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Abstract Tooth enamel, and especially the outer tooth enamel, is a load-resistant shell that benefits mastication but is easily damaged, driving the need for enamel-restorative materials with comparable properties to restore the mastication function and protect the teeth. Synthesizing an enamel analog that mimics the components and hierarchical structure of natural tooth enamel is a promising way to achieve these comparable mechanical properties, but it is still challenging to realize. Herein, we fabricate a hierarchical enamel analog with comparable stiffness, hardness, and viscoelasticity as natural enamel by incorporating three hierarchies of outer tooth enamel based on hierarchical assembly of enamel-like hydroxyapatite hybrid nanowires with polyvinyl alcohol as a matrix. This enamel analog possesses enamel-similar inorganic components and a nanowire-microbundle-macroarray hierarchical structure. It exhibits toughness of 19.80 MPa m1/2, which is 3.4 times higher than natural tooth enamel, giving it long-term fatigue durability. This hierarchical design is promising for scalable production of enamel-restorative materials and for optimizing the mechanical performance of engineering composites.

Abstract Background Glioma is the most common primary brain tumor with high mortality and disability rates. Recent studies have highlighted the significant prognostic consequences of subtyping molecular pathological markers using tumor samples, such as IDH, 1p/19q, and TERT. However, the relative importance of individual markers or marker combinations in affecting patient survival remains unclear. Moreover, the high cost and reliance on postoperative tumor samples hinder the widespread use of these molecular markers in clinical practice, particularly during the preoperative period. We aim to identify the most prominent molecular biomarker combination that affects patient survival and develop a preoperative MRI-based predictive model and clinical scoring system for this combination. Methods A cohort dataset of 2,879 patients was compiled for survival risk stratification. In a subset of 238 patients, recursive partitioning analysis (RPA) was applied to create a survival subgroup framework based on molecular markers. We then collected MRI data and applied Visually Accessible Rembrandt Images (VASARI) features to construct predictive models and clinical scoring systems. Results The RPA delineated four survival groups primarily defined by the status of IDH and TERT mutations. Predictive models incorporating VASARI features and clinical data achieved AUC values of 0.85 for IDH and 0.82 for TERT mutations. Nomogram-based scoring systems were also formulated to facilitate clinical application. Conclusions The combination of IDH-TERT mutation status alone can identify the most distinct survival differences in glioma patients. The predictive model based on preoperative MRI features, supported by clinical assessments, offers a reliable method for early molecular mutation prediction and constitutes a valuable scoring tool for clinicians in guiding treatment strategies.

In this paper, we apply the variational approach for solving the time-space fractal Bogoyavlenskii equation. By the two-scale fractal complex transformation, the fractal modification of Bogoyarlenskii equation is equivalently rewritten as the original Bogoyavlenskii equation. By variational principle, different type solutions including fractal bright soliton solution, fractal bright-like soliton solution, fractal kinky-bright soliton solution and fractal periodic wave solution are provided, which are not touched in the existing literature. Numerical results are presented to show the propagation behaviours.

Photovoltaic (PV) cells, widely adopted in solar energy applications, achieve a maximum efficiency of only 30 % and remain inactive during nighttime. In contrast, solar-thermal power generation has surpassed 50 % efficiency. To address these limitations, we introduce the Solar- Radiative cooling -Thermoelectric system (Solar-RC-TE), integrating solar energy, radiative cooling (RC), and thermoelectric power generation. This system enhances energy density, reduces consumption, lowers costs, and minimizes environmental impact while enabling nighttime power generation. For the optimization of the Solar-RC-TE model to further improve power generation efficiency, we employ the comprehensive three-dimensional methodology of COMSOL, considering material properties, structural configurations, and environmental factors. Research findings reveal that a 710 mm × 710 mm radiative cooling film can generate 386.12 mV of voltage on the thermoelectric generator (TEG). Environmental factors, such as increased solar irradiance, lead to temperature elevation, affecting efficiency. Overheating and higher wind speeds also contribute to decreased TEG efficiency. Regarding materials, improving the thermoelectric figure of merit (ZT) and film emissivity positively impact power generation efficiency. Elevating the film emissivity from 0.7 to 0.89 significantly enhances performance by 1.2 %. These outcomes provide a tangible and practical solution for addressing energy crises and environmental concerns.

Abstract Purpose The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. Methods We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. Results The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). Conclusions After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Lignin, characterized by its amorphous, heavily polymerized structure, is a primary natural source of aromatic compounds, yet its complex constitution poses considerable challenges in its transformation and utilization. Therefore, the selective cleavage of C–C bonds represents a critical and challenging step in lignin degradation, essential for the production of high-value aromatic compounds. In this study, we report a simple electrocatalytic approach for lignin valorization via C–C bond cleavage by developing a nonmetallic electrocatalyst of carbon-based materials. It is found that the hydrophilicity and hydrophobicity of the electrocatalyst have a significant effect on the degradation process. Under mild conditions, the hydrophilic carbon paper exhibits 100% substrate conversion, yielding 97% benzaldehyde and 96% quinone with ionic liquid electrolytes. The mechanism study shows that the carbon catalyst with higher surface defects favors electron transfer in the oxidative cleavage process of C–C bonds. These results signify a substantial advancement in lignin degradation, offering an environmentally friendly, metal-free electrochemical route.

Abstract Sonic hedgehog (SHH) and heat shock protein 90β (HSP90β) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90β is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90β ubiquitylation through deubiquitylase USP31, thus preventing HSP90β degradation and promoting hepatic lipid synthesis. HSP90β significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90β axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90β-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.

Abstract In tonal languages, which are spoken by nearly one-third of the world’s population, speakers precisely control the tension of vocal folds in the larynx to modulate pitch in order to distinguish words with completely different meanings. The specific pitch trajectories for a given tonal language are called lexical tones. Here, we used high-density direct cortical recordings to determine the neural basis of lexical tone production in native Mandarin-speaking participants. We found that instead of a tone category-selective coding, local populations in the bilateral laryngeal motor cortex (LMC) encode articulatory kinematic information to generate the pitch dynamics of lexical tones. Using a computational model of tone production, we discovered two distinct patterns of population activity in LMC commanding pitch rising and lowering. Finally, we showed that direct electrocortical stimulation of different local populations in LMC evoked pitch rising and lowering during tone production, respectively. Together, these results reveal the neural basis of vocal pitch control of lexical tones in tonal languages.

