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Abstract Calcium‐sensing receptor (CaSR), a family C G‐protein‐coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca2+, Mg2+, amino acids (e.g., L‐Trp and L‐Phe), small peptides, anions (e.g., HCO3− and PO43−), and pH. CaSR‐mediated intracellular Ca2+ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein–protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca2+‐dependent cellular physiological processes and in CaSR‐dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G‐protein‐coupled receptors.

Abstract Cadmium (Cd) is a neurotoxic contaminant that induces cognitive decline similar to that observed in Alzheimer's disease (AD). Autophagic flux dysfunction is attributed to the pathogenesis of AD, and this study aimed to investigate the effect of autophagy on environmental Cd‐induced AD progression and the underlying mechanism. Here, Cd exposure inhibited autophagosome‐lysosome fusion and impaired lysosomal function, leading to defects in autophagic clearance and then to APP accumulation and nerve cell death. Proteomic analysis coupled with Ingenuity Pathway Analysis (IPA) identified SIRT5 as an essential molecular target in Cd‐impaired autophagic flux. Mechanistically, Cd exposure hampered the expression of SIRT5, thus increasing the succinylation of RAB7A at lysine 31 and inhibiting RAB7A activity, which contributed to autophagic flux blockade. Importantly, SIRT5 overexpression led to the restoration of autophagic flux blockade, the alleviation of Aβ deposition and memory deficits, and the desuccinylation of RAB7A in Cd‐exposed FAD4T mice. Additionally, SIRT5 levels decrease mainly in neurons but not in other cell clusters in the brains of AD patients according to single‐nucleus RNA sequencing data from the public dataset GSE188545. This study reveals that SIRT5‐catalysed RAB7A desuccinylation is an essential adaptive mechanism for the amelioration of Cd‐induced autophagic flux blockade and AD‐like pathogenesis.

Abstract Proanthocyanidin‐rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen‐deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX‐induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency‐induced bone loss by modulating GM and metabolite‐mediated lipid metabolism.

Abstract Background Differential diagnosis of pancreatic solid lesion (PSL) and prognosis of pancreatic cancer (PC) is a clinical challenge. We aimed to explore the differential diagnostic value of sound speed (SS) obtained from endoscopic ultrasonography (EUS) in PSL and the prognostic value of SS in PC. Methods Patients with PSL in The Third Xiangya Hospital of Central South University from March 2019 to October 2019 were prospectively enrolled, who obtained SS from PSL. Patients were divided into the PC group and the pancreatic benign lesion (PBL) group. SS1 is the SS of lesions and SS2 is the SS of normal tissues adjacent to lesions. Ratio1 is equal to SS1 divided by SS2 of PSL (ratio1 = SS1/SS2). Results Eighty patients were enrolled (24 PBL patients, 56 PC patients). SS1 and ratio1 in PC group were higher compared with PBL group (SS1:1568.00 vs. 1550.00, Z = −2.066, p = 0.039; ratio1: 1.0110 vs. 1.0051, Z = −3.391, p = 0.001). The SS1 in PC (Z = −6.503, p

