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Abstract Fibrosis is an excessive wound-healing response induced by repeated or chronic external stimuli to tissues, significantly impacting quality of life and primarily contributing to organ failure. Organ fibrosis is reported to cause 45% of all-cause mortality worldwide. Despite extensive efforts to develop new antifibrotic drugs, drug discovery has not kept pace with the clinical demand. Currently, only pirfenidone and nintedanib are approved by the FDA to treat pulmonary fibrotic illness, whereas there are currently no available antifibrotic drugs for hepatic, cardiac or renal fibrosis. The development of fibrosis is closely related to epigenetic alterations. The field of epigenetics primarily studies biological processes, including chromatin modifications, epigenetic readers, DNA transcription and RNA translation. The bromodomain and extra-terminal structural domain (BET) family, a class of epigenetic readers, specifically recognizes acetylated histone lysine residues and promotes the formation of transcriptional complexes. Bromodomain-containing protein 4 (BRD4) is one of the most well-researched proteins in the BET family. BRD4 is implicated in the expression of genes related to inflammation and pro-fibrosis during fibrosis. Inhibition of BRD4 has shown promising anti-fibrotic effects in preclinical studies; however, no BRD4 inhibitor has been approved for clinical use. This review introduces the structure and function of BET proteins, the research progress on BRD4 in organ fibrosis, and the inhibitors of BRD4 utilized in fibrosis. We emphasize the feasibility of targeting BRD4 as an anti-fibrotic strategy and discuss the therapeutic potential and challenges associated with BRD4 inhibitors in treating fibrotic diseases.

Abstract High-strength bolts have become indispensable support materials in geotechnical engineering, but the incidence of safety accidents caused by bolt fractures under complex geological conditions is increasing. To address this challenge, this study focuses on a typical roadway in the Xinjulong coal mine, employing a combination of mechanical performance testing, microscopic and macroscopic analyses to investigate the failure mechanism of bolt breakage. The research indicates that the cracks in the failed bolts underground exhibit subcritical patterns, with the presence of oxides and Cl elements, and multiple intergranular fractures internally, consistent with the characteristics of stress corrosion failure. Additionally, inherent defects in the bolts are also a primary cause of failure. For instance, for type A bolts, the levels of P and S elements significantly exceed the normative requirements, forming inclusions, while the low content of elements like Si and V leads to reduced plasticity, toughness, and corrosion resistance. Furthermore, the excessive pitch in type A bolts leads to stress concentration and cracking under complex loads. The study concludes that the synergistic effect of stress corrosion cracking and inherent flaws in bolts are the main causes of failure. Therefore, it is recommended to enhance the reliability and safety of bolt support by optimizing the bolt shape and developing anti-corrosion bolts, thereby achieving long-term stability in underground engineering.

Due to the high melting point, exceptional mechanical properties, and remarkable corrosion resistance exhibited by Al5W, researchers have conducted extensive research on the structural characteristics of Al5W. To identify the lowest energy structures and find new structures, a combination of particle swarm optimization and first-principles calculations was employed to identify energy-favorable Al5W structures under ambient pressure. The experimental P63 phase and the previously predicted R3¯c phase were identified. Notably, a new R32-Al5W phase was proposed. A comparative analysis on the structural stability, elastic, thermodynamic, and electronic properties of these three Al5W phases were conducted. The results indicate that R32-Al5W exhibits favorable thermodynamic stability, with a predicted bulk modulus close to that of R3¯c-Al5W. All the three Al5W phases demonstrate brittle behavior. The P63-Al5W phase displays larger shear anisotropy in the (010) and (001) planes, while the R32-Al5W phase shows greater shear anisotropy on the (100) plane compared to other two phases. Furthermore, employing Clarke’s and Cahill’s models, the minimum thermal conductivity of Al5W phases was predicted, revealing a magnitude order of P63 > R3¯c > R32. Our calculated melting points also conform to this trend.

High-frequency, low-energy impacts consistently inflict damage on the surrounding rock and anchoring structure in deep roadways, leading to ongoing instability. The construction of anchoring support system that can withstand these dynamic impact loads is identified as crucial in deep coal mining. Through theoretical analysis, laboratory experiments, and numerical simulations, the stress transfer and transformation mechanisms within the anchoring structure under such loads are explored. The cumulative damage and progressive failure of the structure are studied, with criteria being proposed for controlling the roadways under dynamic impact conditions. The findings reveal that three primary elements, i.e., compressive stress, tensile stress, and oscillatory effects caused by quick transitions between compression and tension, are responsible for damaging the anchoring structure. Crucially, the failure of anchoring interface under such conditions is primarily due to the medium's compressive strength and uncoordinated deformation. Damage in the anchoring structure accumulates under internal normal forces, leading to failure when the tangential modulus turns negative or the deformation from a single dynamic impact continuously increases contrary to expectations. A significant cumulative-mutation effect is observed under the combined influence of compression, tension, and oscillation, particularly in terms of the loss of pre-tightening force and internal damage in anchoring structure. Internal fissures predominantly exhibit tensile fractures, with an overall deterioration transitioning gradually from oscillatory effects to tensile stress effects, and subsequently to compressive failure effects. To effectively reduce this cumulative damage, it is crucial to improve the coordinated deformation capacity of both the surrounding rock and the anchoring agent. Additionally, increasing the anchoring length not only enhances structural stiffness but also mobilizes a broader range of rock mass for load-bearing, thereby protecting the anchoring interface, ensuring that the shear resistance in the anchoring structure’s bearing area surpasses the internal normal driving force during dynamic impacts, and mitigating the effects of oscillation can effectively reduce the cumulative damage degree of the anchoring structure. Finally, a new guideline for controlling the roadways under dynamic impact loading is proposed. The guideline, characterized by low energy, high resistance, and an allowance for compression, includes strategies such as far-field unloading, strong support in the near field, modification of fractured surrounding rock, maintaining pre-tightening force, and incorporating compression structures. It aims to provide an effective guidance for the maintenance and control of roadways in similar conditions.

