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The purpose of this study is to investigate the indirect effects on the properties of ZrO2 films deposited by atomic layer deposition (ALD) when an Mg-Ca alloy is modified through equal-channel angular pressing (ECAP) following extrusion. The study aims to understand how the increase in CaO content in the native oxide layer of the Mg-Ca alloy influences the crystallinity and defect density of the ZrO2 film. Consequently, the corrosion protection performance of the ZrO2 film is enhanced by 1.2 to 1.5 times. A reduction in the anti-scratch property of the ZrO2 film was also observed, with a critical load reduction of 34 μN. This research provides a detailed analysis of the modifications induced by ECAP on the as-extruded Mg-Ca alloy and its subsequent impact on the properties of the ZrO2 film.

Abstract. Background:. Finding an optimal treatment strategy for adolescent idiopathic scoliosis (AIS) patients remains challenging because of its intrinsic complexity. For mild to moderate scoliosis patients with lower skeletal growth potential (Risser 3–5), most clinicians agree with observation treatment; however, the curve progression that occurs during puberty, the adolescent period, and even in adulthood, remains a challenging issue for clinicians. The aim of the study is to investigate the efficacy of Schroth exercise in AIS patients with lower skeletal growth potential (Risser 3–5) and moderate scoliosis (Cobb angle 20°–40°). Methods:. From 2015 to 2017, data of 64 patients diagnosed with AIS in Peking University Third Hospital were reviewed. Forty-three patients underwent Schroth exercise were classified as Schroth group, and 21 patients underwent observation were classified as observation group. Outcomes were measured by health-related quality of life (HRQOL) and radiographic parameters. HRQOL was assessed using the visual analog scale (VAS) scores for back, Scoliosis Research Society-22 (SRS-22) patient questionnaire. Radiographic spinopelvic parameters were obtained from anteroposterior and lateral X-rays. The pre-treatment and post-treatment HRQOL and radiographic parameters were tested to validate Schroth exercise efficacy. The inter-rater reliability of the radiographic parameters was tested using the interclass correlation coefficient (ICC). The paired t test was used to examine HRQOL and radiographic parameters. Clinical relevance between C2-C7 sagittal vertical axis (SVA) and thoracic kyphosis was analyzed using Spearman correlation. Results:. In Schroth group, VAS back score, SRS-22 pain, and SRS-22 self-image domain were significantly improved from pre-treatment 3.0 ± 0.8, 3.6 ± 0.5, and 3.5 ± 0.7 to post-treatment 1.6 ± 0.6 (t = 5.578, P = 0.013), 4.0 ± 0.3 (t = −3.918, P = 0.001), and 3.7 ± 0.4 (t = −6.468, P

The complete mitochondrial genome (mitogenome) of Miroplana shenzhensis Yu & Wang, is reported in the present study, representing the second mitogenome recorded in the suborder Maricola. The circular mitogenome is 14,344 bp in length, containing 12 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNAs. Comparative analysis on mitochondrial gene order reveals a rearrangement in the suborder Maricola, indicating that mitochondrial gene order is conserved only in Continenticola, and is divergent across Tricladida. Phylogenetic analysis shows M. shenzhensis is clustered with an another marine triclad, forming a well-supported monophyletic group of Maricloan.

ObjectiveThe mortality rate of ovarian cancer (OC) is the highest among all gynecologic cancers. To predict the prognosis and the efficacy of immunotherapy, we identified new biomarkers.MethodsThe Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) databases were used to extract ovarian cancer transcriptomes. By performing the co-expression analysis, we identified necroptosis-associated long noncoding RNAs (lncRNAs). We used the least absolute shrinkage and selection operator (LASSO) to build the risk model. The qRT-PCR assay was conducted to confirm the differential expression of lncRNAs in the ovarian cancer cell line SK-OV-3. Gene Set Enrichment Analysis, Kaplan-Meier analysis, and the nomogram were used to determine the lncRNAs model. Additionally, the risk model was estimated to evaluate the efficacy of immunotherapy and chemotherapy. We classified necroptosis-associated IncRNAs into two clusters to distinguish between cold and hot tumors.ResultsThe model was constructed using six necroptosis-associated lncRNAs. The calibration plots from the model showed good consistency with the prognostic predictions. The overall survival of one, three, and five-year areas under the ROC curve (AUC) was 0.691, 0.678, and 0.691, respectively. There were significant differences in the IC50 between the risk groups, which could serve as a guide to systemic treatment. The results of the qRT-PCR assay showed that AL928654.1, AL133371.2, AC007991.4, and LINC00996 were significantly higher in the SK-OV-3 cell line than in the Iose-80 cell line (P < 0.05). The clusters could be applied to differentiate between cold and hot tumors more accurately and assist in accurate mediation. Cluster 2 was more vulnerable to immunotherapies and was identified as the hot tumor.ConclusionNecroptosis-associated lncRNAs are reliable predictors of prognosis and can provide a treatment strategy by screening for hot tumors.

