Paris polyphylla ethanol extract and polyphyllin I ameliorate adenomyosis by inhibiting epithelial-mesenchymal transition.

BACKGROUND: The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored. PURPOSE: The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances. METHODS: To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results. RESULTS: Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFß1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFß1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFß1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen. CONCLUSIONS: PPE and PPI efficiently impede the development of EMT by inhibiting the TGFß1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.

[Identification and expression analysis of whole gene family of Isatis indigotica 4-coumarate: CoA ligase].

The 4-coumarate: CoA ligase(4CL) is a key enzyme in the upstream pathway of phenylpropanoids such as flavonoids, soluble phenolic esters, lignans, and lignins in plants. In this study, 13 4CL family members of Arabidopsis thaliana were used as reference sequences to identify the 4CL gene family candidate members of Isatis indigotica from the reported I. indigotica genome. Further bioinformatics analysis and analysis of the expression pattern of 4CL genes and the accumulation pattern of flavonoids were carried out. Thirteen 4CL genes were obtained, named Ii4CL1-Ii4CL13, which were distributed on chromosomes 1, 2, 3, 4, and 6. The analysis of the gene structure and conserved structural domains revealed the intron number of I. indigotica 4CL genes was between 1 and 12 and the protein structural domains were highly conserved. Cis-acting element analysis showed that there were multiple response elements in the promoter sequence of I. indigotica 4CL gene family, and jasmonic acid had the largest number of reaction elements. The collinearity analysis showed that there was a close relationship between the 4CL gene family members of I. indigotica and A. thaliana. As revealed by qPCR results, the expression analysis of the 4CL gene family showed that 10 4CL genes had higher expression levels in the aboveground part of I. indigotica. The content assay of flavonoids in different parts of I. indigotica showed that flavonoids were mainly accumulated in the aboveground part of plants. This study provides a basis for further investigating the roles of the 4CL gene family involved in the biosynthesis of flavonoids in I. indigotica.

Nitric oxide synthase and its function in animal reproduction: an update.

Nitric oxide (NO), a free radical labile gas, is involved in the regulation of various biological functions and physiological processes during animal reproduction. Recently, increasing evidence suggests that the biological role and chemical fate of NO is dependent on dynamic regulation of its biosynthetic enzyme, three distinct nitric oxide synthase (NOS) according to their structure, location and function. The impact of NOS isoforms on reproductive functions need to be timely elucidated. Here, we focus on and the basic background and latest studies on the development, structure, importance inhibitor, location pattern, complex functions. Moreover, we summarize the exactly mechanisms which involved some cell signal pathways in the regulation of NOS with cellular and molecular level in the animal reproduction. Therefore, this growing research area provides the new insight into the important role of NOS male and female reproduction system. It also provides the treatment evidence on targeting NOS of reproductive regulation and diseases.

[Cloning and catalytic analysis of Isatis indigotica chalcone isomerase in vitro].

Chalcone isomerase is a key rate-limiting enzyme in the biosynthesis of flavonoids in higher plants, which determines the production of flavonoids in plants. In this study, RNA was extracted from different parts of Isatis indigotica and reverse-transcribed into cDNA. Specific primers with enzyme restriction sites were designed, and a chalcone isomerase gene was cloned from I. indigotica, named IiCHI. IiCHI was 756 bp in length, containing a complete open reading frame and encoding 251 amino acids. Homology analysis showed that IiCHI was closely related to CHI protein of Arabidopsis thaliana and had typical active sites of chalcone isomerase. Phylogenetic tree analysis showed that IiCHI was classified into type Ⅰ CHI clade. Recombinant prokaryotic expression vector pET28a-IiCHI was constructed and purified to obtain IiCHI recombinant protein. In vitro enzymatic analysis showed that the IiCHI protein could convert naringenin chalcone into naringenin, but could not catalyze the production of liquiritigenin by isoliquiritigenin. The results of real-time quantitative polymerase chain reaction(qPCR) showed that the expression level of IiCHI in the aboveground parts was higher than that in the underground parts and the expression level was the highest in the flowers of the aboveground parts, followed by leaves and stems, and no expression was observed in the roots and rhizomes of the underground parts. This study has confirmed the function of chalcone isomerase in I. indigotica and provided references for the biosynthesis of flavonoid components.

[Developments in Research on the Relationship Between Porphyromonas gingivalis and Non-Oral Diseases].

