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Abstract Cervical cancer is a major health concern, particularly in developing countries with limited medical resources. This study introduces two models aimed at improving cervical tumor segmentation: a semi‐automatic model that fine‐tunes the Segment Anything Model (SAM) and a fully automated model designed for efficiency. Evaluations were conducted using a dataset of 8586 magnetic resonance imaging (MRI) slices, where the semi‐automatic model achieved a Dice Similarity Coefficient (DSC) of 0.9097, demonstrating high accuracy. The fully automated model also performed robustly with a DSC of 0.8526, outperforming existing methods. These models offer significant potential to enhance cervical cancer diagnosis and treatment, especially in resource‐limited settings.

A major concern in science education is how to help students form science identity to increase their aspiration for STEM careers. Given the key role of experiences in individual's science identity formation, STEM experiences related to project-based learning (PBL) have received increasing attention in recent years. The purpose of this study was to examine how high school students' science identity has been affected by the multi-dimensional STEM-PBL experiences, i.e., scientific inquiry, technological application, engineering design, and mathematics processing. Employing two independent questionnaires, we quantitatively investigated the correlation between multi-dimensional STEM-PBL experiences and science identity with 400 high school students (grades 7-12) from a range of public schools in China. Results indicated that the level of students' engineering design experiences was the lowest compared to the other three dimensions. Regression analysis revealed that three dimensions of STEM experiences, scientific inquiry, technological application, and mathematics processing, were significant and positive predictors of science identity. Engineering design experiences, however, failed to predict science identity.

The lateral earth pressure at rest is typically considered in situations where lateral wall movements are negligible. Determining the coefficient of lateral earth pressure at rest (referred to as K0) often relies on established classical equations. However, these equations often overlook the influence of the width of the backfill soil on lateral earth pressure. While this omission is generally acceptable when the backfill soil is wide enough, there are instances where a retaining wall supports backfill soils of limited width, such as basement walls between adjacent buildings. Yet, there is limited research addressing the impact of narrow backfill in such scenarios. We aimed to address this gap by investigating variations in K0 values under different conditions, including backfill width and soil properties. Using ABAQUS for numerical simulations, we refined and validated our model using relevant laboratory experimental data. Subsequently, the validated model was applied to various simulation scenarios. For narrow backfill widths (ranging from 0.1 to 0.7 times the retaining wall height), our findings indicated a general decrease in K0 values with decreasing backfill widths, often smaller than those estimated using classical equations. Additionally, along the depth of the wall, K0 values tended to decrease with increasing depth for narrow backfill widths. These findings contribute to our understanding of the impact of narrow backfill on K0.

Steel beams are widely used load-bearing components in bridge construction. They are prone to internal stress concentration under low-frequency vibrations caused by natural disasters and adverse loads, leading to microcracks and fractures, thereby accelerating the instability of steel components. Therefore, dynamic stress monitoring of steel beams under low-frequency vibrations is crucial to ensure structural safety. This study proposed an external stress sensor based on PMN-PT material. The sensor has the advantages of high sensitivity, comprehensive frequency response, and fast response speed. To verify the accuracy and feasibility of the sensor in actual engineering, the LETRY universal testing machine and drop hammer impact system were used to carry out stress monitoring tests and finite element simulations on scaled I-shaped steel beams with PMN-PT sensors attached. The results show that: (1) The PMN-PT sensor has exceptionally high sensitivity, maintained at 1.716~1.726 V/MPa in the frequency range of 0~1000 Hz. The sensor performance is much higher than that of PVDF sensors with the same adhesive layer thickness. (2) Under low-frequency random vibration, the sensor’s time domain and frequency domain output voltages are always consistent with the waveform of the applied load, which can reflect the changes in the structural stress state in real time. (3) Under the impact of a drop hammer, the sensor signal response delay is only 0.001 s, and the sensitivity linear fitting degree is above 0.9. (4) The simulation and experimental results are highly consistent, confirming the superior performance of the PMN-PT sensor, which can be effectively used for stress monitoring of steel structures in low-frequency vibration environments.

Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.

Understanding the land use and land cover (LULC) pattern of the Qinghai Tibet Plateau in China is crucial to support the structural and functional integrity of the ecological barrier of the plateau. This information has significant implications not only for the ecological environment and regional development of the plateau but also for the broader environmental impact at regional and global levels. It is critical to comprehend the spatial pattern and ascertain the underlying causes of land use and land cover in significant areas of the Qinghai Tibet Plateau. This can enable the formulation and implementation of context-specific policies and measures that can contribute to enhancing the ecological security barrier function of the plateau. This study focused on the core area of the Qinghai Tibet Plateau - the Qiangtang Plateau. Based on surface cover data from 2020 and ASTER GDEMV3 data, distribution indices and geographic detectors were used to explore the quantitative impact of land use/cover spatial patterns and terrain factors on land use/cover spatial distribution. The results showed the following: 1) The land use/cover space of the Qiangtang Plateau was dominated by grassland and bare land. Specifically, grassland had the greatest area, accounting for approximately 63.94% of the plateau area and covering an area of 449,983 km2. Grassland was widely distributed in most areas of the plateau. Bare land was the second-largest land cover type, with an area of 186,302 km2, accounting for 26.47% of the plateau area. Bare land was primarily located in the western and northern parts of the plateau. 2) The spatial differentiation of land use/cover in the Qiangtang Plateau was significant. Grasslands were primarily distributed in low mountainous areas characterized by high relief, gentle slopes, and low roughness. In contrast, bare land was mainly distributed in low mountainous areas with high relief, steep slopes, and low roughness. 3) The main drivers of the spatial distribution of land use/cover on the Qiangtang Plateau were elevation, roughness, and relief. Moreover, the interactions between these three terrain factors and other environmental variables significantly influenced the land use/cover pattern in the study area.

ABSTRACT To investigate the combined function of the novel oral mTOR inhibitor, everolimus, with antifungal agents and their potential mechanisms against Exophiala dermatitidis, the CLSI microliquid-based dilution method M38-A2, chequerboard technique, and disk diffusion testing were performed. The efficacy of everolimus was evaluated in combination with itraconazole, voriconazole, posaconazole, and amphotericin B against 16 clinically isolated strains of E. dermatitidis. The synergistic effect was determined by measuring the MIC and fractional inhibitory concentration index. Dihydrorhodamine 123 was used for the quantification of ROS levels. The differences in the expression of antifungal susceptibility-associated genes were analyzed following different types of treatment. Galleria mellonella was used as the in vivo model. While everolimus alone showed minimal antifungal effects, combinations with itraconazole, voriconazole, posaconazole, or amphotericin B resulted in synergy in 13/16 (81.25%), 2/16 (12.5%), 14/16 (87.75%), and 5/16 (31.25%) of isolates, respectively. The disk diffusion assay revealed that the combination of everolimus and antifungal drugs showed no significant increase in the inhibition zones compared with the single agent, but no antagonistic effects were observed. Combination of everolimus and antifungal agents resulted in increased ROS activity (everolimus + posaconazole versus posaconazole [P < 0.05], everolimus + amphotericin B versus amphotericin B [P < 0.002]). Simultaneously, compared to mono-treatment, the combination of everolimus + itraconazole suppressed the expression of MDR2 (P < 0.05) and the combination of everolimus + amphotericin B suppressed the expression of MDR3 (P < 0.05) and CDR1B (P < 0.02). In vivo, combinations of everolimus and antifungal agents improved survival rates, particularly the combination of everolimus + amphotericin B (P < 0.05). In summary, the in vivo and in vitro experiments performed in our study suggest that the combination of everolimus with azoles or amphotericin B can have synergistic effects against E. dermatitidis, potentially due to the induction of ROS activity and inhibition of efflux pumps, providing a promising new approach for the treatment of E. dermatitidis infections. IMPORTANCE Cancer patients with E. dermatitidis infection have high mortality if untreated. Clinically, the conventional treatment of E. dermatitidis is poor due to the long-term use of antifungal drugs. In this study, we have for the first time investigated the interaction and action mechanism of everolimus combined with itraconazole, voriconazole, posaconazole, and amphotericin B on E. dermatitidis in vitro and in vivo, which provided new ideas and direction for further exploring the mechanism of drug combination and clinical treatment of E. dermatitidis.

