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Abstract Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide.

Abstract Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients are at a high risk of developing metastases in the brain. However, research focusing on treatment strategies for hormonal receptor positive (HR+), HER2+ BC patients with brain metastases (BM) remains limited. Thus, a multi-center, prospective trial was conducted in China. Women over the age of 18 who were naive to whole brain radiotherapy and had estrogen receptor (ER)/progesterone-receptor (PgR) positive, HER2+ BM were treated with palbociclib, fulvestrant, trastuzumab and pyrotinib, until disease progression or the development of intolerable side effects. The primary endpoint was objective response rate (ORR) in the central nervous system (CNS). This ongoing study is still recruiting participants and is registered with ClinicalTrials.gov (NCT04334330). This report presents the findings from an interim analysis. From December 4, 2020, to November 2, 2022, 15 patients were enrolled. Among the 14 patients who were evaluable for clinical response, the ORR was 35.7% (95% CI: 12.8–64.9%), with a CNS–ORR of 28.6% (95% CI: 8.4–58.1%). The median follow-up period was 6.3 months (range, 2.1–14.3 months), during which the median progression-free survival (PFS) was 10.6 months (95% CI: 4.3–16.9 months), and the median time to CNS progression was 8.5 months (95% CI: 5.9–11.1 months). The most common adverse event was diarrhea (93%), with 33% having grade 3 and 6.7% having grade 4. The study suggests that the combination of palbociclib, trastuzumab, pyrotinib and fulvestrant offers a promising chemo-free treatment strategy for HR+, HER2+ BC patients with BM.

ObjectiveThe purpose of this study was to explore the potential mechanism of Helicobacter pylori (Hp) eradication by probiotic therapy through 16S rRNA gene sequencing technology and untargeted metabolomics.MethodsTwenty four Hp-infected children were recruited from the Shanxi Bethune Hospital, and 24 healthy children were recruited as a blank control group. Group A: fecal samples from 24 healthy children. Group B: fecal samples of 24 children with Hp infection. Group B1 (n = 15): fecal samples of group B treated with probiotic therapy for 2 weeks. Group B2 (n = 19): fecal samples of group B treated with probiotic therapy for 4 weeks. The above fecal samples were analyzed by 16S rRNA gene sequencing technology and untargeted metabolomics.ResultsThere was no significant difference in alpha diversity and beta diversity among the four groups, but many bacteria with statistical difference were found in each group at the bacterial genus level and phylum level. LEfSe results showed that in group B, Porphyromonadaceae, Shigella and other microorganisms related to intestinal microecological dysbiosis were enriched. And in group B2, abundant characteristic microorganisms were found, namely Bacillales and Prevotella. KEGG metabolic pathway enrichment analysis showed that groups B1 and B2 were involved in 10 metabolic pathways potentially related to probiotic treatment: purine metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, glyoxylic acid and dicarboxylic acid metabolism, unsaturated fatty acid biosynthesis, fatty acid extension, fatty acid degradation, pyrimidine metabolism, fatty acid biosynthesis.ConclusionProbiotic therapy can inhibit Hp to some extent and can relieve gastrointestinal symptoms, making it a preferred therapy for children with Hp infection and functional abdominal pain. Hp infection can reduce the diversity of intestinal microbes, resulting in the disturbance of intestinal microbiota and changes in the relative abundance of microbiota in children, while probiotic therapy can restore the diversity of intestinal microbes and intestinal microecological balance.

Abstract Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.

Abstract Zinc bromine flow batteries (ZBFBs) are well suited for stationary energy storage due to their attractive features of high energy density and low cost. Nevertheless, the ZBFBs suffer from low power density and limited efficiency owing to the relatively severe polarization of the Br2/Br− redox couple. Herein, a three‐dimensional (3D) hierarchical composite electrode based on core‐shell Ni/NiO heterostructures anchored on graphite felt (Ni/NiO@GF) is designed to promote the kinetics of the Br2/Br− couple, so as to improve the power density and efficiency of the ZBFB. In this design, the highly conductive carbon felt and Ni cores provide a composite electrode with a 3D electron transporting framework to guarantee excellent electronic conductivity, while the NiO shells possess great absorption ability to Br2 and brilliant catalytic activity for the Br2/Br− redox reaction to reduce the electrochemical polarization. As a result, an enhanced ZBFB with Ni/NiO@GF electrode shows an outstanding energy efficiency of 86% at 20 mA cm−2 and can be operated at a current density of up to 160 mA cm−2 with a respectable energy efficiency of 67%. These results exhibit a promising strategy to fabricate catalytic electrodes for high‐performance ZBFBs.