Porphyromonas gingivalis ( P. gingivalis) is a common periodontal pathogen. Recently, there has been increasing evidence suggesting that P. gingivalis is not only a common pathogen in the oral cavity, but is also closely associated with non-oral diseases, including inflammatory bowel disease, cancer, cardiovascular diseases, Alzheimer's disease, rheumatoid arthritis, diabetes mellitus, premature birth and non-alcoholic hepatitis, etc. Herein, we reviewed the developments in recent years in research on the relationship between P. gingivalis, a periodontal pathogen, and non-oral diseases, which will help determine whether P. gingivalis could be used as an auxiliary diagnostic biomarker or a potential therapeutic target for these non-oral diseases, thus contributing to the development of treatment strategies for the relevant diseases.

Low Dimensional Nanostructure-Assisted Long-Range Surface Plasmon Resonance Sensors With High Figure of Merit.

Long-range surface plasmon resonance (LRSPR) sensors have been extensively studied by virtue of their extremely narrow full width at half maxima (FWHM) characteristics, but their low sensitivity remains an important factor limiting the figure of merit (FOM), making the sensors have difficulties in detecting small refractive index changes accurately. To address this problem, this paper proposes and demonstrates a low dimensional nanostructure (Au nanospheres, WS2) assisted LRSPR sensor to achieve an effective enhancement of the sensor interfaced electric field and thus improve the sensitivity. The performance parameters of the two sensors are compared with the LRSPR sensor by finite element method analysis, and the results showed that the assistance of the low dimensional nanostructure has a positive effect on the sensor. The first refractive index sensing experiment of the WS2-assisted LRSPR sensor was realized with a 25.47% increase in sensitivity and a 7.13% increase in FOM simultaneously, and the Au nanospheres-assisted LRSPR sensor with a 29.23% increase in sensitivity and a 15.95% increase in FOM simultaneously. The introduction of low dimensional nanostructures provides a flexible and effective means of sensitization for LRSPR sensors, making the plasmon resonance sensors combine high sensitivity, narrow FWHM and high FOM, which have promising applications in biochemical sensing.

Discovery and characterization of a novel cGAS covalent inhibitor for the treatment of inflammatory bowel disease.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, acts as a nucleotidyl transferase that catalyzes ATP and GTP to form cyclic GMP-AMP (cGAMP) and plays a critical role in innate immunity. Hyperactivation of cGAS-STING signaling contributes to hyperinflammatory responses. Therefore, cGAS is considered a promising target for the treatment of inflammatory diseases. Herein, we report the discovery and identification of several novel types of cGAS inhibitors by pyrophosphatase (PPiase)-coupled activity assays. Among these inhibitors, 1-(1-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)prop-2-yn-1-one (compound 3) displayed the highest potency and selectivity at the cellular level. Compound 3 exhibited better inhibitory activity and pathway selectivity than RU.521, which is a selective cGAS inhibitor with anti-inflammatory effects in vitro and in vivo. Thermostability analysis, nuclear magnetic resonance and isothermal titration calorimetry assays confirmed that compound 3 directly binds to the cGAS protein. Mass spectrometry and mutation analysis revealed that compound 3 covalently binds to Cys419 of cGAS. Notably, compound 3 demonstrated promising therapeutic efficacy in a dextran sulfate sodium (DSS)-induced mouse colitis model. These results collectively suggest that compound 3 will be useful for understanding the biological function of cGAS and has the potential to be further developed for inflammatory disease therapies.

Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma.

Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.

[Pollution Characteristics and Influencing Factors of PM2.5 in Shanxi Province Based on Wavelet Transform].