Pile composite foundations (PCFs) have been commonly applied in reinforcement engineering to adjust the vertical stiffness of foundations, due to the displacement control design criteria for foundations. PCFs that have dissimilar pile lengths, located over inclined bedrock, have shown significantly different vertical behaviors from PCFs with equal pile lengths, placed over a semi-infinite medium. However, the vertical behaviors of dissimilar PCFs over inclined bedrock cannot be predicted with the current theoretical methods, although they have been widely adopted in engineering. An analytical method is proposed in this investigation to analyze the vertical bearing characteristics of dissimilar PCFs over inclined bedrock. A pile–soil system is decomposed into fictitious piles and extended soil, and then a control equation to determine the axial force along the fictitious piles is established, stemming from the compatibility conditions between them. The vertical behaviors of dissimilar PCFs can be obtained by solving the control equation with iterative procedures, and the equation is verified by two field load tests of single piles from the Honghe bridge and a numerical case. Then, the settlement and load transfer behaviors of 3 × 1 dissimilar PCFs and their influence factors are analyzed, and the results are as follows. (1) Obvious differences can be observed concerning the axial force distribution, settlement w, and load-sharing ratio (LSR) of each pile element for different pile–soil stiffness ratios (Ep/Es). (2) The LSR of pile 1 increases from 0.074 to 0.253 for the rigid pile and from 0.062 to 0.161 for the flexible pile condition when the cushion stiffness Kc changes from 1 × 104 kN/m to 3 × 108 kN/m. The non-dimensional vertical stiffness of the foundation, N0/wdEs, increases from 10.21 to 28.95 for the rigid pile condition and increases from 8.69 to 14.44 for the flexible pile condition, when Kc increases from 1 × 104 kN/m to 4 × 105 kN/m. (3) The neutral layer depth of the pile zn, the average settlement w, and the differential settlement wd of each element head decrease with Kc, and no negative friction zone exists (zn = 0 m) for all the pile elements when Kc> 2 × 105 kN/m. (4) The N0/wdEs decreases with the distance between the pile bottom and the inclined bedrock Δ. For the rigid and flexible pile conditions, the N0/wdEs is 22.16 and 13.48 for Δ = 1 m, and 13.13 and 10.10 for Δ = 8 m. The wd reaches 16.7 mm and 4.0 mm for Δ = 1 m and Δ = 8 m, respectively. (5) The N0/wdEs increases almost linearly with an increase in l/d for the rigid pile condition, and it gradually decreases for the flexible pile condition. The developed model can improve the design and analysis of PCFs located over inclined bedrock under vertical loading.

Abstract Saponins are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflammatory, vasoprotective and antimicrobial properties. Pulsatilla chinensis (P. chinensis, Bai Tou Weng, 白頭翁) has been used medically in China for thousands of years for the treatment of diseases caused by bacteria, and it is rich in triterpenoid saponins. In recent decades, anemoside B4 (Pulchinenoside C) is well studied since it has been used as a quality control marker for P. chinensis. At the same time, more and more other active compounds were found in the genus of Pulsatilla. In this review, we summarize the pharmacological activities of Pulsatilla saponins (PS) and discuss the cellular or molecular mechanisms that mediate their multiple activities, such as inducing cancer cell apoptosis, inhibiting tumor angiogenesis, and protecting organs via anti-inflammatory and antioxidant measures. We aim to provide comprehensive analysis and summary of research progress and future prospects in this field to facilitate further study and drug discovery of PS.

