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This article presents a wideband sub-terahertz (sub-THz) inline transition from microstrip line (MSL) to rectangular waveguide (RWG). The transition employs the bow-tie antenna to achieve a compact inline transition and wideband impedance matching with the RWG, resulting in bigger bandwidths than the transitions using dipoles. In order to overcome the substrate width limitations of conventional probes, the perfect magnetic conductor (PMC) packaging concept is used in this article, resulting in a better integration ability with large-sized monolithic microwave integrated circuits (MMICs). Two back-to-back transition prototypes related to different angles of the bow-tie antenna have been fabricated to evaluate the transition performances in the sub-THz band. The tested large-sized substrates have a large width of 10.826 mm and a length of 10.8 mm, and the length of the MSL is 9.28 mm. According to the experimental results, in the 110–170-GHz band, prototype I has a reflection coefficient of less than -11 dB and an insertion loss of 1.79–2.6 dB, while prototype II has a reflection coefficient of less than -8.5 dB and an insertion loss of 1.52–2.5 dB.

Sensing is envisioned as a key network function of the sixth-generation (6G) mobile networks. Artificial intelligence (AI)-empowered sensing fuses features of multiple sensing views from devices distributed in edge networks for the edge server to perform accurate inference. This process, known as multi-view pooling, creates a communication bottleneck due to multi-access by many devices. To alleviate this issue, we propose a task-oriented simultaneous access scheme for distributed sensing called Over-the-Air Pooling (AirPooling). The existing Over-the-Air Computing (AirComp) technique can be directly applied to enable Average-AirPooling, which exploits the waveform superposition property of a multi-access channel to implement fast over-the-air averaging of pooled features. However, despite being most popular in practice, the over-the-air maximization, called Max-AirPooling, is not AirComp realizable given the fact that AirComp addresses only a limited subset of functions. We tackle the challenge by proposing the novel generalized AirPooling framework that can be configured to support both Max- and Average-AirPooling by controlling a configuration parameter and extended to even other pooling functions. The former is realized by adding to AirComp the designed pre-processing at devices and post-processing at the server. To characterize the End-to-End (E2E) sensing performance in object recognition, the theory of classification margin is applied to relate the classification accuracy and the AirPooling error, which allows the latter to be a tractable surrogate of the former. Furthermore, the analysis reveals an inherent tradeoff of Max-AirPooling between the accuracy of the pooling-function approximation and the effectiveness of noise suppression. Using the tradeoff, we make an attempt to optimize the configuration parameter of Max-AirPooling, yielding a sub-optimal closed-form method of adaptive parametric control. Experimental results obtained on real-world datasets show that AirPooling provides sensing accuracies close to those achievable by the traditional digital air interface but dramatically reduces the communication latency, by up to an order of magnitude.

IMPORTANCE: Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval of tropomyosin receptor kinase inhibitors (larotrectinib and entrectinib) for patients with solid tumors, including advanced thyroid carcinomas, harboring NTRK gene fusions. OBSERVATIONS: The relative rarity and diagnostic complexity of NTRK gene fusion events in thyroid carcinoma present several challenges for clinicians, including variable access to robust methodologies for comprehensive NTRK fusion testing and poorly defined algorithms of when to test for such molecular alterations. To address these issues in thyroid carcinoma, 3 consensus meetings of expert oncologists and pathologists were convened to discuss diagnostic challenges and propose a rational diagnostic algorithm. Per the proposed diagnostic algorithm, NTRK gene fusion testing should be considered as part of the initial workup for patients with unresectable, advanced, or high-risk disease as well as following the development of radioiodine-refractory or metastatic disease; testing by DNA or RNA next-generation sequencing is recommended. Detecting the presence of NTRK gene fusions is important to identify patients eligible to receive tropomyosin receptor kinase inhibitor therapy. CONCLUSIONS AND RELEVANCE: This review provides practical guidance for optimal integration of gene fusion testing, including NTRK gene fusion testing, to inform the clinical management in patients with thyroid carcinoma.