The existing trajectory planning research mainly considers the safety of the obstacle avoidance process rather than the anti-rollover requirements of heavy vehicles. When there are driving risks such as rollover and collision, how to coordinate the game relationship between the two is the key technical problem to realizing the anti-rollover trajectory planning under the condition of driving risk triggering. Given the above problems, this paper studies the non-cooperative game model construction method of the obstacle avoidance process that integrates the vehicle driving risk in a complex traffic environment. Then it obtains the obstacle avoidance area that satisfies both the collision and rollover profit requirements based on the Nash equilibrium. A Kmeans-SMOTE risk clustering fusion is proposed in this paper, in which more sampling points are supplemented by the SMOTE oversampling method, and then the ideal obstacle avoidance area is obtained through clustering algorithm fusion to determine the optimal feasible area for obstacle avoidance trajectory planning. On this basis, to solve the convergence problems of the existing multi-objective particle swarm optimization algorithm and analyze the influence of weight parameters and the diversity of the optimization process, this paper proposes an anti-rollover trajectory planning method based on the improved cosine variable weight factor MOPSO algorithm. The simulation results show that the trajectory obtained based on the method proposed in this paper can effectively improve the anti-rollover performance of the controlled vehicle while avoiding obstacles.

BackgroundWith the number of people with dementia dramatically increasing over time and dementia becoming a major health concern worldwide, scales have been developed to assess the stigma socially attached to this neurodegenerative disorder. There are, however, almost no available methods and assessment constructs for person-centered translation of dementia public stigma scales.ObjectiveTo develop such a method and such an assessment construct by translating the Dementia Public Stigma Scale (DPSS) into standard written Chinese.MethodsWe translated the DPSS following three major steps: (1) literal translation and mistranslation identification; (2) panel discussions of items with problematic translations; and (3) the final checking of the translated scale. Informed by the translation and adaptation process, we then developed a method for person-centered translation of dementia public stigma scales. Based on this method and our panel discussions, we finally proposed a tripartite assessment construct for quality evaluation of the translation of dementia public stigma scales.ResultsForward and backward translation did not work sufficiently in dementia public stigma scale translation. Mistranslations were induced by three major causes, including confusion caused by multiple Chinese meanings of the immediate Chinese direct translation, the lack of immediate Chinese direct translation because of varying positive/negative emotions attached to multiple translations, and the lack of culture-specific idioms in Chinese. Based on these factors, we proposed a tripartite dementia translation assessment construct. Following this assessment tool, we determined the best Chinese version that could further be tested for its psychometric properties among the public.ConclusionA method and an assessment construct for person-centered translation of dementia public stigma scales were developed. Such a method and such an assessment construct could be followed in the translation of dementia public stigma scales and the translation evaluation of such scales.

This paper focuses on the variational approach for solving the (3+1)-dimensional shallow water wave equation. Some families of soliton-type solutions and periodic wave solutions are given, and some remarks about the variational formulation for the special (2+1)-dimensional shallow water wave equation in [Gu, et al. Results in Physics, 45 (2023) 106213] are provided. Numerical results are presented to show the propagation behaviour.

Abstract Background Thyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy. Methods In this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed. Results During the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels. Conclusions TD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.

In this paper, we consider a fractional nonlinear oscillator for a mass attached to a stretched elastic wire. The coupling technique based on the fractional complex transform and the global residue harmonic balance method is proposed for solving this fractional oscillator. The approximated periodic solutions and frequencies are provided without complicated computation and discretization. The frequency–amplitude relationship is investigated to show its monotonic property. Numerical approximations for the nonlinear oscillator with integer or fractional orders are compared with the approximations by some existing methods. Numerical results confirm the effectiveness and robustness of the proposed method.

Hepatitis B Surface Antigen (HBsAg) seroclearance is the highest treatment goal recommended by the current guidelines for hepatitis B. Levels of antibodies to HBsAg (anti-HBs) are strongly associated with HBsAg recurrence, but hepatitis B vaccination may increase the anti-HBs seroconversion rate and reduce recurrence. We conducted a retrospective clinical study to ascertain the effect of this vaccination on the seroconversion rate and levels of protective anti-HBs after HBsAg. In this retrospective study, we distributed a questionnaire through an online survey platform to collect information related to hepatitis B vaccination in patients with functional cure of hepatitis B with Interferon-α (IFNα) therapy. We enrolled 320 patients who achieved functional cure from IFNα therapy. Of these, 219 patients had received hepatitis B vaccination according to their personal preference and drug accessibility after HBsAg seroclearance, whereas the remaining 101 patients did not receive hepatitis B vaccination. The anti-HBs seroconversion rate of 78.1% in the vaccinated group was significantly greater than that in the unvaccinated group (41.6%) (p < 0.001). Stratified comparisons with anti-HBs of ≥ 100 IU/L and ≥ 300 IU/L showed that both proportions in the vaccinated group were greater than those in the unvaccinated group (71.2% vs. 32.7% and 56.2% vs. 17.8%, respectively, all p-values < 0.001). Logistic regression analysis showed that the odds ratio of vaccination was 4.427, which was the strongest influencing factor for anti-HBs, reaching 100 IU/L or higher. Hepatitis B vaccination in patients after HBsAg seroclearance not only increased the anti-HBs seroconversion rate but also significantly increased antibody levels, with good safety, indicating the clinical value of vaccine therapy for patients with functional cure.

Abstract Sepsis‐induced muscle atrophy often increases morbidity and mortality in intensive care unit (ICU) patients, yet neither therapeutic target nor optimal animal model is available for this disease. Here, by modifying the surgical strategy of cecal ligation and puncture (CLP), a novel sepsis pig model is created that for the first time recapitulates the whole course of sepsis in humans. With this model and sepsis patients, increased levels of the transcription factor zinc finger BED‐type containing 6 (ZBED6) in skeletal muscle are shown. Protection against sepsis‐induced muscle wasting in ZBED6‐deficient pigs is further demonstrated. Mechanistically, integrated analysis of RNA‐seq and ChIP‐seq reveals dedicator of cytokinesis 3 (DOCK3) as the direct target of ZBED6. In septic ZBED6‐deficient pigs, DOCK3 expression is increased in skeletal muscle and myocytes, activating the RAC1/PI3K/AKT pathway and protecting against sepsis‐induced muscle wasting. Conversely, opposite gene expression patterns and exacerbated muscle wasting are observed in septic ZBED6‐overexpressing myotubes. Notably, sepsis patients show increased ZBED6 expression along with reduced DOCK3 and downregulated RAC1/PI3K/AKT pathway. These findings suggest that ZBED6 is a potential therapeutic target for sepsis‐induced muscle atrophy, and the established sepsis pig model is a valuable tool for understanding sepsis pathogenesis and developing its therapeutics.