Fisetin (Fis), quercetin (Que), and myricetin (Myr) are flavonols with similar structure but different number of hydroxyl groups. The present research focused on the anti-inflammatory effect of these three flavonols in lipopolysaccharide-stimulated RAW264.7 cells. The number and site of hydroxyl group in flavonols obviously affected their anti-inflammation activity. These flavonols suppressed the overproduction of nitric oxide. Fis showed the best activity with an inhibition rate of 52% at 20 μM. Moreover, the flavonols reduced the levels of ROS, TNF-α, and IL-6. The mechanistic study showed that they inhibited the activation of NF-κB and MAPK pathways by suppressing the phosphorylation of IκBα, p65, JNK, ERK, p38, MEK, and reducing the nuclear translocation of NF-κB p65. In addition, the metabolism of the flavonols was examined. The results indicated that Fis was both methylated and glucuronidated. Que and Myr were mainly transformed into methylated products. This study highlights the anti-inflammatory activity of flavonols, particularly Fis, which has the potential for the prevention or treatment of inflammation as an adjuvant medicine or food additive.

Multiple cellular activities, including protein and lipid synthesis, ribosome biogenesis, and metabolic processes, are regulated by the target of rapamycin (TOR) pathway. Recent research suggests that the TOR might play an important role in various physiological functions of pathogenic fungi, such as nutrient sensing, stress response, and cell cycle progression. Given their robust immunosuppressant and antitumor activities, TOR inhibitors are widely used in clinical settings. In the present study, a microdilution checkerboard-based approach was employed to assess the interactions between the oral mammalian target of rapamycin (mTOR) inhibitor everolimus (EVL) and antifungal agents in the treatment of Aspergillus species derived from 35 clinical isolates in vitro. The results revealed that EVL exhibited promising inhibitory synergy with itraconazole (ITC), posaconazole (POS), and amphotericin B (AMB) for 85.7%, 74.2%, and 71.4%, respectively. In contrast, EVL exhibited minimal synergistic inhibitory activity (14.3%) when applied in combination with voriconazole (VRC). Antagonistic interactions were not observed. In vivo experiments conducted in Galleria mellonella revealed that EVL in combination with antifungal agents improved the larva survival rates in the ITC, VRC, POS, and AMB groups by 18.3%, 13.3%, 26.7%, and 13.3%, respectively. These data suggest that the combination treatment with antifungal agents and antifungal agents holds promise as a means of alleviating clinical aspergillosis.

Invasive candidiasis is the primary reason for the increased cases of mortality in a medical environment. The resistance spectra of Candida species to antifungal drugs have gradually expanded. Particularly, the resistance spectra of Candida auris are the most prominent. Hsp90 plays a protective role in the stress response of fungi and facilitates their virulence. In contrast, Hsp90 inhibitors can improve the resistance of fungi to antifungal drugs by regulating the heat resistance of Hsp90, which destroys the integrity of the fungal cell walls. Hsp90 inhibitors thus offer a great potential to reduce or address fungal drug resistance. The drugs tested for the resistance include itraconazole, voriconazole, posaconazole, fluconazole, and 17-AAG. A total of 20 clinical strains of Candida were investigated. The broth microdilution checkerboard technique, as adapted from the CLSI M27-A4 method, was applied in this study. We found that 17-AAG alone exerted limited antifungal activity against all tested strains. The MIC range of 17-AAG was 8 to >32 μg/ml. A synergy was observed among 17-AAG and itraconazole, voriconazole, and posaconazole against 10 (50%), 7 (35%), and 13 (65%) of all isolates, respectively. Moreover, the synergy between 17-AAG and fluconazole was observed against 5 (50%) strains of azole-resistant Candida. However, no antagonism was recorded overall. Our result adequately verifies the influence of 17-AAG on the formation of Candida spp. biofilm. Moreover, we determined that with the use of rhodamine 6G to detect drug efflux and that of dihydrorhodamine-123 to detect intracellular reactive oxygen species (ROS), treatment with 17-AAG combined with azole drugs could inhibit the efflux pump of fungi and promote the accumulation of ROS in the fungal cells, thereby inducing fungal cell apoptosis. Thus, the mechanism of 17-AAG combined with azoles can kill fungi. Our results thus provide a new idea to further explore drugs against drug-resistant Candida spp.

