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Background: Maduramicin (MAD) is an anticoccidial veterinary drug, but it frequently causes fatal poisonings in poultry, livestock, or humans. However, there is no specific antidote or guidance on first aid for MAD poisoning. Aim: The aim of the present study is to evaluate the acute toxicity and toxicokinetics of MAD after oral exposure, so as to make a foundation for developing diagnostic and therapeutic protocols for human intoxication. Methods: Five groups of rats (eight-to-nine-week-old male Wistar rats) were orally administered MAD via gavage at doses of 0, 4.64, 10.0, 21.5, or 46.4 mg/kg bw for only one time. The survival rates of the rats were observed over the following 14 days to assess acute toxicity. To evaluate the toxic effects of MAD, two doses (4.8 mg/kg bw and 10 mg/kg bw) were orally administered via gavage. Biochemical parameters including creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, urea, creatinine, serum myoglobin, and urinary myoglobin were measured. Liver, kidney, heart, and hind limb skeletal muscle samples from severely poisoned rats were obtained for pathological examination. For toxicokinetic analysis, samples of serum, urine, and feces from the 4.8 mg/kg bw dose group were analyzed using high-performance liquid chromatography-tandem mass spectrometry. Results: The LD50 of MAD in male Wistar rats was determined to be 6.81 mg/kg bw. In the 10 mg/kg bw group, elevated serum urea levels and increased myoglobin levels in both serum and urine indicated renal injury and potential muscle damage. Toxicokinetics in serum revealed that following oral administration of 4.8 mg/kg bw MAD, peak serum concentration of 59.8 ± 8.9 μg/L was achieved at 30.0 ± 13.9 h. MAD exhibited a slow elimination from the blood with an elimination half-life of 72.9 ± 36.8 h and a mean residence time of 79.6 ± 25.5 h. Additionally, fecal excretion of MAD was found to be greater than urinary excretion. Conclusion: MAD is a highly toxic veterinary drug which requires careful handling. The primary effects of poisoning include kidney injury and suspected rhabdomyolysis. It is excreted very slowly after oral administration. Promoting toxin excretion in individuals poisoned by MAD could potentially serve as an effective treatment method until a specific antidote is identified.

Objectives: This study aimed to analyze each myocardial segment's ischemic burden, scarring, function, and viability by late gadolinium enhancement (LGE) imaging and stress-MRI using adenosine. Materials and methods: Semi-quantitative and qualitative parameters of myocardial segments were obtained by stress-MRI. Moreover, segments without perfusion defect were defined as the no ischemic group, segments with a perfusion defect of ≤50% were defined as a low ischemic burden group, and segments with a perfusion defect of >50% were defined as a high ischemic burden group. “Segmental wall thickening (SWT)” was defined as the absolute difference between the end-diastolic and end-systolic wall thickness. Finally, viability was defined by dysfunctional myocardium (50%. Among the different ischemic burden groups, there were significant differences in LGE volume (p ​ ​0.05). Conclusions: Stress MRI parameters can accurately and detailly assess myocardial viability and function, so multi-parameter joint assessment of CTO patients by stress MRI may help in treatment decisions.

Modern insecticide substitutes using acetylcholine receptors (nAChR) as biochemical targets, such as neonicotinoid insecticides (NNIs), have been extensively researched. Only 12 compounds have been experimentally realized since the initial discovery of imidacloprid. Increasingly, the bottleneck in this field is to rapidly determine the synthesizability of NNI substitutes. Here, we designed a coupled evaluation system for synthesis prediction and validation, including the synthesis probability, reaction path difficulty, and electron transfer characteristics of NNIs and their substitutes. Firstly, a total of 1475 eigenvalues were generated and 52 critical eigenvalues were screened out through the Pearson’s correlation coefficient. The positive and unlabeled (PU) machine learning was constructed using the critical eigenvalues NNIs, including 12 experimentally synthesized NNIs (positive samples) and 73 unsynthesized NNI substitutes (unlabeled samples). Results identified 3 NNI substitutes that were highly promising candidates for synthesis (synthesis probability > 0.5). The results of density functional theory demonstrated the ranking of their reaction ease was UN-1 (31.4 kcal/mol) > UN-2 (81.6 kcal/mol) > UN-3 (3.35 ×103 kcal/mol). Time-dependent density functional theory revealed that changes in the electron distribution and electron excitation type were critical factors affecting their synthesizability, and the local excitation type was more favorable for the synthesizability of NNI substituents. The findings provide significant guidance for NNIs synthesis, reducing the possible space of unlabeled samples to 95.89% of their original size, while also minimizing the cost of research on subsequent NNI substitutes.