Abstract Background Changes in vascular function are closely associated with the development of cardiovascular disease (CVD). Pulse wave velocity (PWV) is a potential indicator of vascular dysfunction; it allows noninvasive assessment of arterial stiffness. Currently, evidence for the effects of different classes of antidiabetic drugs on arterial stiffness remains limited. In this study, a network meta‐analysis (NMA) was performed to explore the associations between changes in arterial stiffness and first‐line antidiabetic drugs by evaluating PWV in patients with different metabolic abnormalities. Methods We systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until 25 August 2022, without language restrictions. The primary outcome was the change in PWV (ΔPWV) in all included studies; subgroup analysis was performed for patients with abnormal glucose metabolism, including prediabetes and diabetes mellitus. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs) as effect sizes to evaluate the ΔPWV. Results Among the 2257 candidate articles identified in the initial search, 18 RCTs were eventually included in the analysis. In all studies, two classes of new antidiabetic drugs, glucagon‐like peptide‐1 receptor (GLP‐1R) agonists and sSodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors, improved arterial stiffness by decreasing PWV compared with placebo (MD = −1.11, 95% CI: −1.94 to 0.28) and (MD = −0.76, 95% CI: −1.45 to −0.08). A conventional antidiabetic drug, metformin, also showed similar efficacy compared with placebo (MD = −0.73, 95% CI: −1.33 to −0.12). Finally, in subgroup studies of patients with abnormal glucose metabolism diseases, GLP‐1R agonists (MD = −1.06, 95% CI: −2.05 to −0.10) significantly decreased PWV compared with placebo. Conclusion Three classes of antidiabetic drugs—GLP‐1R agonists, SGLT‐2 inhibitors, and metformin—have the potential to improve arterial stiffness. Among the six classes of antidiabetic drugs analyzed, GLP‐1R agonists constitute the only class of drugs that improves arterial stiffness in patients with abnormal glucose metabolism diseases.

Abstract Background and Aims Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning‐based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS‐guided fine‐needle aspiration (EUS‐FNA) in real time. Methods This is a prospective study. The CH‐EUS MASTER system is composed of Model 1 (real‐time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH‐EUS examinations followed by EUS‐FNA were recruited. All patients underwent CH‐EUS and were diagnosed both by endoscopists and CH‐EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS‐FNA with or without CH‐EUS MASTER guidance. Results Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH‐EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH‐EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH‐EUS MASTER guided EUS‐FNA, and were not significantly different compared to the control group. CH‐EUS MASTER‐guided EUS‐FNA significantly improved the first‐pass diagnostic yield. Conclusion CH‐EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. Trial registration number: NCT04607720.

Abstract Insect speciation is among the most fascinating topics in evolutionary biology; however, its underlying mechanisms remain unclear. Allopatric speciation represents one of the major types of speciation and is believed to have frequently occurred during glaciation periods, when climatic oscillation may have caused suitable habitats to be fragmented repeatedly, creating geographical isolation among populations. However, supporting evidence for allopatric speciation of insects in East Asia during the Pleistocene glaciation remains lacking. We aim to investigate the effect of climatic oscillation during the Pleistocene glaciation on the diversification pattern and evolutionary history of hemipteran insects and to test the hypothesis of Pleistocene species stability using spinous assassin bugs Sclomina (Hemiptera: Reduviidae), a small genus widely distributed in southern China but was later found to have cryptic species diversity. Here, using the whole mitochondrial genome (mitogenome) and nuclear ribosomal RNA genes, we investigated both interspecific and intraspecific diversification patterns of spinous assassin bugs. Approximate Bayesian computation, ecological niche modeling, and demographic history analyses were also applied to understand the diversification process and driven factors. Our data suggest that the five species of Sclomina are highly diverged, despite three of them currently being cryptic. Speciation occurred during the Pleistocene when suitable distribution areas were possibly fragmented. Six phylogeographic groups in the type species S. erinacea were identified, among which two groups underwent expansion during the early Last Glacial Period and after Last Glacier Maximum. Our analyses suggest that this genus may have experienced climate‐driven habitat fragmentation and postglacial expansion in the Pleistocene, promoting allopatric speciation and intraspecific diversification. Our results reveal underestimated species diversity in a small insect group and illustrate a remarkable example of allopatric speciation of insects in East Asia promoted by Pleistocene climatic oscillations. These findings provide important insights into the speciation processes and aid the conservation of insect species diversity.

