Mechanical Control of Quantum Transport in Graphene.

2D materials (2DMs) are fundamentally electro-mechanical systems. Their environment unavoidably strains them and modifies their quantum transport properties. For instance, a simple uniaxial strain can completely turn off the conductance of ballistic graphene or switch on/off the superconducting phase of magic-angle bilayer graphene. This article reports measurements of quantum transport in strained graphene transistors which agree quantitatively with models based on mechanically-induced gauge potentials. A scalar potential is mechanically induced in situ to modify graphene's work function by up to 25 meV. Mechanically generated vector potentials suppress the ballistic conductance of graphene by up to 30% and control its quantum interferences. The data are measured with a custom experimental platform able to precisely tune both the mechanics and electrostatics of suspended graphene transistors at low-temperature over a broad range of strain (up to 2.6%). This work opens many opportunities to harness quantitative strain effects in 2DM quantum transport and technologies.

The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models.

BACKGROUND/AIMS: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. METHODS: PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. RESULTS: Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. CONCLUSION: Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.

eALT-F: A New Non-Invasive Staging Method to Identify Medium to High-Risk Patients with HCC from Ultra-High HBV Viral Load Population - China, 2010-2023.

Background: The objective of this study was to examine the clinical characteristics of individuals with ultra-high hepatitis B virus (HBV) viral load and develop a novel staging method for chronic hepatitis B (CHB) that can more effectively identify patients with medium to high hepatocellular carcinoma (HCC) risk. Methods: A total of 2,118 patients with HBV DNA >1×107 IU/mL who visited Peking University People's Hospital between January 2010 and March 2023 were enrolled retrospectively. Clinical data from the first visit were obtained and analyzed. The traditional phases and new 'eALT-F' stages were compared to evaluate the risk of HCC. Results: In the overall patients, more than one-third of the patients were under 30 years old. Additionally, a small proportion of older people (>60 years) also had ultra-high HBV viral load (4.3%). 9.1% and 6.7% of individuals with ultra-high HBV viral load showed FIB-4>3.25 and aMAP≥50, respectively. In the traditional stages of CHB, which are based on HBeAg and alanine aminotransferase (ALT) [the upper limit of normal (ULN) ALT level at 40 IU/L for both men and women], regardless of phase, a certain proportion of patients were at risk of developing HCC (4.1%, 6.4%, 25.0%, and 20.3%). However, in the new 'eALT-F' stages, which are based on HBeAg, ALT (the ULN of ALT level at 30 IU/L for men and 19 IU/L for women), and/or FIB-4 levels (>1.45), aMAP≥50 was only observed in chronic hepatitis patients with positive or negative HBeAg (6.4% and 22.1%, respectively). Conclusions: The 'eALT-F' staging method, based on HBeAg, ALT (males: the ULN of ALT was 30 IU/L, females: 19 IU/L) and/or FIB-4 levels, was more effective in identifying medium to high-risk patients with HCC from patients with ultra-high HBV viral load than the traditional staging methods.

Response of partial nitritation and denitrification processes to high levels of free ammonia in a pilot mature landfill leachate treatment system: Stability and microbial community dynamics.

The high levels of free ammonia (FA) challenge the application of partial nitritation (PN) and denitrification (DN) in the treatment of ammonia-rich wastewater. This study explored the impact of high levels of FA on the PN and DN stability and microbial community dynamics. By reducing reflux and increasing influent load, the concentrations of FA in PN and DN reactors increased from 28.9 mg/L and 140.0 mg/L to 1099.8 mg/L and 868.4 mg/L, respectively. During this process, the performance of PN and DN remained stable. The microbial analysis revealed that the Nitrosomonas exhibited strong tolerance to high levels of FA, and its relative abundance was positively correlated with amoABC (R2 0.984) and hao (R2 0.999) genes. The increase in microbial diversity could enhance the resistance ability of PN against the FA impact. In contrast, high levels of FA had scant influence on the microbial community and performance of DN.

Improving stability and nitrogen removal performance of pilot-scale autotrophic process for mature landfill leachate treatment utilizing in-situ organics.

This study established a stable and efficient pilot-scale denitrification (DN) and partial nitritation (PN) combined with autotrophic nitrogen removal process for mature landfill leachate treatment. A total inorganic nitrogen removal efficiency (TINRE) of 95.3% was achieved without any external carbon source input, including 17.1%, 1.0% and 77.2% of nitrogen removal contributed by the DN, PN and autotrophic processes, respectively. ANAMMOX genus, Ca_Anammoxoglobus (19.4%) was dominant in autotrophic reactor. Moreover, denitrifying bacteria could utilize in-situ organics, including poorly degradable organics, to enhance the nitrogen removal performance of autotrophic process, contributing 3.4% of TINRE. This study provides new insights for the economical, low-carbon, and efficient treatment of mature landfill leachate.