ABSTRACTBackgroundApixaban is a superior direct oral anticoagulant exihibiting interindividual variability in concentration and response in the real world. The present study aimed to identify genetic biomarkers associated with pharmacokinetics (PK) and pharmacodynamics (PD) of apixaban in healthy Chinese subjects.MethodsThis multicenter study included 181 healthy Chinese adults taking a single dose of 2.5 mg or 5 mg apixaban and assessed their PK and PD parameters. Genome-wide single nucleotide polymorphism (SNP) genotyping was performed using the Affymetrix Axiom CBC_PMRA Array. Candidate gene association analysis and genome-wide association study were conducted to identify genes with a predictive value for PK and PD parameters of apixaban.ResultsSeveral ABCG2variants were associated with Cmaxand AUC0-tof apixaban (p < 6.12 × 10−5) and also presented significant differences of anti-Xa3hactivity and dPT3haccording to different ABCG2genotypes (p < 0.05). Besides, ABLIM2variants were found to be associated with PK characteristics and F13A1and C3 variants were associated with PD characteristics of apixaban (p < 9.46 × 10−8).ConclusionABCG2variants were found to be ideal genetic biomarkers for both PK and PD characteristics of apixaban. ABLIM2, F13A1and C3were identified as potential candidate genes associated with inter-individual variability of apixaban. This study was registered on ClinicalTrials.gov NCT03259399.

As a new function of 6G networks, edge intelligence refers to the ubiquitous deployment of machine learning and artificial intelligence (AI) algorithms at the network edge to empower many emerging applications ranging from sensing to auto-pilot. To support relevant use cases, including sensing, edge learning, and edge inference, all require transmission of high-dimensional data or AI models over the air. To overcome the bottleneck, we propose a novel framework of SEMantic DAta Sourcing (SEMDAS) for locating semantically matched data sources to efficiently enable edge-intelligence operations. The comprehensive framework comprises new architecture, protocol, semantic matching techniques, and design principles for task-oriented wireless techniques. As the key component of SEMDAS, we discuss a set of machine learning based semantic matching techniques targeting different edge-intelligence use cases. Moreover, for designing task-oriented wireless techniques, we discuss different trade-offs in SEMDAS systems, propose the new concept of joint semantics-and-channel matching, and point to a number of research opportunities. The SEMDAS framework not only overcomes the said communication bottleneck but also addresses other networking issues including long-distance transmission, sparse connectivity, high-speed mobility, link disruptions, and security. Re-identification experimental results on the CUHK-03 dataset are presented to demonstrate the performance gain of SEMDAS.

Jiangkou, China, is the battleground site where, in 1646, Zhang Xianzhong, the peasant uprising leader, fought against Yang Zhan, the general of the Southern Ming government. The fierce and powerful Zhang Xianzhong was defeated in this battle, and his enormous quantities of gold and silver objects sank to the bottom of the Min River. From archaeological excavations conducted from 2016 to 2020, the excavators have confirmed that Zhang Xianzhong's objects are dominated by gold and silver items, ingots, coins, and jewels. The discovery at the battleground of Jiangkou is important because almost all of the remains are firsthand historical materials that are useful in studying the politics, economy, and military affairs of the Ming dynasty during the 17th century.

The sixth-generation (6G) mobile networks are expected to feature the ubiquitous deployment of machine learning and artificial intelligence (AI) algorithms at the network edge. With rapid advancements in edge AI, the time has come to realize intelligence downloading onto edge devices (e.g., smartphones and sensors). To materialize this version, we propose a novel technology in this article called in-situ model downloading, which aims to achieve transparent and real-time replacement of on-device AI models by downloading from an AI library in the network. Its distinctive feature is the adaptation of downloading to time-varying situations (e.g., application, location, and time), devices' heterogeneous storage-and-computing capacities, and channel states. A key component of the presented framework is a set of techniques that dynamically compress a downloaded model at the depth-level, parameter-level, or bit-level to support adaptive model downloading. We further propose a virtualized 6G network architecture customized for deploying in-situ model downloading with the key feature of a three-tier (edge, local, and central) AI library. Furthermore, experiments are conducted to quantify 6G connectivity requirements and research opportunities pertaining to the proposed technology are discussed.