Purpose: Pure mucinous breast cancer (PMC) is a rare histological type with a favourable prognosis. However, cases with recurrence have been reported and diagnosed in clinical practice. The mechanisms underlying PMC recurrence remain unknown. In this study, we aimed to identify the prognostic factors associated with PMC. Materials and methods: A total of 166 patients diagnosed with PMC were included. We compared the clinicopathological characteristics between patients with and without recurrence. The 21-gene assay was performed in 10 patients with recurrence and 20 TNM stage-matched patients without recurrence. Whole-exon sequencing was performed in 12 PMC primary tumours and four positive lymph nodes (LNs). Results: Tumour size, lymph node status and TNM staging differed significantly between recurrent group and non-recurrent group. And the 21-gene recurrence scores did not differ significantly between recurrent group and its TNM stage-matched non-recurrent group. The most frequently mutated genes in the primary tumours of regional LN-positive PMCs were ADCY10 (3/6) and SHANK3 (3/6), and they more recurrently harboured gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2. And these alterations were not detected in primary tumours of regional LN-negative PMCs. Conclusion: TNM stage is an important prognostic factor in PMC. Although we revealed that regional LN-positive PMCs show increased occurrence of duplication variants at 15q23, 17q23.2 and 20p11.21, and deletion variants at 21p11.2. Further investigation, including multi-omics studies, are needed and may provide additional insights into the nature of PMC.

This study addresses challenges related to imprecise edge segmentation and low center point accuracy, particularly when mushrooms are heavily occluded or deformed within dense clusters. A high-precision mushroom contour segmentation algorithm is proposed that builds upon the improved SOLOv2, along with a contour reconstruction method using instance segmentation masks. The enhanced segmentation algorithm, PR-SOLOv2, incorporates the PointRend module during the up-sampling stage, introducing fine features and enhancing segmentation details. This addresses the difficulty of accurately segmenting densely overlapping mushrooms. Furthermore, a contour reconstruction method based on the PR-SOLOv2 instance segmentation mask is presented. This approach accurately segments mushrooms, extracts individual mushroom masks and their contour data, and classifies reconstruction contours based on average curvature and length. Regular contours are fitted using least-squares ellipses, while irregular ones are reconstructed by extracting the longest sub-contour from the original irregular contour based on its corners. Experimental results demonstrate strong generalization and superior performance in contour segmentation and reconstruction, particularly for densely clustered mushrooms in complex environments. The proposed approach achieves a 93.04% segmentation accuracy and a 98.13% successful segmentation rate, surpassing Mask RCNN and YOLACT by approximately 10%. The center point positioning accuracy of mushrooms is 0.3%. This method better meets the high positioning requirements for efficient and non-destructive picking of densely clustered mushrooms.

To return vegetable remnants to soil in situ and understand parameters that determine their decomposition efficiency, the tomato remnant length, soil moisture, soil temperature and dosage of a microbial decomposer (MD) have been evaluated through a laboratory experiment using a nylon mesh bag in this study. The results showed that the residual remnant weight, and total carbon content increased 28.49 % and 32.65 %, respectively with two different remnant lengths (∼0.5 cm and ∼2.5 cm), while the decay rate and organic carbon breakdown rate decreased by 6.14 % and 7.48 %, respectively. When the relative water content in soil increased, the residual remnant weight and total carbon content first decreased and then increased, while the trend of the decay rate (16.94 % with 80 % soil water content) and organic carbon breakdown rate (9.96 % with 60 % soil water content) were opposite. At a high MD dosage (7 % or 9 % of the total compost weight), both rates of remnants were greater than those at the low dosage (1 %), with an increase of 38.63 % or 36.19 % and 15.89 % or 15.78 %, respectively. With an increase in soil temperature, both residual remnant weight and total carbon content decreased first and then increased, while both decomposition rate and organic carbon breakdown rate increased first and then decreased by 27.35 % and 22.78 %, respectively at 45 °C, compared with those at 30 °C. It was concluded that the decomposition rate was significantly correlated with the remnant length and the MD dosage, while the organic carbon breakdown rate was significantly associated with all four parameters evaluated. The optimal decomposing efficiency was achieved through cutting tomato remnants to a length of ∼0.5 cm, maintaining soil relative moisture content at 89 %, keeping soil temperature at 50 °C, and adding 7 % microbial decomposer MD to chopped tomato cuttings.

