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Rain gauges are able to measure point rainfall with high accuracy compared with remote sensing observations. However, a single rain gauge cannot provide continuous spatial coverage, and thus, rain gauge networks need to be designed in a way that will provide optimum rainfall information with a minimum number of gauges. While relatively inaccurate but long-term larger-scale satellite rainfall measurements are an ideal dataset to provide insight into local storm characteristics, such as rainfall patterns and local topographic influences on rainfall, these key characteristics would be useful in designing rain gauge networks. This article proposes a new scheme for a large-scale rain gauge network design that uses complementary data from satellite rainfall measurements. Principal component analysis (PCA), the elbow method, the intra-group sum of squares error and the gap statistic were used to calculate the optimum number of rain gauges respectively, while the locations of rain gauges were determined by cluster analysis with the influence of rainfall amount. The results show that PCA is the most effective method with multilevel variances, providing an optimum reference design number at 80% variances. In addition, the rainfall zones in Kenya had a close relationship with land cover, and more gauges will have to be deployed in the mountainous areas to reflect rainfall variations during the warm season in Kenya. The proposed scheme can also be used for other types of ground observation station designs in conjunction with remotely sensed hydrometeorological factors such as soil moisture, evapotranspiration and ice cover.

Dependable and accurate battery remaining useful life (RUL) prediction is essential for ensuring the safety and reliability of battery systems. To improve the dynamic traceability of the battery degradation process for RUL prediction under different loading profiles, this paper presents an improved RUL prediction method, which is established from the combination of the linear optimization resampling particle filter (LORPF) with the sliding-window gray model (SGM). Major innovations are presented as follows: (1) To increase the accuracy of RUL prediction, a linear optimization combination is proposed to overcome the particle diversity deficiency in the resampling process of the standard PF, i.e. the LORPF; (2) To improve the traceability of the LORPF in predicting degradation trajectory, the SGM is employed to update the state variables of the state–space model in the LORPF. Additionally, an SGM-LORPF framework is constructed for RUL prediction. The performance of the SGM-LORPF is synthetically verified by data from two types of batteries under different loading profiles. Prediction test results indicate that the SGM-LORPF can achieve accurate RUL prediction under both constant current discharge conditions (relative error within 7.20%) and dynamic current discharge conditions (relative error within 2.75%). Moreover, using only a small amount of historical data, the proposed SGM-LORPF framework can acquire accurate results. The experimental outcome indicates that the SGM-LORPF has considerable efficiency and a wide range of practicality.

Esophageal cancer is one of the most commonly diagnosed malignant gastrointestinal tumors. The aim of the study was to explore the diagnostic values of anti-POSTN and anti-TIMP1 autoantibodies in esophageal squamous cell carcinoma (ESCC). Differentially expressed genes (DEGs) associated with esophageal cancer were screened out by the LIMMA method in the Gene Expression Profiling Interactive Analysis (GEPIA) platform. Search Tool for the Retrieval of Interacting Genes (STRING) was used to construct the protein–protein interaction (PPI) based on highly DEGs. The candidate hub genes were the intersection genes calculated based on degree and Maximal Clique Centrality (MCC) algorithms via Cytoscape. A total of 370 participants including 185 ESCC patients and 185 matched normal controls were enrolled in enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of autoantibodies corresponding to POSTN and TIMP1 proteins. A total of 375 DEGs with high expression were obtained in esophageal cancer. A total of 20 hub genes were acquired using the cytoHubba plugin by degree and MCC algorithms. The expression levels of anti-POSTN and anti-TIMP1 autoantibodies were higher in the sera of ESCC patients (p < 0.05). Anti-POSTN autoantibody can diagnose ESCC patients with an AUC of 0.638 at the specificity of 90.27% and sensitivity of 27.57%, and anti-TIMP1 autoantibody can diagnose ESCC patients with an AUC of 0.585 at the specificity of 90.27% and sensitivity of 20.54% (p < 0.05). In addition, anti-POSTN and anti-TIMP1 autoantibodies can distinguish ESCC patients from normal controls in most clinical subgroups (p < 0.05). In conclusion, anti-POSTN and anti-TIMP1 autoantibodies may be considered the potential biomarkers in the clinical diagnosis of ESCC.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer with heterogeneous outcomes and diverse therapeutic responses. However, the understanding of the potential mechanism behind LUAD initiation and progression remains limited. Increasing evidence shows the clinical significance of the interaction between immune and hypoxia in tumor microenvironment. To mine reliable prognostic signatures related to both immune and hypoxia and provide a more comprehensive landscape of the hypoxia-immune genome map, we investigated the hypoxia-immune-related alteration at the multi-omics level (gene expression, somatic mutation, and DNA methylation). Multiple strategies including lasso regression and multivariate Cox proportional hazards regression were used to screen the signatures with clinical significance and establish an incorporated prognosis prediction model with robust discriminative power on survival status on both the training and test datasets. Finally, combing all the samples, we constructed a robust model comprising 19 signatures for the prognosis prediction of LUAD patients. The results of our study provide a comprehensive landscape of hypoxia-immune related genetic alterations and provide a robust prognosis predictor for LUAD patients.

ObjectiveTimely and accurate forecast of infectious diseases is essential for achieving precise prevention and control. A good forecasting method of infectious diseases should have the advantages of interpretability, feasibility, and forecasting performance. Since previous research had illustrated that the spatial transmission network (STN) showed good interpretability and feasibility, this study further explored its forecasting performance for infectious diseases across multiple regions. Meanwhile, this study also showed whether the STN could overcome the challenges of model rationality and practical needs.MethodsThe construction of the STN framework involved three major steps: the spatial kluster analysis by tree edge removal (SKATER) algorithm, structure learning by dynamic Bayesian network (DBN), and parameter learning by the vector autoregressive moving average (VARMA) model. Then, we evaluated the forecasting performance of STN by comparing its accuracy with that of the mechanism models like susceptible-exposed-infectious-recovered-susceptible (SEIRS) and machine-learning algorithm like long-short-term memory (LSTM). At the same time, we assessed the robustness of forecasting performance of STN in high and low incidence seasons. The influenza-like illness (ILI) data in the Sichuan Province of China from 2010 to 2017 were used as an example for illustration.ResultsThe STN model revealed that ILI was likely to spread among multiple cities in Sichuan during the study period. During the whole study period, the forecasting accuracy of the STN (mean absolute percentage error [MAPE] = 31.134) was significantly better than that of the LSTM (MAPE = 41.657) and the SEIRS (MAPE = 62.039). In addition, the forecasting performance of STN was also superior to those of the other two methods in either the high incidence season (MAPE = 24.742) or the low incidence season (MAPE = 26.209), and the superiority was more obvious in the high incidence season.ConclusionThis study applied the STN to the forecast of infectious diseases across multiple regions. The results illustrated that the STN not only had good accuracy in forecasting performance but also indicated the spreading directions of infectious diseases among multiple regions to a certain extent. Therefore, the STN is a promising candidate to improve the surveillance work.

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is one of the most lethal nematode species, which causes pine wilt disease (PWD), a devastating forest disease. To date, no effective methods have been developed to control the disease; hence, rapid precise detection of B. xylophilus is of great significance. Traditional molecular diagnostic methods are time-consuming and require sophisticated instruments or skilled operators, which are unavailable in resource-limited settings. A specific, sensitive, and field-applicable diagnostic method is urgently needed. In this study, we developed a diagnostic method using recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD) for the rapid on-site detection of B. xylophilus. The false-positive signals from primer-dependent artifacts were eliminated using a probe, and base substitutions were included in the primer and probe. The entire detection process for the RPA-LFD assay can be completed under 38°C within approximately 30 min, including 15 min for crude nematode genomic DNA (gDNA) extraction and master mix preparation, 15 min for the RPA-LFD assay. This assay displayed high specificity toward B. xylophilus and showed no cross-reactions with closely related species, including Bursaphelenchus mucronatus and Bursaphelenchus doui. The sensitivity of this assay had a detection limit as low as 1 pg of B. xylophilus purified genomic DNA. Furthermore, the application of the RPA-LFD assay in simulated spiked pinewood samples showed accurate detection results. The RPA-LFD assay in this study successfully detected B. xylophilus in less than 30 min, providing a novel alternative for the simple, sensitive, and specific detection of B. xylophilus and showed potential for B. xylophilus point-of-care testing (POCT) in resource-limited areas or in field.