Abstract Objectives Executive function in people with depression is linked to the integrity of white matter fibers in the brain. We hypothesized that the maze tests in neuropsychological tests assessed reasoning and problem‐solving abilities dependent on the integrity of brain white matter fibers, and assessed this relationship using diffusion tensor imaging (DTI) in depressed patients and healthy controls. Methods Participants aged from 18 to 50 years were recruited from Zhumadian Second People's Hospital from July 2018 to August 2019. The sample included 33 clinically diagnosed individuals with major depressive disorder (MDD) and 24 healthy volunteers (HVs). All subjects underwent Neuropsychological assessment battery (NAB) maze tests and DTI. Tract‐based spatial statistics technology in FSL software was used to process DTI data, and threshold‐free cluster enhancement (TFCE) was used to perform multiple comparison corrections. The fractional anisotropy (FA) of white matter fibers in the MDD group and HVs group were compared and extracted. Pearson correlation was used to analyze the relationship between FA and NAB scores and HAMD scores. Results The mean NAB maze test score for the MDD group was lower than the HVs group, and the difference was statistically significant (F = 11.265, p = .037). The FA value of the body of corpus callosum and cerebral peduncle right in the depression group was lower than that in the healthy control group, and the difference was statistically significant (p

Abstract Background Locoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC. Materials and Methods Patients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD‐1 inhibitors) were divided into two groups. Progression‐free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier method, Cox regression model. Patients were matched with propensity score matching. Results Among 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non‐clear cell type (p = 0.044), more advanced T stage (p = 0.006), higher number (p = 0.043) but smaller size of lesions (p = 0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5 months, p = 0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5 months, p = 0.001). The 2‐year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p = 0.084). Local therapy was associated with better PFS (HR 0.37; p = 0.0003) and OS (HR 0.23; p = 0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients. Conclusions Local therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC.

2D metal–organic frameworks (2D‐MOFs) have been extensively studied as promising materials in the fields of electrocatalysis, drug delivery, electronic devices, etc. However, few studies have explored the application potential of 2D‐MOFs in novel neuromorphic computing devices. Herein, an optoelectronic neuromorphic transistor based on a 2D‐MOF/polymer charge‐trapping layer is reported. It is found that the large specific surface area, stable crystal structure, and highly accessible active sites in 2D‐MOFs make them excellent charge‐trapping materials for the devices, which are beneficial for mimicking the memory and learning functions observed in the organism's nervous systems. Different types of synaptic behaviors have been realized in the 2D‐MOF‐based neuromorphic devices under stimuli signal, e.g., paired‐pulse facilitation, excitatory postsynaptic current, short‐term memory, and long‐term memory. More interestingly, emotion‐adjustable learning behavior is realized by changing the value of the source–drain voltage. This work can shed light on the application of 2D‐MOFs in neuromorphic computing and will contribute to the further development of neuromorphic computing devices. An interactive preprint version of the article can be found at DOI: https://doi.org/10.22541/au.165530836.62586068/v1.

Abstract 2D polymers (2DPs) have attracted increasing interests in sensors, catalysis, and gas storage applications. Furthermore, 2DPs with unique band structure and tunable photophysical properties also have immense potential for application in photonic neuromorphic computing. Here, photonic synaptic transistors based on 2DPs as the light‐tunable charge‐trapping medium are developed for the first time. The resulted organic transistors can successfully emulate common synaptic functions, including excitatory postsynaptic current, pair‐pulse facilitation, the transition of short‐term memory to long‐term memory, and dynamic filtering. Benefitting from the high photosensitivity of the 2DP, the devices can be operated under a low operating voltage of −0.1 V, and achieve an ultralow energy consumption of ~0.29 pJ per event. In addition, the heterostructure formed between the 2DP and organic semiconductor enables spectrum‐dependent synaptic responses, which facilitates the simulation of visual learning and memory processes in distinct emotional states. The underlying mechanism of spectrum‐dependent synaptic‐like behaviors is systematically validated with in situ atomic force microscopy based electrical techniques. The spectrum‐enabled tunability of synaptic behaviors further promotes the realization of optical logic functions and associative learning. This work inspires the new application of 2DPs in photonic synapses for future neuromorphic computing.