ObjectiveThe primary objective of this study is to investigate the mechanism by which Bacillus coagulans TBC169 accelerates intestinal function recovery in patients who have undergone gynecological laparoscopic surgery, using metabolomics and gut microbiota analysis.MethodsA total of 20 subjects were selected and randomly divided into two groups: the intervention group (n = 10) receiving Bacillus coagulans TBC169 Tablets (6 pills, 1.05 × 108 CFU), and the control group (n = 10) receiving placebos (6 pills). After the initial postoperative defecation, fecal samples were collected from each subject to analyze their gut microbiota and metabolic profiles by high-throughput 16S rRNA gene sequencing analysis and untargeted metabonomic.ResultsThere were no statistically significant differences observed in the α-diversity and β-diversity between the two groups; however, in the intervention group, there was a significant reduction in the relative abundance of unclassified_Enterobacteriaceae at the genus level. Furthermore, the control group showed increased levels of Holdemanella and Enterobacter, whereas the intervention group exhibited elevated levels of Intestinimonas. And administration of Bacillus coagulans TBC169 led to variations in 2 metabolic pathways: D-glutamine and D-glutamate metabolism, and arginine biosynthesis.ConclusionThis study demonstrated that consuming Bacillus coagulans TBC169 after gynecological laparoscopic surgery might inhibit the proliferation of harmful Enterobacteriaceae; mainly influence 2 pathways including D-glutamine and D-glutamate metabolism, and arginine biosynthesis; and regulate metabolites related to immunity and intestinal motility; which can help regulate immune function, maintain intestinal balance, promote intestinal peristalsis, and thus accelerate the recovery of intestinal function.

Granule size distribution of wheat starch is an important characteristic that could affect the functionality of wheat (Triticum aestivum L.) products. Lodging is a major limiting factor for wheat production. Few studies have been conducted to clarify how lodging influences the granule size distribution and viscosity parameters of starch in wheat grains. Two growing seasons, two high-yield winter wheat cultivars, and five artificial lodging treatments were imposed. The results indicated that lodging significantly reduced the content of starch and increased that of protein. Additionally, lodging caused a marked drop in both starch and protein yields. The relative loss of grain yield, starch yield, harvest index, and protein yield all differed remarkably among lodging treatments with a ranking of L2 > L1 > L4 > L3. Lodging also led to a reduction in the proportion (both by volume and by surface area) of B-type granules and a corresponding increase in that of A-type granules, and the more serious the lodging degree, the greater effect on the changes in these proportions. The smaller starch granules predominated in number, even though their collective contribution to the overall volume is was relatively minor. Meanwhile, it was found that the peak viscosity, hold viscosity, final viscosity, breakdown viscosity, and rebound value of wheat starch were significantly decreased by lodging. Correlation analysis showed that the peak and final viscosities were negatively correlated with volume percentages of A-type starch granules, but were positively correlated with B-type granules. This indicates that B-type granules have higher peak and final viscosities compared with A-type granules in wheat kernels. Lodging can reduce the proportion of B-type starch granules, and thus reduce the peak and the final viscosity in wheat grain.

ObjectiveThe purpose of this study was to compare the clinical characteristics and outcomes of children with cryptorchidism testicular torsion between the younger age group and the older age group.MethodsWe collected the clinical data of children with cryptorchidism complicated with testicular torsion in our hospital from January 1, 2013 to January 1, 2023. The patients were divided into two groups: the younger age group (1month∼4 years old, n = 7) and the older age group (4∼18 years old, n = 7). The differences of clinical manifestations and surgical results between the two groups were compared.ResultsA total of 14 patients with unilateral cryptorchidism testicular torsion were included in this study, including 9 on the left side and 5 on the right side. The main clinical manifestations were pain /swelling of groin. The rate of crying in the younger age group was significantly higher than those in the older age group [(5,71.4%) vs. (0,0.0%), P 0.05]. The ipsilateral testicular salvage rate in the younger age group was 14.3% (1/7), which was lower than the older age group 57.1% [(4/7), P > 0.05]. The degree of testicular torsion in younger age group was more severe than the older age group [720(360, 1,080)° vs. 360(270, 360)°, P > 0.05].ConclusionsThe overall salvage rate of cryptorchidism testicular torsion is low. Although the duration of symptoms in the older age group was longer, the salvage rate of the older age group seemed to be higher than that in the younger age group. In addition, physical and imaging examination of the reproductive system should be carried out in time to identify the children with cryptorchidism testicular torsion in the early stage.