Modern linguistic theories and network science propose that language and speech processing are organized into hierarchical, segregated large-scale subnetworks, with a core of dorsal (phonological) stream and ventral (semantic) stream. The two streams are asymmetrically recruited in receptive and expressive language or speech tasks, which showed flexible functional segregation and integration. We hypothesized that the functional segregation of the two streams was supported by the underlying network segregation. A dynamic conditional correlation approach was employed to construct framewise time-varying language networks and k-means clustering was employed to investigate the temporal-reoccurring patterns. We found that the framewise language network dynamics in resting state were robustly clustered into four states, which dynamically reconfigured following a domain-separation manner. Spatially, the hub distributions of the first three states highly resembled the neurobiology of speech perception and lexical-phonological processing, speech production, and semantic processing, respectively. The fourth state was characterized by the weakest functional connectivity and was regarded as a baseline state. Temporally, the first three states appeared exclusively in limited time bins (∼15%), and most of the time (> 55%), state 4 was dominant. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the four states significantly predicted individual linguistic performance. These findings suggest a domain-separation manner of language network dynamics in resting state, which forms a dynamic “meta-network” framework to support flexible functional segregation and integration during language and speech processing.

To evaluate the prediction model comprised of patients’ laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case–control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030–0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768–71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006–0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040–0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138–13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.

This paper focuses on the numerical investigation of a fractal modification of capillary oscillator by using a coupling technique based on the two-scale transformation and the global residue harmonic balance method. This fractal oscillator can be transformed as the classical capillary oscillator with the help of the two-scale transformation. We further obtain an approximated oscillator by using Taylor approximation. The approximations or frequencies are given by applying the global residue harmonic balance method without discretization. Numerical sensitive analysis of the approximations about different parameters is considered in detail. Compared results with Runge–Kutta method and homotopy perturbation method are given to illustrate the efficiency and stability of the present technology.

Abstract Background Traumatic brain injury, one of the leading causes of death in adults under 40 years of age in the world, is frequently caused by mechanical shock, resulting in diffuse neuronal damage and long-term cognitive dysfunction. Many existing TBI animal models revival with expensive equipment or special room are needed or the processes of operations are complex and not easy to be widely used. Therefore, a simpler TBI model needs to be designed. Methods Our TBI model is an innovation of the modeling method through air guns shutting rubber bullets. A core facet is the application of our designed rubber bullet impact device. It could focus the hitting power to the fixed site of the brain, thus triggering a mild closed head injury. Moreover, the degree of damage can be adjusted by the times of shots. Results Our model induced blood-brain barrier leakage and diffused neuronal damage. Besides, it led to an increased level of Tau phosphorylation and resulted in cognitive dysfunction within several weeks post-injury. Conclusion Our TBI model is not only simple and time-saving but also can simulate mild brain injuries in clinical. It is suitable for exploring pathobiological mechanisms as well as a screening of potential therapies for TBI.

IntroductionAlthough we had identified that the methylation of AHNAK was a good diagnostic marker for hepatopathy, here we speculate that there was also another marker, STAP1, whose methylation also involved in the detection of hepatopathy.MethodsWe investigated the methylation levels of the AHNAK and STAP1 in peripheral blood mononuclear cells of chronic hepatitis B (CHB) patients, compensatory liver cirrhosis (CLC) patients, decompensated liver cirrhosis (DCLC) patients, hepatocellular carcinoma (HCC) patients and healthy controls by methylation-specific PCR. We also evaluated the differences and changes of methylation and expression of AHNAK and STAP1 at different stages of liver disease using the TCGA and GEO public datasets.ResultsMethylation level of STAP1 in PBMC was positively correlated with the course of liver cancer. The combination of AHNAK and STAP1 methylation was able to predict differrent HBV related hepatopathy. The GEO datasets also supported that the methylation of AHNAK and STAP1 was associated with different types of hepatopathy. The TCGA data showed that the levels of methylation and expression of STAP1 were down-regulated in HCC. We also found the STAP1 methylation level in PBMC and T cells was associated with age, gender, alcohol drinking and anti-HBe. Hyper-methylation of STAP1 was correlated with the poor prognosis of patients but its expression had no association.ConclusionWe concluded that combination of AHNAK and STAP1 methylation in peripheral blood immune cells can be used as a diagnostic marker for HBV related hepatopathy and STAP1 methylation may be a potential prognostic marker for HBV related HCC. Our clinical study registration number was ChiCTR2000039860.

Background/Aims: To investigate postpartum hepatic flares and associated factors in highly viremic pregnant patients in the immune tolerance phase who adopted telbivudine (LdT) treatment in the last trimester to reduce vertical transmission of hepatitis B virus. Methods: Hepatitis B e antigen (HBeAg)-positive, highly viremic pregnant women were recruited for this prospective study. Treatment with LdT was started from 28 weeks of gestation. Virological and biochemical markers were examined before LdT treatment, antepartum and postpartum. Serial blood samples at the same time were collected to detect cytokines and cortisol (COR). Results: Fifty-six of 153 patients (36.6%) had postpartum hepatic flares, defined as a 2-fold increase in alanine aminotransferase 6 weeks after delivery. Age and the antepartum alanine aminotransferase and postpartum HBeAg levels were independent influencing factors of postpartum hepatic flares. Cytokines showed no regularity during or after pregnancy. Compared with the patients with no postpartum flares, the patients with flares had lower baseline interferon γ and COR levels (p=0.022 and p=0.028) and higher postpartum interferon γ levels (p=0.026). Conclusions: A high proportion of highly viremic and immune-tolerant pregnant patients treated with LdT in the last trimester had postpartum hepatic flares, which implied that these patients entered the immune clearance phase after delivery. Thus, this may create an appropriate opportunity for re-antiviral therapy.