AimsTo elucidate the clinicopathological features and the diagnostic value of mutation specific antibody H3F3 K36M of chondroblastoma (CB) in China.MethodsClinicopathological profiles were retrieved, and immunohistochemistry was performed on 185 CB specimens and the control group.ResultsOur series included 307 patients with a mean age of 22.1 years. Long tubular bones (63.8%, 196/307) were most commonly involved, followed by short bones of the hands and feet (22.1%, 68/307), sesamoid bones (8.1%, 25/307), flat bones and irregular bones (5.9%, 18/307). The most commonly involved site was the proximal femur, followed by distal femur, proximal humerus and calcaneus. The average age in the long bones group (20.3 years) was significantly younger than the short bones group (24.9 years) (p<0.001), sesamoid bones group (24.4 years) (p=0.02) and flat bones and irregular bones group (29.1 years) (p<0.001). Microscopically, aneurysmal bone cyst-like change (63.6%, 117/184), necrosis (43.5%, 80/184) and chicken-wire calcification (26.1%, 48/184) were variably noted. In rare cases, cortical destruction, soft tissue and lymphovascular invasion were identified. Positive immunoreaction with H3F3 K36M was examined in all non-decalcified, all EDTA decalcified, 87.1% hydrochloric acid (HCl) decalcified CB samples and the high-grade sarcoma secondary to CB, but not the control group.ConclusionsCB usually involves the long tubular bones in younger age group. H3F3 K36M can identify K36M mutation with 100% specificity and 100% sensitivity in non-decalcified and EDTA decalcified samples, more than 80% sensitivity in HCl decalcified samples. Virtually, all CBs harbour an H3K36M mutation.

The deployment of inference services at the network edge, called edge inference, offloads computation-intensive inference tasks from mobile devices to edge servers, thereby enhancing the former’s capabilities and battery lives. In a multiuser system, the joint allocation of communication-and-computation (C2) resources (i.e., scheduling and bandwidth allocation) is made challenging by adopting efficient inference techniques, batching and early exiting, and further complicated by the heterogeneity in users’ requirements on accuracy and latency. Batching groups multiple tasks into a single batch for parallel processing to reduce time-consuming memory access and thereby boosts the throughput (i.e., completed task per second). On the other hand, early exiting allows a task to exit from a deep-neural network without traversing the whole network, thereby supporting a tradeoff between accuracy and latency. In this work, we study optimal C2 resource allocation with batching and early exiting, which is an NP-complete integer programming problem. A set of efficient algorithms are designed under the criterion of maximum throughput by tackling the challenge. First, consider the case with batching but without early exiting. The target problem is solved optimally using a proposed best-shelf-packing algorithm that nests a threshold-based scheme, which selects users with the best channels and meeting the computation-time constraints, in a sequential search for the maximum batch size. Next, consider the general case with batching and early exiting. A low-complexity sub-optimal algorithm for C2 resource allocation is developed by modifying the preceding algorithm to exploit early exiting for latency reduction. On the other hand, the optimal approach is developed based on nesting a depth-first tree-search with intelligent online pruning into a sequential search for the maximum batch size. The key idea is to derive pruning criteria based on the simple greedy solution for the target problem without a bandwidth constraint and apply the result to designing an intelligent online pruning scheme. Experimental results demonstrate that both optimal and sub-optimal C2 resource allocation algorithms can leverage integrated batching and early exiting to double the inference throughput compared with conventional schemes.