Background and objective: Osteosarcoma is a common primary malignant tumor of bone, and doxorubicin is one of the most widely used therapeutic drugs. While the problem of doxorubicin resistance limits the long-term treatment benefits in osteosarcoma patients. The role of miRNAs and their target genes in osteosarcoma have become increasingly prominent. Currently, there is no report on miR-506-3p reversing doxorubicin resistance by targeting STAT3 in osteosarcoma. The purpose of this study was to investigate the molecular mechanism that overexpression of miR-506-3p reverses doxorubicin resistance in drug-resistant osteosarcoma cells.Methods: Doxorubicin-resistant osteosarcoma cells (U-2OS/Dox) were constructed by intermittent stepwise increasing stoichiometry. The target genes of miR-506-3p were predicted by bioinformatics approach and the targeting relationship between miR-506-3p and STAT3 was detected using dual luciferase reporter assay. U-2OS/Dox cells were treated with miR-506-3p overexpression and STAT3 silencing respectively. Then Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of JAK2/STAT3 signaling pathway, drug-resistant and apoptotic associated molecules. The migration and invasion were assessed by cell scratch assay and transwell assay. The cell proliferative viability and apoptosis were investigated by CCK8 assay and flow cytometry assay.Results: U-2OS/Dox cells were successfully constructed with a 14.4-fold resistance. MiR-506-3p is directly bound to the 3′-UTR of STAT3 mRNA. Compared with U-2OS cells, the mRNA expression of miR-506-3p was reduced in U-2OS/Dox cells. Overexpression of miR-506-3p decreased the mRNA expression levels of JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and decreased the protein expression levels of p-JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and conversely increased Bax expression. It also inhibited the proliferation, migration and invasion of U-2OS/Dox cells and promoted cells apoptosis. The results of STAT3 silencing experiments in the above indicators were consistent with that of miR-506-3p overexpression.Conclusion: Overexpression of miR-506-3p could inhibit the JAK2/STAT3 pathway and the malignant biological behaviors, then further reverse doxorubicin resistance in drug-resistant osteosarcoma cells. The study reported a new molecular mechanism for reversing the resistance of osteosarcoma to doxorubicin chemotherapy and provided theoretical support for solving the clinical problems of doxorubicin resistance in osteosarcoma.

In the artistic sports program, the referee' scores directly determine the final results of the athletes. Wushu is a artistic sport that has a Chinese characteristic and has the potential to become an official competition at the Summer Olympic. In this study we tested whether a red uniform color affects Wushu Routine practitioners' ratings of athletes' position or movement of Wushu Routine. We also tested whether the effect varied depending on the gender of the athlete and the practitioner, and depending on whether female practitioners were in the ovulation phase of their menstrual cycle. Male (Experiment 1: N = 72) and female (Experiment 1: N = 72; Experiment 2: N = 52) participants who major in Wushu Routine were recruited to take a referee's perspective and rate the movement quality of male and female athletes wearing red or blue uniforms. The results of Experiment 1 showed that both male and female athletes wearing red uniform (compared to blue uniform) received higher ratings (p = .002, η2 = .066; p = .014, η2 = .043), and the red effect was especially strong when male practitioners rated female athletes (p = .002, η2 = .069). The results of Experiment 2, in an all-female sample, showed that in most cases there was no difference in ratings made by women in the ovulation and non-ovulation phases of their menstrual cycle, with the exception of their ratings of male athletes wearing red; in this condition, women gave higher ratings when they were in the ovulation phase of their cycle (p = .026). The results suggest that there is a red effect in an artistic sport like Wushu Routine, in which gender and the female menstrual cycle play an important role.

ObjectiveTo investigate the prevalence and impact factors of depressive symptoms among grass-roots civil servants in Jiaxing city for providing evidence to conduct psychological intervention in the staff. MethodsUsing convenient sampling, an online self-administered survey was carried out among 5 780 civil servants (aged 18 – 60 years) working in government departments at district/county level and below in Jiaxing city, Zhejiang province during November – December 2021, with a self-designed questionnaire and Self-Rating Depression Scale (SDS). Multivariate logistic regression model was adopted in analyses on influencing factors of depressive symptoms among the grass-roots staff. ResultsAmong the 5 295 valid participants (91.6% of the civil servants surveyed), 1 330 (25.12%) were assessed as having depressive symptoms and the proportions of the participants having mild, moderate, and severe depression symptoms were 17.79%, 6.04%, and 1.28%, respectively. The detection rate of depressive symptoms differed significantly by gender, administrative rank of working entity, age, educational background and annual income (P < 0.05 for all). Binary multivariate logistic regression analysis showed that the middle-aged participants (31 – 40 years) had a higher risk of depressive symptoms (odds ratio [OR] = 1.303, 95% confidence interval [95%CI]:1.077 – 1.577) but the elder participants (51 – 60 years) had a lower risk (OR = 0.592, 95%CI: 0.451 – 0.777) compared to the young participants aged 18 – 30 years and that female participants had a lower risk of depressive symptoms (OR = 0.702, 95%CI: 0.609 – 0.809) in contrast to male participants. ConclusionDepressive symptoms are prevalent among grass-roots civil servants, especially among the male and middle-aged civil servants, in Jiaxing city.