In this paper, we propose a combined technique for solving the fractional modification of the nonlinear oscillator with coordinate-dependent mass. It is an efficient method based on the fractional complex transform and the global residue harmonic balance method (called as FCT-GRHBM). The approximations and frequencies of this fractional nonlinear oscillator are given without linearization. Numerical comparisons with Runge–Kutta method are provided to confirm the efficiency of FCT-GRHBM. The sensitive analysis of the log errors and the frequencies with respect to different parameters is also investigated in detail.

Abstract This paper focuses on the numerical investigation of a strongly nonlinear oscillator with cubic and harmonic restoring force. We transform this oscillator as a free damped cubic-quintic Duffing oscillator equation by Taylor approximation. The approximated solutions with high accuracy are provided by using the global residue harmonic balance method (GRHBM) without any discretization or restrict assumptions. The sensitive analysis of the approximation or the frequency with respect to the amplitude is considered in detail. Numerical comparisons with Runge–Kutta method and harmonic balance method are given to show the efficiency and stability of GRHBM.

ObjectiveIn clinical practice, a substantial proportion of chronic hepatitis B virus (HBV) infections that do not fit into any of the usual immune states are considered to be in the “grey zone (GZ)”. This study aimed to investigate the effect of the change in antiviral therapy indication on identifying significant hepatic injury among GZ patients.MethodsPatients with chronic HBV infections and a persistent normal alanine aminotransferase (ALT) level (PNALT) who underwent ultrasonography-guided percutaneous liver biopsy were examined retrospectively. Evidenced hepatic injury (EHI) was defined as an inflammation grade ≥2 (≥G2) and/or fibrosis stage ≥2 (≥F2). Complete clinical data, liver inflammation, and fibrosis grades were collected, and the levels of cytokines were detected by the Luminex technique, all of which were analysed to investigate the immune and histopathology states of the liver.ResultsA total of 347 patients with chronic HBV infections and PNALT were categorized into immune tolerant (IT, n = 108), inactive HBV surface antigen (HBsAg) carrier (IHC, n = 61), GZ-1 (HBeAg positive in GZ, n = 92), and GZ-2 (HBeAg negative in GZ, n = 68) phases. Among them, 51.3% were in the GZ phase, and 50.1% presented with EHI. The IL-6 levels were higher in the EHI group than in the non-EHI group (2.77 vs. 1.53 pg/ml, Z = −13.32, p = 0.028). The monocyte chemoattractant protein 1 (MCP-1) level was positively correlated with HBV DNA (R = 0.64, p < 0.001) and HBeAg (R = 0.5, p < 0.001) but negatively correlated with fibrosis grade (R = −0.26, p = 0.048). The ratio of EHI in the GZ phase was 60.55%, which was significantly higher than that in patients in the IT (39.8%) and IHC phases (37.7%) (χ2 = 10.4, p = 0.006). A total of 46.69% of all patients exceeded the new ALT antiviral treatment threshold (30 U/L for men and 19 U/L for women). The EHI values in the IT and IHC phases below the new ALT threshold were 32.6% and 37.8%, respectively, whereas higher EHI values of 67.4% and 68.4% were seen in GZ-1 and GZ-2 patients, respectively, exceeding the new ALT threshold, and the difference was statistically significant (χ2 = 11.13, p < 0.001; χ2 = 14.22, p = 0.002). The median age in our cohort was 38.91 years, and only 21.03% were less than 30 years old. The EHI values in the IT and IHC patients

BackgroundIn China, it is common for pregnant women with a high load of hepatitis B virus (HBV) to take nucleos(t)ide analogue (NA) to prevent maternal-to-child transmission of HBV. However, the impact of NA intervention on virological and biochemical parameters in pregnant and postpartum women and the safety of drug cessation remain unclear. A prospective observational cohort was established in this study to analyze the clinical characteristics of hepatitis flares in pregnant and postpartum chronic HBV carriers, with or without NA intervention.MethodsPregnant women who were chronic HBV carriers were enrolled in this study and divided into an NA intervention group and a non-intervention group according to their preferences. Liver function, HBV DNA level, and HBV serological markers were regularly measured during pregnancy and at approximately 6 weeks, 12 weeks, 24 weeks, 36 weeks, and 48 weeks postpartum.ResultsA total of 417 patients were enrolled, including 303 in the NA intervention group and 114 in the non-intervention group. The incidence rates of postpartum hepatitis flares in both groups were higher than that of during pregnancy (45.7% vs 10.9%, p < 0.001; 41.2% vs 17.7%, p < 0.001). The second trimester was the peak of the incidence of flares during pregnancy and the incidence peak of postpartum flares was about 6 weeks postpartum. A total of 98% (145/148) of postpartum flares occurred within 24 weeks postpartum. After drug cessation, the incidence rate of flares was 34.1% (44/129).ConclusionIn pregnant chronic HBV carriers, a certain proportion of hepatitis flares occurred during pregnancy and postpartum regardless of whether NA intervention was used, and the incidence of postpartum flares (44.6%) was significantly higher than that (12.8%) of during pregnancy. The flare incidence peaked at approximately 6 weeks postpartum, which may be the time period suitable for treatment. Since 98% of postpartum flares occurred within 24 weeks postpartum, the follow-up after drug cessation should be at least 24 weeks postpartum.

Abstract Rearrangements involving anaplastic lymphoma kinase (ALK) gene have been reported in ~5% of non–small‐cell lung cancer patients. These rearrangements are characterized by the identification of various rare fusion partners, with unknown clinical significance. Specifically, the concurrence of different ALK fusions within the same patient, as well as its impact on therapeutic response to ALK tyrosine kinase inhibitors (ALK‐TKIs), are rarely reported. Here, we report a 46‐year‐old female who was diagnosed with lung adenocarcinoma and identified carrying concurrent DCTN1‐ALK and ALK‐CLIP4 rearrangements by next generation sequencing (NGS) (638‐gene panel). This patient showed partial response to crizotinib with a progress‐free survival of 12 months and was then administered alectinib. Our report highlighted the importance of NGS testing in identifying rare ALK rearrangements and provided a novel insight into understanding the efficacy of ALK‐TKI in this subset of patients.