To discover novel natural-product-based insecticide candidates, herein, a variety of osthole-derived N-benzoylthioureas were synthesized and assessed for their insecticidal activities against three insect pests. An insecticidal assay showed that most of the target osthole-derived N-benzoylthioureas displayed a more potent and broad-spectrum insecticidal effect than the parent osthole after the introduction of N-benzoylthioureas on the C-3′ position of osthole. Compound B24displayed the most potent growth inhibitory (GI) effect on Mythimna separataWalker, with a final corrected mortality rate of 82.1% when treated with a concentration of 1 mg/mL, which was 1.64- and 1.53-fold higher in comparison to osthole and the botanical insecticide toosendanin, respectively. Compounds B22, B23, and B25displayed a more promising aphicidal effect on Myzus persicaeSulzer, and their LD50values were 0.015, 0.017, and 0.019 μg/larvae, respectively, superior to the commercially available insecticide rotenone (0.024 μg/larvae). Derivatives B19, B20, B23, and B25displayed more potent larvicidal activity against Plutella xylostellaLinnaeus, with LC50values of 0.22, 0.26, 0.15, and 0.30 mg/mL, respectively, exceeding that of rotenone (0.37 mg/mL). Furthermore, both compounds B19and B23against P. xylostellawere found to be more effective than rotenone in a control efficacy assay under greenhouse conditions. The structure–activity relationship (SAR) suggested that osthole-derived N-benzoylthioureas are more active in most cases when the R group is an electron-withdrawing group than when it is an electron-donating group, especially for halogenated groups. Additionally, the potent compounds B19and B23possessed good selectivity and were less toxic to non-target organisms. This study suggests that these osthole-derived N-benzoylthioureas could be further studied in depth as eco-friendly natural product pesticides in crop protection.

Natural products are an abundant and environmentally friendly source for controlling plant pathogens and insect pests. Toward the development of new natural product-based pesticides, here, a series of osthole-based isoxazoline derivatives were prepared by [3 + 2] annulation and evaluated for their insecticidal activities and toxicities. The structures of all osthole-based isoxazoline derivatives were characterized by various spectral analyses, and derivative B13was further confirmed by X-ray crystallography. Among all the osthole derivatives, B2displayed the most promising growth inhibitory effect on Mythimna separatawith a final corrected mortality rate of 96.4% ± 3.3, which was 1.80 times higher than those of both osthole and toosendanin. Derivative B13displayed the most promising larvicidal activity against Plutella xylostellawith an LC50value of 0.220 mg/mL, which was superior to rotenone. Furthermore, both B13and B21also exhibited better control efficacy against P. xylostellathan rotenone in the pot experiments. Additionally, the toxicity evaluation suggested that these osthole-based isoxazoline derivatives showed relatively low toxicity toward nontarget organisms. Given these results, osthole derivatives B2, B13, and B21could be deeply developed as natural insecticidal agents in agriculture.

An efficient TfOH-catalyzed cascade C–H/N–H annulation of indole-2-carboxamides with benzoquinones has been developed for the synthesis of tetracyclic indolo[2,3-c]quinolinones. This reaction exhibits excellent chemo-/regioselectivity, achieving functionalization of the C-3 of indole and N–H of the amide moiety to form the new C–C and C–N bonds. Various expected products were synthesized from readily available starting materials in good to high yields with a wide substrate scope and good functional group tolerance. Among all synthetic products, 3dshowed the most potent cytotoxicity toward the 4T1 cancer cell line with an IC50value of 0.62 ± 0.05 μM. In vivostudy demonstrated that 3dremarkably suppressed 4T1 xenograft tumor growth without body weight loss.