The total cyanide and arsenic in a cyanide residue of a gold mine exceed the standard requirements. The process of hydrogen peroxide oxidation decomposition cyanide and ferrous sulfate complexation fixation arsenic is studied. The results showed that in the cyanogen removal section, the amount of hydrogen peroxide added was 2 ml/L, the reaction time was 2 h, in the arsenic fixation section, the amount of ferrous sulfate added was 0.5 g/L, the amount of hydrogen peroxide added was 1 ml/L, the amount of sulfuric acid added was 6.5 ml/L, and the reaction time was 1 h. After the treatment of cyanide removal and arsenic fixation, the total cyanide concentration and arsenic concentration in the toxic leaching solution of the cyanogen residue are 0.25 mg/L and 0.55 mg/L, which meets the standard requirements and can be stored in the tailings pond.

Despite various known topological polar structures, the dynamic property of isolated ones is still poorly understood. Here, the authors show the controlled nucleation and ability to move of isolated three-fold vertices under an applied electric field.

Background and objective: IBS-D is a common functional bowel disease with complex etiology and without biomarker. The pathological and physiological basis of IBS-D focuses on visceral hypersensitivity. However, its epigenetic mechanism remains elusive. Our study aimed to integrate the relationship between differentially expressed miRNAs, mRNAs and proteins in IBS-D patients in order to reveal epigenetic mechanism of visceral hypersensitivity from transcription and protein levels and provide the molecular basis for discovering biomarkers of IBS-D.Methods: The intestinal biopsies from IBS-D patients and healthy volunteers were obtained for high-throughput sequencing of miRNAs and mRNAs. The differential miRNAs were selected and verified by q-PCR experiment followed by target mRNA prediction. Biological functions were respectively analyzed for target mRNAs, differential mRNAs and the previously identified differential proteins in order to explore the characteristic involved visceral hypersensitivity. At last, interaction analysis of miRNAs, mRNAs and proteins was performed for the epigenetic regulation mechanism from transcription and protein levels.Results: Thirty-three miRNAs were found to be differentially expressed in IBS-D and five of them were further confirmed, including upregulated hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p and downregulated hsa-miR-219a-5p, hsa-miR-19b-1-5p. In addition, 3,812 differential mRNAs were identified. Thirty intersecting molecules were found from the analysis on the target mRNAs of miRNAs and mRNAs. Fourteen intersecting molecules were obtained from the analysis on the target mRNAs and proteins, and thirty-six intersecting molecules were identified from analysis on the proteins and different mRNAs. According to the integrated analysis of miRNA-mRNA-protein, we noticed two new molecules COPS2 regulated by hsa-miR-19b-1-5p and MARCKS regulated by hsa-miR-641. Meanwhile some critical signaling pathways in IBS-D were found such as MAPK, GABAergic synapse, Glutamatergic synapse, and Adherens junction.Conclusion: The expressions of hsa-miR-641, hsa-miR-1843, hsa-let-7d-3p, hsa-miR-219a-5p, and hsa-miR-19b-1-5p in the intestinal tissues of IBS-D patients were significantly different. Moreover, they could regulate a variety of molecules and signaling pathways, which were involved in the multifaceted and multilevel mechanism of visceral hypersensitivity of IBS-D.

Large strain gradient is crucial for flexoelectricity. Here, the authors reveal the generality and tunability of large strain gradients at grain boundaries in oxides, explaining the possible effects on the electrical activities of ceramics.

Abstract Inter-individual differences of drug responses could be attributed to genetic variants of pharmacogenes such as cytochrome P450 (CYP), phase 2 enzymes, and transporters. In contrast to extensive studies on the genetic polymorphisms of CYP gene, genetic mutation spectrum of other pharmacogenes was under-representative in the pharmacogenetics investigations. Here we studied the genetic variations of 125 pharmacogenes including drug transporters, non-CYP phase 1 enzymes, phase 2 enzymes, nuclear receptors and others in Chinese from the Chinese Millionome Database (CMDB), of which 38,188 variants were identified. Computational analyses of the 2554 exonic variants found 617 deleterious missense variants, 91.1% of which were rare, and of the 54 loss-of-function (splice acceptor, splice donor, start lost, and stop gained) variants, 53 (98.1%) were rare. These results suggested an enrichment of rare variants in functional ones for pharmacogenes. Certain common functional variants including NUDT15 13:48611934 G/A (rs186364861), UGT1A1 2:234676872 C/T (rs34946978), and ALDH2 12:112241766 G/A (rs671) were population-specific for CMDB Chinese because they were absent (with a zero of variant allele frequency) or very rare in other gnomAD populations. These findings might be useful for the further pharmacogenomics research and clinical application in Chinese.