Scedosporium and Lomentospora infections in humans are generally chronic and stubborn. The use of azoles alone cannot usually inhibit the growth of these fungi. To further explore the combined effect of multiple drugs and potential mechanisms of action, we tested the antifungal effects of tacrolimus (FK506) and everolimus in combination with azoles in vitro and in vivo on 15 clinical strains of Scedosporium/Lomentospora species and detected the level of Rhodamine 6G, ROS activity, and apoptosis. The in vitro results showed that the combinations of tacrolimus with itraconazole, voriconazole, and posaconazole showed synergistic effects on 9 strains (60%), 10 strains (73%), and 7 strains (47%), respectively, and the combinations of everolimus with itraconazole, voriconazole, and posaconazole showed synergistic effects on 8 strains (53%), 8 strains (53%), and 7 strains (47%), respectively. The synergistic effects might correspond to the elevated ROS activity (the tacrolimus + itraconazole group compared to the itraconazole group, (P < 0.05)), early apoptosis (itraconazole (P < 0.05) and voriconazole (P < 0.05) combined with everolimus), and late apoptosis (the tacrolimus + itraconazole group compared to the itraconazole group, (P < 0.01); the tacrolimus + posaconazole group compared to the posaconazole group, (P < 0.05)), but not inhibition of efflux pump activity. Our in vitro results suggested that a combination of tacrolimus or everolimus and azoles have a synergistic effect against Scedosporium/Lomentospora. The synergistic mechanisms of action might be triggering excessive ROS activity and apoptosis. In vivo, the survival rate of G. mellonella (sixth instar larvae) was significantly improved by tacrolimus alone, everolimus alone, azoles alone, and tacrolimus and everolimus combined with azoles separately (P < 0.05 for the tacrolimus group; P < 0.01 for the everolimus group and the itraconazole group; P = 0.0001 for the tacrolimus and posaconazole group; P < 0.0001 for other groups except the everolimus and itraconazole group, everolimus and posaconazole group, and tacrolimus and itraconazole group). From the results, we infer that the combination of tacrolimus or everolimus with azoles has obvious synergistic effect on Scedosporium/Lomentospora, and might enhance the level of apoptosis and necrosis. However, the synergistic effects were not related to the efflux pump. In conclusion, from our in vitro and in vivo study, tacrolimus and everolimus combined with azoles may have a synergistic effect in the treatment against Scedosporium/Lomentospora, improving the drug activity of azoles and promoting a better prognosis for patients.

Paleoclimatic researches have revealed that the East Asian summer monsoon (EASM) strengthened and precipitation increased in north China during the early to middle Holocene. The lacustrine landform and sediment recorded approximately simultaneous Holocene high lake levels. However, relatively few studies have been reported involving the quantitative reconstruction of precipitation and lake areas in the Mu Us Desert (MUD), northwest edge area of the modern EASM. Based on the lacustrine landform, and by using the lake hydrologic model, this study quantitatively reconstructed precipitation and lake areas during the early to middle Holocene in the MUD. The results revealed the following: 1) A total of 127 paleolakes existed in the closed drainage area during the early to middle Holocene. The area of paleolakes was 896.1 km2, which is 2.96 times that of modern lakes. The relative height between the highstand and the modern lake surface is ∼5–9 m. 2) Precipitation during the early to middle Holocene decreased from 550 mm in the southeast to 350 mm in the northwest. The 400 mm isohyet moved 130–170 km to the northwest, roughly coincident with the modern 250 mm isohyet. 3) The relative increase in precipitation was ∼32–60%, and the increase in the west was significantly higher than in the east. The precipitation gradient in much of the MUD was lower than the present. The results show that the monsoon edge area and monsoon rain belt migrated to the northwest during the early to middle Holocene. The MUD was stably dominated by the EASM. Data also showed that the spatio-temporal pattern of the climate during the early to middle Holocene was relatively humid with a decreased precipitation gradient for millennia.