Abstract Biological invasion has been a serious global threat due to increasing international trade and population movements. Tracking the source and route of invasive species and evaluating the genetic differences in their native regions have great significance for the effective monitoring and management, and further resolving the invasive mechanism. The spotted lanternfly Lycorma delicatula is native to China and invaded South Korea, Japan, and the United States during the last decade, causing severe damages to the fruits and timber industries. However, its global phylogeographic pattern and invasion history are not clearly understood. We applied high‐throughput sequencing to obtain 392 whole mitochondrial genome sequences from four countries to ascertain the origin, dispersal, and invasion history of the spotted lanternfly. Phylogenomic analyses revealed that the spotted lanternfly originated from southwestern China, diverged into six phylogeographic lineages, and experienced northward expansion across the Yangtze River in the late Pleistocene. South Korea populations were derived from multiple invasions from eastern China and Japan with two different genetic sources of northwestern (Loess Plateau) and eastern (East Plain) lineages in China, whereas the each of Japan and the United States had only one. The United States populations originated through single invasive event from South Korea, which served as a bridgehead of invasion. The environmental conditions, especially the distribution of host Ailanthus trees, and adaptability possibly account for the rapid spread of the spotted lanternfly in the native and introduced regions.

Abstract Objectives To investigate the prognostic value of magnetic resonance imaging (MRI)‐determined cervical lymph node (CLN) size in nasopharyngeal carcinoma (NPC). Methods We retrospectively reviewed 2066 patients with NPC treated with intensity‐modulated radiotherapy, and randomly divided them into two groups, in a 1:1 ratio. One group was used for training (the training group), and the other one was for internal validation (the validation group). All patients had undergone MRI examination and the maximal axial diameters (MAD) of the axial plane of all positive nodes had been measured and recorded. Results Of 683 patients with CLN metastases in the training group (n = 1033), MAD = 4 cm was associated with worse OS (64.7% vs 84.6%, P

Background & Aim. Ferulic acid (FA), the main effective ingredient in Angelica sinensis, has been widely recognized as the cause of angiogenesis and proliferation of human umbilical vein endothelial cells (HUVECs). This study is mainly aimed at investigating the effect of FA on the apoptosis of HUVECs, which may play a key role in angiogenesis. Materials and Methods. CCK-8 (cell counting kit-8), Western blotting and Annexin V-FITC/PI staining were used to detect cell viability and apoptosis after hypoxia stimulation. The level of microRNA-92 a (miR-92 a) was detected by qRT-PCR.. Then, the assays of flow cytometry and the annexin V/PI staining kit were applied to value the impact of FA on hypoxia-induced cell proliferation, cell cycle distribution, and apoptosis. Furthermore, the inhibitor and mimic of miR-92a were also administrated to explore the role of miR-92a in this process. Student’s t-test was used to explore the differences between two groups, while one-way analysis of variance (ANOVA) was used to explore the differences between more than two groups. Results. The results showed that hypoxia stimulation significantly inhibited HUVEC viability and proliferation, such as remarkably decreasing the expression of CDK2, CDK4, and cyclin D1 in HUVECs. The results of annexin V-FITC/PI apoptosis detection showed that hypoxia culture significantly induced HUVEC apoptosis, which indicated that hypoxia stimulation significantly inhibited viability and proliferation of HUVECs but caused cell apoptosis and the expression of miR-92a. Meanwhile, FA remarkably protected HUVECs from hypoxia-induced inhibition of viability and proliferation, as well as the enhancement of apoptosis and miR-92a expression. Furthermore, suppression of miR-92a enhanced the protective effects of FA on hypoxia-induced HUVECs, while activation of miR-92a reversed those effects. Conclusion. Our study reported that FA preserved HUVECs from hypoxia-induced injury via regulating miR-92a, which facilitated the understanding of the protective capacity of FA in hypoxia-caused HUVEC injury.