PurposeRegional cortical thickness or volume analyses based upon structural MRI scans have been employed to study the pathophysiology of primary craniocervical dystonia (CCD). In the present study, brain connectivity network analyses based upon morphological distribution similarities among different brain areas were used to study the network disruption in individuals affected by CCD.MethodsThe T1 MRI scans were completed for 37 patients with CCD and 30 healthy controls, with individual brain structural networks being constructed based upon gray matter (GM) similarities in 90 regions within the brain. Area under the curve (AUC) values for each network parameter were determined, and the GRETNA program was used to conduct a graph theory-based measurement of nodal and global network properties. These properties were then compared between healthy controls and those with CCD. In addition, relationships between nodal properties and the severity of clinical dystonia were assessed through Spearman's correlation analyses.ResultsRelative to individuals in the control group, patients with CCD exhibited decreased local nodal properties in the right globus pallidus, right middle frontal gyrus, and right superior temporal pole. The degree of centrality as well as the node efficiency of the right globus pallidus were found to be significantly correlated with ocular dystonic symptom. The node efficiency of right middle frontal gyrus was significantly related to the total motor severity. No nodal properties were significantly correlated with oral dystonic motor scores. Among CCD patients, the right hemisphere exhibited more widespread decreases in connectivity associated with the motor related brain areas, associative cortex, and limbic system, particularly in the middle frontal gyrus, globus pallidus, and cingulate gyrus.ConclusionsThe assessment of morphological correlations between different areas in the brain may represent a sensitive approach for detecting alterations in brain structures and to understand the mechanistic basis for CCD at the network level. Based on the nodal properties identified in this study, the right middle frontal gyrus and globus pallidus were the most severely affected in patients with CCD. The widespread alterations in morphological connectivity, such as the cortico-cortical and cortico-subcortical networks, further support the network mechanism as a basis for CCD.

COVID-19 is spreading widely, and the pandemic is seriously threatening public health throughout the world. A comprehensive study on the optimal sampling types and timing for an efficient SARS-CoV-2 test has not been reported. We collected clinical information and the values of 55 biochemical indices for 237 COVID-19 patients, with 37 matched non-COVID-19 pneumonia patients and 131 healthy people in Inner Mongolia as control. In addition, the results of dynamic detection of SARS-CoV-2 using oropharynx swab, pharynx swab, and feces were collected from 197 COVID-19 patients. SARS-CoV-2 RNA positive in feces specimen was present in approximately one-third of COVID-19 patients. The positive detection rate of SARS-CoV-2 RNA in feces was significantly higher than both in the oropharynx and nasopharynx swab (P < 0.05) in the late period of the disease, which is not the case in the early period of the disease. There were statistically significant differences in the levels of blood LDH, CRP, platelet count, neutrophilic granulocyte count, white blood cell number, and lymphocyte count between COVID-19 and non-COVID-19 pneumonia patients. Finally, we developed and compared five machine-learning models to predict the prognosis of COVID-19 patients based on biochemical indices at disease onset and demographic characteristics. The best model achieved an area under the curve of 0.853 in the 10-fold cross-validation.

Personal ornaments are key archaeological remains to investigate prehistoric symbolic systems, and, whenever hard animal remains were used for their manufacture, explore topics on the status attributed to faunal resources by past human groups. Since the onset of the Upper Paleolithic, animal tooth pendants have been widely used in Eurasia as personal adornments or grave goods. However, only two Late Paleolithic Chinese sites have yielded such adornment types until today, i.e., Zhoukoudian Upper Cave, near Beijing, and Xiaogushan, in the Liaoning Province. Here, we present results from the multidisciplinary analysis of a perforated animal tooth from QG10, a multi-stratified archaeological site located on the Ordos Plateau between the arid and sub-arid belts of Northwest China. Although only partially preserved, zooarchaeological analysis indicates the tooth is a right upper canine of a female red deer (Cervus elaphus). Scraping marks on the labial aspect suggest the tooth was extracted from the animal maxillary shortly after its death. Technological analysis of the perforation confirms it was made by rotation with the help of a lithic point hafted onto a drill. The root and occlusal aspect of the tooth were further modified with five sets of notches and incisions, including four incisions making a hashtag pattern on the occlusal aspect. Technological and morphometric analyses indicate these sets were made by two, perhaps three, individual, i.e., one left-handed and one, perhaps two right-handed, with different tools and techniques. Use wear analysis suggests that the adornment was affixed to the body with the tooth crown facing upward. Finally, chemical characterization of red and black residues still adhering to the root indicates that hematite and charcoal may have been used in the production of an adhesive that would have helped stabilize the personal ornament on the body. Collectively, our results and interpretations shed a new light on the complexity of Late Glacial symbolic system carried by populations living in Northern China. We argue this perforated red deer tooth was introduced in the site following a number of social exchanges over long distance and a long period of time rather than produced in situ.

Abstract Background Epothilone B is a natural product that stabilizes microtubules, similar to paclitaxel (Taxol); therefore, epothilone B and several derivatives have shown obvious antitumour activities. Some of these products are in clinical trials, and one (ixabepilone, BMS) is already on the market, having been approved by the FDA in 2007. The terminal step in epothilone B biosynthesis is catalysed by the cytochrome P450 enzyme EpoK (CYP167A1), which catalyses the epoxidation of the C12–C13 double bond (in epothilone C and D) to form epothilone A and B, respectively. Although redox partners from different sources support the catalytic activity of EpoK in vitro, the conversion rates are low, and these redox partners are not applied to produce epothilone B in heterologous hosts. Results Schlegelella brevitalea DSM 7029 contains electron transport partners that efficiently support the catalytic activity of EpoK. We screened and identified one ferredoxin, Fdx_0135, by overexpressing putative ferredoxin genes in vivo and identified two ferredoxin reductases, FdR_0130 and FdR_7100, by whole-cell biotransformation of epothilone C to effectively support the catalytic activity of EpoK. In addition, we obtained strain H7029-3, with a high epothilone B yield and found that the proportion of epothilone A + B produced by this strain was 90.93%. Moreover, the whole-cell bioconversion strain 7029-10 was obtained; this strain exhibited an epothilone C conversion rate of 100% in 12 h. Further RT-qPCR experiments were performed to analyse the overexpression levels of the target genes. Gene knock-out experiments showed that the selected ferredoxin (Fdx_0135) and its reductases (FdR_0130 and FdR_7100) might participate in critical physiological processes in DSM 7029. Conclusion Gene overexpression and whole-cell biotransformation were effective methods for identifying the electron transport partners of the P450 enzyme EpoK. In addition, we obtained an epothilone B high-yield strain and developed a robust whole-cell biotransformation system. This strain and system hold promise for the industrial production of epothilone B and its derivatives.

