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Hepatocellular cancer (HCC) is a serious illness with high prevalence and mortality throughout the whole world. For advanced HCC, immunotherapy is somewhat impactful and encouraging. Nevertheless, a substantial proportion of patients with advanced HCC are still unable to achieve a durable response, owing to heterogeneity from clonal variability and differential expression of the PD-1/PD-L1 axis. Recently, heat shock factor 1 (HSF1) is recognized as an important component of tumor immunotherapeutic response as well as related to PD-L1 expression in cancer. However, the mechanism of HSF1 regulating PD-L1 in cancer, especially in HCC, is still not fully clear. In this study, we observed the significantly positive correlation between HSF1 expression and PD-L1 expression in HCC samples; meanwhile combination expressions of HSF1 and PD-L1 served as the signature for predicting prognosis of patients with HCC. Mechanistically, HSF1 upregulated PD-L1 expression by inducing APOJ expression and activating STAT3 signaling pathway in HCC. In addition, we explored further the potential values of targeting the HSF1-APOJ-STAT3 axis against CD8+ T cells-mediated cancer cells cytotoxicity. These findings unveiled the important involvement of HSF1 in regulating PD-L1 expression in HCC as well as provided a novel invention component for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade.

In this paper, we develop a novel soft-clipping discrete beta GARCH (ScDBGARCH) model that provides an available method to model bounded time series with under-dispersion, equi-dispersion or over-dispersion. The new model not only allows positive dependence, but also negative dependence. The stochastic properties of the models are established, and these results are, in turn, used in the analysis of the asymptotic properties of the conditional maximum likelihood (CML) estimator of the new model. In addition, we apply the new model to measles infection to show its improved performance.

Abstract Introduction Case of double primary cancer of the prostate and rectum is rare, prostate cancer involving the postoperative intestinal anastomotic mucosal tissue is even rarer. Case presentation We report a case of rectal cancer discovered 1 year after a diagnosis of prostate cancer and a tumour in the postoperative anastomotic intestinal mucosal tissue involving prostatic adenocarcinoma at 1 year after the diagnosis of rectal cancer. Due to the poor differentiation of both prostate and rectal cancers, there are some pitfalls in the diagnosis of intestinal mucosal lesions at an anastomosis. The lack of an accurate diagnosis of a tumour in anastomosis intestinal mucosal tissue will affect treatment and patient survival. Conclusions The pathologists should have a detailed understanding of the patient's medical history and carefully observe the histopathological morphology and, if necessary, immunohistochemistry or other techniques should be used to assist in the pathological diagnosis and avoid both misdiagnosis and missed diagnosis.

Recently, there has been a growing interest in integer-valued time series models, especially in multivariate models. Motivated by the diversity of the infinite-patch metapopulation models, we propose an extension to the popular bivariate INAR(1) model, whose innovation vector is assumed to be time-dependent in the sense that the mean of the innovation vector is linearly increased by the previous population size. We discuss the stationarity and ergodicity of the observed process and its subprocesses. We consider the conditional maximum likelihood estimate of the parameters of interest, and establish their large-sample properties. The finite sample performance of the estimator is assessed via simulations. Applications on crime data illustrate the model.

In the past, most threshold models considered a single threshold variable. However, for some practical applications, models with two threshold variables may be needed. In this paper, we propose a two-threshold-variable integer-valued autoregressive model based on the binomial thinning operator and discuss some of its basic properties, including the mean, variance, strict stationarity, and ergodicity. We consider the conditional least squares (CLS) estimation and discuss the asymptotic normality of the CLS estimator under the known and unknown threshold values. The performances of the CLS estimator are compared via simulation studies. In addition, two real data sets are considered to underline the superior performance of the proposed model.