Moiré materials provide fertile ground for the correlated and topological quantum phenomena. Among them, the quantum anomalous Hall (QAH) effect, in which the Hall resistance is quantized even under zero magnetic field, is a direct manifestation of the intrinsic topological properties of a material and an appealing attribute for low-power electronics applications. The QAH effect has been observed in both graphene and transition metal dichalcogenide (TMD) moiré materials. It is thought to arise from the interaction-driven valley polarization of the narrow moiré bands. Here, we show that the newly discovered QAH state in AB-stacked MoTe_{2}/WSe_{2} moiré bilayers is not valley polarized but valley coherent. The layer- and helicity-resolved optical spectroscopy measurement reveals that the QAH ground state possesses spontaneous spin (valley) polarization aligned (antialigned) in two TMD layers. In addition, saturation of the out-of-plane spin polarization in both layers occurs only under high magnetic fields, supporting a canted spin texture. Our results call for a new mechanism for the QAH effect and highlight the potential of TMD moiré materials with strong electronic correlations and spin-orbit interactions for exotic topological states.

Cancer, the second largest human disease, has become a major public health problem. The prediction of chemicals’ carcinogenicity before their synthesis is crucial. In this paper, seven machine learning algorithms (i.e., Random Forest (RF), Logistic Regression (LR), Support Vector Machines (SVM), Complement Naive Bayes (CNB), K-Nearest Neighbor (KNN), XGBoost, and Multilayer Perceptron (MLP)) were used to construct the carcinogenicity triple classification prediction (TCP) model (i.e., 1A, 1B, Category 2). A total of 1444 descriptors of 118 hazardous organic chemicals were calculated by Discovery Studio 2020, Sybyl X-2.0 and PaDEL-Descriptor software. The constructed carcinogenicity TCP model was evaluated through five model evaluation indicators (i.e., Accuracy, Precision, Recall, F1 Score and AUC). The model evaluation results show that Accuracy, Precision, Recall, F1 Score and AUC evaluation indicators meet requirements (greater than 0.6). The accuracy of RF, LR, XGBoost, and MLP models for predicting carcinogenicity of Category 2 is 91.67%, 79.17%, 100%, and 100%, respectively. In addition, the constructed machine learning model in this study has potential for error correction. Taking XGBoost model as an example, the predicted carcinogenicity level of 1,2,3-Trichloropropane (96−18−4) is Category 2, but the actual carcinogenicity level is 1B. But the difference between Category 2 and 1B is only 0.004, indicating that the XGBoost is one optimum model of the seven constructed machine learning models. Besides, results showed that functional groups like chlorine and benzene ring might influence the prediction of carcinogenic classification. Therefore, considering functional group characteristics of chemicals before constructing the carcinogenicity prediction model of organic chemicals is recommended. The predicted carcinogenicity of the organic chemicals using the optimum machine leaning model (i.e., XGBoost) was also evaluated and verified by the toxicokinetics. The RF and XGBoost TCP models constructed in this paper can be used for carcinogenicity detection before synthesizing new organic substances. It also provides technical support for the subsequent management of organic chemicals.