Dynamic load on anchoring structures (AS) within deep roadways can result in cumulative damage and failure. This study develops an experimental device designed to test AS under triaxial loads. The device enables the investigation of the mechanical response, failure mode, instability assessment criteria, and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths. The results show that the peak bearing strength is positively correlated with the anchoring matrix strength, anchorage length, and edgewise compressive strength. The bearing capacity decreases significantly when the anchorage direction is severely inclined. The free face failure modes are typically transverse cracking, concave fracturing, V-shaped slipping and detachment, and spallation detachment. Besides, when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength, loading rate, and anchorage inclination angle increase, the failure intensity rises. Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend. Under cyclic loads, the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability. Finally, a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.

As field effect transistors are reduced to nanometer dimensions, experimental and theoretical research has shown a gradual change in noise generation mechanisms. There are few studies on noise theory for small nanoscale transistors, and Monte Carlo (MC) simulations mainly focus on 2D devices with larger nanoscale dimensions. In this study, we employed MC simulation techniques to establish a 3D device simulation process. By setting device parameters and writing simulation programs, we simulated the raw data of channel current noise for a silicon-based metal–oxide–semiconductor field-effect transistor (MOSFET) with a 10 nm channel length and calculated the drain output current based on these data, thereby achieving static testing of the simulated device. Additionally, this study obtained a 3D potential distribution map of the device channel surface area. Based on the original data from the simulation analysis, this study further calculated the power spectral density of the channel current noise and analyzed how the channel current noise varies with gate voltage, source–drain voltage, temperature, and substrate doping density. The results indicate that under low-temperature conditions, the channel current noise of the 10 nm MOSFET is primarily composed of suppressed shot noise, with the proportion of thermal noise in the total noise slightly increasing as temperature rises. Under normal operating conditions, the channel current noise characteristics of the 10 nm MOSFET device are jointly characterized by suppressed shot noise, thermal noise, and cross-correlated noise. Among these noise components, shot noise is the main source of noise, and its suppression degree decreases as the bias voltage is reduced. These findings are consistent with experimental observations and theoretical analyses found in the existing literature.

Electromagnetic scattering is a routine tool for rapid, non-contact characterization of particle media. In previous work, the interaction targets of scattering intensity, scattering efficiency, and extinction efficiency of Bessel pincer light-sheet beams were all aimed at dielectric spheres. However, most particles in nature are charged. Considering the boundary condition on a charged sphere, the beam shape coefficients (BSCs) (pmn,qmn) of the charged spherical particle illuminated by a Bessel pincer light-sheet beam are obtained. The extinction, scattering, and absorption efficiencies are derived under the generalized Lorenz–Mie theory (GLMT) framework. This study reveals the significant differences in scattering characteristics of Bessel pincer light-sheet beams on a charged particle compared to traditional beams. The simulations show a few apparent differences in the far-field scattering intensity and efficiencies between charged and natural spheres under the influence of dimensionless size parameters. As dimensionless parameters increase, the difference between the charged and neutral spheres decreases. The effects of refractive index and beam parameters on scattering, extinction, and absorption coefficients are different but tend to converge with increasing dimensionless parameters. When applied to charged spheres with different refractive indices, the scattering, extinction, and absorption efficiencies of Bessel pincer light-sheet beams change with variations in surface charge. However, once the surface charge reaches saturation, these efficiencies become stable. This study is significant for understanding optical manipulation and super-resolution imaging in single-molecule microbiology.

Objectives Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies. Methods During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3–V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform. Results The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05). Conclusions The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

IntroductionWith an incidence rate as high as 46%-58%, hypoglycemia is a common complication of glycemic management among those suffering from type 2 diabetes mellitus(T2DM). According to preclinical research, hypoglycemia episodes may impair cognition by harming neurons. However, there is still controversy regarding the clinical evidence for the relationship between hypoglycemic events and the likelihood of cognitive impairment. Furthermore, little research has been done on the dose-response association between hypoglycemia incidents and the possibility of cognitive impairment. To address these knowledge gaps, the present research intends to update the comprehension of the association among hypoglycemic events and the risk of cognitive impairment and to clarify the correlation between dose and response by incorporating the most recent investigations.Method and analysisThis work has developed a protocol for a systematic review and meta-analysis that will examine, via a well-organized assessment of several databases, the relationship between the incidence of hypoglycemia and the probability of cognitive impairment. Observational studies investigating the connection between hypoglycemia episodes and cognitive impairment will be included. The databases that will be searched are PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), Cochrane Library, Embase, the China National Knowledge (CNKI), Wan Fang, the Chinese Science and Technology Periodical Database (VIP), and Du Xiu. Literature from the establishment of each database to December 2023 will be included in the search. Two researchers will independently screen the studies that satisfy the requirements for both inclusion and exclusion. A third researcher will be asked to mediate any disputes. The methodological caliber of the studies included will be assessed utilizing the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal method. With regard to GRADE, which stands for Grading of Recommendations, Assessment, Development, and Evaluation, the quality of the evidence will be evaluated. ROBIS Tool will be used to evaluate the risk of bias in the development of the systematic review. If the data is accessible, meta-analysis and dose-response curve analysis will be employed by Stata software. However, if the data does not allow for such analysis, a descriptive review will be performed.Discussion and conclusionHypoglycemic episodes may raise the likelihood of cognitive impairment, according to earlier investigations. This study will update the relevant evidence and explore the dose-response connection between hypoglycemic episodes and cognitive impairment. The results of this review will have significant effects on decision-making by individuals with diabetes, healthcare providers, and government policy institutions.Trial registrationProspero registration number: CRD42023432352.