To improve the gas sensitivity of reduced oxide graphene (rGO)-based NO2 room-temperature sensors, different contents (0–3 wt%) of rGO, ZnO rods, and noble metal nanoparticles (Au or Ag NPs) were synthesized to construct ternary hybrids that combine the advantages of each component. The prepared ZnO rods had a diameter of around 200 nm and a length of about 2 μm. Au or Ag NPs with diameters of 20–30 nm were loaded on the ZnO-rod/rGO hybrid. It was found that rGO simply connects the monodispersed ZnO rods and does not change the morphology of ZnO rods. In addition, the rod-like ZnO prevents rGO stacking and makes nanocomposite-based ZnO/rGO achieve a porous structure, which facilitates the diffusion of gas molecules. The sensors’ gas-sensing properties for NO2 were evaluated. The results reveal that Ag@ZnO rods-2% rGO and Au@ZnO rods-2% rGO perform better in low concentrations of NO2 gas, with greater response and shorter recovery time at the ambient temperature. The response and recovery times with 15 ppm NO2 were 132 s, 139 s and 108 s, 120 s, and the sensitivity values were 2.26 and 2.87, respectively. The synergistic impact of ZnO and Au (Ag) doping was proposed to explain the improved gas sensing. The p-n junction formed on the ZnO and rGO interface and the catalytic effects of Au (Ag) NPs are the main reasons for the enhanced sensitivity of Au (Ag)@ZnO rods-2% rGO.

BackgroundThere is still lack of reliable predictors for hepatitis B surface antigen (HBsAg) clearance. Recent studies have shown that the levels of large (LHBs) and medium hepatitis B surface proteins (MHBs) are closely related to antiviral efficacy. This study aimed to investigate the possibility of LHB and MHB levels to predict HBsAg clearance.MethodsAn inactive HBsAg carriers (IHCs) cohort that had received pegylated interferon (Peg-IFN) treatment was divided into the HBsAg-cleared group (R group) and the HBsAg non-cleared group (NR group) based on whether HBsAg was cleared at 96 weeks. We detected the levels of LHBs and MHBs to evaluate the possibility of predicting HBsAg clearance.ResultsThere were 39 patients in the R group and 21 in the NR group. The total HBsAg, LHB, and MHB levels at baseline and at 12 weeks were significantly lower in the R group than in the NR group (all p< 0.05). Multivariate logistic regression indicated that LHB and MHB levels at baseline and 12 weeks were independent predictors of HBsAg clearance (OR = 0.435, p = 0.016; OR = 0.136, p = 0.003; OR = 0.137, p = 0.033; OR = 0.049, p = 0.043). The area under the curve (AUC) for the baseline and 12-week LHB and MHB levels was 0.827-0.896, which were greater than that of the total HBsAg level at baseline and 12-week (AUC: 0.654-0.755). Compared with the prediction results of a single indicator, the combination of LHB and MHB levels had better value in predicting HBsAg clearance. The AUCs of combination factor 1, constructed from baseline LHB and MHB, and combination factor 2, constructed from 12-week LHB and MHB, were 0.922 and 0.939, respectively, and the sensitivity (82.05%-100.00%) and specificity (85.71%-100.00%) were both high. The combined indicators based on baseline LHBs ≤ 13.99 ng/mL and MHBs ≤ 7.95 ng/mL predicted HBsAg clearance rate of more than 90%.ConclusionBaseline and 12-week LHB and MHB levels can predict HBsAg clearance obtained by Peg-IFN therapy in IHCs, and the predictive value is higher than that of the total HBsAg levels.

BackgroundStudies about the retreatment and predictors for patients with hepatitis B recurrence after functional cure are rare. This study aimed to evaluate the effect of retreatment, outcome, and potential predictors of recurrence in patients with recurrence after functional cure.MethodsA long-term follow-up was conducted with 32 cumulatively obtained patients who relapsed after cessation of pegylated interferon (Peg-IFN)-based antiviral treatment. The decision of whether to treatment or which therapeutic method to use [Peg-IFN or nucleos(t)ide analogs (NAs)] was based on the patient’s preferences and wishes. The rate of achieving functional cure and the clinical outcomes of different therapeutic methods were analyzed. Hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) levels were detected in patients with blood samples during follow-up to evaluate the predictive ability of recurrence.ResultsThe follow-up time of 32 recurrence cases was 42–532 weeks after recurrence (median 226 weeks). In the 20 patients who received retreatment (15 received Peg-IFN and 5 received NAs only), the rate of functional cure was 65.0% (13/20); it was 86.7% (13/15) in the patients retreated with Peg-IFN. Three cases experienced recurrence again. Five patients received NA treatment, and no functional cure was achieved. No drug intervention was administered for 12 patients, 2 of them with hepatitis B virus (HBV) DNA spontaneous clearance, and one patient achieved spontaneous hepatitis B surface antigen (HBsAg) clearance during follow-up. Patients who relapsed after functional cure with Peg-IFN treatment did not have liver cirrhosis or hepatocellular carcinoma during the follow-up, regardless of whether they received retreatment. Anti-HBs and anti-HBc levels at the end of therapy were predictors of recurrence (p < 0.001, p = 0.023). The value of combining the above two indicators in predicting recurrence was further improved, the areas under the receiver operating characteristic curves were 0.833, at combining predictors >-0.386, the predictive sensitivity and specificity for recurrence were 86.67% and 90.62%.ConclusionThe functional cure rate was above 80% for patients with recurrence treated by Peg-IFN. During the follow-up, liver cirrhosis and hepatocellular carcinoma were not observed in all recurrence cases. High levels of anti-HBs and anti-HBc at the time of drug discontinuation are less likely to relapse.

In this paper, a numerical approach based on the two-scale fractal transformation and the global residue harmonic balance method (called as TSFT-GRHBM), is proposed for finding the approximated solutions of a fractal modification of Yao–Cheng oscillator with He’s fractal derivative. The approximated frequency for the classical Yao–Cheng oscillator is given. The approximations with high accuracy for the fractal or classical Yao–Cheng oscillator are also presented, and compared with Runge–Kutta method (RK). The numerical sensitive analysis of the approximations is further considered with respect to different amplitudes and parameters. Numerical results confirm the efficiency and stability of this method.

Different languages rely on different vocal sounds to convey meaning. Here the authors show that language-general coding of pitch occurs in the non-primary auditory cortex for both tonal (Mandarin Chinese) and non-tonal (English) languages, with some language specificity on the population level.