The primary objective of the study was to assess the values of serum anti-Müllerian hormone (AMH) levels and the combined index for the prediction of number of oocytes retrieved (NOR) and number of good-quality embryos (GQE) in infertile women undergoing IVF/ICSI treatment. A group of 521 infertile women aged 21–46 years were recruited as subject in this study. Serum AMH, hormones, and antral follicle count (AFC) were measured. The infertile women were categorized into three groups: 21–34 years (reproductive age), 35–39 years (reproductive age), and 40–46 years (advanced-age infertile). The predictive accuracy of variables was analyzed by the receiver operating characteristic (ROC) curve. AFC, AFC/age ratio, AMH/age ratio, and ovarian response prediction index (ORPI) decreased gradually, while AMH decreased significantly with increase in age. Moreover, NOR and GQE were positively correlated with AFC, AMH, AFC/age ratio, AMH/age ratio, and ORPI (P

The agriculture field is one of the most important fields where computational techniques play an imperative role for decision-making whether it is the automation of watering of plants, controlling of humidity levels, and detection of plant diseases and growth of plants. There are problems in the conventional methods where newer computational techniques and image processing methods are not used to keep track of growth of plants. The traditional image capturing and processing models have problems of large image segmentation error, excessive feature extraction time, and poor recognition output. In order to overcome the problems in the traditional plant growth methods based on image processing automations, computer image processing with computational method has been proposed to analyze the plant growth by utilizing state recognition method for corn and rice crops. An image acquisition platform is established on the basis of CMOS image sensor for crop image acquisition. The binary processing is performed, and then the images are segmented to reduce error of segmentation results in the traditional methods. To extract image features of corn and rice crops, convolution neural network (CNN) with newer architecture is used. According to contour information of images, the block wavelet transform method is used for feature adaptive matching. The binary tree structure is used to divide the growth period of corn and rice crops. The fuzzy mathematical model is also devised to identify the characteristics of crops in different growth periods and to complete the identification of growth state. Experimental results show that the proposed method effectively improves problems of traditional methods with better image recognition effect and reduces the time of feature recognition. The time to extract features by the proposed method is 1.4 seconds, whereas comparative methods such as random forest (RF) take 3.8 s and other traditional techniques take 4.9 s. Segmentation result error of the recognition method is also reduced significantly.

Abstract Backgrounds Colorectal carcinoma (CRC) is a common malignant tumor. Increasing evidences indicated that CRC showed a resistance to 5‐fluorouracil (5‐FU) and further resulted in a poor prognosis. In this study, we aim to investigate the effect of long noncoding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) on cell viability, sensitivity to 5‐FU, and autophagy of CRC cell lines. Methods MTT (3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐Htetrazolium bromide) was used to detect cell viability, immunofluorescent staining was used to detect autophagy puncta, and luciferase reporter system was used to determine binding ability between miR‐34a and NEAT1 or putative targets. Additionally, indicated mRNAs and protein expressions were determined by qRT‐PCR or western blotting, respectively. Results We found that NEAT1 expression was increased in CRC tissues and cells, which showed a negative correlation with miR‐34a expression. In addition, NEAT1 knockdown noticeably inhibited the proliferation of CRC cells and enhanced 5‐FU sensitivity. It revealed that NEAT1 knockdown suppressed the LC3 puncta and the expressions of Beclin‐1, ULK1, and ratio of LC3II/I. Overexpression of miR‐34a showed similar trends with NEAT1 knockdown. miR‐34a was validated to target the putative binding sites in 3′‐UTR of HMGB1, ATG9A, and ATG4B, which are involved in the activation of autophagy. Inhibition of miR‐34a or overexpression of HMGB1 could effectively reverse elevated 5‐FU sensitivity upon NEAT1 knockdown. In addition, 3‐MA reversed NEAT1 overexpression‐induced resistance in HT29 cells. Conclusion These findings indicate that LncRNA NEAT1 could target miR‐34a and promote autophagy to facilitate 5‐FU chemoresistance in CRC.