Based on the daily average concentration of PM2.5, social influencing factor data, and meteorological data of 11 cities in Shanxi Province from 2015 to 2019, the concentration period of PM2.5 was determined using wavelet transform. The correlation between PM2.5 and social influencing factors and meteorological factors was explored respectively through Spearman correlation and the wavelet coherence spectrum, and the main influencing factors of long-term and short-term management and control of PM2.5 were determined. The results showed that the concentration of PM2.5 in Shanxi Province showed an upward trend from 2015 to 2017, with an average annual increase rate of 4.3% and a downward trend from 2018 to 2019, with an average annual decrease rate of 4.2%. The average concentration of PM2.5 showed a "U" distribution, with the highest value in January (95 µg·m-3) and the lowest in August (34 µg·m-3); the average value in winter was approximately twice that in summer. The ρ(PM2.5) in southern cities such as Linfen was 62 µg·m-3, and the average value in Datong and other northern cities was 45 µg·m-3, which was high in the south and low in the north. There were significant periodic changes in PM2.5 concentration in the 11 cities, including a long period of approximately 293 d and a short period of approximately 27 d. Among them, the energy consumption level and industrial structure were the strong driving factors affecting the PM2.5 concentration in the long period of Shanxi Province. In the short period, it was greatly affected by the change in atmospheric circulation, and different cities were affected by typical meteorological factors. Linfen, Yuncheng, Datong, Shuozhou, and Xinzhou were vulnerable to wind speed; Jinzhong and Luliang were vulnerable to temperature; and Taiyuan, Jincheng, Yangquan, and Changzhi were uniquely and significantly affected by relative humidity. Therefore, industrial structure adjustment and energy structure adjustment are key to the long-term control of atmospheric PM2.5 and the long-term improvement of air quality in Shanxi Province. The differential impact of different urban meteorological factors on PM2.5 should be considered when carrying out short-term regional joint prevention and control.

Research advances on surface plasmon resonance biosensors.

The surface plasmon resonance (SPR) phenomenon is of wide interest due to its sensitivity to changes in surface refractive index for the label-free, highly sensitive and rapid detection of biomarkers. This paper reviews research progress on SPR biosensors modified with different substrate structures and surface materials, surface plasmon resonance imaging (SPRI), and SPR-enhanced electrochemiluminescent (ECL) biosensors for applications in biosensing in the last five years. This paper focuses on the research on the application of the SPR phenomenon in the field of bio-detection, reviews the sensing characteristics of SPR biosensors with substrate structures of prisms, gratings, and optical fibers, and summarizes and analyzes the sensitivity and interference resistance of SPR sensors with surface modification of different materials (high-refractive index dielectric films, metallic micro- and nanostructures, and surface antifouling materials). Considering that imaging is an important tool for biomedical detection, this paper reviews the research progress on SPRI technology in the field of biomedical detection. In addition, this paper also reviews the research progress on SPR-enhanced ECL biosensors in the field of biosensing. Finally, this paper provides an outlook on the development trends of biosensing technology in terms of portable high-precision SPR sensors, reduction of self-loss of thin film materials, optimization of image processing techniques and simplification of electrode modification for ECL sensors.

Genetically Encoded Sensor Enables Endogenous RNA Imaging with Conformation-Switching Induced Fluorogenic Proteins.

Genetically encoded molecular tools are crucial for live cell RNA imaging, and few are available for endogenous RNA imaging. We develop a new genetically encoded sensor using conformation switching RNA induced fluorogenic proteins that enable multicolor and signal-amplified imaging of endogenous RNAs. The sensor system is designed with an RNA sensing module and a degron-fused fluorescent protein reporter. Target RNA induces conformation switching of the RNA sensing module to form RNA aptamers that stabilize the degron-fused protein for fluorogenic imaging. This sensor is demonstrated for high-contrast imaging of survivin mRNA abundance and dynamics in live cells. Moreover, the sensor system is extended to a multicolor palette by screening fluorogenic proteins of distinct colors, and engineered into a signal amplifier using the split fluorescent protein design. The sensor is further exploited for imaging lncRNA MALAT-1 and its translocation dynamics during mitosis. Our sensor system can afford a valuable platform for RNA imaging in biomedical research and clinical theranostics.

Effects of shoe weight on landing impact and side-to-side asymmetry.

Shoes of different weights affect proprioception. Drop jump (DJ) tasks are often used to explore the risks and mechanisms of lower limb injuries. Leg dominance mainly refers to differences between the dominant and nondominant legs. Eight males and eight females participated in this study. The weights of the shoes in this investigation were 255 g, 335 g, and 415 g, and the heights of the DJ were 30 cm, 40 cm, and 50 cm. The side-to-side asymmetry of the time of contact initiation for the 30DJ was greater than that of the 40DJ and 50DJ, and the asymmetry for shoes weighing 415 g and 355 g was greater than that for shoes weighing 255 g. When the drop height increased, the side-to-side asymmetry of the peak ground reaction force (PGRF). also increased. The ground contact time increased as the drop height increased to 50DJ. Higher drop heights caused greater side-to-side asymmetry of the PGRF. Heavier shoes caused the peak ground reaction force time (PGRFT) in the nondominant leg to appear earlier, reduced the jump height and affected the performance. Heavier shoes caused greater side-to-side asymmetry at the initial ground contact and at the ground contact time, affecting training effectiveness.