Abstract Background With evidence of warming climates, it is important to understand the effects of heat stress in farm animals in order to minimize production losses. Studying the changes in the brain proteome induced by heat stress may aid in understanding how heat stress affects brain function. The hypothalamus is a critical region in the brain that controls the pituitary gland, which is responsible for the secretion of several important hormones. In this study, we examined the hypothalamic protein profile of 10 pigs (15 ± 1 kg body weight), with five subjected to heat stress (35 ± 1 °C; relative humidity = 90%) and five acting as controls (28 ± 3 °C; RH = 90%). Result The isobaric tags for relative and absolute quantification (iTRAQ) analysis of the hypothalamus identified 1710 peptides corresponding to 360 proteins, including 295 differentially expressed proteins (DEPs), 148 of which were up-regulated and 147 down-regulated, in heat-stressed animals. The Ingenuity Pathway Analysis (IPA) software predicted 30 canonical pathways, four functional groups, and four regulatory networks of interest. The DEPs were mainly concentrated in the cytoskeleton of the pig hypothalamus during heat stress. Conclusions In this study, heat stress significantly increased the body temperature and reduced daily gain of body weight in pigs. Furthermore, we identified 295 differentially expressed proteins, 147 of which were down-regulated and 148 up-regulated in hypothalamus of heat stressed pigs. The IPA showed that the DEPs identified in the study are involved in cell death and survival, cellular assembly and organization, and cellular function and maintenance, in relation to neurological disease, metabolic disease, immunological disease, inflammatory disease, and inflammatory response. We hypothesize that a malfunction of the hypothalamus may destroy the host physical and immune function, resulting in decreased growth performance and immunosuppression in heat stressed pigs.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation.Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method.Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed.Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Renal fibrosis (RF) is the end stage of several chronic kidney diseases. Its series of changes include excessive accumulation of extracellular matrix, epithelial-mesenchymal transition (EMT) of renal tubular cells, fibroblast activation, immune cell infiltration, and renal cell apoptosis. RF can eventually lead to renal dysfunction or even renal failure. A large body of evidence suggests that natural products in traditional Chinese medicine (TCM) have great potential for treating RF. In this article, we first describe the recent advances in RF treatment by several natural products and clarify their mechanisms of action. They can ameliorate the RF disease phenotype, which includes apoptosis, endoplasmic reticulum stress, and EMT, by affecting relevant signaling pathways and molecular targets, thereby delaying or reversing fibrosis. We also present the roles of nanodrug delivery systems, which have been explored to address the drawback of low oral bioavailability of natural products. This may provide new ideas for using natural products for RF treatment. Finally, we provide new insights into the clinical prospects of herbal natural products.

Aborycin is a type I lasso peptide with a stable interlocked structure, offering a favorable framework for drug development. The aborycin biosynthetic gene cluster gul from marine sponge-associated Streptomyces sp. HNS054 was cloned and integrated into the chromosome of S. coelicolor hosts with different copies. The three-copy gul-integration strain S. coelicolor M1346::3gul showed superior production compared to the one-copy or two-copy gul-integration strains, and the total titer reached approximately 10.4 mg/L, i.e., 2.1 times that of the native strain. Then, five regulatory genes, phoU (SCO4228), wblA (SCO3579), SCO1712, orrA (SCO3008) and gntR (SCO1678), which reportedly have negative effects on secondary metabolism, were further knocked out from the M1346::3gul genome by CRISPR/Cas9 technology. While the ΔSCO1712 mutant showed a significant decrease (4.6 mg/L) and the ΔphoU mutant showed no significant improvement (12.1 mg/L) in aborycin production, the ΔwblA, ΔorrA and ΔgntR mutations significantly improved the aborycin titers to approximately 23.6 mg/L, 56.3 mg/L and 48.2 mg/L, respectively, which were among the highest heterologous yields for lasso peptides in both Escherichia coli systems and Streptomyces systems. Thus, this study provides important clues for future studies on enhancing antibiotic production in Streptomyces systems.