There are few reports about the role of B10 cells in acute hepatitis B (AHB) infection. In this study, based on 48 acute hepatitis B infected patients, we analysis the correlation of B10 cells with HBV clinical prognosis. The results showed that B10 was positively correlated with HBsAg and HBeAg and inversely correlated with anti-HBs. The level of B10 in one week before HBsAg clearance was significantly lower than 2 weeks prior to HBsAg clearance and after 1-2 weeks of HBsAg clearance. B10 cell frequency displayed no correlation with HBV DNA; however, it showed significant temporal synchronization with hepatic inflammatory markers such as ALT. B10 level also associated with hospitalization time. These results indicated that B10 is closely related to the clinical prognosis of acute HBV infection.

BackgroundThe extent of the increase in postpartum alanine transaminase (ALT) varies significantly among pregnant women in the immune tolerance stage of nucleoside analogue (NA) intervention, so this study is an attempt to analyze the clinical features of patients with and without postpartum hepatitis flare and preliminarily explore the differences in their immune functions.MethodsPregnant women with a gestational age of 24–28 w and in the immune tolerance stage of NA intervention for hepatitis B virus (HBV) infection were included and divided into a hepatitis group (Group 1) and a nonhepatitis group (Group 2) according to the ALT level at 6–12 w after childbirth. The clinical features were analyzed, and the phenotypes, functions, and cytokines of clusters of differentiation CD8+ T cells in the two groups of patients were detected using flow cytometry before and after childbirth.ResultsA total of 15 patients with postpartum hepatitis flare were enrolled in Group 1, and 10 matched patients were selected as controls for Group 2. Compared with the individuals in Group 2, the postpartum clinical features in Group 1 included a remarkable elevation of the ALT level on the basis of a relatively low HBV DNA level, usually accompanied by a decline in hepatitis B virus surface antigen levels as well as HBeAg levels. In addition, CD8+ T cell activation was enhanced after childbirth in Group 1. In particular, there was a notable difference in the activation of TEMRA subsets, and the frequency of CD8+ T cells expressing perforin and granzyme B increased.ConclusionThe changes in the immune characteristics of CD8+ T cells may play a certain role in breaking down immune tolerance in patients with postpartum hepatitis flare, and the indexes related to activating and killing functions may help to indicate the population with hepatitis flare after childbirth.

This study investigated the effects of Cordyceps militaris (CM) on intestinal barrier function and gut microbiota in a pig model. A total of 160 pigs were randomly allocated to either a control group (fed the basal diet) or a CM group (fed the basal diet supplemented with 300 mg/kg CM). CM improved intestinal morphology and increased the numbers of goblet cells and intraepithelial lymphocytes. CM also elevated the expression of zona occluden-1, claudin-1, mucin-2 and secretory immunoglobulin A. Furthermore, the mucosal levels of pro-inflammatory cytokines were downregulated while the levels of anti-inflammatory cytokines were upregulated in the CM group. Mechanistically, CM downregulated the expression of key proteins of the TLR4/MyD88/NF-κB signaling pathway. Moreover, CM altered the colonic microbial composition and increased the concentrations of acetate and butyrate. In conclusion, CM can modulate the intestinal barrier function and gut microbiota, which may provide a new strategy for improving intestinal health.

Nanoscale heterostructured zinc oxide/reduced graphene oxide (ZnO/rGO) materials with p–n heterojunctions exhibit excellent low temperature NO2 gas sensing performance, but their doping ratio modulated sensing properties remain poorly understood. Herein, ZnO nanoparticles were loaded with 0.1~4% rGO by a facile hydrothermal method and evaluated as NO2 gas chemiresistor. We have the following key findings. First, ZnO/rGO manifests doping ratio-dependent sensing type switching. Increasing the rGO concentration changes the type of ZnO/rGO conductivity from n-type (1.4% rGO). Second, interestingly, different sensing regions exhibit different sensing characteristics. In the n-type NO2 gas sensing region, all the sensors exhibit the maximum gas response at the optimum working temperature. Among them, the sensor that shows the maximum gas response exhibits a minimum optimum working temperature. In the mixed n/p-type region, the material displays abnormal reversal from n- to p-type sensing transitions as a function of the doping ratio, NO2 concentration and working temperature. In the p-type gas sensing region, the response decreases with increasing rGO ratio and working temperature. Third, we derive a conduction path model that shows how the sensing type switches in ZnO/rGO. We also find that p–n heterojunction ratio (np–n/nrGO) plays a key role in the optimal response condition. The model is supported by UV-vis experimental data. The approach presented in this work can be extended to other p–n heterostructures and the insights will benefit the design of more efficient chemiresistive gas sensors.

The rac-GR24, an artificial analog of strigolactone, is known for its roles in inhibiting branches, and previous studies have reported that it has a certain mechanism to relieve abiotic stress, but the underlying metabolic mechanisms of mitigation for drought-induced remain unclear. Therefore, the objectives of this study were to identify associated metabolic pathways that are regulated by rac-GR24 in alfalfa (Medicago sativa L.) and to determine the metabolic mechanisms of rac-GR24 that are involved in drought-induced root exudate. The alfalfa seedling WL-712 was treated with 5% PEG to simulate drought, and rac-GR24 at a concentration of 0.1 µM was sprayed. After three days of treatment, root secretions within 24 h were collected. Osmotic adjustment substances and antioxidant enzyme activities were measured as physiological indicators, while LS/MS was performed to identify metabolites regulated by rac-GR24 of root exudate under drought. The results demonstrated that rac-GR24 treatment could alleviate the negative effects from drought-induced on alfalfa root, as manifested by increased osmotic adjustment substance content, cell membrane stability, and antioxidant enzyme activities. Among the 14 differential metabolites, five metabolites were uniquely downregulated in plants in rac-GR24 treatment. In addition, rac-GR24 could relieve drought-induced adverse effects on alfalfa through metabolic reprogramming in the pathways of the TCA cycle, pentose phosphate, tyrosine metabolism, and the purine pathway. This study indicated that rac-GR24 could improve the drought resistance of alfalfa by influencing the components of root exudates.

BackgroundExpanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.MethodsWe searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.ResultsA total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.ConclusionThis study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.