Abstract Ips subelongatus is a major pest that infects larch plantations over large areas of northern and northeastern China. Ips species are closely associated with ophiostomatoid fungi that are morphologically well-adapted for dispersal by beetles. These associations result in important threat for coniferous forests worldwide. The aim of this study was to characterize the ophiostomatoid communities associated with I. subelongatus infesting Larix species and sympatric Pinus sylvestris var. mongolica in northeastern China forests. Morphological and multilocus phylogenetic approaches (based on six markers: ITS, LSU, 60S, β-tubulin, EF-1α, and CAL gene regions) allowed identifying 14 species of four genera (Ceratocystiopsis, Endoconidiophora, Leptographium and Ophiostoma). Eight species are showed to be new to science. Most strains resided in two Ophiostoma species complexes, viz. the O. clavatum and the O. ips complexes, all together accounting for 76.8% of all isolates. Ophiostoma hongxingense sp. nov., O. peniculi sp. nov., and O. subelongati sp. nov. (O. clavatum complex) and O. pseudobicolor sp. nov. (O. ips complex) were the four dominant species. The ophiostomatoid communities associated with larch bark beetles, I. cembrae and I. subelongatus, in Europe and Asia, China and Japan, also were compared. These comparisons showed distinct, specific assemblage patterns.

For the surface-mount permanent magnet synchronous motors (SPMSM) with fractional slot concentrated windings, the winding distribution of per phase under different poles is uneven, which results in unbalanced magnetic pull (UMP) between the stator and rotor. UMP has an important impact on the performance and service life of the motor. In this paper, a new permanent magnet (PM) structure is proposed to reduce UMP and torque fluctuation of the fractional slot SPMSM. Furthermore, a 48p/54s SPMSM is taken as an example, the proposed PM structure is optimized by the Taguchi method which can comprehensively consider the control factors and noise factors. The effects of various variables and process error on UMP, torque fluctuation and robustness of results are analyzed respectively. Finally, the optimized PM structure is obtained, which improves the operation stationarity.

Abstract Skin, the largest organ in the human body, is sensitive to external stimuli. In recent years, an increasing number of skin‐inspired electronics, including wearable electronics, implantable electronics, and electronic skin, have been developed because of their broad applications in healthcare and robotics. Physical sensors are one of the key building blocks of skin‐inspired electronics. Typical physical sensors include mechanical sensors, temperature sensors, humidity sensors, electrophysiological sensors, and so on. In this review, we systematically review the latest advances of skin‐inspired mechanical sensors, temperature sensors, and humidity sensors. The working mechanisms, key materials, device structures, and performance of various physical sensors are summarized and discussed in detail. Their applications in health monitoring, human disease diagnosis and treatment, and intelligent robots are reviewed. In addition, several novel properties of skin‐inspired physical sensors such as versatility, self‐healability, and implantability are introduced. Finally, the existing challenges and future perspectives of physical sensors for practical applications are discussed and proposed.

The development of the green economy has significantly impact the traditional mining industry. Mining enterprises must invest in green technology to reduce the environmental pollution caused by flying dust and soil erosion and are subject to increased scrutiny to be socially responsible when conducting their business. To address this issue, we consider a competitive mining supply chain system consisting of two excavators and two exclusive retailers. Among them, the excavators have a certain sense of corporate social responsibility (CSR), that is, in addition to pursuing economic profits, they also consciously pay attention to the interests of consumers. We establish three different game models that two excavators exhibit no CSR behaviour (NN), two excavators exhibit CSR behaviour (SS) and one excavator exhibits CSR behaviour (SN). We examine the optimal decision-making strategies and analyse the impact of social responsibility. Analytical results show that the optimal strategies of mining supply chain are different under different supply chain structures. The optimal decisions of the mining supply chain members are the same in each case under the NN and SS models. In the SN model, the optimal decision strategy value of mining supply chain members is always greater than non-socially responsible supply chain members. In SS model, when the intensity of social responsibility competition is low, two excavators reduce the wholesale price, and retailers reduce the sales price; when the intensity of social responsibility competition is strong, two excavators will increase the wholesale price, and retailers will increase the sales price. These help to promote product sales and increase the profits of the supply chain system. In SN model, with the increase of social responsibility competition intensity, the wholesale price of two excavators and the sales price of retailers first increased and then decreased. Finally, numerical examples illustrated to justify the proposed model.

Background: Ovarian cancer is one of the most common female cancers, with a high incidence worldwide. Aberrant expression of low‐density lipoprotein (LDL) receptor‐related protein 8 (LRP8) and microRNA (miR)-362-3p is involved in the pathogenesis of different cancers. Methods: We aimed to elucidate the underlying mechanism of the miR-362-3p-LRP8 axis in ovarian cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine miR-362-3p and LRP8 expression in ovarian cancer tissues and cells. The luciferase assay was used to determine the relationship between miR-362-3p and LRP8. The function of overexpression of miR-362-3p and LRP8 was determined by assessing the cell viability using the cell counting kit 8 (CCK-8) assay, proliferation using 5′‑bromo-2′-deoxyuridine (BrdU) assay, migration using wound healing assay, invasion using transwell assay, and the protein expression levels of matrix metalloproteinase (MMP)-2, MMP9, and integrin α5 or β1 using western blotting assays in ovarian cancer cells. Results: miR-362-3p expression levels were decreased in ovarian cancer tissues and cells and negatively correlated with LRP8 levels. Overexpression of miR-362-3p dramatically repressed cell growth. Furthermore, overexpression of LRP8 significantly facilitated the proliferation, migration, and invasion of ovarian cancer cells, which counteracted the inhibitory effect of miR-362-3p on ovarian cancer cell growth. Conclusions: We reported that miR-362-3p hampered cell growth by repressing LRP8 expression in ovarian cancer cells. Our results provide new insights into ovarian cancer, involving both miR-362-3p and LRP8, which can be used as potential biomarkers for the treatment of ovarian cancer.

To achieve sustainable operations management of an interbasin water transfer (IBWT) project, we proposed and analyzed decentralized and coordination decision models of water-green-degree (WGD) efforts for the IBWT project, based on the thinking of green supply chain within an extended framework of joint pricing and inventory management. Subsequently, detailed numerical and sensitivity analyses are carried out, which is followed by theoretical and practical insights. The following can be drawn from the research: (1) the IBWT project would achieve better operational performance through making WGD efforts and implementing green supply chain management. (2) Coordination strategy outperforms the decentralized one in terms of the operational performance in the management of IBWT green supply chain. (3) A revenue and cost sharing contract based on Nash bargaining could help promote coordination of the IBWT green supply chain.

Silkworm silk, which is obtained from domesticated Bombyx mori (B. mori), can be produced in a large scale. However, the mechanical properties of silkworm silk are inferior to its counterpart, spider dragline silk. Therefore, researchers are continuously exploring approaches to reinforce silkworm silk. Herein, we report a facile and scalable hot stretching process to reinforce natural silk fibers obtained from silkworm cocoons. Experimental results show that the obtained hot-stretched silk fibers (HSSFs) retain the chemical components of the original silk fibers while being endowed with increased β-sheet nanocrystal content and crystalline orientation, leading to enhanced mechanical properties. Significantly, the average modulus of the HSSFs reaches 21.6±2.8 GPa, which is about twice that of pristine silkworm silk fibers (11.0±1.7 GPa). Besides, the tensile strength of the HSSFs reaches 0.77±0.13 GPa, which is also obviously higher than that of the pristine silk (0.56±0.08 GPa). The results show that the hot stretching treatment is effective and efficient for producing superstiff, strong, and tough silkworm silk fibers. We anticipate this approach may be also effective for reinforcing other natural or artificial polymer fibers or films containing abundant hydrogen bonds.