Abstract Head neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors which ranks the sixth incidence in the world. Although treatments for HNSCC have improved significantly in recent years, its recurrence rate and mortality rate remain high. Myosin genes have been studied in a variety of tumors, however its role in HNSCC has not been elucidated. GSE58911 and GSE30784 gene expression profile analysis were performed to detect significantly dys-regulated myosin genes in HNSCC. The Cancer Genome Atlas (TCGA) HNSCC database was used to verify the dys-regulated myosin genes and study the relationship between these genes and prognosis in HNSCC. The results showed that MYL1, MYL2, MYL3, MYH2, and MYH7 were down-regulated, while MYH10 was up-regulated in patients with HNSCC. Interestingly, MYL1, MYL2, MYH1, MYH2, and MYH7 were shown to be unfavorable prognostic markers in HNSCC. It is also worth noting that MYL1 was a specific unfavorable prognostic biomarker in HNSCC. MYL1, MYL2, MYL3, MYH2, MYH7, and MYH10 promoted CD4 + T cells activation in HNSCC. MYL1 was proved to be down-regulated in HNSCC tissues compared to normal tissues at protein levels. MYL1 overexpression had no effect on proliferation, but significantly promoted migration of Fadu cells. MYL1 increased EGF and EGFR protein expression levels. Moreover, there is a positive correlation between MYL1 expression and Tcm CD8 cells, Tcm CD4 + cells, NK cells, Mast cells, NKT cells, Tfh cells and Treg cells in HNSCC. Overall, MYL1 facilitates tumor metastasis and correlates with tumor immune infiltration in HNSCC and these effects may be associated with the EGF/EGFR pathway.

Using first-principles calculations, we conducted a comprehensive investigation into the crystal structures, mechanical properties, and electronic structures of Ta4CN3 and Ta2CN compounds through the substitution of Ta atoms with transition metals (Cr, Hf, Mo, Nb, Ti, V, W, and Zr). Sixteen stoichiometric TM4CN3 and TM2CN (TM = Cr, Hf, Mo, Nb, Ti, V, W, and Zr) systems were examined using elastic constants, thermal stability and phonon dispersion calculations. As a result, we identified eight stable structures. Subsequently, we systematically examined the mechanical properties of these eight stable phases. The calculated mechanical properties revealed exceptional hardness values for both Cr2CN and Mo2CN compounds, reaching 21.5 GPa and 21.4 GPa, respectively. The calculation of the electronic properties unequivocally established the metallic nature of these structures. These findings open up new avenues for the development of innovative materials with enhanced properties and performance.

The newly synthesized ternary carbide Mo2Ga2C (P63/mmc, Z = 2) with novel double-Ga layers, the firstly reported member of the well-known MAX-like phases, is stimulating extensive research interests. Here, motivated by the recent experimental and theoretical works, the high-pressure structure evolution behavior of Mo2Ga2C up to 150 GPa has been extensively investigated using an efficient crystal structure search approach combined with first-principles calculations. Besides the experimental high-pressure trigonal P-3m1 phase, a new orthorhombic Amm2 phase was firstly identified and was confirmed to be dynamically stable above 90 GPa. The occurrence of this Amm2 phase follows the strong twist of CMo6 octahedrons in P-3m1 phase and the coordination number of Mo increases from six to seven under compression. Pressure-induced phase transition from P63/mmc to P-3m1 at 22 GPa and P-3m1 to Amm2 at 90 GPa was characterized as first order with a volume reduction of 2.3% and 2.5%, respectively. Inspections of electronic and crystal structures suggested an enhanced Ga–Ga covalent hybridization in the predicted Amm2 phase, which becomes much less compressible under compression. The mechanical parameters and elastic anisotropy behaviors of both P63/mmc and P-3m1 phases were then systematically studied, and the (101¯0)[1¯21¯0] directions were found to be their possible dislocations slip system.

There are various new structures with superior performance for Heusler alloy materials that are widely used in spintronic materials, thermoelectric materials, and other fields. In this study, three new Ag-based full-Heusler alloys (Ag2TiGa, Ag2VGa, and Ag2TiTl) are proposed. The stability, mechanical properties, and electronic properties of these three new Ag-based Heusler alloys were studied using first-principles calculations. The results showed that the compression resistance, shear resistance, stiffness, and elastic anisotropy of Ag2VGa were greater than those of Ag2TiGa and Ag2TiTl, whereas the ductility of Ag2TiGa and Ag2TiTl was better than that of Ag2VGa. The spin density of states of Ag2VGa has evident spin splitting near the Fermi level, and the total magnetic moment of the Ag2VGa structure is 2.28 µB, which indicates that Ag2VGa is magnetic. These studies enrich research on Ag-based Heusler alloys and provide theoretical references for subsequent theoretical and experimental research.

Glycyrol (GC) is one natural active product. Imiquimod-induced psoriasis-like Balb/c mouse models were established. The model mice were intraperitoneally injected with cyclosporine A (CsA) and GC for 8 days followed by a series of biological detections. GC had little toxicity according to the levels of peripheral blood cells, hemoglobin, blood urea nitrogen (BUN), and serum creatinine (CRE), while CsA significantly increased the levels of BUN and CRE. GC decreased the splenic index and reduced the expressions of IL-6, IL-23, and CXCL-3 in the model mice and IL-6, CXCL-1, and CXCL-2 in the inflammatory HaCaT cells. The half inhibition concentration (IC50) of GC on HaCaT cells was 29.72 μmol/L, resulting in improved apoptosis, enhanced expressions of p21, BAX, and BIK, and reduced expressions of BCL-2. GC is an immunosuppressive agent against psoriasis-like symptoms by anti-inflammatory effects, which provides a strategy for the discovery of anti-psoriatic natural products.

Introduction: As a successor to Haiyang-2A (HY-2A), HY-2B is China’s second marine dynamic satellite. Equipped with a scanning microwave radiometer (SMR), it can measure the precipitable water vapor (PWV) over the oceans, providing valuable climate and weather insights. This study aims to evaluate the accuracy of HY-2B SMR PWV data from January 2019 to December 2021 using various validation methods.Methods: to validate HY-2B SMR PWV, fifth-generation European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis (ERA5) data, radiosonde data, and global navigation satellite system (GNSS) observations are used.Results: the validation shows that the HY-2B SMR PWV data agree well with the ERA5 PWV data, with a root mean square error (RMSE) of 1.61 mm and a mean value of 0.71 mm. However, RMSEs of approximately 3.5 mm are observed when comparing the HY-2B SMR PWV data to GNSS and radiosonde data, likely due to temporal and spatial gaps. Geographically, there are greater differences between the HY-2B SMR and ERA5 in lower-latitude areas. The reason could be attributed to a higher water vapor content and more frequent cloudy weather in the areas.Discussion: The results demonstrate that the HY-2B SMR PWV meets requirement (RMSE≤3.5 mm). The HY-2B SMR PWV has a high quality, with a slight observational drift of only 0.1 mm/year, but regular validation and calibration are still necessary.