Brain morphometric alterations involve multiple brain regions on progression of the disease in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and exhibit age-related degenerative changes during the pathological aging. Recent advance in brain morphometry as measured using MRI have leveraged Person-Based Similarity Index (PBSI) approach to assess the extent of within-diagnosis similarity or heterogeneity of brain neuroanatomical profiles between individuals of healthy populations and validate in neuropsychiatric disorders. Brain morphometric changes throughout the lifespan would be invaluable for understanding regional variability of age-related structural degeneration and the substrate of inflammatory demyelinating disease. Here, we aimed to quantify the neuroanatomical profiles with PBSI measures of cortical thickness (CT) and subcortical volumes (SV) in 263 MS, 207 NMOSD, and 338 healthy controls (HC) from six separate central datasets (aged 11–80). We explored the between-group comparisons of PBSI measures, as well as the advancing age and sex effects on PBSI measures. Compared to NMOSD, MS showed a lower extent of within-diagnosis similarity. Significant differences in regional contributions to PBSI score were observed in 29 brain regions between MS and NMOSD (P

Polybrominated biphenyls (PBBs) can bioaccumulate in nature and are toxic to humans. Long-time exposure to PBBs in pregnant women can lead to the birth of an infant with abnormal conditions. Hence, in this study, we used molecular docking, molecular dynamics, Taguchi experimental design, and fractional factorial experimental design to identify the developmental toxicity characteristics of 10 typical developmental toxic pollutants such as PBBs to which humans are frequently exposed. Furthermore, the correlation and sensitivity analyses of molecular developmental toxicity and structural parameters were performed. The molecular key structural parameters of the pollutants affecting human development were screened. Moreover, the supplementary food factors that could alleviate the developmental toxicity of pollutants were screened to develop supplementary food schemes to prevent or alleviate human developmental toxicity in the special population (e.g., pregnant women, infants) exposed to the pollutants. The results showed that the developmental toxicity was controlled by the main effects of the 10 pollutants. Among the 10 pollutants with developmental toxicity, the most significant pollutant with the main effects was PBB-153 (37.06%). In addition, the correlation and sensitivity analyses of the molecular developmental toxicity of the pollutants and structural parameters showed that the total energy value and infrared C–H vibration frequency of the pollutants were significantly correlated with human developmental toxicity. Accordingly, 15 supplementary food cofactors were selected for the Taguchi experiment design, among which the top seven cofactors were designed by fractional factorial analysis. The most significant cofactor that alleviated the developmental toxicity of PBB-153 exposure was the combination of carotene and docosahexaenoic acid (DHA), with an improvement of 17.28%. The combination of carotene and DHA significantly alleviated the effects of toxicity caused by most of the other pollutants, indicating that the selected supplementary food has certain universality. In this study, we developed a method to identify the characteristics of the developmental toxicity of pollutant exposure and developmental toxicity alleviation. Our study provided theoretical support for the regulation strategy of developmental toxicity caused by pollutants such as PBBs.

From the end of 2018 in China, the Big-data Driven Price Discrimination (BDPD) of online consumption raised public debate on social media. To study the consumers’ attitude about the BDPD, this study constructed a semantic recognition frame to deconstruct the Affection-Behavior-Cognition (ABC) consumer attitude theory using machine learning models inclusive of the Labeled Latent Dirichlet Allocation (LDA), Long Short-Term Memory (LSTM), and Snow Natural Language Processing (NLP), based on social media comments text dataset. Similar to the questionnaires published results, this article verified that 61% of consumers expressed negative sentiment toward BDPD in general. Differently, on a finer scale, this study further measured the negative sentiments that differ significantly among different topics. The measurement results show that the topics “Regular Customers Priced High” (69%) and “Usage Intention” (67%) occupy the top two places of negative sentiment among consumers, and the topic “Precision Marketing” (42%) is at the bottom. Moreover, semantic recognition results that 49% of consumers’ comments involve multiple topics, indicating that consumers have a pretty clear cognition of the complex status of the BDPD. Importantly, this study found some topics that had not been focused on in previous studies, such as more than 8% of consumers calling for government and legal departments to regulate BDPD behavior, which indicates that quite enough consumers are losing confidence in the self-discipline of the platform enterprises. Another interesting result is that consumers who pursue solutions to the BDPD belong to two mutually exclusive groups: government protection and self-protection. The significance of this study is that it reminds the e-commerce platforms to pay attention to the potential harm for consumers’ psychology while bringing additional profits through the BDPD. Otherwise, the negative consumer attitudes may cause damage to brand image, business reputation, and the sustainable development of the platforms themselves. It also provides the government supervision departments an advanced analysis method reference for more effective administration to protect social fairness.