Abstract Background Glycine tabacina (Labill.) Benth, one of the traditional Chinese herbal medicines, has been used for treatment of nephritis, osteoporosis, rheumatism, and menopausal syndrome. The aim of this study was to illuminate the therapeutic effect and mechanism of Glycine tabacina aqueous extract (GATE) in the treatment of nephrotic syndrome (NS). Methods UHPLC-DAD-MS/MS was used to analyze the chemical profile of GATE. Adriamycin (ADR)-induced NS mouse model and network pharmacology methods were conducted to explore the protective effect and mechanism of GATE on NS treatment. Results GATE administration significantly ameliorated symptoms of proteinuria and hyperlipidemia in NS mice, as evidenced by reduced excretion of urine protein and albumin, and decreased plasma levels of total cholesterol and triglyceride. Decreased blood urea nitrogen (BUN) and creatinine levels in NS mice suggested that GATE could prevent renal function decline caused by ADR. GATE treatment also inhibited ADR-induced pathological lesions of renal tissues as indicated by periodic acid Schiff staining. Six flavonoids of GATE were identified by using UHPLC-DAD-MS/MS. Network pharmacology analysis indicated that the protection of GATE in treating NS might be associated with the regulation of oxidative stress and inflammation. In addition, the in vivo experiment validated that treatment with GATE markedly decreased reactive oxygen species production, malonaldehyde level, and increased superoxide dismutase activity both in plasma and renal tissues. TNF-α level in plasma and protein expression in kidney were significantly decreased in GATE treatment groups. Conclusions Combination of network pharmacology analysis and experimental verification revealed that GATE exerts anti-NS effect possibly through modulating oxidative stress and inflammation, suggesting the potential application of GATE or its derivatives in the prevention and treatment of NS and other related kidney diseases.

ABSTRACT In the present study, in vitro and in vivo interactions of TOR inhibitor AZD8055 and azoles, including itraconazole, voriconazole, posaconazole and fluconazole, against a variety of pathogenic fungi were investigated. A total of 69 isolates were studied via broth microdilution checkerboard technique, including 23 isolates of Aspergillus spp., 20 isolates of Candida spp., 9 isolates of Cryptococcus neoformans complex, and 17 isolates of Exophiala dermatitidis. The results revealed that AZD8055 individually did not exert any significant antifungal activity. However, synergistic effects between AZD8055 and itraconazole, voriconazole or posaconazole were observed in 23 (33%), 13 (19%) and 57 (83%) isolates, respectively, including azole-resistant A. fumigatus strains and Candida spp., potentiating the efficacy of azoles. The combination effect of AZD8055 and fluconazole was investigated against non-auris Candida spp. and C. neoformans complex. Synergism between AZD8055 and fluconazole was observed in six strains (60%) of Candida spp., resulting in reversion of fluconazole resistance. Synergistic combinations resulted in 4-fold to 256-fold reduction of effective MICs of AZD8055 and azoles. No antagonism was observed. In vivo effects of AZD8055-azole combinations were evaluated by survival assay in Galleria mellonella model infected with A. fumigatus strain AF002, E. dermatitidis strain BMU00038, C. auris strain 383, C. albicans strain R15, and C. neoformans complex strain Z2. AZD8055 acted synergistically with azoles and significantly increased larvae survival (P < 0.05). In summary, the results suggested that AZD8055 combined with azoles may help to enhance the antifungal susceptibilities of azoles against pathogenic fungi and had the potential to overcome azole resistance issues. IMPORTANCE Limited options of antifungals and the emergence of drug resistance in fungal pathogens has been a multifaceted clinical challenge. Combination therapy represents a valuable alternative to antifungal monotherapy. The target of rapamycin (TOR), a conserved serine/threonine kinase from yeast to humans, participates in a signaling pathway that governs cell growth and proliferation in response to nutrient availability, growth factors, and environmental stimuli. AZD8055 is an orally bioavailable, potent, and selective TOR kinase inhibitor that binds to the ATP binding cleft of TOR kinase and inhibits both TORC1 and TORC2. Synergism between AZD8055 and azoles suggested that the concomitant application of AZD8055 and azoles may help to enhance azole therapeutic efficacy and impede azole resistance. TOR inhibitor with fungal specific target is promising to be served as combination regimen with azoles.