Abstract Background Preoperative deep vein thrombosis (DVT) of the lower extremities delays surgery in patients with femoral shaft fractures and impairs functional recovery. However, studies on preoperative DVT in patients with femoral shaft fractures are still rare. This study was aimed to retrospectively analyze the preoperative incidence, location and risk factors associated with DVT in patients with femoral shaft fractures. Methods Data of patients with femoral shaft fractures and treated with surgery at the Third Hospital of Hebei Medical University were retrospectively collected from January 2013 to December 2019. The information collected included demographic data, comorbidities, injury-related data and laboratory tests. Patients were divided into DVT and non-DVT groups. Univariate and multivariate logistic regression analyses were performed to determine independent risk factors. Results A total of 432 patients were included in this study, of whom 114 (26.4%) patients were diagnosed with preoperative DVT (all asymptomatic) and injured extremities of 78.1% (89/114) were investigated. Multivariate analysis showed that older age (increase in each 10 years), delay time from injury to operation (in each day), FIB > 4 g/L were independent risk factors for preoperative DVT. Conclusion Patients with femoral shaft fractures (especially the elderly and patients with the above-mentioned conditions) are at the risk of DVT right from admission to surgery hence should be intensively monitored and provided with prompt treatment to prevent DVT.

Abstract Purpose This study aimed to investigate the incidence, location, and related factors of preoperative deep venous thrombosis (DVT) in patients with isolated patellar fractures. Methods Patients with an isolated patellar fracture, admitted between January 2013 and December 2019 at our institution, were retrospectively analyzed. Upon admission, patients underwent routine Doppler ultrasound scanning (DUS) of the bilateral lower extremities to detect DVT; those with DVT were assigned to the case group and those without DVT to the control group. Patients in both groups did not perform preoperative off-bed weight-bearing exercises. Data on demographics, comorbidities, and laboratory test results upon admission were extracted. Variables were evaluated between the two groups using univariate analyses, and independent risk factors associated with DVT were identified by logistic regression analysis. Results During the study period, 827 patients were included, of whom 5.8% (48/827) were found to have preoperative DVT. In DVT patients, 85.4%(41/48) were injured, 8.3%(4/48) were not injured, and 6.3%(3/48) were lower limbs. Multivariate analysis showed that male (male vs. female, odds ratio, OR = 2.25), delayed from injury to DUS (in each day, OR = 1.29), and elevated plasma D-dimer level (> 0.5 µg/mL, OR = 2.47) were independent risk factors associated with DVT. Conclusions Despite the low prevalence of DVT after an isolated patellar fracture, this study underscores the importance of identifying those with a high risk of DVT, especially those with multiple identifiable factors, and encourage the early targeted use of anti-thromboembolic agents to reduce DVT occurrence.

Abstract As a variant of highly efficient electrical discharge machining (EDM), the die-sinking mixed-gas atomization discharge ablation process (DMA-DAP) uses an atomized dielectric formed by a mixed gas, which mainly composed of oxygen and supplemented by nitrogen, and water medium as the discharge medium. In this technology, the oxygen in the medium is used for exothermic oxidation, and the vaporization and explosion of the water generates a chip removal force for highly efficient erosion. The present work uses single-factor tests to compare the characteristics of processing the difficult-to-machine material titanium-alloy special-shaped cavities using either DMA-DAP or EDM. The current, pulse width, pulse interval, and dielectric pressure are selected as the single-factor processing parameters, and how they influence the material removal rate (MRR), electrode relative wear rate (ERWR) and the surface morphology of the processed square cavities is analyzed. The results show that with DMA-DAP, the MRR is more than 12 times that of EDM, the ERWR is reduced by more than 98%, and the surface morphology is relatively good. Finally, taking an aero-engine radial diffuser as the profiling object, DMA-DAP realizes a profiling sample in the form of a variable-cross-section cavity that EDM cannot process, and the efficient die-sinking processing ability of DMA-DAP is verified.

The survival outcome of triple-negative breast cancer (TNBC) remains poor, with difficulties still existing in prognosis assessment and patient stratification. Pyroptosis, a newly discovered form of programmed cell death, is involved in cancer pathogenesis and progression. The role of pyroptosis in the tumor microenvironment (TME) of TNBC has not been fully elucidated. In this study, we disclosed global alterations in 58 pyroptosis-related genes at somatic mutation and transcriptional levels in TNBC samples collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Based on the expression patterns of genes related to pyroptosis, we identified two molecular subtypes that harbored different TME characteristics and survival outcomes. Then, based on differentially expressed genes between two subtypes, we established a 12-gene score with robust efficacy in predicting short- and long-term overall survival of TNBC. Patients at low risk exhibited a significantly better prognosis, more antitumor immune cell infiltration, and higher expression of immune checkpoints including PD-1, PD-L1, CTLA-4, and LAG3. The comprehensive analysis of the immune landscape in TNBC indicated that alterations in pyroptosis-related genes were closely related to the formation of the immune microenvironment and the intensity of the anticancer response. The 12-gene score provided new information on the risk stratification and immunotherapy strategy for highly heterogeneous patients with TNBC.

A sudden cardiac event in patients with heart disease can lead to a heart attack in extreme cases. Therefore, prompt interventions for the particular heart situation and periodic monitoring are critical. This study focuses on a heart sound analysis method that can be monitored daily using multimodal signals acquired with wearable devices. The dual deterministic model-based heart sound analysis is designed in a parallel structure that uses two bio-signals (PCG and PPG signals) related to the heartbeat, enabling more accurate heart sound identification. The experimental results show promising performance of the proposed Model III (DDM-HSA with window and envelope filter), which had the highest performance, and S1 and S2 showed average accuracy (unit: %) of 95.39 (±2.14) and 92.55 (±3.74), respectively. The findings of this study are anticipated to provide improved technology to detect heart sounds and analyze cardiac activities using only bio-signals that can be measured using wearable devices in a mobile environment.