An Ideal Hallmark Closest to Complete Cure of Chronic Hepatitis B Patients: High-sensitivity Quantitative HBsAg Loss.

In the era of antiviral therapy, the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus (HBV) replication to the pursuit of serological clearance of HBs surface antigen (HBsAg). Based on the life cycle of HBV, HBsAg originates from covalently closed circular DNA (cccDNA) and integrated HBV DNA, thus reflecting their transcriptional activity. Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA. HBsAg loss improves the recovery of abnormal immune function, which in turn, may further promote the clearance of residual viruses. Combined with functional cure and the great improvement of clinical outcomes, the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B (CHB). For many other risk factors besides HBV itself, patients with HBsAg loss still need regular monitoring. In this review, we summarized the evolution of CHB treatment, the origin of serum HBsAg, the pattern of HBsAg seroclearance, and the effect of HBsAg loss on immune function and disease outcomes. In addition, we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.

High-temperature exposure and risk of spontaneous abortion during early pregnancy: a case-control study in Nanjing, China.

As one of the most common complications of early pregnancy, spontaneous abortion is associated with environmental factors, but reports estimating the effect of ambient temperature on spontaneous abortion are still inconclusive. Herein, a case-control study (1002 cases and 2004 controls) in Nanjing, China, from 2017 to 2021 was conducted to evaluate the association between temperature exposure and the risk of spontaneous abortion by using distributed lag nonlinear model (DLNM). As a result, daily mean temperature exposure and early spontaneous abortion showed a nonlinear relationship in 14-day lag periods. Moreover, taking the median temperature (17 °C) as a reference, gradually increased positive effects of high temperature on spontaneous abortion could be found during the 4 days prior to hospitalization, and the highest odds ratio (OR) of 2.07 (95% confidence interval (CI): 1.36, 3.16) at extremely hot temperature (33 °C) was observed at 1 lag day. The results suggested that high-temperature exposure in short times during early pregnancy might increase the risk of SAB. Thus, our findings highlight the potential risk of short-term high-temperature exposure during early pregnancy, and more evidence was given for the effects of climate change on maternal health.

Incomplete response to ursodeoxycholic acid in primary biliary cholangitis: criteria, epidemiology, and possible mechanisms.

INTRODUCTION: As a common autoimmune disease with the characteristic of early complication, primary biliary cholangitis (PBC) leads to an increasing number of mortalities among people with end-stage liver disease (ESLD) waiting for liver transplantation. Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for PBC, and a good response to treatment could acquire an ideal prognosis. Patients with poor UDCA response usually have more adverse outcomes and worse survival, therefore, the management of this group become a major consideration. AREAS COVERED: Due to the complexity of race and environment for PBC, different criteria for UDCA response exhibit various predictive performances. Factors affecting UDCA response conditions include gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities, while no agreement has been reached. In this review, we mainly focus on cellular senescence, immune-mediated damage, and vitamin D deficiency as possible mechanisms for UDCA non-responders. EXPERT OPINION: The pathogenesis of PBC has yet to be clarified. Immunology-related mechanisms and therapy targets ought to be the main effort made for further study. Irrespective of the response condition, UDCA is recommended for routine administration in all PBC patients without contraindication. Ongoing clinical trials of second-line and additional therapy exhibit promising prospects.

The ASK-SEAT: a competency-based assessment scale for students majoring in clinical medicine.