Aims: Leucine zipper downregulated in cancer 1 (LDOC1) inhibits tumor growth in several cancers. However, the expression and function of LDOC1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we aimed to investigate how LDOC1 influenced tumor progression and the biological functions of HCC.Methods: The transcription levels of LDOC1 were determined using the GEPIA and UALCAN online databases and a real-time polymerase chain reaction. Western blot and immunohistochemistry were used to validate the protein levels of LDOC1. The online Kaplan-Meier Plotter was applied for survival analysis. Then lentivirus transfection was used to construct LDOC1 exogenous overexpression cell lines. Proliferation, clone formation, cell cycle, apoptosis, and migration assays were performed with the LDOC1-upregulated Huh7 and Hep3B cell lines. The phosphorylated and total levels of AKT and mTOR were determined using a Western blot to explore the potential molecular mechanism of LDOC1.Results: In the GEPIA and UALCAN analyses, LDOC1 was lowly expressed in tumors, had high expression in normal tissue samples (p < 0.05), and negatively correlated with tumor grade progression. The down-regulation of LDOC1 in HCC was validated with real-time polymerase chain reaction, Western blot, and immunohistochemistry (all p < 0.05). LDOC1 transcription levels were negatively associated with overall, progression-free, recurrence-free, and disease-specific survival (all p < 0.05). The functional experiments suggested that the overexpression of LDOC1 contributed to increased G1 and G2 stages in Huh7, while increased G2 stage in Hep3B, and decreased cell proliferation, clone formation, and migration, as well as increased the apoptosis rate compared with the control group (all p < 0.05). Furthermore, LDOC1 up-regulation reduced the p-AKT/AKT and p-mTOR/mTOR, which indicates an inactivation of the AKT/mTOR pathway.Conclusion: The tumor-suppressor LDOC1 varied in HCC and non-HCC tissues, which can serve as a candidate prognostic biomarker. LDOC1 influenced survival by affecting proliferation, colony formation, cell cycle, apoptosis, and migration ability, which might be attributed to the AKT/mTOR inhibition in HCC.

Federated learning (FL) has been widely used in both academia and industry all around the world. FL has advantages from the perspective of data security, data diversity, real-time continual learning, hardware efficiency, etc. However, it brings new privacy challenges, such as membership inference attacks and data poisoning attacks, when parts of participants are not assumed to be fully honest. Moreover, selfish participants can obtain others’ collaborative data but do not contribute their real local data or even provide fake data. This violates the fairness of FL schemes. Therefore, advanced privacy and fairness techniques have been integrated into FL schemes including blockchain, differential privacy, zero-knowledge proof, etc. However, most of the existing works still have room to enhance the practicality due to our exploration. In this paper, we propose a Blockchain-based Pseudorandom Number Generation (BPNG) protocol based on Verifiable Random Functions (VRFs) to guarantee the fairness for FL schemes. Next, we further propose a Gradient Random Noise Addition (GRNA) protocol based on differential privacy and zero-knowledge proofs to protect data privacy for FL schemes. Finally, we implement both two protocols on Hyperledger Fabric and analyze their performance. Simulation experiments show that the average time that proof generation takes is 18.993 s and the average time of on-chain verification is 2.27 s under our experimental environment settings, which means the scheme is practical in reality.

A Physical Protection System (PPS) protect critical assets and nuclear materials of the Nuclear Power Plant (NPP) from a malicious attack to avoid an unacceptable radioactive consequence. The growing threat of terrorism makes NPPs a huge challenge. After the PPS is developed or threat updated, it must be evaluated, usually need re-design to ensure it still meets the objectives. Due to the complexity of effectiveness evaluation, the authors have developed a Virtual Force on Force System (VFFS).

Binomial autoregressive models are frequently used for modeling bounded time series counts. However, they are not well developed for more complex bounded time series counts of the occurrence of n exchangeable and dependent units, which are becoming increasingly common in practice. To fill this gap, this paper first constructs an exchangeable Conway–Maxwell–Poisson-binomial (CMPB) thinning operator and then establishes the Conway–Maxwell–Poisson-binomial AR (CMPBAR) model. We establish its stationarity and ergodicity, discuss the conditional maximum likelihood (CML) estimate of the model’s parameters, and establish the asymptotic normality of the CML estimator. In a simulation study, the boxplots illustrate that the CML estimator is consistent and the qqplots show the asymptotic normality of the CML estimator. In the real data example, our model takes a smaller AIC and BIC than its main competitors.