Abstract Purpose In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). Methods A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter®, a microfluidic‐based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. Results Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P

Background: Oxidized low-density lipoprotein (oxLDL) induces vascular endothelial cell (VEC) injury and atherosclerosis through activating endoplasmic reticulum stress. Expression of glucose-regulated protein 94 (Grp94) is induced by endoplasmic reticulum stress and Grp94 is involved in cardiovascular diseases. This study aimed to determine the role of Grp94 in oxLDL-induced vascular endothelial cell injury and atherosclerosis.Methods and Results: An inhibitor of Grp94, HCP1, was used to investigate the role of Grp94 in oxLDL-induced VEC injury in human umbilical vein endothelial cells and atherosclerosis in apolipoprotein E−/− mice. Results showed that HCP1 inhibited autophagy and apoptosis induced by oxLDL in VECs. And we found that Grp94 might interact with adenosine monophosphate-activated protein kinase (AMPK) and activate its activity. HCP1 inhibited AMPK activity and overexpression of Grp94 blocked the effect of HCP1. Besides, HCP1 activated the activity of mechanistic target of rapamycin complex 1 (mTORC1), co-treatment with AMPK activator acadesine eliminated the effect of HCP1 on mTORC1 activity as well as autophagy. In apolipoprotein E−/− mice, HCP1 suppressed autophagy and apoptosis of atherosclerotic plaque endothelium. In addition, HCP1 increased the content of collagen, smooth muscle cells, and anti-inflammatory macrophages while reducing the activity of MMP-2/9 and pro-inflammatory macrophages in the atherosclerotic lesion.Conclusion: HCP1 inhibited oxLDL-induced VEC injury and promoted the stabilization of atherosclerotic plaque in apoE−/− mice. Grp94 might be a potential therapeutic target in the clinical treatment of atherosclerosis.

The pressure-induced phase transitions of MoAlB have been fully studied to provide insights into the typical MAB phases under high pressure. A novel high-pressure monoclinic structure (C2/m, Z = 4) was firstly identified for the MoAlB above 234 GPa, using the first principles crystal structure prediction approach. First-order structure transition character of MoAlB from the ambient-pressure orthorhombic Cmcm phase to this high-pressure monoclinic C2/m phase was demonstrated by a volume drop of 1.28%. Inspections of crystal structures showed that the occurrence of C2/m phase follows the slip in the metallic Al-Al layers and the fracture of linear zigzag B-B chains in the Cmcm phase under compression, confirming the earlier reports. Our argument has been also supported by the softening of elastic constant under high pressure. Phonon curves calculations suggest the high-pressure C2/m phase can be quenchable to ambient pressure. The electronic and mechanical properties of this novel C2/m phase have thus been systematically investigated.

Quantum state tomography strategy via weak value is valid for arbitrary dimensional systems, and can be easily realized. However, the efficiency of quantum state tomography strategy via weak value is lower than that of the conventional quantum state tomography (QST), especially for high-dimensional systems. To improve the efficiency of the scheme, we propose a two-step adaptive quantum state tomography via weak value for pure states (AQSTW). In AQSTW, by using appropriate measurement strength, the efficiency of AQSTW is significantly larger than that of the conventional QST, especially for high-dimensional systems. And AQSTW can be easily implemented. These results demonstrate AQSTW may be useful in the measurements of the unknown quantum states.

In the framework of Generalized Lorenz–Mie theory (GLMT), based on the expansion results of electromagnetic field radiation components of Bessel pincer light sheets beam acting on dielectric particles of arbitrary size, the expression of radiation force components in a Cartesian coordinate system is obtained by using the Maxwell stress tensor method. On the one hand, the effects of the refractive index and the equivalent radius of spherical particles on the distribution of radiation force are discussed; On the other hand, the influence of beam scaling parameter and beam order of Bessel pincer light sheets beam on the distribution of radiation force are investigated. The results indicate that the changes of particle’s refractive index and effective radius only affect the distribution of radiation force. However, the beam scaling parameter and beam order of Bessel pincer light sheets beam have a very sharp impact on the convergence position, distribution range and bending degree far away from the wave source of the radiation force. Single-beam optical tweezers using the self-focusing and self-bending Bessel pincer light-sheets beam are crucial for applications such as single molecule biophysics, optical manipulation and particle separation/clearing.

Using first-principles calculations, a new type of the full-Heusler alloy, namly, Ag2ScGe, with XA configuration, is proposed. The unit cell of the Ag2ScGe alloy consists of 16 atoms, and it is found that there may be two different phases: XA and L21. To determine the stable configuration of the Ag2ScGe alloy, we calculated the formation energy, energy curve, and phonon spectrum of the two configurations of the Ag2ScGe alloy and finally determined the new stable structure, i.e. the XA configuration of the Ag2ScGe alloy. Calculations of the mechanical properties and electronic properties show that this new structure exhibits the properties of a ductile and metallic material with elastic anisotropy. In addition, by calculating the optical properties of this new alloy, it is concluded that Ag2ScGe alloy is a good absorber in the visible light region.

Chemoresistance is a daunting challenge to the prognosis of patients with breast cancer. Signal transducer and activator of transcription (STAT) 5a plays vital roles in the development of various cancers, but its function in breast cancer is controversial, and its role in chemoresistance in breast cancer remains unexplored. Here we identified STAT5a as a chemoresistance inducer that regulates the expression of ABCB1 in breast cancer and can be targeted by pimozide, an FDA-approved psychotropic drug. First, we found that STAT5a and ABCB1 were expressed at higher levels in doxorubicin-resistant cell lines and chemoresistant patients, and their expression was positively correlated. Then, we confirmed the essential roles of STAT5a and ABCB1 in doxorubicin resistance in breast cancer cells and the regulation of ABCB1 transcription by STAT5a. Subsequently, the efficacy of pimozide in inhibiting STAT5a and sensitizing doxorubicin-resistant breast cancer cells was tested. Finally, we verified the role of STAT5a in doxorubicin resistance in breast cancer and the efficacy of pimozide in reversing this resistance in vivo. Our study demonstrated the vital role of STAT5a in doxorubicin resistance in breast cancer. Targeting STAT5a might be a promising strategy for treating doxorubicin-resistant breast cancer. Moreover, repurposing pimozide for doxorubicin resensitization is attractive due to the safety profile of pimozide.