ABSTRACTNeonatal acute respiratory distress syndrome (ARDS) has high morbidity and mortality rates worldwide, but there is a lack of pharmacologic treatment and clinical targeted therapies. In this study, we aimed to explore the effects of Lipocalin-2 (LCN2) on ferroptosis-mediated inflammation and oxidative stress in neonatal ARDS and the potential mechanism. In this study, we established an in vivo ARDS mouse model and an in vitro ARDS cell model by LPS (Lipopolysaccharide) stimulation. Lung tissue injury was evaluated by wet/dry ratios and histopathological examination. LCN2 expression was detected by qRT-PCR and Western blot. Inflammatory factors, oxidative stress and apoptosis were also detected. Ferroptosis was identified by detection of Fe2+level and ferroptosis-associated protein expressions. Mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) pathway signaling was examined by Western blot analysis. The data revealed that LCN2 expression was significantly upregulated in neonatal mice with ARDS. Interference with LCN2 protected LPS-induced lung in neonatal mouse by reducing the radio of wet/dry and alleviating pathological damages. In addition, LCN2 silencing repressed LPS-induced inflammation, oxidative stress in vivo and in vitro, as well as apoptosis. Meanwhile, decreased level of Fe2+and transferrin while increased levels of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) were observed. The expression MAPK/ERK pathway was inhibited by depletion of LCN2. The present results suggest that LCN2 knockdown protected LPS-induced ARDS model via inhibition of ferroptosis-related inflammation and oxidative stress by inhibiting the MAPK/ERK pathway, thereby presenting a novel target for the treatment of ARDS.

In this paper, a new approach to design terahertz (THz) E-plane crossover coupler is reported. By cascading two symmetrical septum polarizers, a simple structure with wide operating bandwidth and high isolation performance is achieved. The working principle is explained by operating waveguide modes. To simplify the optimization process, the scattering matrix (S-matrix) of the crossover is calculated. Two prototypes loaded and unloaded electromagnetic band gap (EBG) are fabricated and measured. The electrical contact problem at assembly plane is eliminated by the prototype loaded EBG. A measured bandwidth of 17.3% from 92.5 to 110 GHz for reflection and isolation coefficients < −15 dB and transmission coefficient > −2 dB is achieved.

Steviol glycosides, obtained from leaves of Stevia rebaudianaBertoni (stevia) or produced via bioconversion and biosynthesis, are diterpenes used by the food/dietary supplement industry as zero-calorie sweeteners derived from natural sources. JECFA 2017 is the most updated international standardized method but it runs for 80 min per sample with suboptimal separations on several critical pairs for its high-performance liquid chromatography-ultraviolet (HPLC-UV) determination. We developed and validated a rapid and economic HPLC-UV method using the superficially porous particle column to determine 13 steviol glycosides (stevioside, dulcoside A, rubusoside, steviobioside, and rebaudioside A–F, I, M, and N). Baseline separation with a minimum resolution of 1.5 for 13 steviol glycosides was achieved within only 14 min of separation time. The hydrocarbon stationary phase with additional steric interactions from the isobutyl side chains on the C18 ligand was shown to be an important contributor to chromatographic selectivity of several critical pairs of steviol glycosides. The method was proven to perform suitably on columns from three different manufacturers and two HPLC instruments. The method was further used to perform a single-lab validation on eight food and supplement products with multiple matrices. The results ranged from 0.05% w/w rebaudioside A for a hard-candy finished product to 100.8% w/w purity for a rebaudioside M raw ingredient. The validation test results showed that the method was linear, suitable, specific, accurate, and precise. The method is therefore suitable to be considered as a new industrial standard for quality control analysis for stevia products.

Aim:We aimed to identify genetic variants associated with ACE inhibitor (ACEI)-induced cough.Materials & methods:A nested case–control study was performed among hypertensive Chinese patients receiving enalapril-only therapy. Whole-exome sequencing and genome-wide association analysis were performed. Results:We identified that PNPT1rs13015243 (odds ratio [OR]: 0.47; 95% CI: 0.34–0.66; p=7.45×10-6), PNPT1rs13009649 (OR: 0.48; 95% CI: 0.35–0.67; p=9.96×10-6) and PCGF3rs1044147 (OR: 2.67; 95% CI: 1.71–4.17; p=9.91×10-6) were significantly associated with ACEI-induced cough. Nearly genome-wide significant associations in previously reported candidate risk genes CLASP1, ACE, CES1, CPN1, XPNPEP1, PDE11Aor SLC38Awere detected in our dataset.Conclusion:Our results suggest that ACEI-induced cough is associated with noncoding SNPs of PNPT1and PCGF3, all of which are independent of the bradykinin pathway.Study registration:NCT03259399.