Abstract Background Clinical features of cough variant asthma (CVA) in Chinese adults are largely uncertain. Methods A total of 303 patients newly diagnosed as uncontrolled asthma (symptom control and future risk of adverse outcomes), including 175 CVA and 128 classic asthma (CA), were enrolled in this retrospective survey. Clinical features including basic characteristics, pulmonary function, airway hyperresponsiveness (AHR) and cell counts of induced sputum, were compared retrospectively. All patients were classified into four inflammatory subtypes based on the counts of induced sputum eosinophils and neutrophils as eosinophilic (E), neutrophilic (N), mixed granulocytic (M), and paucigranulocytic (P) subtypes. Inflammatory subtype distribution was also compared. Results Compared with CA patients, CVA patients were younger (P = 0.009), had a higher prevalence of female patients (P = 0.001), higher parameter values of baseline pulmonary function (P ≤ 0.01 for all), shorter duration of disease (P = 0.002), lower AHR (P = 0.001) and lower sputum eosinophil% (P = 0.009). There was a difference in the AHR distribution as the percentage of moderate and severe AHR in CVA was significantly lower than in CA (41.72% VS 64.70%, P = 0.001). The inflammatory subtype distribution was different as the proportion of E and M subtypes in CVA was lower than in CA (56.0% vs 67.19%, P = 0.049). The proportion of subtype P was the lowest and subtype M was the highest in both CVA and CA patients. There was a similar negative correlation of sputum eosinophil% with AHR in CVA and CA (r = − 0.337, P

AimsIn the cancer-related research field, there is currently a major need for a greater number of valuable biomarkers to predict the prognosis of hepatocellular carcinoma (HCC). In this study, we aimed to screen hub genes related to immune cell infiltration and explore their prognostic value for HCC.MethodsWe analyzed five datasets (GSE46408, GSE57957, GSE74656, GSE76427, and GSE87630) from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). A protein–protein interaction network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes; then, the hub genes were identified. Functional enrichment of the genes was performed on the Metascape website. Next, the expression of these hub genes was validated in several databases, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and Human Protein Atlas. We explored the correlations between the hub genes and infiltrated immune cells in the TIMER2.0 database. The survival curves were generated in GEPIA2, and the univariate and multivariate Cox regression analyses were performed using TIMER2.0.ResultsThe top ten hub genes [DNA topoisomerase II alpha (TOP2A), cyclin B2 (CCNB2), protein regulator of cytokinesis 1 (PRC1), Rac GTPase-activating protein 1 (RACGAP1), aurora kinase A (AURKA), cyclin-dependent kinase inhibitor 3 (CDKN3), nucleolar and spindle-associated protein 1 (NUSAP1), cell division cycle-associated 5 (CDCA5), abnormal spindle microtubule assembly (ASPM), and non-SMC condensin I complex subunit G (NCAPG)] were identified in subsequent analysis. These genes are most markedly enriched in cell division, suggesting their close association with tumorigenesis. Multi-database analyses validated that the hub genes were upregulated in HCC tissues. All hub genes positively correlated with several types of immune infiltration, including B cells, CD4+ T cells, macrophages, and dendritic cells. Furthermore, these hub genes served as independent prognostic factors, and the expression of these hub genes combing with the macrophage levels could help predict an unfavorable prognosis of HCC.ConclusionIn sum, these hub genes (TOP2A, CCNB2, PRC1, RACGAP1, AURKA, CDKN3, NUSAP1, CDCA5, ASPM, and NCAPG) may be pivotal markers for prognostic prediction as well as potentially work as targets for immune-based intervention strategies in HCC.

The difference between the planetary differential mechanism and the planetary closed differential mechanism is analyzed by examples of planetary transmission mechanism. The evolution process of RV reducer from one tooth differential cycloid needle wheel reducer is analyzed，the concept that the crank shaft is a negative 1 tooth sun wheel in a tooth differential meshing drive is proposed and the transmission ratio equivalent calculation is carried out. The power flow diagram of RV reducer is equivalent，and the transmission power distribution ratio formula of each branch is obtained，and the essence of planetary closed differential motion of RV reducer is revealed. This theoretical analysis is instructive for the forward design of the RV reducer.