Heart sounds and heart rate (pulse) are the most common physiological signals used in the diagnosis of cardiovascular diseases. Measuring these signals using a device and analyzing their interrelationships simultaneously can improve the accuracy of existing methods and propose new approaches for the diagnosis of cardiovascular diseases. In this study, we have presented a novel smart stethoscope based on multimodal physiological signal measurement technology for personal cardiovascular health monitoring. The proposed device is designed in the shape of a compact personal computer mouse for easy grasping and attachment to the surface of the chest using only one hand. A digital microphone and photoplehysmogram sensor are installed on the bottom and top surfaces of the device, respectively, to measure heart sound and pulse from the user’s chest and finger simultaneously. In addition, a high-performance Bluetooth Low Energy System-on-Chip ARM microprocessor is used for pre-processing of measured data and communication with the smartphone. The prototype is assembled on a manufactured printed circuit board and 3D-printed shell to conduct an in vivo experiment to test the performance of physiological signal measurement and usability by observing users’ muscle fatigue variation.

A tetragonal high-pressure phase of PtAs2 with I4/mmm symmetry was first discovered above 90 GPa by using first principle swarm intelligence structure search technique. The first order structure transition character of PtAs2 from the ambient-pressure cubic pyrite phase to this tetragonal HP phase was confirmed by a large volume reduction of 8.1%. During structure transition, the independent As2 dimers in the pyrite phase were twisted and connected with each other under compression to form three-dimensional As puckered networks in the tetragonal HP phase, accompanied by the increase of the coordination of Pt from 6 to 8. Compared to the semiconducting pyrite phase, the metallic feature of this tetragonal HP phase has been demonstrated by the electronic structure analyses.

Abstract Background Recombinant human calcineurin B subunit (rhCNB) has been shown to be an immune‐stimulatory protein promoting cytokine production and inducing phenotypic maturation of Dendritic cells (DCs). In vivo, it has good antitumor efficacy, and has potential as an antitumor drug. Exogenous rhCNB was found to be internalized into tumor cells via the Toll‐like receptor 4 (TLR4) complex, but it was not known whether its immuno‐modulatory and antitumor functions involved entry by this same route. Methods The production and secretion of the cytokines and chemokines in innate immune cells induced by rhCNB were determined by ELISA, and the expression of CD40, CD80, CD86, and MHCII was analyzed by FACs. Experimental Lewis lung cancer (LLC) model was prepared in C57 BL/6 wild‐type (WT) mice, TLR4−/− mice or their littermates by the inoculation of LLCs in their right armpit, and then administrated daily intraperitoneal injections (0.2 mL) of normal saline, rhCNB 20 mg/kg, and rhCNB 40 mg/kg, respectively. Results Recombinant human calcineurin B subunit promoted the production of antitumor cytokines by innate immune cells, and culture supernatants of rhCNB‐stimulated immune cells induced apoptosis of LLCs. In addition, rhCNB up‐regulated CD40, CD80, CD86, and MHCII expression in macrophages and DCs in TLR4+ cells but failed to do so in TLR4 deficient cells. rhCNB also induced the formation of CD4+ and CD8+T cells in splenocytes from WT mice, but not from TLR4‐deficient littermates. Intraperitoneal administration of WT C57BL/6 mice with rhCNB resulted in a 50% reduction in LLC tumor growth, but failed to inhibit tumor growth in TLR4−/− littermates. Conclusions The in vivo antitumor and immunomodulatory effects of rhCNB are mediated by the TLR4. This conclusion is important for the further understanding and development of rhCNB as an antitumor drug.

A new cubic superhard large-cell carbon allotrope with 200 carbon atoms per unit cell (named c-C200) is theoretically predicted by the unbiased swarm structure searching techniques combined with the first-principles calculations. The phonon and elastic constants calculations show that c-C200 is dynamically and mechanically stable. The calculated hardness of c-C200 is 47 GPa, which means that c-C200 is a potential superhard material. The calculated electronic band structure of c-C200 shows that it is a quasi-direct band gap semiconductor with a gap of 2.781 eV.

We report a novel high-pressure cubic cF24 phase of TaSi2 which is stable above 185 GPa through first-principles swarm intelligence structure search method. Results on enthalpy difference show that the structural transition of TaSi2 from the ambient hexagonal C40 phase to cF24 phase is first order with a volume drop of 4.1%. Under compression, the formation of cubic cF24 phase originates from the dramatic polymerization of one dimensional helical Si chain in the low-pressure C40 phase creating peculiar 3D Si tetrahedrons framework embedded in diamond-like Ta sublattice. The emergence of 3D Si tetrahedrons framework in cF24 phase are suggested to be the main causes for its weaker metallic nature compared to the hexagonal C40 phase.

Carbon is known to form a number of allotropes due to its ability to exist in different hybridizations. Here, based on first-principles calculations combined with crystal structure searching method, a new hexagonal carbon allotrope named h-C63 was proposed. The calculated elastic constants and phonon calculations confirm that h-C63 is dynamically and mechanically stable. We show that h-C63 is a potential superhard material with the hardness of 58.8 GPa, and electronic structure calculations show that this h-C63 is metallic. Keywords: Carbon, Superhard material, First-principles calculations

Quercitrin (YDHH) is a natural dietary flavonoid extracted from Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn.). Psoriasis is a chronic immune-mediated dermatosis. In this study, we report that YDHH had no obvious cytotoxicity and inhibited the proliferation of LPS-stimulated HaCaT keratinocytes. Furthermore, oral administration of YDHH alleviated imiquimod-induced psoriasis-like dermatitis in mice, significantly attenuating the excessive proliferation and abnormal differentiation of keratinocytes, and reducing inflammatory cell infiltrates. YDHH treatment lowered the expression of cytokines related to psoriasis, especially those on the IL-23/Th17 axis. Furthermore, it dramatically inhibited the Th17 cell response regulated by the JAK/STAT signalling pathway. In addition, it was less toxic to the liver and kidneys of mice than the classical immunosuppressant cyclosporine A. Taken together, these findings indicate that YDHH could be useful as a functional food supplement for protection against psoriasis.