Currently, hydrogels simultaneously featuring high strength, high toughness, superior recoverability, and benign anti-fatigue properties have demonstrated great application potential in broad fields; thus, great efforts have been made by researchers to develop satisfactory hydrogels. Inspired by the double network (DN)-like theory, we previously reported a novel high-strength/high-toughness hydrogel which had two consecutive energy-dissipation systems, namely, the unzipping of coordinate bonds and the dissociation of the crystalline network. However, this structural design greatly damaged its stretchability, toughness recoverability, shape recoverability, and anti-fatigue capability. Thus, we realized that a soft/ductile matrix is indispensable for an advanced strong tough hydrogel. On basis of our previous work, we herein reported a modified energy-dissipation model, namely, a “binary DN-like structure” for strong tough hydrogel design for the first time. This structural model comprises three interpenetrated polymer networks: a covalent/ionic dually crosslinked tightened polymer network (stiff, first order network), a constrictive crystalline polymer network (sub-stiff, second order network), and a ductile/flexible polymer network (soft, third order network). We hypothesized that under low tension, the first order network served as the sacrificing phase through decoordination of ionic crosslinks, while the second order and third order networks together functioned as the elastic matrix phase; under high tension, the second order network worked as the energy dissipation phase (ionic crosslinks have been destroyed at the time), while the third order network played the role of the elastic matrix phase. Owing to the “binary DN-like” structure, the as-prepared hydrogel, in principle, should demonstrate enhanced energy dissipation capability, toughness/shape recoverability, and anti-fatigue/anti-tearing capability. Finally, through a series of characterizations, the unique “binary DN-like” structure was proved to fit well with our initial theoretical assumption. Moreover, compared to other energy-dissipation models, this structural design showed a significant advantage regarding comprehensive properties. Therefore, we think this design philosophy would inspire the development of advanced strong tough hydrogel in the future.

Surface water and groundwater (SW-GW) are an inseparable whole, having a tightly coupled hydraulic relationship and frequent inter-transformation. As such, the quantitative calculation of water exchange between SW-GW is a difficult challenge. To address this issue, we propose the use of a physically based and distributed hydrological model, called WEP-L, in order to analyze the effects of the SW-GW interaction and its spatiotemporal variation characteristics in the Xiaoqing River basin. We demonstrate that the SW-GW interaction is significantly affected by season. The simulated annual average exchange volume of SW-GW above the control section of Huangtaiqiao Station from 1980 to 2020 is found to be 54.79 m3/s. The exchange volumes of SW-GW in the wet and dry season are 28.69 m3/s and 13.46 m3/s, respectively, accounting for 48.75% and 22.87% of the whole year. In addition, considering two types of climate change scenarios, the exchange capacity of SW-GW increases by 0.42m3/s when the rainfall increases by 5%, while the exchange capacity decreases by only 0.2 m3/s when the temperature increases by 0.2 °C. This study provides insights for the quantification of the SW-GW interaction at the regional scale, which will benefit our understanding of the water cycle and evolution of water resources in Xiaoqing River basin.

A practical and efficient Suzuki coupling of phenols has been developed by using trans-NiCl(o-Tol)(PCy3)2/2PCy3 as a catalyst in the presence of tosyl fluoride as an activator. The key for the direct use of phenols lies in the compatibility of the nickel catalyst with tosyl fluoride (TsF) and its sulfur(VI) fluoride exchange (SuFEx) with CAr-OH. Water has been found to improve the one-pot process remarkably. The steric and electronic effects and the functional group compatibility of the one-pot Suzuki coupling of phenols appear to be comparable to the conventional one of pre-prepared aryl tosylates. A series of electronically and sterically various biaryls could be obtained in good to excellent yields by using 3–10 mol% loading of the nickel catalyst. The applications of this one-pot procedure in chemoselective derivatization of complex molecules have been demonstrated in 3-phenylation of estradiol and estrone.

Decomposition is vital for nutrient cycling and is sensitive to atmospheric nutrient depositions. However, the influences and underlying mechanisms of nutrient deposition on the long-term decomposition of leaves and absorptive roots remain unclear. Here, we explored the responses of leaves and absorptive roots to nutrient deposition (control, +N, +P, and +NP) in Pinus massoniana and Schima superba forests in subtropical China based on two stages (early-stage (1-year) and late-stage (3-year)) of a decomposition experiment. The chemical factions (acid-unhydrolysable residue (AUR), cellulose, and hemicellulose concentrations) and microbial enzymatic activities (hydrolase and oxidase) were also determined. The +N treatment had persistent negative effects on absorptive root decomposition, except for P. massoniana during the late stage. The +P treatment had a positive effect on leaf decomposition in all stages. The +NP treatment had a positive effect on leaf decomposition during the late stage. The increasing decomposition rates of foliar under +P treatment were more correlated with the increasing acid phosphatase activity than chemical factions, indicating a microbial mechanism. The decreasing decomposition rates of roots under +N treatment were weakly correlated with increasing AUR concentrations and strongly correlated with decreasing oxidase activity during the late stage, indicating both chemical and microbial mechanisms. Overall, our findings highlight that, despite contrasting responses to nutrient deposition, the mechanisms underlying aboveground and belowground decomposition tend to converge as decomposition progresses.

Although broiler ascites syndrome (AS) has been extensively studied, its pathogenesis remains unclear. The lack of cardiopulmonary function in broilers causes relative hypoxia in the body; hence, the lung is the main target organ of AS. However, the transcriptome of AS lung tissue in broilers has not been studied. In this study, an AS model was successfully constructed, and lung tissues of three AS broilers and three healthy broilers were obtained for RNA sequencing (RNA-seq) and pathological observation. The results showed that 614 genes were up-regulated and 828 genes were down-regulated in the AS group compared with the normal group. Gene Ontology (GO) functional annotation revealed the following up-regulated genes: FABP4, APLN, EIF2AK4, HMOX1, MMP9, THBS1, TLR4, BCL2; and down-regulated genes: APELA, FGF7, WNT5A, CDK6, IL7, IL7R, APLNR. These genes have attracted much attention in cardiovascular diseases such as pulmonary hypertension. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that multiple metabolic processes were enriched, indicating abnormal lung metabolism of AS in broilers. These findings elucidate the potential genes and signal pathways in the lungs of broilers with AS and provide a potential target for studying the pathogenesis and preventing AS.

Purpose – The purpose of this paper is to explore the impact of supply capacity constraint, water delivery loss and fairness concern on the operational decisions/efficiency of the IBWT supply chain under the random precipitation. Design/methodology/approach – Two game-theoretic decision models for the IBWT supply chain coordination considering water delivery loss without/with fairness concern under the supply capacity constraint and random precipitation are developed, analyzed and compared. On this basis, the corresponding numerical analyses are conducted and compared to derive the corresponding management insights and policy implications. Findings – The research results indicate that the two-part tariff contract could effectively coordinate the IBWT supply chain and achieve operational performance improvement; the binding supply capacity constraint makes the water capacity to be allocated among IBWT distributors in accordance with fair shortage allocation rule and reduces the profit (or utility) of the IBWT supply chain and its members; the existence of fairness concern reduces the utility of the IBWT supply chain and its members; a lower precipitation utilization factor in the case with non-binding capacity constraint is beneficial for improving the profit/utility of the IBWT supply chain while a higher precipitation utilization factor in the case with binding capacity constraint is beneficial for improving the profit/utility of the IBWT supply chain; and reducing the water delivery loss rate, the mainline transfer cost, the branch-line transfer cost, the holding cost and the shortage cost and setting a higher retail price are beneficial for improving the profit/utility of the IBWT supply chain. Originality/value – Two innovative coordination decision models under random precipitation are developed, analyzed and compared through game-theoretic approaches to investigate the impact of supply capacity constraint, water delivery loss and fairness concern on the operational decisions/efficiency of the IBWT supply chain, which have enhanced the optimization decision theory for the operations management of IBWT projects and provided a better decision support for the IBWT stakeholders to make better operations strategies.