Based initially on microfossils, Nostolepis is one of the first known ‘acanthodians’, which constitute a paraphyletic assemblage of plesiomorphic members of the total group Chondrichthyes. Its wide distribution has potential implications for stratigraphic comparisons worldwide. Six species of Nostolepis have been reported in China, including one species from the Xitun Formation (Lochkovian, Lower Devonian) of Qujing, eastern Yunnan. Acid preparation of rock samples from the Xitun Formation has yielded abundant acanthodian remains. Based on both morphological and histological examinations, here we identify five species of Nostolepis, including two new species. N. qujingensis sp. nov. is characterized by thin scales devoid of the neck anteriorly and the dentine tubules rarely present in the anterior part of the crown. N. digitus sp. nov. is characterized by parallel ridges on anterior and lateral margins of the crown, and the neck constricted and ornamented with pore openings. We extend the duration of N. striata in China from the Pridoli of Silurian (Yulungssu Formation) to the Lower Devonian in Qujing and report the first occurrences of N. amplifica and N. consueta in this region. This study increases the diversity of the Lower Devonian Xitun Fauna and provides a better understanding of the paleogeographic distribution of Nostolepis.

Galeaspids are an endemic clade of jawless stem-gnathostomes known as ostracoderms. Their existence illuminates how specific characteristics developed in jawed vertebrates. Sinogaleaspids are of particular interest among the galeaspids but their monophyly is controversial because little is known about Sinogaleaspis xikengensis. Newly discovered sinogaleaspids from the Lower Silurian of Jiangxi, China provide a wealth of data and diagnostic features used to establish the new genus, Rumporostralis gen. nov., for Sinogaleaspis xikengensis. A morphological study showed that the sensory canal system of sinogaleaspids had mosaic features similar to those of three known galeaspids. There are 3–8 pairs of transverse canals in the Sinogaleaspidae, which suggests that the sensory canal system of galeaspid probably had a grid distribution with transverse canals arranged throughout the cephalic division. Phylogenetic analysis of Galeaspida supports the monophyly of the Sinogaleaspidae, consisting of Sinogaleaspis, Rumporostralis, and Anjiaspis. However, Shuyu and Meishanaspis form another monophyletic group, Shuyuidae fam. nov., which is outside all other eugaleaspidiforms. We propose a cladistically-based classification of Galeaspida based on our analysis.

The Sinacanthida ordo nov. and Mongolepidida are spine- and scale-based taxa whose remains encompass some of the earliest reported fossils of chondrichthyan fish. Investigation of fragmentary material from the Early Silurian Tataertag and Ymogantau Formations of the Tarim Basin (Xinjiang Uygur Autonomous Region, China) has revealed a diverse mongolepidid and sinacanthid fauna dominated by mongolepids and sinacanthids in association with abundant dermoskeletal elements of the endemic 'armoured' agnathans known as galeaspids. Micro-computed tomography, scanning electron microscopy and histological sections were used to identify seven mongolepid genera (including Tielikewatielepis sinensis gen. et sp. nov., Xiaohaizilepis liui gen. et sp. nov. and Taklamakanolepis asiaticus gen. et sp. nov.) together with a new chondrichthyan (Yuanolepis bachunensis gen. et sp. nov.) with scale crowns consisting of a mongolepid-type atubular dentine (lamellin). Unlike the more elaborate crown architecture of mongolepids, Yuanolepis gen. nov. exhibits a single row of crown elements consistent with the condition reported in stem chondrichthyans from the Lower Devonian (e.g. in Seretolepis, Parexus). The results corroborate previous work by recognising lamellin as the main component of sinacanthid spines and point to corresponding developmental patterns shared across the dermal skeleton of taxa with lamellin and more derived chondrichthyans (e.g. Doliodus, Kathemacanthus, Seretolepis and Parexus). The Tarim mongolepid fauna is inclusive of coeval taxa from the South China Block and accounts for over two-thirds of the species currently attributed to Mongolepidida. This demonstrates considerable overlap between the Tarim and South China components of the Lower Silurian Zhangjiajie Vertebrate Fauna.