Racemization in cataractous lens from diabetic and aging individuals: analysis of Asp 58 residue in αA-crystallin.

Cataract is the leading cause of visual impairment globally. Racemization of lens proteins may contribute to cataract formation in aging individuals. As a special type of age-related cataract (ARC), diabetic cataract (DC) is characterized by the early onset of cortical opacification and finally developed into a mixed type of cortical and nuclear opacification. We compared racemization of Asp 58 residue, a hotspot position in αA-crystallin, from the cortex and nucleus of diabetic and age-matched senile cataractous lenses, by identifying L-Asp/L-isoAsp/D-Asp/D-isoAsp by mass spectrometry. Compared to nondiabetic cataractous lenses, DC lenses showed a significantly increased cortex/nucleus ratio of D-Asp 58, which originated primarily from an increased percentage of D-Asp 58 in the lens cortex of DC. Moreover, patients diagnosed with diabetes for over 10 years showed a lower cortex/nucleus ratio of D-isoAsp 58 in the lens compared with those who had a shorter duration of diabetes, which originated mainly from an increased percentage of D-isoAsp 58 in the lens nucleus of DC with increasing time of hyperglycemia. Further analysis confirmed decreased protein solubility in diabetic cataractous lenses. The different racemization pattern in DC may be distinguished from ARC and influence its phenotype over the protracted duration of diabetes.

Influences of Different Drop Height Training on Lower Extremity Kinematics and Stiffness during Repetitive Drop Jump.

Drop jump (DJ) is often used as a plyometric exercise to improve jumping performance. Training from improper drop heights and for improper durations lead to unfavorable biomechanical changes in the lower extremities when landing, which result in reduced training effects and even lower extremity injuries. Purpose. To study the effects of repeated DJ training at drop heights of 30 cm, 40 cm, and 50 cm (drop jump height (DJH) 30, DJH40, and DJH50) on lower extremity kinematics and kinetics. The 1st, 50th, 100th, 150th, and 200th DJs (DJ1, DJs50, DJs100, DJs150, and DJs200) were recorded by using a BTS motion capture system and force platform. The MATLAB software was used to compare the kinematic and stiffness data of DJ1, DJs50, DJs100, DJs150, and DJs200 with one-way ANOVA repeated measure. If there were significant differences, the LSD method was used for post hoc comparisons. Methods. Twenty healthy male Division III athlete volunteers were selected as subjects, and 200 drop jumps (DJs200) were performed from DJH30, DJH40, and DJH50. Results. The jumping height (JH), contact time (CT), and GRF increased with drop height, and the stiffness of the legs and ankle at DJH30 was higher than that at DJH40 and DJH50 (p < 0.05). Conclusion. Within DJs200, training at DJH50 yield the high impact easily leads to lower extremity injury; training at DJH30 can increase the stiffnesses of the legs and ankle joints, thus effectively utilizing the SSC benefits to store and release elastic energy, reducing the risk of lower extremity musculoskeletal injury. Therefore, coaches can choose different drop heights and training quantities for each person to better prevent lower extremity injury.

Effects of Acupuncture on Explosive Force Production by the Healthy Female Shoulder Joint.

BACKGROUND: Acupuncture is often used to treat chronic conditions, such as pain. In recent years, given the importance of the explosive forces generated by shoulder muscles for the completion of motor tasks, studies in which nerves were stimulated through acupuncture to increase the explosive forces were conducted. This study explored the effect of acupuncture on explosive force production by the muscles of the female shoulder joint. METHODS: Eighteen healthy women underwent shoulder adduction (Add), abduction (Abd), flexion (Flex), and extension (Ext) tests with an isokinetic measurement system. Acupuncture was used to stimulate the Zhongfu (LU1), Tianfu (LI3), Xiabai (LU4), Binao (LI14), Naohui (SJ13), Jianliao (SJ14), and Xiaoluo (SJ12) points, and electromyography (EMG) signals were recorded before and after acupuncture. RESULTS: After acupuncture, there was a significant difference in the average maximum work, the average maximum power, the average maximum speed, the total work in Add/Abd and Flex/Ext, the EMG signals, and the stiffness of the muscles in Abd and Ext (P < 0.05). There were no significant differences in the average maximum torque in Abd or Flex. CONCLUSION: Based on the results, there may be a significant correlation between the manipulation of different acupoints by acupuncture and the average maximum torque and stiffness. Acupuncture may stimulate nerves to activate muscles and induce a postactivation potentiation effect that improves explosive force production. Therefore, acupuncture as an auxiliary tool may increase the explosive forces generated by acupoint-related muscles by stimulating nerves.