Excess zeros is a common phenomenon in time series of counts, but it is not well studied in asymmetrically structured bivariate cases. To fill this gap, we first considered a new first-order, bivariate, random coefficient, integer-valued autoregressive model with a bivariate innovation, which follows the asymmetric Hermite distuibution with five parameters. An attractive advantage of the new model is that the dependence between series is achieved by innovative parts and the cross-dependence of the series. In addition, the time series of counts are modeled with excess zeros, low counts and low over-dispersion. Next, we established the stationarity and ergodicity of the new model and found its stochastic properties. We discuss the conditional maximum likelihood (CML) estimate and its asymptotic property. We assessed finite sample performances of estimators through a simulation study. Finally, we demonstrate the superiority of the proposed model by analyzing an artificial dataset and a real dataset.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme in the DNA repair process and the target of several FDA-approved inhibitors. Several of these inhibitors have been radiolabeled for non-invasive imaging of PARP-1 expression or targeted radiotherapy of PARP-1 expressing tumors. In particular, derivatives of olaparib and rucaparib, which have reduced trapping potency by PARP-1 compared to talazoparib, have been radiolabeled for these purposes. Here, we report the first radiosynthesis of [18F]talazoparib and its in vitro and in vivo evaluation. Talazoparib (3a″) and its bromo- or iodo-derivatives were synthesized as racemic mixtures (3a, 3b and 3c), and these compounds exhibit high affinity to PARP-1 (Ki for talazoparib (3a″): 0.65 ± 0.07 nM; 3a: 2.37 ± 0.56 nM; 3b: 1.92 ± 0.41 nM; 3c: 1.73 ± 0.43 nM; known PARP-1 inhibitor Olaparib: 1.87 ± 0.10 nM; non-PARP-1 compound Raclopride: >20,000 nM) in a competitive binding assay using a tritium-labeled PARP-1 radioligand [3H]WC-DZ for screening. [18F]Talazoparib (3a″) was radiosynthesized via a multiple-step procedure with good radiochemical and chiral purities (98%) and high molar activity (28 GBq/μmol). The preliminary biodistribution studies in the murine PC-3 tumor model showed that [18F]talazoparib had a good level of tumor uptake that persisted for over 8 h (3.78 ± 0.55 %ID/gram at 4 h and 4.52 ± 0.32 %ID/gram at 8 h). These studies show the potential for the bromo- and iodo- derivatives for PARP-1 targeted radiotherapy studies using therapeutic radionuclides.

ObjectiveThe aim of this study is to evaluate the performance of different platelet counting methods (optical, impedance, fluorescence and hand counting) applied in different analysers by comparing with the international flow cytometric reference method (IRM).MethodsA total of 333 blood samples from different subgroups (168 cases with thrombocytopenia, 136 cases with normal platelet counts and 29 cases with thrombocytosis) were tested. Regarding IRM as the gold standard, we compared the accuracy and precision of different platelet count methods; i.e. LH780 (impedance), BC-6000 Plus (optical (O) and impedance (I)), Sysmex XN-9000 (optical (O), impedance (I), fluorescence (F)), and hand counting.ResultsSysmex XN-9000-F (r = 0.988) had the best correlation with IRM for thrombocytopenic samples; BC-6000 Plus-I (r = 0.966) was more relevant to IRM than any other method for samples with normal platelet counts. Correlation between Sysmex XN-9000-I (r = 0.960) and IRM was the highest among these methods for samples with thrombocytosis. For bias evaluation, the average bias of Sysmex XN-9000-F was -1.5 × 109/L (95% LA = -9.4 to +6.4) for samples with thrombocytopenia, compared with IRM. BC-6000 Plus-I had a small mean difference with IRM for samples with normal platelet counts or thrombocytosis. Moreover, all evaluated methods had acceptable sensitivity, specificity, and concordance rates as compared with IRM in the diagnosis of thrombocytopenia and thrombocytosis.ConclusionsPlatelet counting by Sysmex XN-9000-F is more accurate than other methods for thrombocytopenic samples. BC-6000 Plus-I has superior association and consistency for normal platelet counts. As for thrombocytosis patients, Sysmex XN-9000-I has the highest correlation with IRM while Sysmex XN-9000-O has the highest diagnosis efficacy.