Visual representation in school textbooks plays an important role for physics teaching and learning. The integration of graphics with text has drawn attention of physics educators in recent years due to the close relationship between graphics and relevant text. The purpose of this study is to examine visual representation of optical content in three physics textbooks commonly used in China and Singapore. Based on a revised version of graphical analysis protocol, this study focuses on two aspects of visual representation: (i) presentation of graphics, and (ii) integration of graphics with corresponding text. The content analysis approach was adopted as the research methodology with 115 graphics taken from the three physics textbooks being the analysis target. The results show that the three textbooks had considerable differences in terms of graphical presentations and that they contained a small percentage of high systematical representations. On integration of graphics with text, each textbook was found to be unique. Based on the results of this study, some recommendations are provided for visual representation in physics textbooks so as to enhance the effectiveness of textbooks on teaching and learning, such as highlighting physical and semantic integration of text with graphics.

Candida species are the most common fungal pathogens to infect humans, and can cause life-threatening illnesses in individuals with compromised immune systems. Fluconazole (FLU) is the most frequently administered antifungal drug, but its therapeutic efficacy has been limited by the emergence of drug-resistant strains. When co-administered with minocycline (MIN), FLU can synergistically treat clinical Candida albicans isolates in vitro and in vivo. However, there have been few reports regarding the synergistic efficacy of MIN and azoles when used to treat FLU-resistant Candida species, including Candida auris. Herein, we conducted a microdilution assay wherein we found that MIN and posaconazole (POS) showed the best in vitro synergy effect, functioning against 94% (29/31) of tested strains, whereas combinations of MIN+itraconazole (ITC), MIN+voriconazole (VOR), and MIN+VOR exhibited synergistic activity against 84 (26/31), 65 (20/31), and 45% (14/31) of tested strains, respectively. No antagonistic activity was observed for any of these combinations. In vivo experiments were conducted in Galleria mellonella, revealing that combination treatment with MIN and azoles improved survival rates of larvae infected with FLU-resistant Candida. Together, these results highlight MIN as a promising synergistic compound that can be used to improve the efficacy of azoles in the treatment of FLU-resistant Candida infections.

Berberine (BBR), a major active component of Rhizoma coptidis , is one of the most promising agents for breast cancer adjuvant therapy. It is well accepted that BBR could exhibit remarkable anticancer efficacy with few side effects, and when treated with chemotherapeutic agents in combination, BBR could enhance the chemosensitivity of cancer cells. Our previous study reported that low-dose BBR (LDB) induced hormetic effect and attenuated the anticancer activity of chemotherapeutic agents. However, the underlying mechanisms are still unclear. In this study, we confirmed that LDB could promote cancer cell proliferation and antagonize the anti-breast cancer activities of chemotherapeutic agents. And the mechanisms were proved to be induction of autophagy and antioxidation by LDB. Our results showed that LDB could mildly induce reactive oxygen species, raise the level of autophagy by promoting the phosphorylation of adenosine monophosphate-activated protein kinase, and promote antioxidant enzymes expression through activating nuclear factor erythroid 2-related factor 2 in breast cancer cells. These findings revealed a potential negative impact of BBR on its adjuvant anti-breast cancer therapy, providing guidance for a safe and effective use of naturally originated medicines in the clinic.