Leak detection and location of water supply pipelines is an important area of research, and it is especially important to find the leakage location in time and repair them. In view of the problem, that a large amount of noise is mixed in the detection signal when the pipeline leaks, it will inevitably affect the detection and positioning effect. In this paper, a denoising algorithm based on improved module maximum is proposed. Firstly, a discrete binary wavelet transform is carried out on the noisy signal, and the module maximum point corresponding to the wavelet transform coefficients, on each scale, is obtained. Secondly, different thresholds are used for the module maximum of different scale layers and the wavelet coefficients are reconstructed according to the retained module maximum and their extremums. Thirdly, the alternative projection algorithm is used to effectively suppress the false oscillations in the reconstructed signal, improve the quality of the reconstructed signal, and obtain the noise reduction signal. Finally, according to the theory of the negative pressure wave, the inflection point of the negative pressure wave is identified by the wavelet decomposition method, and the location of leakage point is determined. In order to verify the effectiveness of the proposed algorithm, a leakage simulation experiment system of water supply pipeline is built. The analysis of the results shows that, compared with the wavelet denoising method and the EMD-based method, the method proposed in this paper achieves a better denoising effect, obtains a smoother pressure signal, retains the signal waveform characteristics, and identifies the obvious inflexion point of the negative pressure wave. The minimum relative error of leakage point location is 0.9%, and the maximum relative error is 2.5%.

In modeling time-to-event data with long-term survivors, the proportional hazards model is widely used for its easy and direct interpretation as well as the flexibility to accommodate the past information and allow time-varying predictors. This becomes most relevant when the mortality of individuals converges with time, and the estimation and inference based upon the proportional odds model can often yield more accurate and reasonable results than the classical Cox’s proportional hazards model. Along with the fast development of the data science technologies, computational challenges for survival data with increasing sample size and diverging parameter dimension exist. Currently, existing methods for analyzing such data are computationally inconvenient. In this paper, we propose efficient computational methods for analyzing survival data in the proportional odds model, where the nonparametric maximum likelihood approach is combined with the minorization-maximization (MM) algorithm and the regularization scheme to yield fast and accurate estimation and inferential procedures. The illustration of the methodology using extensive simulation studies and then the application to the Veterans’ Administration lung cancer data is also given.

The ensemble transfer entropy (TEensemble) refers to the transfer entropy estimated from an ensemble of realizations. Due to its time-resolved analysis, it is adapted to analyze the dynamic interaction between brain regions. However, in the traditional TEensemble, multiple sets of surrogate data should be used to construct the null hypothesis distribution, which dramatically increases the computational complexity. To reduce the computational cost, a fast, efficient TEensemble with a simple statistical test method is proposed here, in which just one set of surrogate data is involved. To validate the improved efficiency, the simulated neural signals are used to compare the characteristics of the novel TEensemble with those of the traditional TEensemble. The results show that the time consumption is reduced by two or three magnitudes in the novel TEensemble. Importantly, the proposed TEensemble could accurately track the dynamic interaction process and detect the strength and the direction of interaction robustly even in the presence of moderate noises. The novel TEensemble reaches its steady state with the increased samples, which is slower than the traditional method. Furthermore, the effectiveness of the novel TEensemble was verified in the actual neural signals. Accordingly, the TEensemble proposed in this work may provide a suitable way to investigate the dynamic interactions between brain regions.

The COVID-19 mRNA vaccine is one of the most effective strategies used to fight against COVID-19. Recently, venous thromboembolism (VTE) events after COVID-19 mRNA vaccination have been reported in various research. Such a concern may hamper the ongoing COVID-19 vaccination campaign. Based on the US Vaccine Adverse Event Reporting System data, this modified self-controlled case series study investigated the association of COVID-19 mRNA vaccination with VTE events among US adults. We found the VTE incidence rate in the recommended dose interval does not change significantly after receiving COVID-19 mRNA vaccines. This conclusion still holds if the analysis is stratified by age and gender. The VTE onset may not be significantly associated with COVID-19 mRNA vaccination.

Direct electrical stimulation (DES) has been widely applied in both guidance of lesion resection and scientific research; however, the design and selection of intraoperative cognitive mapping tasks have not been updated in a very long time. We introduce updated mapping tasks for language and non-language functions and provide recommendations for optimal design and selection of intraoperative mapping tasks. In addition, with DES becoming more critical in current neuroscientific research, a task design that has not been widely used in DES yet (subtraction and conjunction paradigms) was introduced for more delicate mapping of brain functions especially for research purposes. We also illustrate the importance of designing a common task series for DES and other non-invasive mapping techniques. This review gives practical updated guidelines for advanced application of DES in clinical and neuroscientific research.

This paper applies the VIM-Padé technique for solving a nonlinear free vibration of a conservative oscillator. It is a combined method based on the variational iteration method, Laplace transformation and the Padé approximation. An approximated solution with extremely high accuracy can be obtained with ease. Runge-Kutta method is adopted to verify the efficiency of the technique.

BackgroundElectrocorticography (ECoG) has been utilized in many epilepsy cases however, the use of this technique for evaluating electrophysiological changes within tumoral zones is spare. Nonetheless, epileptic activities seem to arise from the neocortex surrounding the gliomas suggesting a link between epileptogenesis and glioma cell infiltration in the peritumoral area. The purpose of this study was to implement novel scale-free measures to assess how cortical physiology is altered by the presence of an invasive brain tumor.MethodsTwelve patients undergoing an awake craniotomy for resection of a supratentorial glioma were included. ECoG data over the main tumor and the exposed surroundings was acquired intra-operatively just prior to tumor resection. Six of the patients presented with seizures and had data acquired both in the awake and anesthetic state. The corresponding anatomical location of each electrode in relation to the macroscopically-detectable tumor was recorded using the neuronavigation system based on structural anatomical images obtained pre-operatively. The electrodes were classified into tumoral, healthy or peritumoral based on the macroscopically detectable tumoral tissue from the pre-operative structural MRI.ResultsThe electrodes overlying the tumoral tissue revealed higher power law exponent (PLE) values across tumoral area compared to the surrounding tissues. The difference between the awake and anesthetic states was significant in the tumoral and healthy tissue (p < 0.05) but not in the peritumoral tissue. The absence of a significant PLE reduction in the peritumoral tissue from the anesthetic to the awake state could be considered as an index of the presence or absence of infiltration of tumor cells into the peritumoral tissue.ConclusionsThe current study portrays for the first time distinct power law exponent features in the tumoral tissue, which could provide a potential novel electrophysiological marker in the future. The distinct features seen in the peritumoral tissue of gliomas seem to indicate the area where both the onset of epileptiform activity and the tumor infiltration take place.