Abstract Background Abnormal activation of the classic Wnt signaling pathway is closely related to the occurrence of epithelial cancers. B-cell lymphoma 9 (BCL9), a transcription factor, is a novel oncogene discovered in the classic Wnt pathway and promotes the occurrence and development of various tumors. Ovarian cancer is the gynecological malignant tumor with the highest mortality because it is difficult to diagnose early, and easy to relapse and metastasis. The expression and role of BCL9 in epithelial ovarian cancer (EOC) have not been studied. Thus, in this research, we aimed to investigate the expression and clinical significance of BCL9 in EOC tissues and its effect on the malignant biological behavior of human ovarian cancer cells. Methods We detect the expression of BCL9 in ovarian epithelial tumor tissues and normal ovarian tissues using immunohistochemistry and analyzed the relationship between it and clinicopathological parameters and patient prognosis. The expression of proteins was detected by Western blot. The MTT assay, flow cytometry, the scratch assay, and the transwell assay were used to detect cell proliferation, apoptosis, migration, and invasion, respectively. A total of 374 ovarian cancer tissue samples were collected using TCGA database. A gene set enrichment analysis of BCL9 was performed. Results BCL9 was overexpressed in EOC tissues. The level of BCL9 expression was correlated with the 5-year progression-free survival rate and overall survival rate in ovarian cancer patients and independently predicted the risk of ovarian cancer recurrence. Low BCL9 expression inhibited proliferation, invasion and migration of EOC cells, decreased MMP2 and MMP9 expression of ES-2 cell line, increased the BAX/BCL2 ratio and promoted apoptosis of EOC cells. Conclusion BCL9 is overexpressed in epithelial ovarian tumors, resulting in a poor prognosis for ovarian cancer patients. Low BCL9 expression can promote ovarian cancer cell apoptosis, inhibit proliferation and migration. BCL9 promotes the development of ovarian cancer.

Abstract Background Deep-brain stimulation targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High-frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait, can be limited or cause further impairment. While this can be alleviated via relatively low-frequency stimulation (LFS) in selected patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable-frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial. Methods/design We propose a multicenter, double-blind clinical trial involving 11 study hospitals and an established deep-brain stimulation team. The participants will be divided into a VFS and a constant-frequency stimulation group. The primary outcome will be changes in stand–walk–sit task scores after 3 months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with constant-frequency stimulation. Discussion This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future. Trial registration ClinicalTrials.gov, NCT03053726. Registered on February 15, 2017.

Previous studies have shown that zinc (Zn) accumulation in shoot and grain increased as applied nitrogen (N) rate increased only when Zn supply was not limiting, suggesting a synergistic effect of N on plant Zn accumulation. However, little information is available about the effects of different mineral N sources combined with the presence or absence of Zn on the growth of both shoot and root and nutrient uptake. Maize plants were grown under sand-cultured conditions at three N forms as follows: NO3– nutrition alone, mixture of NO3–/NH4+ with molar ratio of 1:1 (recorded as mixed-N), and NH4+ nutrition alone including zero N supply as the control. These treatments were applied together without or with Zn supply. Results showed that N forms, Zn supply, and their interactions exerted a significant effect on the growth of maize seedlings. Under Zn-sufficient conditions, the dry weight (DW) of shoot, root, and whole plant tended to increase in the order of NH4+ < NO3– < mixed-N nutrition. Compared with NH4+ nutrition alone, mixed-N supply resulted in a 27.4 and 28.1% increase in leaf photosynthetic rate and stomatal conductance, which further resulted in 35.7 and 33.5% of increase in shoot carbon (C) accumulation and shoot DW, respectively. Furthermore, mixed-N supply resulted in a 19.7% of higher shoot C/N ratio vs. NH4+ nutrition alone, which means a higher shoot biomass accumulation, because of a significant positive correlation between shoot C/N ratio and shoot DW (R2 = 0.682***). Additionally, mixed-N supply promoted the greatest root DW, total root length, and total root surface area and synchronously improved the root absorption capacity of N, iron, copper, manganese, magnesium, and calcium. However, the above nutrient uptake and the growth of maize seedlings supplied with NH4+ were superior to either NO3– or mixed-N nutrition under Zn-deficient conditions. These results suggested that combined applications of mixed-N nutrition and Zn fertilizer can maximize plant growth. This information may be useful for enabling integrated N management of Zn-deficient and Zn-sufficient soils and increasing plant and grain production in the future.

Despite Panax notoginseng (Sanchi: the root and rhizome) is globally popular serving as the source of food additives, health-care products, and traditional Chinese medicines (TCMs), the saponin difference between the root (PNR) and two aerial parts (leaf, PNL; flower bud, PNF) that can be vicariously used, remains unclear. Authentication of Sanchi, particular from the Chinese patent medicines (CPMs), poses great challenges. Ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS)-based untargeted metabolomics and quantitative assay by UHPLC-UV were utilized to establish the “Identification Markers” for Sanchi. Targeted monitoring of multiple identification markers was performed for authenticating Sanchi simultaneously from 15 different CPMs. Dimension-enhanced profiling by UHPLC/IM-QTOF-MS in the negative high-definition MSE (HDMSE) mode and in-house library-driven peak annotation could characterize totally 328 ginsenosides (133 from PNR, 125 from PNL, and 161 from PNF). Multivariate statistical analysis of the PNR/PNL/PNF samples (45 batches) identified 27 potential markers. Five major markers (notoginsenoside R1, ginsenosides Rg1, -Rb1, -Rb2, and -Rb3) thereof were quantitatively assayed by a fully validated UHPLC-UV (detected at 203 nm) approach. The application of selective ion monitoring (SIM) of 12 differential saponins coupled with UHPLC separation could precisely identify Sanchi from 15 different CPMs (45 batches). Holistic difference in ginsenosides among three parts of P. notoginseng was unveiled, and the markers deduced may assist to identify the illicit substitution of leaf or flower as the root in the TCM compound formulae. Conclusively, the integration of untargeted metabolomics and quantitative analysis can provide reliable information enabling the precise authentication of TCM.

Understanding the responses of canopy conductance (gc) to environmental factors would help ecologists to obtain further insight into the carbon and water exchange processes and forecast future changes in ecosystems under global climate change. Therefore, we investigated the seasonal and interannual variations in the gc based on 12 years of flux data that were observed by an eddy covariance system in a subtropical coniferous forest. Furthermore, by teasing out the dominant factors step by step, the specific gc responses to environmental factors were clarified, and the divergent responses in contrasting climatic years were determined. The multiyear mean gc was 3.46 ± 0.36 mm·s−1, and the gc peaked in April and declined to a minimum in October in most years. The vapor pressure deficit (VPD) was the most important factor that inhibited the gc, and the gc decreased sharply when the VPDs were greater than 1.8 kPa. Without high VPD stress, the gc increased linearly with air temperature (Ta) when the Ta was below 27 °C, after which it decreased. When the high VPD and Ta stresses were excluded, the gc increased with the net radiation (Rn) following a logistic growth model. The gc increased logarithmically with the soil water content at 5 cm depth (SWC5). The effects of the soil water content at 50 cm depth (SWC50) emerged under water stress or temperature stress conditions, which indicated that the forest utilized deep soil water to defend against environmental stress. Additionally, divergent responses of the gc to environmental factors in different climatic years were found. The results of this study provide detailed information on the gc variations and their specific responses to the environmental factors, which would improve the understanding of gc and help accurately estimate gc.