Evidence for the quantum spin Hall effect (QSHE) has been reported in several experimental systems, in the form of edge conductance approaching a quantized value at zero magnetic field. However, another fundamental feature of the QSHE, that of spin-momentum locking in the edge channel, has not been demonstrated. Here, we report that in an applied magnetic field the edge conductance in monolayer WTe_{2}, a candidate QSHE material, is suppressed by the component of the field perpendicular to a particular axis, implying that the spin in the edge states lies along this axis. Surprisingly, the axis is independent of edge orientation, chemical potential, and sample, being fixed relative to the monolayer crystal structure, lying at (40±2)° to the layer normal within the mirror plane. This finding is consistent with a theoretical model in which the bulk bands nearest the Fermi energy have the same parity, leading to simple spin texture with a single, momentum-independent spin axis that is inherited by the edge modes. In addition, the results strengthen the case for spin-momentum locking and, therefore, that monolayer WTe_{2} is a natural two-dimensional topological insulator exhibiting the QSHE.

Various processes were used to prepare Zr-0.4Sn-1Nb-0.3Fe zirconium alloy plate samples, including hot rolling at 620,650,700℃ without aging and hot rolling at 700℃ after aging with 10 and 50 h at 480℃, respectively. The second phase particles (SPPs) of Zr-0.4Sn-1Nb-0.3Fe zirconium alloy were investigated by SEM and TEM. The results show that the mean diameter of SPPs is within 100 nm under different process conditions. Homogeneous and fine secondary phases distribute dispersively at 620℃, and most of these SPPs are Zr(Nb,Fe)2 with a C14 hexagonal close packed (HCP) structure. When hot rolling at 650℃, the β-Nb precipitates are also observed in addition to Zr(Nb,Fe)2 particles, and the distribution of SPPs is bunching and clustering. As the hot rolling temperature increases to 700℃, the SPPs present in a wide variety of sizes and non-uniform distribution, and the number of β-Nb particles increases. Aging prior to hot rolling is helpful to improve the uniform distribution of SPPs, as the aging time extends, the mean diameter of SPPs becomes larger. With the increase of hot rolling temperature, the average Nb/Fe ratio of Zr-Nb-Fe particles increases firstly and then decreases at the range of 620℃ to 700℃, aging processing leads to the further reduce of Nb/Fe ratio. Therefore, homogeneous and fine secondary phases distribute dispersively can be obtained when hot rolling at 620℃, which is beneficial to improve the combination property of zirconium alloys. Key words: Hot rolling, Zr-Sn-Nb-Fe zirconium alloy, Second phase particles, Aging treatment

The 438-370-million-year-old galeaspids, diversified armoured jawless vertebrates ('ostracoderms') from China and northern Vietnam, were assumed to have a benthic feeding habit in a coastal, marine environment. Here, we describe two new genera of galeaspid fishes, Platylomaspis gen. nov. and Nanningaspis gen. nov. from the Middle Palaeozoic of China. The two new forms are characterized by a rostral process and strikingly broad ventral rim, and clustered with Gumuaspis to form a new family, Gumuaspidae, which represents the most primitive clade of Polybranchiaspiformes. They extend the earliest occurrence of Polybranchiaspiformes backward about 19 million years, and expand its geographical distribution from southern China and northern Vietnam to the Tarim Basin, northwestern China. The new taxa exhibit many morphological convergences with modern rays, and might specify a new kind of lifestyle of galeaspids, the half burrowing habit. Probably benefiting from the new lifestyle, the Gumuaspidae has become the longest lasting galeaspid family. The new findings demonstrated that the demersal galeaspids had developed three different kinds of lifestyles: semi-infaunal benthic (half buried), epibenthic, and suprabenthic (nektonic) habits to accommodate to differentiated ecological niches, and reached the peak of their diversity by the Pragian of the Early Devonian.