Objective: The purpose of this meta-analysis was to investigate the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) of patients with Parkinson's disease (PD) and to determine the optimal rTMS parameters, such as the intensity, frequency and the delivered pattern of rTMS stimulation.Methods: EMBASE, PubMed, Web of Science, MEDLINE, and Cochrane data bases were researched for papers published before March 12, 2018. Studies investigating the anti-depression effects of rTMS over PFC in patients with PD were considered. The main outcomes of pre- and post-rTMS treatment as well as score changes were all extracted. The mean effect size was estimated by calculating the standardized mean difference (SMD) with 95% confidence interval (CI) by using fixed or random effect models as appropriate.Results: Nine studies containing 137 PD patients with depression were included. The pooled results showed significant pre-post anti-depressive effects of rTMS over PFC in PD patients with depression (SMD = −0.80, P < 0.00001). The subgroup analyses of stimulation intensity, frequencies, and models also revealed significant effects (Intensities: 90% RMT: SMD = −1.16, P = 0.0006; >100% RMT: SMD = −0.82, P < 0.0001. Frequencies: < 1.0 Hz: SMD = −0.83, P = 0.03; 5.0 Hz: SMD = −1.10, P < 0.0001; ≥10.0 Hz: SMD = −0.55, P = 0.02. Models: Continuous: SMD = −0.79, P < 0.0001; Discontinuous: SMD = −0.84, P = 0.02). But the results of the studies with place-controlled designs were not significant (Overall: SMD = −0.27, P = 0.54. Intensities: 90% RMT: SMD = 0.27, P = 0.68; 100% RMT: SMD = −0.32, P = 0.33. Frequencies: 5.0 Hz: SMD = −0.87, P = 0.10; ≥10.0 Hz: SMD = 0.27, P = 0.66. Models: Continuous: SMD = −0.28, P = 0.68; Discontinuous: SMD = −0.32, P = 0.33). The greater effect sizes of rTMS with 90% RMT, 5.0 Hz in discontinuous days can be observed rather than the other parameters in both kinds of analyses across study design.Conclusions: rTMS may have a significant positive pre-post anti-depressive effect over PFC on patients with depression, especially by using 5.0 Hz frequency with 90% RMT intensity in discontinuous days, which may produce better effects than other parameters. The real effect, though, was not different from that of the placebo. Future studies with larger sample sizes and high-quality studies are needed to further corroborate our results and to identify the optimal rTMS protocols.

Rab26 GTPase modulates the trafficking of cell surface receptors, such as G protein-coupled receptors including α2-adrenergic receptors in some cell types. However, the effect of Rab26 on β2-adrenergic receptor (β2-AR) trafficking or/and Toll-like receptor 4 (TLR4) expression in human pulmonary microvascular endothelial cells (HPMECs) is still unclear. Here, we investigated the role of Rab26 in regulating the expression of β2-ARs and TLR4 in HPMECs and the effect of these receptors’ imbalance on endothelial cell barrier function. The results showed that there was unbalance expression in these receptors, where β2-AR expression was remarkably reduced, and TLR4 was increased on the cell membrane after lipopolysaccharide (LPS) treatment. Furthermore, we found that Rab26 overexpression not only upregulated β2-ARs but also downregulated TLR4 expression on the cell membrane. Subsequently, the TLR4-related inflammatory response was greatly attenuated, and the hyperpermeability of HPMECs also was partially relived. Taken together, these data suggest that basal Rab26 maintains the balance between β2-ARs and TLR4 on the cell surface, and it might be a potential therapeutic target for diseases involving endothelial barrier dysfunction.

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [3H]TH287 to MTH1 was evaluated in live glioblastoma cells (U251MG) through saturation and competitive binding assays, together with in vitro enzymatic assays. Furthermore, TH287 was radiolabeled with carbon-11 for in vivo microPET studies. Saturation binding assays show that [3H]TH287 has a dissociation constant (Kd) of 1.97 ± 0.18 nM, Bmax of 2676 ± 122 fmol/mg protein for U251MG cells, and nH of 0.98 ± 0.02. Competitive binding assays show that TH287 (Ki: 3.04 ± 0.14 nM) has a higher affinity for MTH1 in U251MG cells compared to another well studied MTH1 inhibitor: (S)-crizotinib (Ki: 153.90 ± 20.48 nM). In vitro enzymatic assays show that TH287 has an IC50 of 2.2 nM in inhibiting MTH1 hydrolase activity and a Ki of 1.3 nM from kinetics assays, these results are consistent with our radioligand binding assays. Furthermore, MicroPET imaging shows that [11C]TH287 gets into the brain with rapid clearance from the brain, kidney, and heart. The results presented here indicate that radiolabeled TH287 has favorable properties to be a useful tool for measuring MTH1 in vitro and for further evaluation for in vivo PET imaging MTH1 of brain tumors and other central nervous system disorders.

Matrix stiffening is a feature of pulmonary fibrosis, and is amplified by lung myofibroblasts. Here the authors find that a6 integrin expression is upregulated on lung myofibroblasts in response to matrix stiffness, and this integrin is required for myofibroblast invasion, and fibrosis in an experimental disease model.