In this experimental study, we evaluated the protective effects and the safety of main flavanones derived from Rhizoma Drynariae (Gusuibu) in vitro and in vivo. The MTT assay showed that compared with vehicle treatment, treatment with such flavanones as neoeriocitrin, naringin, and naringenin significantly promoted the viability of osteocyte-like cells. Quantitative real-time PCR showed that neoeriocitrin and naringin significantly attenuated mRNA expressions of RANKL and SOST in osteocyte-like cells. In rats with retinoic acid-induced osteoporosis, total flavonoid of Rhizoma Drynariae (TFRD), naringin, and naringenin significantly increased the number of trabeculae and improved trabecular bone structure compared with no treatment, without affecting liver and renal function. In addition, naringenin and naringin administration significantly increased bone mineral density of femur neck and femur shaft compared with the osteoporotic model rats. Western blot analysis showed that naringenin and naringin significantly attenuated protein expressions of bone resorption-related factors (TRAP, RANKL and RANK), and inhibited sclerostin expression compared with the osteoporotic model rats. On the other hand, naringin markedly increased protein expressions of ALP and PTH1R, and TFRD and naringenin also promoted PTH1R expression compared with the model rats. In conclusion, such flavanones as naringenin and naringin exhibited antiresorptive properties, and naringin particularly showed potential benefits for osteoporosis treatment.

The tracked-wheeled mobile robot has gained significant attention in military, agricultural, construction, and other fields due to its exceptional mobility and off-road capabilities. Therefore, it is an ideal choice for reconnaissance and exploration tasks. In this study, we proposed a multi-jointed tracked-wheeled compound mobile robot that can overcome various terrains and obstacles. Based on the characteristics of multi-jointed robots, we designed two locomotion modes for the robot to climb stairs and established the kinematics/dynamics equations for its land movement. We evaluated the robot’s stability during slope climbing, its static stability during stair climbing, and its ability to cross trenches. Based on our evaluation results, we determined the key conditions for the robot to overcome obstacles, the maximum height it can climb stairs, and the maximum width it can cross trenches. Additionally, we developed a simulation model to verify the robot’s performance in different terrains and the reliability of its stair-climbing gait. The simulation results demonstrate that our multi-jointed tracked-wheeled compound mobile robot exhibits excellent reliability and adaptability in complex terrain, indicating broad application prospects in various fields and space missions.

The majority of polar structures emerging naturally in ferroelectrics are topologically trivial. Here, the authors demonstrate reconstruction of topologically trivial strip-like domain architecture into arrays of polar vortex in (PbTiO3)10/(SrTiO3)10 superlattice.

While the role of PbTiO3 in PbTiO3/SrTiO3 superlattices has been widely studied, little attention is paid to possible polar topologies in SrTiO3. Here, the authors create atomic-scale vortex–antivortex pairs in the superlattices, expanding the understanding of topological structures.

Our study aims to explore the active components and mechanisms of the Danshen-Guizhi drug pair in treating ovarian cancer by network pharmacology and in vitro experiment. The “component-target-pathway” diagram of the Danshen-Guizhi drug pair was established by network pharmacology, and the effective active components, important targets as well as potential mechanisms of the Danshen-Guizhi drug pair were analyzed. The predicted results were verified by molecular docking and in vitro experiments. The main active components of the Danshen-Guizhi drug pair in the treatment of ovarian cancer are salviolone, luteolin, β-sitosterol and tanshinone IIA. The main core target is PTGS2. The pathways involved mainly include the cancer pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. The molecular docking results showed that salviolone and tanshinone IIA had good binding ability to the target. The expression of PTGS2 mRNA and PGE2 in ovarian cells were significantly inhibited by salviolone. The mechanism of the Danshen-Guizhi drug pair in the treatment of ovarian cancer may be regulating cell proliferation, apoptosis and tumor immunity. This provides a theoretical basis for the clinical development and application of the Danshen-Guizhi drug pair.

In order to improve the security effect of image information, this paper studies the reversible information hiding of the digital images combined with the pixel combination algorithm and proposes an improved simulated annealing algorithm using the incremental calculation method of statistical functions. Moreover, according to the gray gradient information contained in the image, this paper proposes an automatic threshold determination algorithm suitable for the unimodal gray distribution images and uses this algorithm to complete the threshold determination and binary segmentation of all images. In addition, this paper optimizes the model by transforming the isolated pores inside the model and removing the isolated matrix area. Through comparative experiments, it can be seen that the reversible information hiding method for digital images based on the pixel combination algorithm proposed in this paper has a good image information confidentiality effect.

Abstract Drought has become an important factor limiting crop yields in China. As an important greenhouse horticultural crop in China, the research of tomato (Solanum lycopersicum L. cv. Jinpeng No.10) is of great theoretical and practical significance. In the study, four different relative soil moisture contents (74% to 80%, 55% to 61%, 47% to 52%, and 25% to 30%) were used to induce drought stress. We investigated changes in photosynthetic gas exchange, chlorophyll fluorescence, and other related physiological parameters in response to different relative soil moisture contents. Drought inhibited the photosynthesis of tomato significantly, as shown by a clear decline in the net photosynthetic rate. Our results indicated stomatal limitation and nonstomatal limitation were responsible for the photosynthesis reduction.