Objectives Polycyclic aromatic hydrocarbons (PAHs) have been proven to be a risk factor for cardiovascular disease in coke oven workers, and increased plasma viscosity is a signal for higher risk of catching up cardiovascular disease. We want to explore whether the plasma viscosity is affected by the concentration of PAHs.Design Our study is a cross-sectional dose–response study.Setting Participants in this study came from a coke plant in Taiyuan, Shanxi.Participants We used data of 693 coke oven workers in Taiyuan.Primary and secondary outcome measures We assumed that plasma viscosity would increase as the concentration of PAHs metabolites in urine increases. We found that 2-hydroxyfluorene (OHFLU2) and plasma viscosity have a stable linear relationship in different statistical methods.Results We found that plasma viscosity increased by 1.14 (mPa.s,30/s) for each ng/mL of 2-OHFLU urinary (correlation coefficient range: 0.54–1.74, p

Excitatory (glutamatergic) synaptic transmission underlies many aspects of brain activity and the genesis of normal human behavior. The postsynaptic scaffolding proteins SAP90/PSD-95-associated proteins (SAPAPs), which are abundant components of the postsynaptic density (PSD) at excitatory synapses, play critical roles in synaptic structure, formation, development, plasticity, and signaling. The convergence of human genetic data with recent in vitro and in vivo animal model data indicates that mutations in the genes encoding SAPAP1–4 are associated with neurological and psychiatric disorders, and that dysfunction of SAPAP scaffolding proteins may contribute to the pathogenesis of various neuropsychiatric disorders, such as schizophrenia, autism spectrum disorders, obsessive compulsive disorders, Alzheimer’s disease, and bipolar disorder. Here, we review recent major genetic, epigenetic, molecular, behavioral, electrophysiological, and circuitry studies that have advanced our knowledge by clarifying the roles of SAPAP proteins at the synapses, providing new insights into the mechanistic links to neurodevelopmental and neuropsychiatric disorders.

Soil moisture is a crucial component of the water cycle and plays an important role in regional weather and climate. However, owing to the lack of In Situ observations, an accurate understanding of the spatiotemporal variations of soil moisture (SM) on the Tibetan Plateau (TP) is still lacking. In this study, we used three gridded SM products to characterize the spatiotemporal features of SM on the TP during the warm season (May to August). We analyzed the fifth-generation European Centre for Medium-Range Weather Forecasts atmospheric reanalysis (ERA5), Global Land Data Assimilation System (GLDAS), and Soil Moisture Active Passive (SMAP) datasets and used station observation data and triple collocation to quantify product accuracy and consistency. Results of the evaluation based on observation data show that both ERA5 and GLDAS overestimate SM, while the accuracy of SMAP is high. In terms of capturing the temporal variations of SM measured at stations, the performance of ERA5 and that of SMAP are superior to that of GLDAS. According to the evaluation based on triple collocation, SMAP exhibits the smallest random error over the TP and the highest temporal correlation with the unknown true SM in eastern TP. For SMAP, SM variability is the largest in the southern TP. For ERA5 and GLDAS, variability in the western TP is substantially larger than that for SMAP. Low-frequency (30–90 days) variations are the largest contributor to TP SM intraseasonal variability. Relative to SMAP, the contribution of high-frequency variations is low in ERA5 and GLDAS. Land-atmosphere coupling is stronger (weaker) in the western (southeastern) TP, which is relatively dry (wet). Our evaluation of SM product performance over the TP may facilitate the use of these products for disaster monitoring and climate and hydrological studies.

This experiment aimed to synthesize a biomimetic mineralized hydrophilic polyurethane dentin primer containing DDDEEKC peptide (DDDEEKC-PU) to fill dentin tubules and induce mineralization. The degree of conversion (DC) was tested. Dentin samples were acid-etched and treated with DDDEEKC-PU. They were immersed in stimulated human fluid (SBF) for 7, 14 and 28 days. Dentin permeability, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and Vickers hardness were measured. After 28 days, regenerated minerals were deposited on resin tags which were confirmed to be hydroxyapatite (HAp). The minerals reduced the dentin permeability and improved the microhardness. DDDEEKC-PU was able to fill dental tubules immediately and induce mineralization simultaneously.

Introduction: As of June 7, 2021, the outbreak of Coronavirus Disease 2019 (COVID-19) has spread to more than 200 countries. The global number of reported cases is more than 172.9 million, with more than 3.7 million deaths, and the number of infected individuals is still growing rapidly. Consequently, events and activities around the world were canceled or postponed, and the preparation for sporting events were greatly challenged. Under such circumstances, about 11,000 athletes from ~206 countries are arriving in Tokyo for the 32nd Summer Olympic Games. Therefore, it is urgently necessary to assess the occurrence and spread risk of COVID-19 for the Games.Objectives: To explore effective prevention and control measures for COVID-19 in large international events through simulations of different interventions according to risk assessment.Methods: We used a random model to calculate the number of initial infected patients and used Poisson distribution to determine the number of initial infected patients based on the number of countries involved. Furthermore, to simulate the COVID-19 transmission, the susceptible-exposed-symptomatic-asymptomatic-recovered-hospitalized (SEIARH) model was established based on the susceptible-exposed-infectious-recovered (SEIR) mathematical model of epidemic diseases. According to risk assessment indicators produced by different scenarios of the simulated interventions, the risk of COVID-19 transmission in Tokyo Olympic Games was assessed.Results: The current COVID-19 prevention measures proposed by the Japan Olympic Committee need to be enhanced. And large-scale vaccination will effectively control the spread of COVID-19. When the protective efficacy of vaccines is 78.1% or 89.8%, and if the vaccination rate of athletes reaches 80%, an epidemic prevention barrier can be established.

Atezolizumab, an immune checkpoint inhibitor, has been approved for use in clinical practice in non-small cell lung cancer (NSCLC) patients, but potential biomarkers for response stratification still need further screening. In the present study, a total of 399 patients with high-quality ctDNA profiling results were included. The mutation status of ubiquitin-like conjugation (UBL) biological process genes (including ABL1, APC, LRP6, FUBP1, KEAP1, and TOP2A) and clinical information were further integrated. The results suggested that the patients with the clinical characteristics of male or history of smoking had a higher frequency of UBL mutation positivity [UBL (+)]; the patients who were UBL (+) had shorter progression-free survival (PFS) (1.69 vs. 3.22 months, p = 0.0007) and overall survival (8.61 vs. 16.10 months, p < 0.0001) than those patients with UBL mutation negativity [UBL (–)]; and more promising predictive values were shown in the smoker subgroup and ≤ 3 metastasis subgroup. More interestingly, we found the predictor has more performance in TP53-negative cohorts [training in an independent POPLAR and OAK cohorts (n = 200), and validation in an independent MSKCC cohort (n = 127)]. Overall, this study provides a predictor, UBL biological process gene mutation status, not only for identifying NSCLC patients who may respond to atezolizumab therapy but also for screening out the potential NSCLC responders who received other immune checkpoint inhibitors.

The study aims to explore the diagnostic value of anti-GNA11 autoantibody in esophageal squamous cell carcinoma (ESCC) from multiple levels. Autoantibody against GNA11 with the highest diagnostic performance was screened out from the customized protein microarray. A total of 486 subjects including ESCC patients and matched normal controls were recruited in the verification and validation phases by using enzyme-linked immunosorbent assay (ELISA). Western blotting analysis was used to verify the ELISA results. Immunohistochemistry (IHC) was used to evaluate GNA11 expression in ESCC tissues and para-tumor tissues. In addition, a bioinformatics approach was adopted to investigate the mRNA expression of GNA11 in ESCC. Results indicated that the level of anti-GNA11 autoantibody in ESCC patients was significantly higher than that in the normal controls, and it can be used to distinguish ESCC patients from normal individuals in clinical subgroups (p < 0.05), as revealed by both ELISA and Western blotting. The receiver operating characteristic (ROC) curve analysis showed that anti-GNA11 autoantibody could distinguish ESCC patients from normal controls with an area under the ROC curve (AUC) of 0.653, sensitivity of 10.96%, and specificity of 98.63% in the verification cohort and with an AUC of 0.751, sensitivity of 38.24%, and specificity of 88.82% in the validation cohort. IHC manifested that the expression of GNA11 can differentiate ESCC tissues with para-tumor tissues (p < 0.05), but it cannot be used to differentiate different pathological grades and clinical stages (p > 0.05). The mRNA expression of GNA11 in ESCC patients and normal controls was different with a bioinformatics mining with The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data in Gene Expression Profiling Interactive Analysis (GEPIA). In summary, anti-GNA11 autoantibody has the potential to be a new serological marker in the diagnosis of ESCC.