Olive trees, originated from Mediterranean, have been cultivated in China for decades and show great adaption to local environment. However, research on this topic is limited. In this study, the major qualitative characteristics and changes of olive grown in southwest China were investigated. The results showed that oil accumulated during fruit development and reached its maximum value when fruit had fully ripened. Phenolic and flavonoid contents increase rapidly in the early growth stage (0–90 DAFB) and then begin to decrease as fruit ripens. Compared with olive from the Mediterranean, olive from China has special characteristics: higher moisture content in the fruit combined with lower percentages of unsaturated fatty acids and oil content. This is due to southwest China's climate which is wetter and cooler compared to the Mediterranean. Our study suggests that southwest China's higher annual rainfall might contribute to higher fruit moisture content while its low temperatures would be conducive to higher unsaturated fatty acid levels in the fruit.

Background and Purpose. This meta-analysis aimed to evaluate the therapeutic potential of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional hemisphere on upper limb motor recovery and cortex plasticity after stroke. Methods. Databases of PubMed, Medline, ScienceDirect, Cochrane, and Embase were searched for randomized controlled trials published before Jun 31, 2017. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Resting motor threshold (rMT) and motor-evoked potential (MEP) were also examined. Results. Twenty-two studies of 1 Hz LF-rTMS over the contralesional hemisphere were included. Significant efficacy was found on finger flexibility (SMD = 0.75), hand strength (SMD = 0.49), and activity dexterity (SMD = 0.32), but not on body function (SMD = 0.29). The positive changes of rMT (SMD = 0.38 for the affected hemisphere and SMD = −0.83 for the unaffected hemisphere) and MEP (SMD = −1.00 for the affected hemisphere and SMD = 0.57 for the unaffected hemisphere) were also significant. Conclusions. LF-rTMS as an add-on therapy significantly improved upper limb functional recovery especially the hand after stroke, probably through rebalanced cortical excitability of both hemispheres. Future studies should determine if LF-rTMS alone or in conjunction with practice/training would be more effective. Clinical Trial Registration Information. This trial is registered with unique identifier CRD42016042181.

Purpose. The aim of this study was to evaluate the effects of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) on stroke patients with motor dysfunction and to investigate the underlying neural mechanism. Methods. Fifteen stroke patients were assigned to the rTMS treatment (RT) group and conventional treatment (CT) group. Patients in the RT received 10 Hz rTMS stimulation on the ipsilesional primary motor cortex for 10 days plus conventional treatment of CT, which consisted of acupuncture and antiplatelet aggregation medication. Difference in fractional anisotropy (FA) between pretreatment and posttreatment and between two groups was determined. Correlations between FA values and neurological assessments were also calculated. Results. Both groups significantly improved the neurological function after treatment. rTMS-treated patients showed better improvement in Fugl-Meyer Assessment (FMA) score and increased FA value in motor-related white matter and gray matter cortices compared with CT-treated patients and pretreatment status. Besides, the increased FA value in the ipsilesional posterior limb of the internal capsule in RT group was significantly correlated with the improved FMA score. Significance. HF-rTMS could be a supplement therapy to CT in improving motor recovery in patients with stroke. And this benefit effect may be achieved through modulating the ipsilesional corticospinal tracts and motor-related gray matter cortices.

Paenibacillus polymyxa A-8, which secretes β-mannosidase, was isolated from the soil sample under a pine tree located in the "Laoban" mountain region of Sichuan, China. The β-mannosidase gene (MANB) was isolated from P. polymyxa A-8, using primers according to the complete genome. The MANB (2,550 bp) encoding 849 amino acid residues was expressed in Escherichia coli. The specific activities of β-mannosidase produced by P. polymyxa A-8 and E. coli pET30a-MANB were 12 nkat/mg and 635 nkat/mg respectively. SDS-PAGE analysis indicated that the molecular mass of the recombinant MANB was approximately 96 kDa. The recombinant MANB was active between pH 7.0-8.5 with the maximum activity at pH 7.0. It had good pH stability and adaptability. The MANB had the optimal temperature of 35°C and was relatively stable at 35-40°C. In addition, the MANB activity was enhanced by K+, Ca2+, Mn2+, and Mg2+ and inhibited by Zn2+, Cu2+, and Hg2+.