BackgroundAutophagy is a “self-feeding” phenomenon of cells, which is crucial in mammalian development. Long non-coding RNA (lncRNA) is a new regulatory factor for cell autophagy, which can regulate the process of autophagy to affect tumor progression. However, poor attention has been paid to the roles of autophagy-related lncRNAs in breast cancer.ObjectiveThis study aimed to construct an autophagy-related lncRNA signature that can effectively predict the prognosis of breast cancer patients and explore the potential functions of these lncRNAs.MethodsThe RNA sequencing (RNA-Seq) data of breast cancer patients was collected from The Cancer Genome Atlas (TCGA) database and the GSE20685 database. Multivariate Cox analysis was implemented to produce an autophagy-related lncRNA signature in the TCGA cohort. The signature was then validated in the GSE20685 cohort. The receiver operator characteristic (ROC) curve was performed to evaluate the predictive ability of the signature. Gene set enrichment analysis (GSEA) was used to explore the potential functions based on the signature. Finally, the study developed a nomogram and internal verification based on the autophagy-related lncRNAs.ResultsA signature composed of 9 autophagy-related lncRNAs was determined as a prognostic model, and 1,109 breast cancer patients were divided into high-risk group and low-risk group based on median risk score of the signature. Further analysis demonstrated that the over survival (OS) of breast cancer patients in the high-risk group was poorer than that in the low-risk group based on the prognostic signature. The area under the curve (AUC) of ROC curve verified the sensitivity and specificity of this signature. Additionally, we confirmed the signature is an independent factor and found it may be correlated to the progression of breast cancer. GSEA showed gene sets were notably enriched in carcinogenic activation pathways and autophagy-related pathways. The qRT-PCR identified 5 lncRNAs with significantly differential expression in breast cancer cells based on the 9 lncRNAs of the prognostic model, and the results were consistent with the tissues.ConclusionIn summary, our signature has potential predictive value in the prognosis of breast cancer and these autophagy-related lncRNAs may play significant roles in the diagnosis and treatment of breast cancer.

This paper investigates the air–ground cooperative time-varying formation-tracking control problem of a heterogeneous cluster system composed of an unmanned ground vehicle (UGV) and an unmanned aerial vehicle (UAV). Initially, the structure of the UAV–UGV formation-control system is analyzed from the perspective of a cooperative combat system. Next, based on the motion relationship between the UAV–UGV in a relative coordinate system, the relative motion model between them is established, which can clearly reveal the physical meaning of the relative motion process in the UAV–UGV system. Then, under the premise that the control system of the UAG is closed-loop stable, the motion state of the UGV is modeled as an input perturbation. Finally, using a linear quadratic optimal control theory, a UAV–UGV formation-maintenance controller is designed to track the reference trajectory of the UGV based on the UAV–UGV relative motion model. The simulation results demonstrate that the proposed controller can overcome input perturbations, model-constant perturbations, and linearization biases. Moreover, it can achieve fast and stable adjustment and maintenance control of the desired UAV–UGV formation proposed by the cooperative combat mission planning system.

Hybrid perovskites are highly promising for photovoltaic applications, but they are prone to decomposition. Here, the authors probe the stability of CH3NH3PbI3 films in a transmission electron microscope, defining the threshold conditions to avoid damage under the electron beam, and describing a decomposition pathway.

Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it “HepG2.RL1”. Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection. Keywords: N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-D- cytidine, Hepatitis B virus, HepG2.RL1 cells, Lamivudine-resistant, rtL180M/M204V

Understanding ferroelectricity at reduced dimensions will be important for future sub-nanoscale devices based on ferroelectrics. Using high resolution electron microscopy; Gaoet al., observe the existence of a measurable polarization at a thickness of just 1.5-unit cells

Menopause is an endocrine-related transition that induces a number of physiological and potentially pathological changes in middle-aged and elderly women. The intention of this research was to investigate the influence of menopause on the intricate relationships between major biochemical metabolites. The study involved metabolic profiling of 186 metabolic markers measured in blood plasma collected from 120 healthy female participants. We developed a method of network analysis using differential correlation that enabled us to detect and characterize differences in metabolites and changes in inter-relationships in pre- and post-menopausal women. A topological analysis was performed on the differential network that uncovered metabolite differences in pre-and post-menopausal women. In this analysis, our method identified two key metabolites, sphingomyelins and phosphatidylcholines, which may be useful in directing further studies into menopause-specific differences in the metabolome, and how these differences may underlie the body's response to stress and disease following the transition from pre- to post-menopausal status for women.