Abstract Background Intensity‐modulated radiotherapy (IMRT) provides excellent local control in nasopharyngeal carcinoma (NPC). We investigated whether simplifying 8th American Joint Committee on Cancer staging system T categories improves prognostic value. Methods We used 2191 NPC patients as a training set and 414 patients separately as an independent, external validation cohort. Results In the training set, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS) were not significantly different between the 8th edition T2/T3 (P = 0.610, 0.380 and 0.353, respectively). Merging T2 and T3 to proposed T2 (proT2) provided significant differences in LRFS, DFS, and OS between proposed T categories. Proposed T categories had similar c‐indices for LRFS, DFS, and OS (vs the 8th edition), which was validated in the external cohorts. Moreover, for DFS, the adjusted HRs of the proT2N0 (3.8), proT1N1 (3.8), and proT2N1 (6.0) subsets were similar; the adjusted HRs of the proT3N0 (7.0), proT3N1 (11.4), proT1N2 (11.0), proT2N2 (11.6), and proT3N2 (13.3) subsets were similar; the adjusted HRs of the proT1N3 (17.8), proT2N3 (15.3), and proT3N3 (26.4) subsets were similar; the results of the adjusted HRs for OS had the same rule. Defining proT1N0 as stage I; proT1N1/proT2N0‐1 as stage II; proT3N0‐2/proT1‐2N2 as stage III; and proT1‐3N3 as stage IVa generated orderly, significant differences in DFS and OS between stages in the training set and external validation cohort. Conclusions In the IMRT era, three T categories are more reasonable (merging T2/T3 into T2) and proT3N0‐2 (the 8th edition T4N0‐2) should be down‐staged to stage III.

Yak (Bos grunniens) is an animal mainly living on the Tibetan Plateau. Yak skin is a valuable resource that is wasted in the meat production process. This study aimed to prepare yak skin gelatin hydrolysates (YSGH) from yak skin through enzymatic hydrolysis and investigate functional characterization of YSGH. We showed that trypsin was more effective than neutrase, papain, and pepsin in increasing the degree of hydrolysis (DH) of YSGH. The conditions of enzymatic hydrolysis were optimized using central composite design (CCD) and response surface method (RSM), and the highest DH value of 31.96% was obtained. We then analyzed the amino acid compositions and molecular weight distribution of peptides in YSGH. The obtained YSGH exhibited certain antioxidant activity and excellent ACE-inhibitory activity (IC50 = 0.991 mg/mL). In addition, the solubility (98.79%), emulsification, and foaming properties of YSGH developed here were also evaluated. With these physicochemical and biological functions, YSGH had potential applications in food, pharmaceuticals, and cosmetics as an ingredient.

Nonlinear seismic behaviors of different boundary conditions of transmission line system under earthquake loading are investigated in this paper. The transmission lines are modeled by cable element accounting for the nonlinearity of the cable. For the suspension type, three towers and two span lines with spring model (Model 1) and three towers and four span lines’ model (Model 2) are established, respectively. For the tension type, three towers and two span lines’ model (Model 3) and three towers and four span lines’ model (Model 4) are created, respectively. The frequencies of the transmission towers and transmission lines of the suspension type and tension type are calculated, respectively. The responses of the suspension type and tension type are investigated using nonlinear time history analysis method, respectively. The results show that the responses of the transmission tower and transmission line of the two models of the suspension type are slightly different. However, the responses of transmission tower and transmission line of the two models of the tension type are significantly different. Therefore, in order to obtain accurate results, a reasonable model should be considered. The results could provide a reference for the seismic analysis of the transmission tower-line system.

