration through hindering actin filament polymerization via increasing RhoA expression and decreasing Rac1 expression. The present study might enrich the basic knowledge of ACTA2 in NSC migration and open an avenue for enhancing NSC migration potential, subsequently providing an intervention target for functional recovery after CNS injury.