Y3Fe5O12 (YIG) is a promising candidate for spin wave devices. In the thin film devices, the interface between YIG and substrate may play important roles in determining the device properties. Here, we use spherical aberration-corrected scanning electron microscopy and spectroscopy to study the atomic arrangement, chemistry and electronic structure of the YIG/Gd3Ga5O12 (GGG) interface. We find that the chemical bonding of the interface is FeO-GdGaO and the interface remains sharp in both atomic and electronic structures. We provide an efficient method to study the interface chemical bonding, and these results give necessary information for understanding the properties of interface and also for atomistic calculation.

BACKGROUND: Emerging evidence suggests that microRNAs play a critical role in the pathogenesis of breast cancer. Several molecular epidemiological studies were conducted in recent years to evaluate the association between has-miR-146a rs2910164 polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. METHODOLOGY/PRINCIPAL FINDINGS: We performed a meta-analysis of 6 case-control studies that included 4238 breast-cancer cases and 4469 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, this meta-analysis showed that the rs2910164 polymorphism was not associated with a significantly increased risk of breast cancer in all genetic models (for GC vs GG: OR = 1.00, 95% CI = 0.90-1.09, P(heterpgeneity) = 0.364; for CC vs GG: OR = 1.16, 95% CI = 0.98-1.36, P(heterpgeneity) = 0.757; for GC+CC vs GG: OR = 1.02, 95% CI = 0.93-1.12, P(heterpgeneity) = 0.562; for CC vs GC+GG: OR = 1.10, 95% CI = 0.96-1.26, P(heterpgeneity) = 0.441). However, in the stratified analysis by ethnicity, we found the rs2910164 polymorphism was associated with increased breast cancer risk among Europeans in homozygote comparison (CC vs. GG: OR = 1.29, 95%CI = 1.02-1.63, P(heterpgeneity) = 0.950, P = 0.032) and recessive model (CC vs. GC+GG: OR = 1.31, 95%CI = 1.05-1.65, P(heterpgeneity) = 0.839, P = 0.019). No publication bias was found in the present study. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests, for the first time, that the CC homozygote of rs2910164 may contribute to breast cancer susceptibility in Europeans.

ABSTRACT Antiviral drug resistance is the most important factor contributing to treatment failure using nucleos(t)ide analogs such as lamivudine for chronic infection with hepatitis B virus (HBV). Development of a system supporting efficient replication of clinically resistant HBV strains is imperative, and new antiviral drugs are needed urgently to prevent selection of drug-resistant HBV mutants. A novel fluorinated cytidine analog, NCC (N-cyclopropyl-4′-azido-2′-deoxy-2′-fluoro-β-d-cytidine), was recently shown to strongly inhibit human HBV in vitro and in vivo. This study was designed to evaluate the antiviral activity of NCC against lamivudine-resistant HBV. We generated a stable cell line encoding the major pattern of lamivudine-resistant mutations rtL180M/M204V and designated it "HepG2.RL1". Immuno-transmission electron microscopic examination and enzyme-linked immunosorbent assay were used to detect secretion of HBV-specific particles and antigens. Quantification of extracellular DNA and intracellular DNA of HepG2.RL1 cells by quantitative real-time polymerase chain reaction revealed >625-fold and >5556-fold increases in the 50% inhibitory concentration of lamivudine, respectively, compared with that for the wild-type virus. The results showed that NCC inhibited DNA replication and HBeAg production in wild-type or lamivudine-resistant HBV in a dose-dependent manner. In conclusion, screening for antiviral compounds active against lamivudine-resistant HBV can be carried out with relative ease using hepG2.RL1 cells. NCC is a potential antiviral agent against wild-type HBV and clinical lamivudine-resistant HBV and deserves evaluation for the treatment of HBV infection.

Zanthoxylum bungeanum Maxim (ZBM) belongs to Rutaceae family and has been used as traditional spice and herb for hundreds of years in China. Accumulating evidence suggests a series of pharmacological effects associated with ZBM. This review aims to provide a systematic analysis of the composition, structural properties, pharmacology, and pharmacokinetics of ZBM. Chemical composition analysis of ZBM showed that the main compositions were volatile oil, amide compounds, flavonoids, alkaloids, coumarins, lignans, and phenylpropanoids. Interestingly, ZBM exhibits a wide range of significant biological activities including antiinflammatory and analgesic effect, anesthetic effect, neuroprotective effect, antiobesity activity, antineoplastic activity, antibacterial, and other activities. However, there is currently no comprehensive review available on ZBM. Therefore, an up-to-date research was accomplished through systematic searching of multiple electronic databases. In a word, this review summarizes the recent researches investigating the chemical composition and biological properties which will provide a better understanding about the health benefits and preclinical assessment of novel application of ZBM. [ABSTRACT FROM AUTHOR]