BACKGROUND: To validate a competency-based assessment scale for students majoring in clinical medicine, ASK-SEAT. Students' competency growth across grade years was also examined for trends and gaps. METHODS: Questionnaires were distributed online from May through August in 2018 to Year-2 to Year-6 students who majored in clinical medicine at the Shantou University Medical College (China). Cronbach alpha values were calculated for reliability of the scale, and exploratory factor analysis employed for structural validity. Predictive validity was explored by correlating Year-4 students' self-assessed competency ratings with their licensing examination scores (based on Kendall's tau-b values). All students' competency development over time was examined using the Mann-Whitney U test. RESULTS: A total of 760 questionnaires meeting the inclusion criteria were analyzed. The overall Cronbach's alpha value was 0.964, and the item-total correlations were all greater than 0.520. The overall KMO measure was 0.966 and the KMO measure for each item was greater than 0.930 (P < 0.001). The eigenvalues of the top 3 components extracted were all greater than 1, explaining 55.351, 7.382, and 5.316% of data variance respectively, and 68.048% cumulatively. These components were aligned with the competency dimensions of skills (S), knowledge (K), and attitude (A). Significant and positive correlations (0.135 < Kendall's tau-b < 0.276, p < 0.05) were found between Year-4 students' self-rated competency levels and their scores for the licensing examination. Steady competency growth was associated with almost all indicators, with the most pronounced growth in the domain of skills. A lack of steady growth was seen in the indicators of "applying the English language" and "conducting scientific research & innovating". CONCLUSIONS: The ASK-SEAT, a competency-based assessment scale developed to measure medical students' competency development shows good reliability and structural validity. For predictive validity, weak-to-moderate correlations are found between Year-4 students' self-assessment and their performance at the national licensing examination (Year-4 students start their clinical clerkship during the 2nd semester of their 4th year of study). Year-2 to Year-6 students demonstrate steady improvement in the great majority of clinical competency indicators, except in the indicators of "applying the English language" and "conducting scientific research & innovating".

Anti-obesity effect of Auricularia heimuer fruiting body alcohol extraction on obese mice and crucial metabolite pathway analysis by liquid chromatography-tandem mass spectrometry.

In recent years, the increasing obese and overweight population has become a worldwide public health problem, as there is no effective medication to control obesity. Auricularia heimuer is rich in active substances that have potential biologically active functions. The anti-obesity effect and mechanism of Auricularia heimuer fruiting body alcohol extraction (AHA, 150-600 mg/kg·bw) was investigated in obese mice by assessing changes in endogenous liver metabolites using a liquid chromatography-tandem mass spectrometry approach. The aim of this study was to identify an effective food to control human obesity. AHA of 600 mg/kg·bw (HC) significantly decreased body weight and improved serum biochemistry indices. Sixty-eight liver metabolites were identified and significantly separated among the normal, high-fat diet (HFD), and HC groups. Moreover, the metabolic analysis revealed that HC significantly regulated specific metabolites in mice including amino acids, lipids, and carbohydrate compounds. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that HC was significantly involved in different metabolite pathways including arachidonic acid metabolism, galactose metabolism, carbohydrate digestion and absorption, linoleic acid metabolism, and starch and sucrose metabolism. Eight weeks after supplementing with HC, major metabolites in related pathways that were disrupted by an HFD were restored to normal levels, suggesting that HC had anti-obesity activity.

The beneficial effects of Agaricus blazei Murrill on hepatic antioxidant enzymes and the pancreatic tissue recovery in streptozotocin-induced diabetic rats.

Agaricus blazei Murrill (ABM), is a medicinal mushroom, has beneficial effects on diabetes mellitus. In this study, ABM extracts (ethanol extract, EE and ethyl acetate extract, EA) were evaluated to explore the beneficial effect on hepatic antioxidant activity and recovery of the pancreatic tissue in streptozotocin-induced diabetic rats. The hepatic antioxidant activities of ABM extracts were analyzed by superoxide dismutase, catalase activity, glutathione, aspartate transaminase, and alanine transaminase. Moreover, the effects of ABM extracts on pancreatic tissue restoration were investigated by histopathological analysis. The results revealed that the EA showed a better protective effect on hepatic antioxidant activity and recovery of the impaired pancreatic tissues, compared to EE. The results suggested that ABM treatment could effectively reduce oxidative stress and contribute to pancreatic tissue recovery. Therefore, ABM could be used as a functional food to control diabetes. PRACTICAL APPLICATIONS: The research may contribute to the development of ABM as functional foods or dietary supplements for diabetes in the future.

Real-Time Curvature Detection of a Flexible Needle with a Bevel Tip.

As one of the major methods for the diagnosis and treatment of cancers in their early stages, the percutaneous puncture technique has bright prospect in biopsy, ablation, proximity radiotherapy, and drug delivery. Recent years, researchers found the flexible needle cannot realize feedback control during the puncture surgeries only by path planning. To solve this problem, the flexible needle is tried to achieve real-time detection in this paper. Compared with previous methods, the strain gauges glued on the needle surface rather than the medical imaging techniques is used to collect the information to reconstruct the needle curve, which is benefit to integrate the whole system and obtain a more simple and accurate closed-loop control. This paper presented the math model of curve fitting and analyzed the causes of curve fitting errors. To verify the feasibility of this method, an experiment setup was built. Results from the experiments validated the solution in this paper to be effective.