Breast cancer is one of the most lethal diseases in women; however, the precise etiological factors are still not clear. Genistein (GE), a natural isoflavone found in soybean products, is believed to be a potent chemopreventive agent for breast cancer. One of the most important mechanisms for GE inhibition of breast cancer may involve its potential in impacting epigenetic processes allowing reversal of aberrant epigenetic events during breast tumorigenesis. To investigate epigenetic regulation for GE impedance of breast tumorigenesis, we monitored epigenetic alterations of several key tumor-related genes in an established breast cancer transformation system. Our results show that GE significantly inhibited cell growth in a dose-dependent manner in precancerous breast cells and breast cancer cells, whereas it exhibited little effect on normal human mammary epithelial cells. Furthermore, GE treatment increased expression of two crucial tumor suppressor genes, p21(WAF1) (p21) and p16(INK4a) (p16), although it decreased expression of two tumor promoting genes, BMI1 and c-MYC. GE treatment led to alterations of histone modifications in the promoters of p21 and p16 as well as the binding ability of the c-MYC-BMI1 complex to the p16 promoter contributing to GE-induced epigenetic activation of these tumor suppressor genes. In addition, an orally-fed GE diet prevented breast tumorigenesis and inhibited breast cancer development in breast cancer mice xenografts. Our results suggest that genistein may repress early breast tumorigenesis by epigenetic regulation of p21 and p16 by impacting histone modifications as well as the BMI1-c-MYC complex recruitment to the regulatory region in the promoters of these genes. These studies will facilitate more effective use of soybean product in breast cancer prevention and also help elucidate the mechanisms during the process of early breast tumorigenesis.

The syndrome of high-altitude de-acclimatization commonly takes place after long-term exposure to high altitudes upon return to low altitudes. The syndrome severely affects the returnee's quality of life. However, little attention has been paid to careful characterization of the syndrome and their underlying mechanisms. Male subjects from Chongqing (n = 67, 180 m) and Kunming (n = 70, 1800 m) visited a high-altitude area (3650 m) about 6 months and then returned to low-altitude. After they came back, all subjects were evaluated for high-altitude de-acclimatization syndrome on the 3(rd), 50(th), and 100(th). Symptom scores, routine blood and blood gas tests, and myocardial zymograms assay were used for observation their syndrome. The results showed that the incidence and severity of symptoms had decreased markedly on the 50(th) and 100(th) days, compared with the 3(rd) day. The symptom scores and incidence of different symptoms were lower among subjects returning to Kunming than among those returning to Chongqing. On the 3(rd) day, RBC, Hb, Hct, CK, CK-MB, and LDH values were significantly lower than values recorded at high altitudes, but they were higher than baseline values. On the 50(th) day, these values were not different from baseline values, but LDH levels did not return to baseline until the 100(th) day. These data show that, subjects who suffered high-altitude de-acclimatization syndrome, the recovery fully processes takes a long time (≥ 100(th) days). The appearance of the syndrome is found to be related to the changes in RBC, Hb, Hct, CK, CK-MB, and LDH levels, which should be caused by reoxygenation after hypoxia.

Federated Learning (FL), as an emergent paradigm in privacy-preserving machine learning, has garnered significant interest from scholars and engineers across both academic and industrial spheres. Despite its innovative approach to model training across distributed networks, FL has its vulnerabilities; the centralized server-client architecture introduces risks of single-point failures. Moreover, the integrity of the global model--a cornerstone of FL--is susceptible to compromise through poisoning attacks by malicious actors. Such attacks and the potential for privacy leakage via inference starkly undermine FL's foundational privacy and security goals. For these reasons, some participants unwilling use their private data to train a model, which is a bottleneck in the development and industrialization of federated learning. Blockchain technology, characterized by its decentralized ledger system, offers a compelling solution to these issues. It inherently prevents single-point failures and, through its incentive mechanisms, motivates participants to contribute computing power. Thus, blockchain-based FL (BCFL) emerges as a natural progression to address FL's challenges. This study begins with concise introductions to federated learning and blockchain technologies, followed by a formal analysis of the specific problems that FL encounters. It discusses the challenges of combining the two technologies and presents an overview of the latest cryptographic solutions that prevent privacy leakage during communication and incentives in BCFL. In addition, this research examines the use of BCFL in various fields, such as the Internet of Things and the Internet of Vehicles. Finally, it assesses the effectiveness of these solutions. [ABSTRACT FROM AUTHOR]