Objective To investigate the cervical alignment and the relative range of motion (ROM) in patients with basilar invagination (BI). Methods A total of 40 BI cases (38.1 years old ± 17.9 years old, 19 male and 21 female) and 80 asymptomatic individuals (33.8 years old ± 10.8 years old, 40 male and 40 female) were included. The Skull‐C2/Skull‐BV, Skull‐C7, C2‐C7/BV‐C7 wall angles, C0‐C2/C0‐BV, C0‐C7, C1‐C7, and C2‐C7/BV‐C7 angles were measured in dynamic X‐ray images (including neutral, extension, and flexion positions). Correlation between the upper and lower cervical curvatures were analyzed. The total, extension, and flexion ROMs of these angles were calculated, respectively. Results The BI patients had a smaller C0‐C2/C0‐BV angle (18.2° ± 16.4° vs 30.9° ± 9.3°), but larger C2‐C7/BV‐C7 (32.2° ± 16.1° vs 19.4° ± 10.6°) and C2‐C7/BV‐C7 wall angles (37.8° ± 17.2° vs 23.6° ± 10.2°) than the control group in neutral position. The upper and lower curvatures correlated negatively in neutral (r = −0.371), extension (r = −0.429), and flexion (r = −0.648) positions among BI patients, as well as in extension position (r = −0.317) among control group. The BI patients presented smaller total ROMs in Skull‐C2/Skull‐BV (12.3° ± 16.6° vs 19.7° ± 10.9°), C0‐C2/C0‐BV (8.1° ± 11.1° vs 17.6° ± 10.5°), and C0‐C7 angles (57.8° ± 14.2° vs 78.3° ± 17.9°), but a larger total ROM in C2‐C7/BV‐C7 wall angle (52.8° ± 13.9° vs 27.0° ± 16.1°) than the control group. The BI patients also presented smaller extension ROMs in Skull‐C2/Skull‐BV (6.9° ± 9.4° vs 12.5° ± 9.3°), Skull‐C7 (24.5° ± 10.9° vs 30.7° ± 12.5°), and C0‐C2/C0‐BV angles (4.4° ± 7.8° vs 9.9° ± 8.6°) than the control group. Moreover, the BI patients showed smaller absolute values of flexion ROMs in Skull‐C2/Skull‐BV (−5.2° ± 9.4° vs −7.3° ± 8.0°), C0‐C2/C0‐BV (−3.2° ± 8.8° vs −7.7° ± 8.7°), and C0‐C7 angles (−33.2° ± 13.0° vs −52.8° ± 19.2°), but a larger absolute value of flexion ROM in C2‐C7/BV‐C7 wall angle (−33.9° ± 14.8° vs −8.2° ± 15.1°). Conclusion The cervical spine was stiffer in BI patients than the asymptomatic individuals, especially in the upper cervical curvature. The negative correlation between upper and lower cervical curvatures was more obvious in BI patients.

Background: Currently dual-energy X-ray absorptiometry (DXA) and phantom-based quantitative computed tomography (PB-QCT) have been utilized to diagnose osteoporosis widely in clinical practice. While traditional phantom-less QCT (PL-QCT) is limited by the precision of manual calibration using body tissues, such as fat and muscle. Objective: The aim of this study is to validate the accuracy and precision of one newly-developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis. Methods: A total of 36 patients were enrolled for comparison of BMD measurement between DXA and QCT. CT images of 63 patients were analyzed by both PB-QCT and newly developed automatic PL-QCT system, then the BMD results generated by the automatic PL-QCT were utilized to diagnose osteoporosis. The diagnostic outcomes were compared with that of DXA and PB-QCT to assess the performance of the new system. Results: BMD test results showed that the automatic PL-QCT system had higher precision than previous studies performed with QCT, while maintaining similar capability to diagnose osteoporosis as DXA and PB-QCT. Area under curve (AUC) result of PL-QCT was larger than 0.8 for predicting spine DXA T-score in receiver operating characteristic (ROC) analysis. Pearson correlation analysis (r ​= ​0.99) showed strong linear correlation and Bland-Altman analysis (bias ​= ​3.0mg/cc) indicated little difference between the two methods. The precision result (CV ​= ​0.89%) represented good reproducibility of the new system. Conclusion: The traditional PL-QCT system has relatively low reproducibility due to the manual selection of the region of interest (ROI) of body tissues. Automatic selection of ROI in this new system makes the BMD testing more convenient and improves precision significantly. Compared with traditional BMD measurement methods, the automatic PL-QCT system had higher precision in accurate diagnosis of osteoporosis with great potential in translational research and wide clinical application. Translational potential statement: With high accuracy and precision, the automatic PL-QCT system could serve as an opportunistic screening tool for osteoporosis patients in the future. It could also facilitate related researches by providing more reliable data collection, both retrospectively and longitudinally.