Our understanding of early gnathostome evolution has been hampered by a generally scant fossil record beyond the Devonian. Recent discoveries from the late Silurian Xiaoxiang Fauna of Yunnan, China, have yielded significant new information, including the earliest articulated osteichthyan fossils from the Ludlow-aged Kuanti Formation. Here we describe the partial postcranium of a new primitive bony fish from the Kuanti Formation that represents the second known taxon of pre-Devonian osteichthyan revealing articulated remains. The new form, Sparalepis tingi gen. et sp. nov., displays similarities with Guiyu and Psarolepis, including a spine-bearing pectoral girdle and a placoderm-like dermal pelvic girdle, a structure only recently identified in early osteichthyans. The squamation with particularly thick rhombic scales shares an overall morphological similarity to that of Psarolepis. However, the anterior flank scales of Sparalepis possess an unusual interlocking system of ventral bulges embraced by dorsal concavities on the outer surfaces. A phylogenetic analysis resolves Sparalepis within a previously recovered cluster of stem-sarcopterygians including Guiyu, Psarolepis and Achoania. The high diversity of osteichthyans from the Ludlow of Yunnan strongly contrasts with other Silurian vertebrate assemblages, suggesting that the South China block may have been an early center of diversification for early gnathostomes, well before the advent of the Devonian "Age of Fishes".

This study describes the first general optimization model for complex systems with uncertain parameters and decision variables represented as intervals in CDM forestry projects. We work through a specific example of the optimization method developed for a Clean Development Mechanism (CDM) forestry project in Inner Mongolia, China. This model is designed to optimize the carbon sink capacity of the new forests, and can deal with uncertainties in the carbon sink capacity, average annual rainfall, ecological parameters, and biological characteristics of tree species. The uncertain inputs are presented in the form of intervals, as are several of the optimized output variables. Compared with the project’s originally recommended scheme, the optimized model will absorb and fix between 1,142 and 885,762 tonnes of extra carbon dioxide. Moreover, the ecological and environmental benefits of the project are also raised to various extents.

BACKGROUND: The pectoral and pelvic girdles support paired fins and limbs, and have transformed significantly in the diversification of gnathostomes or jawed vertebrates (including osteichthyans, chondrichthyans, acanthodians and placoderms). For instance, changes in the pectoral and pelvic girdles accompanied the transition of fins to limbs as some osteichthyans (a clade that contains the vast majority of vertebrates--bony fishes and tetrapods) ventured from aquatic to terrestrial environments. The fossil record shows that the pectoral girdles of early osteichthyans (e.g., Lophosteus, Andreolepis, Psarolepis and Guiyu) retained part of the primitive gnathostome pectoral girdle condition with spines and/or other dermal components. However, very little is known about the condition of the pelvic girdle in the earliest osteichthyans. Living osteichthyans, like chondrichthyans (cartilaginous fishes), have exclusively endoskeletal pelvic girdles, while dermal pelvic girdle components (plates and/or spines) have so far been found only in some extinct placoderms and acanthodians. Consequently, whether the pectoral and pelvic girdles are primitively similar in osteichthyans cannot be adequately evaluated, and phylogeny-based inferences regarding the primitive pelvic girdle condition in osteichthyans cannot be tested against available fossil evidence. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first discovery of spine-bearing dermal pelvic girdles in early osteichthyans, based on a new articulated specimen of Guiyu oneiros from the Late Ludlow (Silurian) Kuanti Formation, Yunnan, as well as a re-examination of the previously described holotype. We also describe disarticulated pelvic girdles of Psarolepis romeri from the Lochkovian (Early Devonian) Xitun Formation, Yunnan, which resemble the previously reported pectoral girdles in having integrated dermal and endoskeletal components with polybasal fin articulation. CONCLUSIONS/SIGNIFICANCE: The new findings reveal hitherto unknown similarity in pectoral and pelvic girdles among early osteichthyans, and provide critical information for studying the evolution of pelvic girdles in osteichthyans and other gnathostomes.