Immunotherapy, a chemotherapy-free process, has emerged as a promising therapeutic strategy to prolong the overall survival (OS) of patients with non-small-cell lung cancer (NSCLC). However, effective stratification factors for immunotherapy remain unclear. The purpose of this study was to discuss the potential stratification factors of NSCLC immunotherapy using immune checkpoint inhibitors (ICIs) by integrating genomic profiling and tumor lesion–type information. In this study, 344 patients with NSCLC, whose clinical and tissue (including metastatic and primary lesions) mutation information was available, were included. The potential gene mutation status for predicting the outcomes of immunotherapy was screened by comparing the difference in mutation frequency between responders and non-responders. Our results indicated that the potential predictors of immunotherapy were significantly different, especially between patients with TP53(+) (including metastatic and primary lesions) and TP53(−) (including metastatic and primary lesions). According to this classification, patients with NSCLC who suggested immunotherapy had a higher OS than those who did not (25 months vs. 7 months, P < 0.0001, hazard ratio = 0.39). Collectively, this study provides a new perspective for screening immunotherapy predictors in NSCLC, suggesting that the TP53 mutation status and source of biopsy tissue should be considered during the development of immunotherapy biomarkers.

Background: Although the correlation between body mass index (BMI) and two-stage revision failure of periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) have been frequently reported, the results remain controversial. Therefore, the correlation between them was systematically evaluated and meta-classified in this study. Methods: Literature on the correlation between BMI and two-stage revision failure of PJI following TJA was retrieved in PubMed, Embase and Cochrane Library due May 2020. Stata 13.0 software and Cochrane Collaboration Review Manager software (RevMan version 5.3) were applied to data synthesis, subgroup analysis, analyses of publication bias, and sensitivity. Results: A total of 15 observational studies included 1267 patients, of which 15 studies were included in systematic review and 11 studies in meta-analysis. Eight studies found a correlation between BMI and two-stage revision failure of PJI following TJA, but seven other studies found no correlation. Meta-analysis found that the risk of two-stage revision failure of PJI following TJA significantly boosted by 3.53 times in patients with BMI ≥ 30 kg/m 2 (OR = 3.53; 95% CI = 1.63–7.64 for the BMI ≥ 30 kg/m 2 vs. BMI < 30 kg/m 2 ) and the risk of two-stage revision failure of PJI following TJA significantly increased by 2.92 times in patients with BMI ≥ 40 kg/m 2 ( OR = 2.92; 95% CI = 1.06–8.03 for the BMI ≥ 40 kg/m 2 vs. BMI < 30 kg/m 2 ). The subgroup analysis showed that significant association was observed among the studies performed in TKA ( OR = 3.63; 95% CI = 2.27–5.82), but not among those conducted in THA ( OR = 3.06; 95% CI = 0.42–22.19). A significant association remained consistent, as indicated by sensitivity analyses. Because there are too few studies that can be combined in the included studies, Egger’s and Begg’s tests were not performed. Conclusion: Meta-analysis suggests that the risk of two-stage revision failure of PJI following TJA significantly boosted in obese patients. However, because there may be publication bias of this study, combined overall systematically evaluated and meta-analysis results, we cannot yet conclude that BMI is associated with two-stage revision failure of PJI following TJA.

Combination therapies with chemotherapy and traditional Chinese medicines are attracted increasing attentions for cancer treatment in China. Shengbai decoction (SBD) is a traditional Chinese compound medicine, composed of 6 traditional Chinese herbs. The aim of this study was to investigate the synergistic anti-tumor activity of SBD with cyclophosphamide (CTX) and the possibly underlying mechanisms in treating the hepatoma 22 (H22) -bearing mice. The liver cancer models in C57BL/6 mice were established by injecting with mouse H22 cancer cells. Results showed that combination treatment with SBD and CTX processed a significantly synergistic anti-tumor effect in H22 tumor-bearing mice. Moreover, SBD could not only improve leukopenia caused by CTX, but prolong the survival time of the mice. Furthermore, SBD could upregulate the expressions of the pro-apoptotic genes, including p53, BAD, Cas3 and Bax, and suppress the expression of anti-apoptotic gene Bcl-2. These results suggested that the combination treatment with SBD and CTX had health improving function and less side effects compared with the administration of CTX alone, and SBD could be a promising adjunct agent for liver cancer chemotherapy.

Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting.Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies.Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (β = 0.09, p < 0.0001), posteriorly [slope (β) = 0.04, p < 0.05], and dorsally (β = 0.07, p < 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (β = 0.06, p = 0.053).Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.

BackgroundNeoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients’ overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients.MethodsThis retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry.ResultsNo severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells.ConclusionsNeoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered

Objective: To validate a patient-reported outcome (PRO) measure for patients with tension-type headache (TTH).Methods: Literature analysis, interview, and group discussion were performed to develop an initial TTH-PRO. Thereafter, the initial scale was pre-evaluation in a small range of patients with TTH, and the expert panel made necessary adjustments based on the content feedback. The clinical test was carried out by using the adjusted initial scale. Based on the test results, the items were screened by the method of classical test theory to form the final scale, and the performance evaluation indicators such as validity, reliability, and responsiveness of the final scale were tested.Results: The final formed TTH-PRO scale contained three domains, six dimensions, and 30 items. The split-half reliability, Cronbach's α coefficients, and construct validity of the scale were acceptable, as was feasibility. The responsiveness in the physiological domain was fair, but the overall responsiveness still needed further clinical validation.Conclusions:The TTH-PRO scale has been developed with extensive patient input and demonstrates evidence for reliability and validity. It is complementary to existing evaluation indicators of TTH, emphasizing the patient's experience. Further studies are needed to optimize its items and to verify its clinical applicability for population in more regions and countries.

In the context of the global pandemic of COVID-19, the use and disposal of medical masks have created a series of ethical and environmental issues. The purpose of this paper is to study and evaluate the high temperature properties and thermal storage stability of discarded-mask (DM)-modified asphalt from a multi-scale perspective using molecular dynamics (MD) simulation and experimental methods. A series of tests was conducted to evaluate the physical, rheological, thermal storage stability and microscopic properties of the samples. These tests include softening point, rotational viscosity, dynamic shear rheology (DSR), Fourier transform infrared (FT-IR) spectroscopy and molecular dynamics simulation. The results showed that the DM modifier could improve the softening point, rotational viscosity and rutting factor of the asphalt. After thermal storage, the DM-modified asphalt produced segregation. The difference in the softening point between the top and bottom of the sample increased from 2.2 °C to 17.1 °C when the DM modifier admixture was increased from 1% to 4%. FT-IR test results showed that the main component of the DM modifier was polypropylene, and the DM-modified asphalt was mainly a physical co-blending process. MD simulation results show that the DM modifier can increase the cohesive energy density (CED) and reduce the fractional free volume (FFV) of asphalt and reduce the binding energy between base asphalt and DM modifier. Multi-scale characterization reveals that DM modifiers can improve the high temperature performance and reduce the thermal storage stability of asphalt. It is noteworthy that both macroscopic tests and microscopic simulations show that 1% is an acceptable dosage level.