Cardiac auscultation is one of the most popular diagnosis approaches to determine cardiovascular status based on listening to heart sounds with a stethoscope. However, heart sounds can be masked by visceral sounds such as organ movement and breathing, and a doctor’s level of experience can more seriously affect the accuracy of auscultation results. To improve the accuracy of auscultation, and to allow nonmedical staff to conduct cardiac auscultation anywhere and anytime, a hybrid-type personal smart stethoscope with an automatic heart sound analysis function is presented in this paper. The device was designed with a folding finger-ring shape that can be worn on the finger and placed on the chest to measure photoplethysmogram (PPG) signals and acquire the heart sound simultaneously. The measured heart sounds are detected as phonocardiogram (PCG) signals, and the boundaries of the heart sound variation and the peaks of the PPG signal are detected in preprocessing by an advanced Shannon entropy envelope. According to the relationship between PCG and PPG signals, an automatic heart sound analysis algorithm based on calculating the time interval between the first and second heart sounds (S1, S2) and the peak of the PPG was developed and implemented via the manufactured prototype device. The prototype device underwent accuracy and usability testing with 20 young adults, and the experimental results showed that the proposed smart stethoscope could satisfactorily collect the heart sounds and PPG signals. In addition, within the developed algorithm, the device was as accurate in start-points of heart sound detection as professional physiological signal-acquisition systems. Furthermore, the experimental results demonstrated that the device was able to identify S1 and S2 heart sounds automatically with high accuracy.

Leucine zipper transcription factor like 1 (LZTFL1) is a member of the Bardet–Biedl syndrome gene family. LZTFL1-null mice show the phenotype of obesity, retinal degeneration, and abnormal cilia development. Functionally, LZTFL1 serves as a tumor suppressor and a negative regulator in the hedgehog signaling pathways. The biological function of mammalian LZTFL1 is partially addressed, but data on other model organisms are limited. Zebrafish (Danio rerio) is widely considered as a powerful model to understand the functions of genes implicated in obesity, disease, and cancer. In this study, LZTFL1 homologs were identified in zebrafish (zebrafish LZTFL1). The full-length cDNA of zebrafish LZTFL1 contained 897 bps encoding 298 amino acids. Zebrafish LZTFL1 displayed conserved domains of coil–coil and leucine zipper domain. PCR results showed that zebrafish LZTFL1 was widely distributed in various tissues. Western blot analysis further revealed that zebrafish LZTFL1 was detected to be ectopically expressed in HeLa cells with correct molecular weight. Fluorescence images showed as well that zebrafish LZTFL1 was localized in the cytoplasm. Furthermore, luciferase reporter assay indicated zebrafish LZTFL1 served as a negative regulator in the hedgehog signaling pathway. These data supported that zebrafish was a good model for understanding the biological roles of LZTFL1.

Prestressed anchor support is one of the most important support methods for coal mine roadways. As the coal mining depth increases, the adaptability of existing prestressed anchor has become weaker and weaker, which is mainly reflected in the current anchor prestress is much smaller than the support resistance required for the stability of the roadways and makes it difficult to effectively control the roadways. In order to solve the problem, a group anchor structure was proposed to realize higher prestressed anchor support technology and improve the support status of deep roadways. For coal mine roadways, group anchor structure is a new technology and new topic, and the design method and theoretical basis of the group anchor support are lacking. Therefore, the paper studied the bearing capacity of the group anchors through physical tests and numerical simulations. Among them, a special set of group anchor drawing tooling was designed and processed to match the physical test. The test results show that the group anchor structure can double the bearing capacity and bearing rigidity compared with traditional anchors, and the group anchor support can further optimize the support parameters to improve the bearing capacity of the surrounding rock. Therefore, the group anchor support is helpful to the stability control of the surrounding rock of the deep roadway.

As mining depth extends continuously, complex geological environment and strong mining stress pose serious challenges against excavation safety and higher demand for bolt support. To meet the challenges, a new type of flexible bolt is developed that is free from the limitation of excavation height and can be installed quickly. The flexible bolts have a tail structure which is squeezed together by the locking casing and the steel-strand rod. The tail structure forms the thread through the rolling process, and then can be quickly installed by the nut rotation type, which avoids the disadvantages of the cable tension installation. Through the flexible long bolts, the thick anchoring layer of the roof can be constructed, and the safety control of the roadway is realized. To obtain the optimal specifications, locking casings of three diameters and lengths were used to prepare bolt samples for static tensile test. Test results show that when the diameter of locking casing is fixed, the peak resistance increases as the length of locking casing increases, but the increased amplitude tends to reduce gradually. When the length of locking casing is fixed, too large a diameter makes the mechanical property unstable. Finally, the optimal length and diameter of locking casing are set at 120 and 30 mm, respectively. In addition, cyclic loading tests were conducted, the results of which indicate that cyclic loading does not change the stress state within the bolts and that flexible bolts display a stable mechanical property. Field results indicate that flexible bolts achieve low damage of the surrounding rock and control the maximum roof fracture depth within 2.1 m, thus guaranteeing the roadway safety.

With the increase of mining depth and strength, the evolution of bolt axial force is increasingly becoming important for ensuring the reliability and safety of support. To improve the problem of the existing coal mine roadway pressure-monitoring method, whereby it is difficult to continuously monitor the axial force of the bolt over a long period of time, a full rod fiber bragg grating (FBG) force-measuring bolt and system were designed based on the principle of fiber grating sensing. It was found that a trapezoidal groove is a relatively better groove. The linearity between the center wavelength offset of the fiber grating and the axial force was more than 0.99, and the conversion formula between the axial force of the bolt rod and the wavelength change of the fiber grating were obtained. The real-time monitoring revealed that the axial force of the bolt obviously changed before and after compression. The axial force distribution curve can be divided into the stable zone, growth zone, and peak zone. The influence of the roadway abutment pressure was approximately 130 m ahead of the working face, and the peak area was within the 25–35 m range of the advance working face. The axial force of the bolt rod at the end of the anchorage linearly increased with the tail end of the bolt, the axial force of the free segment was the largest, and the overall stress was essentially the same. The application results demonstrate the feasibility and effectiveness of the FBG full-length force bolt.