In this study, we examined the anti-Helicobactor pylori effects of the main protoberberine-type alkaloids in Rhizoma Coptidis. Coptisine exerted varying antibacterial and bactericidal effects against three standard H. pylori strains and eleven clinical isolates, including four drug-resistant strains, with minimum inhibitory concentrations ranging from 25 to 50 μg/mL and minimal bactericidal concentrations ranging from 37.5 to 125 μg/mL. Coptisine’s anti-H. pylori effects derived from specific inhibition of urease in vivo. In vitro, coptisine inactivated urease in a concentration-dependent manner through slow-binding inhibition and involved binding to the urease active site sulfhydryl group. Coptisine inhibition of H. pylori urease (HPU) was mixed type, while inhibition of jack bean urease was non-competitive. Importantly, coptisine also inhibited HPU by binding to its nickel metallocentre. Besides, coptisine interfered with urease maturation by inhibiting activity of prototypical urease accessory protein UreG and formation of UreG dimers and by promoting dissociation of nickel from UreG dimers. These findings demonstrate that coptisine inhibits urease activity by targeting its active site and inhibiting its maturation, thereby effectively inhibiting H. pylori. Coptisine may thus be an effective anti-H. pylori agent.

Brusatol (BR) is one of the main bioactive components derived from Brucea javanica, a medicinal herb historically used in the treatment of dysenteric disorders (also known as ulcerative colitis(UC)). Due to its poor aqueous solubility, a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) nanoformulation with smaller size, higher negative zeta potential and drug content, and excellent stability was developed. The appearance of BR-SMEDDS remained clear and transparent, and transmission electron microscopy showed microemulsion droplets to be spherical with homogeneous distribution. Pharmacokinetic parameters indicated that oral bioavailability was greatly improved by BR-SMEDDS as compared with aqueous suspension. Meanwhile, the anti-colitis activity of BR-SMEDDS was evaluated on dextran sodium sulfate (DSS)-induced colitis mice model. The result illustrated that the nano-formation significantly reduced the body weight loss, recovered colon length, decreased disease activity index and microscopic score, regulated immune-inflammatory cytokines, diminished oxidative stress and repressed the colonic expression of myeloid differentiation factor 88 (MyD88), toll-like receptor 4 (TLR4) and nuclear factor kappa B p65 (NF-κB p65) proteins. Our findings demonstrated for the first time that BR could effectively attenuate colonic inflammation in mice, at least partially, via favorable regulation of anti-oxidative and anti-inflammatory status and inhibition of the TLR4-linked NF-κB signaling pathway. The BR nano-formulation was superior to BR suspension and sulphasalazine, in treating experimental UC, and exhibited similar effect with azathioprine, with much smaller dosage. The enhanced anti-UC effect of BR might be intimately associated with the improved pharmacokinetic property by SMEDDS. The developed nano-delivery system might thus be a promising candidate for colitis treatment.

PURPOSE: To investigate the effect of renal denervation (RDN) on the blood pressure, left ventricular hypertrophy and myocardial expression of TLR4/NF-κB in spontaneously hypertensive rats (SHR). METHODS: A total of 36 SHR were randomly assigned into control group (D0), RDN group (D) and sham group (S). 12 WKY rats of same age served as controls (WKY group). Rats in the D0 and WKY groups were sacrificed, but rats in the D and S group were sacrificed at one week and six weeks after surgery. The heart was collected and the left ventricle weighted followed by calculation of left ventricular mass index (LVMI). RESULTS: In the D0 group, the blood pressure, LVMI and protein expression of TLR4, NF-κB, TNF-α and IL-6 in the myocardium were markedly higher than that in the WKY group (pOBJETIVO: Investigar o efeito da denervação renal na pressão sanguínea, na hipertrofia do ventrículo esquerdo e a expressão miocárdica de TLR4/NF-kB em ratos espontaneamente hipertensos. MÉTODOS: Trinta e seis SHR ratos foram aleatoriamente distribuídos em grupo controle, grupo denervação renal (D) e grupo sham(S). 12 WKY ratos de mesma idade serviram de controle. Os ratos controles foram sacrificados, mas os ratos com denervação renal e sham foram sacrificados uma semana e seis semanas após a cirurgia. O coração foi retirado e o ventrículo esquerdo pesado seguido pelo cálculo da massa ventricular (LVMI). RESULTADOS: No grupo DO, a pressão sanguínea, LVMI e a expressão proteica de TLR4, NF-κB, TNF-α e IL-6, no miocárdio foram marcadamente maiores do que o grupo WKY (p