CHCHD2 mutations have been reported to cause Parkinson’s disease (PD) by a loss of function in mitochondria. Most reported mutations, however, were missense, which was not the perfect model for a study of haploinsufficiency. Here, a truncated mutation, CHCHD2 p.Pro53Alafs*38, was identified in one familial early-onset PD patient. We generated a human-induced pluripotent stem cell (iPSC) line WCHSCUi001-A from this patient. The generated iPSCs resembled human embryonic stem cells, expressed pluripotency markers, exhibited a normal karyotype and could be differentiated into three germ layers in vitro. This line will be valuable for investigating the disease mechanisms and screening candidate drugs.

Abstract. Background:. Sleep disorders are common but under-researched symptoms in patients with multiple system atrophy (MSA). We investigated the frequency and factors associated with sleep-related symptoms in patients with MSA and the impact of sleep disturbances on disease severity. Methods:. This cross-sectional study involved 165 patients with MSA. Three sleep-related symptoms, namely Parkinson's disease (PD)-related sleep problems (PD-SP), excessive daytime sleepiness (EDS), and rapid eye movement sleep behavior disorder (RBD), were evaluated using the PD Sleep Scale-2 (PDSS-2), Epworth Sleepiness Scale (ESS), and RBD Screening Questionnaire (RBDSQ), respectively. Disease severity was evaluated using the Unified MSA Rating Scale (UMSARS). Results:. The frequency of PD-SP (PDSS-2 score of ≥18), EDS (ESS score of ≥10), and RBD (RBDSQ score of ≥5) in patients with MSA was 18.8%, 27.3%, and 49.7%, respectively. The frequency of coexistence of all three sleep-related symptoms was 7.3%. Compared with the cerebellar subtype of MSA (MSA-C), the parkinsonism subtype of MSA (MSA-P) was associated with a higher frequency of PD-SP and EDS, but not of RBD. Binary logistic regression revealed that the MSA-P subtype, a higher total UMSARS score, and anxiety were associated with PD-SP; that male sex, a higher total UMSARS score, the MSA-P subtype, and fatigue were associated with EDS; and that male sex, a higher total UMSARS score, and autonomic onset were associated with RBD in patients with MSA. Stepwise linear regression showed that the number of sleep-related symptoms (PD-SP, EDS, and RBD), disease duration, depression, fatigue, and total Montreal Cognitive Assessment score were predictors of disease severity in patients with MSA. Conclusions:. Sleep-related disorders were associated with both MSA subtypes and the severity of disease in patients with MSA, indicating that sleep disorders may reflect the distribution and degree of dopaminergic/non-dopaminergic neuron degeneration in MSA.

Based on the relations derived from the Regge phenomenology, we investigate the mass spectrum of radial excitation of tensor meson nonet. The results suggest that the states f2(1810), f2(2010) and K*2 (1980) should be assigned as the first radial excitation of tensor meson. Our prediction can be useful for the assignment of tensor meson nonet in the future. [ABSTRACT FROM AUTHOR]

The growing demand for new products that rely on the accurate identification of a target’s location indoors, while remaining mindful of cost, continues to drive research in this important and challenging area. Researchers are actively pursuing algorithmic improvements to eliminate errors introduced from complex interference factors present in indoor, wireless communication environments. In this work, we adopt a differential signal strength method in the design of our new indoor localization algorithm. The proposed algorithm reduces errors in the time domain by smoothing out the wireless signal fluctuations, thus stabilizing the signal; a single exponential algorithm is applied to the signal strength parameters collected to accomplish this. The target’s position is then computed by utilizing both the plane geometric method and difference localization theory. This combination of techniques is reasonable for the environment under consideration (small scale, wireless), as the multipath effects for the signal are approximately equal under these conditions. In addition, the proposed approach is compatible with a wide variety of technologies (e.g., RFID and Bluetooth); it can be cost-effectively deployed by leveraging an existing hardware infrastructure. The proposed approach has been implemented and experimentally validated. The test results are very promising: they indicate that our algorithm improves the positioning accuracy by 70%–80% in comparison with the trilateration and LANDMARC positioning algorithms.