Effects of the weight of shoes on calf muscle simulation.

The current study investigated the effects of shoes of different weights on calf individual muscle contributions during a running cycle. Twenty male runners ran on a force platform with shoes of four different weights (175 g, 255 g, 335 g, and 415 g). The study evaluated runners' lower extremity muscle forces under the four shoe weight conditions using a musculoskeletal modeling system. The system generates equality and inequality constraint equations to simulate muscle forces. The individual muscle contributions in each calf were determined using these muscle forces. Data were compared using one-way repeated-measure ANOVA. The results revealed significant differences in the contributions of the gastrocnemius lateralis. Post hoc comparisons revealed that running in the 175 g shoes resulted in a larger contribution of the gastrocnemius lateralis than running in the 415 g shoes during the braking phase. Therefore, wearing lightweight shoes while running may promote fatigue in the gastrocnemius muscle during the braking phase. The calf muscle activation results may indicate that an adaptation period is warranted when changing from heavy to lightweight shoes.

[Nitrogen content inversion of wheat canopy leaf based on ground spectral reflectance data]. / åŸºäºŽåœ°é¢è§‚æµ‹å ‰è°±æ•°æ®çš„å†¬å°éº¦å† å±‚å¶ç‰‡æ°®å«é‡åæ¼”æ¨¡åž‹.

Canopy nitrogen content in wheat is a key indicator of wheat grain yield and quality. When using remote sensing technology to predict wheat canopy nitrogen content, a hyperspectral mode with high adaptability and high accuracy is needed to improve the inversion efficiency. We developed a new three-band spectral vegetation index (NEW-NDRE) by combining a two-band spectral index NDRE and the spectral reflectance at 550 nm based on field data collected from different sites, years, with different varieties and nitrogen levels and at multiple growth stages. The NEW-NDRE was compared with 11 traditional spectral vegetation indices in terms of wheat canopy nitrogen content inversion. NEW-NDRE and three traditional indices (NDRE, NDDA and RI-1dB) all closely correlated with wheat canopy nitrogen content. NEW-NDRE displayed the highest correlation with wheat canopy nitrogen content at early grain filling stage, with a coefficient (R2) of 0.9 and a root mean squared error (RMSE) of 0.4. The inversion model developed with the NEW-NDRE was validated with an independent dataset. The relative error (RE) of the model was 9.3%, which was significantly lower than that of NDRE, NDDA and RI-1dB. Generally, NEW-NDRE is a more robust index for wheat canopy nitrogen content inversion than traditional indices through eliminating environmental limitation, and it could be used as a new tool for precise fertilizer application.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

Microstructures and Properties of Sn2.5Ag0.7Cu0.1RE Composite Solders Reinforced with Cu-Coated Graphene Nanosheets Synthesized by Pyrolysis.

Composite solder is a promising route to improve the properties and reliability of Sn-based lead-free solder. In this study, Cu-coated graphene nanosheets (Cu-GNSs) were synthesized using pyrolysis. Cu-GNSs reinforced Sn2.5Ag0.7Cu0.1RE composite lead-free solders were prepared via powder metallurgy. The size, distribution, and adsorption type of Cu nanoparticles on the GNSs were studied. The relation of the Cu-GNSs content and microstructure to the physical, wettability, and mechanical properties of composite solders was discussed. The results show that Cu nanoparticles (with a mean size of 13 nm) present uniform distribution and effective chemisorptions on the GNS. Microstructural evolution of composite solders is dependent on the addition of Cu-GNSs. With increasing Cu-GNSs addition, ß-Sn grains become finer and the eutectic phase proportion becomes larger, while the morphology of the eutectic phase transforms from dispersion to network-type. The improvement of the tensile strength of the composite solder can be attributed to grain refinement and load transfer. While the existence of Cu-GNSs can effectively improve the wettability and slightly change the melting point, it can also lead to the decline of elongation and electrical conductivity of the composite solder.

Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment.

Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.