Background and Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Anti-tumor associated antigen autoantibodies (TAAbs) can be used as biomarkers for tumor detection. The aim of this study was to identify a reliable TAAb as the diagnostic marker for ESCC. Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to screen candidate genes. The mRNA expression of the key gene was then verified by micro array dataset GSE44021 from the Gene Expression Omnibus (GEO) database and the diag nostic value of the corresponding autoantibody to the key gene in ESCC was detected by enzyme-linked im muno sorbent assay (ELISA). Results: CXCL8 was identified as the key gene. The dataset GSE44021 showed that CXCL8 mRNA expression was prominently over-expressed in ESCC tissues compared with normal tissues. ELISA results showed that the level of anti-CXCL8 autoantibody in ESCC patients was significantly higher than in normal controls and the receiver operating char ac teristic (ROC) curve indicated that anti-CXCL8 autoantibody could discriminate ESCC patients from normal controls, with the area under the ROC curve (AUC) for the verification cohort, and the validation cohort were 0.713 and 0.751, respectively. Conclusions: Our study illustrated that anti-CXCL8 autoantibody had good diagnostic value, and may become a candidate biomarker for ESCC.

Microplastics (MPs) have been proven to be one of the major threats to the wastewater treatment system. However, the impact of MPs on microalgae-based wastewater treatment technology are still unknown. In this study, effects of polyvinyl chloride (PVC), polypropylene (PP), and polyethylene (PE) on the removal of nitrogen and phosphorus from synthetic piggery digestate by microalgae were investigated. Results show that the effect of PVC particle size on the growth of microalgae was significant. The effects of PVC content, PP particle size and content, PET particle size and content on the growth of microalgae were all not significant. The removal of ammonia nitrogen by microalgae was influenced significantly by PVC particle size and content, PP particle size and content, the effects of PET particle size and content on the removal of ammonia nitrogen were all not significant. The effects of particle size and content for three MPs on the removal of total phosphorus were all significant. Microalgae cells were bound together after being adsorbed by MPs, which increased the secretion of extracellular polymers and influenced the removal of ammonia nitrogen and total phosphorus.

The present study aimed to explore the effect of intermittent theta-burst stimulation (iTBS) on visual working memory for people suffering from methamphetamine use disorder (MUD). Five sessions of iTBS were carried over the left dorsolateral prefrontal cortex (DLPFC) or the vertex as a sham control, with each session in one day. Orientation free-recall tasks were conducted before the iTBS stimulation, after the first and fifth sessions of stimulation. Results showed that when compared with the sham group, a single session of iTBS over the left DLPFC improved participants’ working memory performance. Specifically, iTBS over the left DLPFC increased the working memory capacity and such effects enlarged with multiple sessions. The present finding suggested that iTBS over DLPFC could be a promising intervention method to enhance the cognitive function of addicts with MUD.

The massive amounts of dust formed during bamboo CNC milling presents serious risks to human health and equipment. The present study aimed to determine the particle size distribution (PSD) and shape characteristics of bamboo milling dust derived from different average chip thicknesses. Spindle speed and feed rate were varied in combination, in setting up two experimental groups having the same average chip thicknesses. Sieving and flatbed scanning image analyses were collectively utilized for the morphological analysis of bamboo dust. The results showed that less than 5% of the particles were below 100 μm in terms of mass, but represented more than 83% in number. Average chip thickness was positively correlated with a mass proportion of bamboo dust with large size, which was preferably generated when reducing spindle speed instead of increasing feed rate. Spindle speed and feed rate individually affected the particle size and particle size distribution instead of average chip thickness. The aspect ratio, roundness and convexity of bamboo milling dust were augmented with a reduction in particle size, indicating that bamboo milling dust with smaller size had more a regular shape, a smoother profile and fewer corners. These findings provide a theoretical basis for better understanding bamboo milling dust and its related control in the bamboo processing industry.

Four actinomycete strains isolated from the coral Acropora austera and coral sand samples from the South China Sea, were found to produce a series of halogenated compounds baring similar ultraviolet absorption based on the analysis of HPLC and LC-MS. The production titers of halogenated compounds from Streptomyces diacarni SCSIO 64983 exceeded those of other similar strains leading us to focus on SCSIO 64983. Four new thiocarbazomycins A–B (1–2), chlocarbazomycin E (3), and brocarbazomycin A (4), together with three known chlocarbazomycins A–C (5–7) containing a carbazole core were identified, and their structures were determined using a combination of spectroscopic analysis including HRESIMS, 1D and 2D NMR. Structurally speaking, compounds 1 and 2 have the rare sulfur-containing carbazole nuclei, and 3 and 4 contain Cl and Br atoms, respectively. Although these compounds have not yet been found to have obvious biological activity, their discovery highlights the role of molecular libraries in subsequent drug discovery campaigns.

The leaves of Panax species (e.g., Panax ginseng-PGL, P. quinquefolius-PQL, and P. notoginseng-PNL) can serve as a source for healthcare products. Comprehensive characterization and unveiling of the metabolomic difference among PGL, PQL, and PNL are critical to ensure their correct use. For this purpose, enhanced profiling and chemometrics were integrated to probe into the ginsenoside markers for PGL/PQL/PNL by ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS). A hybrid scan approach (HDMSE-HDDDA) was established achieving the dimension-enhanced metabolic profiling, with 342 saponins identified or tentatively characterized from PGL/PQL/PNL. Multivariate statistical analysis (33 batches of leaf samples) could unveil 42 marker saponins, and the characteristic ginsenosides diagnostic for differentiating among PGL/PQL/PNL were primarily established. Compared with the single DDA or DIA, the HDMSE-HDDDA hybrid scan approach could balance between the metabolome coverage and spectral reliability, leading to high-definition MS spectra and the additional collision-cross section (CCS) useful to differentiate isomers.

The polysaccharides (PS) have been widely used as biomaterials in drug delivery, due to their excellent biocompatibility, ease of functionalization, and intrinsic biological activities. Among the various PS-based biomaterials, the self-assembled PS nanogels (NG) featuring facile preparation are attracting evergrowing interests in various biomedical applications. Specifically, NG derived from the self-assembly of natural PS well maintain both the physicochemical and biological properties of PS while avoiding the chemical modification or alteration of PS structure, representing a potent drug delivery system for various therapeutic agents. In this review, the natural PS, such as chitosan, alginate, and hyaluronan, for self-assembled NG construction and their advantages in the applications of drug delivery have been summarized. The residues, such as amine, carboxyl, and hydroxyl groups, on these PS provide multiple sites for both ionic cross-linking and metal coordination, which greatly contribute to the formation of self-assembled NG as well as the drug loading, thus enabling a wide biomedical application of PS NG, especially for drug delivery. Future developments and considerations in the clinical translation of these self-assembled PS NG have also been discussed.

Summary: Wearable electronics are receiving increasing attention with the advances of human society and technologies. Among various types of wearable electronics, electronic fibers/textiles, which integrate the comfort and appearance of conventional fibers/textiles with the functions of electronic devices, are expected to play important roles in remote health monitoring, disease diagnosis/treatment, and human-machine interface. This article aims to review the recent advances in electronic fibers/textiles, thus providing a comprehensive guiding reference for future work. First, we review the selection of functional materials and fabrication strategies of fiber-shaped electronic devices with emphasis on the newly developed functional materials and technologies. Their applications in sensing, light emitting, energy harvest, and energy storage are discussed. Then, the fabrication strategies and applications of electronic textiles are summarized. Furthermore, the integration of multifunctional electronic textiles and their applications are summarized. Finally, we discuss the existing challenges and propose the future development of electronic fibers/textiles.