Investigations have indicated that storage pests pose a great threat to global food security by damaging food crops and other food products derived from plants. Essential oils are proven to have significant effects on a large number of stored grain insects. This study evaluated the contact toxicity and fumigant activity of the essential oil extract from the aerial parts of Elsholtzia ciliata and its two major biochemical components against adults and larvae of the food storage pest beetle Tribolium castaneum. Gas chromatography−mass spectrometry analysis revealed 16 different components derived from the essential oil of E. ciliata, which included carvone (31.63%), limonene (22.05%), and α-caryophyllene (15.47%). Contact toxicity assay showed that the essential oil extract exhibited a microgram-level of killing activity against T. castaneum adults (lethal dose 50 (LD50) = 7.79 μg/adult) and larvae (LD50 = 24.87 μg/larva). Fumigant toxicity assay showed LD50 of 11.61 mg/L air for adults and 8.73 mg/L air for larvae. Carvone and limonene also exhibited various levels of bioactivity. A binary mixture (2:6) of carvone and limonene displayed obvious contact toxicity against T. castaneum adults (LD50 = 10.84 μg/adult) and larvae (LD50 = 30.62 μg/larva). Furthermore, carvone and limonene exhibited synergistic fumigant activity against T. castaneum larvae at a 1:7 ratio. Altogether, our results suggest that E. ciliata essential oil and its two monomers have a potential application value to eliminate T. castaneum.

The chemical composition of the essential oil of Etlingera yunnanensis rhizomes and its contact and repellent activities against Tribolium castaneum (Herbst) and Liposcelis bostrychophila (Badonnel) were investigated. The essential oil obtained from E. yunnanensis rhizomes with hydrodistillation was performed by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. The main components of the essential oil were identified to be estragole (65.2%), β-caryophyllene (6.4%), 1,8-cineole (6.4%), limonene (5.2%), and α-pinene (2.4%). It was found that the essential oil of E. yunnanensis rhizomes possessed contact toxicity against T. castaneum and L. bostrychophila (LD50 = 23.33 μg/adult and LD50 = 47.38 μg/cm2, respectively). Estragole, 1,8-cineole, and limonene exhibited stronger contact toxicity (LD50 values of 20.41, 18.86, and 13.40 μg/adult, respectively) than β-caryophyllene (LD50 = 41.72 μg/adult) against T. castaneum adults. Estragole possessed stronger contact toxicity (LD50 = 30.22 µg/cm2) than β-caryophyllene, 1,8-cineole, and limonene (LD50 values of 74.11, 321.20, and 239.62 μg/adult, respectively) against L. bostrychophila adults. Repellency of the crude oil was also evaluated. The essential oil and constituents possessed strong repellent activity against T. castaneum adults. The four individual constituents showed weaker repellent activity than the essential oil against L. bostrychophila adults. The results indicated that the essential oil of E. yunnanensis rhizomes and the individual constituents had the potential to be developed as a natural insecticide and repellent for the control of T. castaneum and L. bostrychophila.

The objective of this study was to analyze six essential oils from Zanthoxylum genus (family Rutaceae) in China and evaluate their repellent activities against Tribolium castaneum and Lasioderma serricorne adults. Six essential oils from Zanthoxylum genus, including Z. armatum, Z. dimorphophyllum, Z. dimorphophyllum var. spinifolium, Z. piasezkii, Z. stenophyllum, and Z. dissitum, were obtained by hydrodistillation and their yields were ranging from 0.02% to 0.53%. Totally, there were 39 chemical components revealed by GC-MS. Among them, some components with high relative content existed in more than three Zanthoxylum species. For instance, both δ-cadinene (1.21%–17.15%) and spathulenol (0.36%–10.19%) appeared in essential oils of Z. dimorphophyllum, Z. piasezkii, Z. stenophyllum, and Z. dissitum which were found to have higher content of sesquiterpenoids. The repellent activities of six essential oil samples against T. castaneum and L. serricorne adults were investigated for the first time. Data demonstrated that six Zanthoxylum species had much stronger repellent activities against T. castaneum than L. serricorne adults, especially in 2 hours after exposure. The results indicate that these six essential oils from Zanthoxylum have significant potential to be developed into natural repellents to control insects in grains, food, and traditional Chinese medicinal materials.