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Shen-Yan-Fang-Shuai formula (SYFSF) is a traditional Chinese herbal formula composed of Astragali Radix, Radix Angelicae Sinensis, Rheum Officinale Baill, and four other herbs. In this study, we identified that SYFSF treatment prevented weight gain, low-grade inflammation and insulin resistance in high-fat diet (HFD)-fed mice. SYFSF also substantially improved gut barrier function, reduced metabolic endotoxemia, as well as systemic inflammation. Sequencing of 16S rRNA genes obtained from fecal samples demonstrated that SYFSF attenuated HFD-induced gut dysbiosis, seen an decreased Firmicutes to Bacteroidetes ratios. Microbial richness and diversity were also higher in the SYFSF-treated HFD group. Furthermore, similar therapeutic effects and changes in gut microbiota profile caused by SYFSF could be replicated by fecal microbiota transfer (FMT). Taken together, our study highlights the efficacy of SYFSF in preventing obesity and related metabolic disorders. Its therapeutic effect is associated with the modulation of gut microbiota, as a prebiotic.

In this paper, we apply the global residue harmonic balance method (GRHBM) for solving the nonlinear differential equation of the circular sector oscillator. The approximated solutions to the initial value problems are provided without linearization. Some remarks about the first order frequency in [Shaban M, et al. Current Applied Physics, 2010] are given. Numerical comparisons with Runge–Kutta method, the modified homotopy perturbation method and Akbari-Ganji’s method are presented to confirm the efficiency of GRHBM.

This study was conducted to determine the effect of a fermented corn–soybean meal [fermented feed (FF)] on the gene expression of immunity in the blood, the level of secretory immunoglobulin A (sIgA), and mucosa-associated bacterial community in the duodenum and colon of grower-finisher pigs. In this study, crossbred barrows (Duroc × Landrace × Large White) were randomly assigned to either an unfermented corn–soybean diet (Ctrl) (n = 6) or an FF diet (n = 6), and then the following were examined: the expression of immunity using real-time reverse transcription polymerase-chain reaction in the blood, sIgA using enzyme-linked immunosorbent assay (ELISA), and changes in the bacterial community using Illumina Hiseq sequencing in the mucosa of the duodenum and colon. Compared with control pigs fed with a standard diet, the results showed that FF caused upregulation of the mRNA expression of Toll-like receptor 3 (TLR3), TLR4, TLR6, and TLR8 in the blood (P < 0.05). Moreover, sequencing of 16S rRNA genes in duodenal mucosa samples indicated that the FF diet had a lower proportion of Tenericutes (P < 0.05) in the duodenal mucosa-associated microbiota, and FF significantly increased the percentage of Rikenellaceae and Christensenellaceae but decreased the abundance of Lachnospiraceae (P < 0.05) in the colonic mucosa-associated microbiota. The ELISA results showed that FF significantly increased the concentration of sIgA in the colonic mucosa (P < 0.05). More importantly, our correlation analysis indicated that the gene expression of immunity in the blood and the concentration of sIgA was associated with colonic mucosa-associated microbiota. Our data provide new knowledge into the adaptation response of the intestine to fermented feeding in monogastric animals.

Purpose: We evaluated the relationship between isocitrate dehydrogenase 1 (IDH1) mutation status and metabolic imaging in patients with nonenhancing supratentorial diffuse gliomas using 11 C-methionine positron emission tomography ( 11 C-MET PET). Materials and Methods: Between June 2012 and November 2017, we enrolled 86 (38 women and 48 men; mean age, 41.9 ± 13.1 years [range, 8-67 years]) patients with newly diagnosed supratentorial diffuse gliomas. All patients underwent preoperative 11 C-MET PET. Tumor samples were obtained and immunohistochemically analyzed for IDH1 mutation status. Results: The mutant and wild-type IDH1 diffuse gliomas had significantly different mean maximum standardized uptake value values (2.73 [95% confidence interval, CI: 2.32-3.16] vs 3.85 [95% CI: 3.22-4.51], respectively; P = .004) and mean tumor-to-background ratio (1.90 [95% CI: 1.65-2.16] vs 2.59 [95% CI: 2.17-3.04], respectively; P = .007). Conclusions: 11 C-methionine PET can noninvasively evaluate the IDH1 mutation status of patients with nonenhancing supratentorial diffuse gliomas.

In this paper, we propose an analytical approach (VIM-Padé) based on the variational iteration method (VIM), Laplace transformation and the Padé approximation. We apply this technique to solve the strongly nonlinear oscillators with cubic and harmonic restoring force. The approximated solutions to the initial value problems are provided and compared with the original variational iteration method solutions and the numerical solutions obtained by Runge-Kutta method. Numerical experiments show that the VIM-Padé technique is efficient for solving the strongly nonlinear oscillators.

Fermented corn-soybean meal (fermented feed, FF) is commonly used in swine production, but the effects of FF on gut health remain unclear. In this study, serum immunity, mRNA abundances of antimicrobial peptides (AMPs) and Toll-like receptors (TLR1-9), bacterial abundance in the duodenum and colon, and colonic metabolic phenotypes were determined in crossbred barrows (Duroc × Landrace × Large White) fed FF or normal feed (unfermented feed, UF) (n = 6). When compared to the UF group, the results showed that serum levels of IgG and IgM were significantly increased in FF group pigs (P < 0.05). FF significantly decreased the abundances of Bacteroides and Verrucomicrobia in the duodenum and decreased the abundances of Bacteroides, Proteobacteria, and Verrucomicrobia in the colon while it significantly increased the abundances of Firmicutes and Actinobacteria (P < 0.05). Furthermore, a Spearman’s correlation analysis showed that serum immunity and the expression of genes related to gut immunity were associated with bacterial strains at the family level. Moreover, differentially abundant colonic microbiota were associated with colonic metabolites. LC-MS data analyses identified a total of 1,351 metabolites that markedly differed between the UF and FF groups. C5-Branched dibasic acid metabolism was significantly upregulated whereas the purine metabolism was significantly downregulated (P < 0.05) in the colonic digesta of pigs in the FF meal group compared to the UF meal group. Collectively, these results indicated that FF meal could influence serum immunity and the expression of genes related to gut immunity, correlating with the gut microbiota and bacterial metabolites in grower-finisher pigs. This study may provide an alternative strategy for improving the intestinal health of grower-finisher pigs.