Today, taking a bath is not only a means to keep clean, but also to reduce fatigue and stress. However, taking a bath with hot water for a long time can also be dangerous, leading to scalding or even a heart attack. To prevent these risks, several studies based on measuring bio-signals have been conducted, but due to high prices, difficulty of use, and restricted functions, these studies’ recommendations cannot be easily adopted by the public. Therefore, developing accurate methods to measure bathing temperature and bathing time should be the most direct approach to solve these problems. In this study, a smart bath assistive device based on an inner water temperature measurement function is proposed. Prior to development of the device, a bathing environment was emulated with six temperature sensors affixed to different depths to find the optimal depth for measuring bathing temperature. According to the measurement results, the device was designed in a mushroom shape with the cap part floating on the water’s surface and housing the electronic components, and temperature sensors within the stem part were immersed in the water approximately 5 cm below the surface to measure the inner water temperature. Due to the low-power consuming Advanced RISC Machine (ARM) processor and waterproof design, the device is able to float in hot water and monitor the bathing temperature variation over a long period of time. The device was compared alongside a commercial analog bathing thermometer to verify the performance of temperature measurements. In addition, a compensation algorithm was developed and programmed into the device to improve the accuracy of measurements. Processed data is transmitted by Bluetooth to a dedicated Android app for data display and storage. The final results show that the proposed device is highly accurate and stable for monitoring bathing temperature.

Based on density functional theory calculations, systematic calculations of the structural properties, elastic anisotropy and mechanical properties of boron alloying aluminum phosphide (BxAl1-xP) ternary mixed crystal have been presented. The results of the lattice parameters, band gaps, elastic constants and elastic modulus accord with the experimental and others published data well. The band structure which is described by CASTEP method indicates they are direct gap semiconductors for the composition x = 0.25, 0.50 and 0.75. Beyond that, we studied the Debye temperatures together with the acoustic velocities for all the BxAl1-xP alloys using the obtained elastic modulus. Finally, we depicted the three dimensional surface constructions to explain the elastic anisotropy using several calculated different anisotropic indexes in our work.

The influence of a polypropylene fiber on the tensile properties of a cement-polymer based thin spray-on liner (TSL) was investigated in this study. Two different contents of fiber were added to the liner, yielding two TSL groups. Tensile tests were performed (in accordance with the ASTM D638 standard) on the two groups of specimens as well as the control group at 1, 7, 14, and 28-day curing. The test result verified the large plasticity and low elastic modulus of the TSL compared with the fiber. SEM examination revealed that fibers lying parallel to the load direction ruptured or were pulled out from the matrix, which was beneficial to the tensile strength, but detrimental to the elongation because of their high stiffness. Other fibers lying perpendicular with the load direction were detrimental to both tensile strength and elongation through aggravating the propagation of the cracks. The tensile strength was improved by fiber incorporation, while the elongation was reduced at all curing. The influence of fibers on tensile toughness was uncertain since tensile toughness depended on strength as well as deformity.

First principles calculations are performed to systematically investigate the electronic structures, elastic, anisotropic and electronic properties of the monoclinic, tetragonal and orthorhombic structures of Si3N4 under pressure. Anisotropy studies show that three Si3N4 phases exhibit a large anisotropy. Furthermore, using the HSE06 hybrid functional, the monoclinic, tetragonal and orthorhombic phases are found to be wide band-gap semiconductors. The pressure induced band gap direct-indirect transition is found for monoclinic Si3N4. The elastic modulus, compressional and shear wave velocities as well as Debye temperatures as a function of pressure in three Si3N4 phases are also investigated in detail.

The structural, mechanical, and electronic properties of the orthorhombic GaN (Pnma-GaN) are investigated at ambient pressure by using first-principles calculations method with the ultrasoft pseudopotential scheme. The elastic constants and phonon calculations reveal Pnma-GaN is mechanically and dynamically stable at ambient pressure. The calculated Young modulus of Pnma-GaN is 170 GPa, which is the three-fifths of wurtzite-GaN. Electronic structure study shows that Pnma-GaN is a direct semiconductor with band gap of 1.847 eV. The anisotropic calculation shows that wurtzite-GaN has a smaller elastic anisotropy than that of Pnma-GaN in Young’s modulus. In addition, when the composition of aluminum increases from 0 to 0.063 in the alloy, the band gap decreases initially and increases afterward for Pnma-Ga1−xAlxN, while, for wurtzite-Ga1−xAlxN, the band gap increases with the increasing composition x. Due to the structural porous feature, Pnma-GaN can also be expected to be a good hydrogen storage material.

Objectives: The aim of this study was to evaluate the diagnostic performance of serum HA and LN as serum markers for predicting significant fibrosis in CHB patients. Methods: Serum HA and LN levels of 87 patients with chronic hepatitis B and 19 blood donors were assayed by RIA. Liver fibrosis stages were determined according to the Metavir scoring-system. The diagnostic performances of all indexes were evaluated by the receiver operating characteristic (ROC) curves. Results: Serum HA and LN concentrations increased significantly with the stage of hepatic fibrosis, which showed positive correlation with the stages of liver fibrosis (HA: r = 0.875, p

Glycyrol is a natural compound extracted from Glycyrrhiza uralensis, first reported by us to be a new immunosuppressant. Here, we demonstrate its beneficial effect in collagen-induced arthritis (CIA) in mice, a model for rheumatoid arthritis (RA) in man, and we document the underlying mechanisms. Peroral administration of glycyrol significantly reduced clinical scores, alleviated cartilage and bone erosion and reduced levels of serum inflammatory cytokines. Glycyrol also decreased delayed-type hypersensitivity, improved carbon clearance and reduced acetic acid-induced capillary permeability. Furthermore, glycyrol decreased NF-κB and NFAT transcriptional activities and inhibited IL-2 expression. The therapeutic effect of glycyrol was associated with down-regulation of both autoimmune and inflammatory reactions. In addition, we demonstrated that glycyrol has minimal acute toxicity in mice. Therefore, we propose that glycyrol may hold promise for future treatment of RA.