A parametric study of tuned mass dampers for a long span transmission tower-line system under wind loads is done in this paper. A three-dimensional finite element model of transmission tower-line system is established by SAP2000 software to numerically verify the effectiveness of the tuned mass damper device. The wind load time history is simulated based on Kaimal spectrum by the harmony superposition method. The equations of motion of a system with tuned mass damper under wind load excitation are proposed, and the schematic of tuned mass damper is introduced. The effects of mass ratio, frequency ratio, damping ratio, the change of the sag of transmission line, and the robustness of TMD are investigated, respectively. Results show that (1) the change of mass ratio has a greater effect on the vibration reduction ratio than those of frequency ratio and damping ratio, and the best vibration reduction ratio of TMD is not the frequency ratio of 1; (2) the sag-span ratio has an insignificant effect on the vibration reduction ratio of transmission tower when the change of sag-span ratio is not large; and (3) the effect of ice should be considered when the robustness study of TMD is carried out.

Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

The effect analysis of strain rate on power transmission tower-line system under seismic excitation is studied in this paper. A three-dimensional finite element model of a transmission tower-line system is created based on a real project. Using theoretical analysis and numerical simulation, incremental dynamic analysis of the power transmission tower-line system is conducted to investigate the effect of strain rate on the nonlinear responses of the transmission tower and line. The results show that the effect of strain rate on the transmission tower generally decreases the maximum top displacements, but it would increase the maximum base shear forces, and thus it is necessary to consider the effect of strain rate on the seismic analysis of the transmission tower. The effect of strain rate could be ignored for the seismic analysis of the conductors and ground lines, but the responses of the ground lines considering strain rate effect are larger than those of the conductors. The results could provide a reference for the seismic design of the transmission tower-line system.

A measurement campaign is introduced for modeling radio channels with either line-of-sight (LoS) or non-line-of-sight (NLoS) connection between user equipment (UE) and NodeB (NB) in an operating universal mobile telecommunications system. A space-alternating generalized expectation-maximization (SAGE) algorithm is applied to estimate the delays and the complex attenuations of multipath components from the obtained channel impulse responses. Based on a novel LoS detection method of multipath parameter estimates, channels are classified into LoS and NLoS categories. Deterministic models which are named “channel maps” and fading statistical models have been constructed for LoS and NLoS, respectively. In addition, statistics of new parameters, such as the distance between the NB and the UE in LoS/NLoS scenarios, the life-distance of LoS channel, the LoS existence probability per location and per NB, the power variation at LoS to NLoS transition and vice versa, and the transition duration, are extracted. These models are applicable for designing and performance evaluation of transmission techniques or systems used by distinguishing the LoS and NLoS channels.

A parametric study of nonlinear seismic response analysis of transmission line structures subjected to earthquake loading is studied in this paper. The transmission lines are modeled by cable element which accounts for the nonlinearity of the cable based on a real project. Nonuniform ground motions are generated using a stochastic approach based on random vibration analysis. The effects of multicomponent ground motions, correlations among multicomponent ground motions, wave travel, coherency loss, and local site on the responses of the cables are investigated using nonlinear time history analysis method, respectively. The results show the multicomponent seismic excitations should be considered, but the correlations among multicomponent ground motions could be neglected. The wave passage effect has a significant influence on the responses of the cables. The change of the degree of coherency loss has little influence on the response of the cables, but the responses of the cables are affected significantly by the effect of coherency loss. The responses of the cables change little with the degree of the difference of site condition changing. The effect of multicomponent ground motions, wave passage, coherency loss, and local site should be considered for the seismic design of the transmission line structures.

A rapid headspace single-drop microextraction gas chromatography mass spectrometry (SDME-GC-MS) for the analysis of the volatile compounds in Herba Asari was developed in this study. The extraction solvent, extraction temperature and time, sample amount, and particle size were optimized. A mixed solvent of n-tridecane and butyl acetate (1 : 1) was finally used for the extraction with sample amount of 0.750 g and 100-mesh particle size at 70°C for 15 min. Under the determined conditions, the pound samples of Herba Asari were directly applied for the analysis. The result showed that SDME-GC–MS method was a simple, effective, and inexpensive way to measure the volatile compounds in Herba Asari and could be used for the analysis of volatile compounds in Chinese medicine.