Aim:Major drawbacks of percutaneous coronary intervention are the high occurrence of repeat revascularization due to restenosis and disease progression. The aim of this study was to find genetic indicators to predict the risk of repeat revascularization. Materials & methods:From April 2015 to June 2016, 143 patients with percutaneous coronary intervention with genetic test results were enrolled. SNPs were measured by OmniZhongHua-8, and the SNPs in pathways genes related to known stenosis-related processes from the KEGG, BioCarta and Gene Cards databases were selected for analysis. Results:Cell–extracellular matrix interactions were the pathways with the most significant SNP (CDH15rs72819363) association with repeat revascularization. Compared with CDH13rs11859453G carriers, the adjusted odds ratio for A carriers was 0.25 and 0.33 at 18 and 30 months. Conclusion:We demonstrated a potential role of the cell–extracellular matrix interactions pathway and the possible biomarker CDH13/CDH15in the development of coronary repeat revascularization.

Carabranolides present characteristic NMR resonances for the cyclopropane moiety, which distinctly differ from those of other compounds and were used for an NMR-guided isolation in this study. As a result, 11 undescribed carabranolides (1–11), along with five known ones (12–16), were isolated from the fruits of Carpesium abrotanoidesL. Compounds 1–11are new esters of carabrol at C-4 with different carboxylic acids. Their structures were elucidated by HRESIMS and NMR spectroscopic data analysis. The biological evaluation showed that compounds 2–4, 15, and 16exhibited significant inhibitory activity against LPS-induced NO release with an IC50value of 5.6–9.1 μM and dose-dependently decreased iNOS protein expression in RAW264.7 cells.

Aim:Genetic polymorphisms may influence the incidence of angiotensin-converting enzyme (ACE) inhibitor-induced cough. This study aims to investigate this association. Methods:Ten electronic databases and PharmGKB were systematically searched. Pooled odds ratio values and their 95% CI were used to assess the association, using the random-effects model. Results:A total of 26 studies were included in the review, 17 of them were included from two separated meta-analysis (ACE I/Dor BDKRB2-58T/C). Significant association was found between ACE I/D I carriers (ACE gene insertion) and ACE inhibitor-induced cough, showing racial and age differences. Conclusion:This study demonstrated that ACE I/Dbut not BDKRB2-58T/Cpolymorphism could be a predictor for the risk of ACE inhibitor-induced cough, especially in east Asians and the aged.

T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes. We demonstrated that hepatocyte-specific Tim-3 overexpression enhances tumor cell growth, whereas Tim-3 inhibition on malignant hepatocytes by anti-Tim-3 antibodies or RNAi suppresses tumor growth both in vitro and in Tim-3 knockout mice. Mechanistically, the hepatocyte-Tim-3 receptor activates NF-κB phosphorylation, which in turn stimulates IL-6 secretion and STAT3 phosphorylation. Our results identify tumor cell-intrinsic functions of Tim-3 in tumorigenesis and suggest that blocking Tim-3 in tumor cells might contribute to the clinical efficacy of anti-Tim-3 antibody treatment in the future tumor therapy.

ABSTRACTThe transcription factor, NFE2-related factor 2 (Nrf2) and autophagy have been implicated in the oxidative-stress response during tumor evolution. However, few studies focus on crosstalk between Nrf2 and autophagy in cancer progression of non-small cell lung cancer (NSCLC). Herein, we evaluated the effect of Nrf2 on autophagy in NSCLC and their role in development of NSCLC. Effect of Nrf2 on overal survival (OS) of NSCLC patients were evaluated. Cell biological behaviors in response to Nrf2 were evaluated by MTT, colony formation assay and flow cytometry. Effect of 3-MA (a classical inhibitor of autophagy) on 95D-Nrf2 cells was also analyzed using flow cytometry. After up/down-regulating Nrf2 in NSCLC cell lines, expression of autophagy-related proteins were evaluated with western blot analysis. The results revealed that Nrf2 was an independent prognositc factor negtively associated with OS of NSCLC patients. Elevated Nrf2 expression promotes NSCLC progression, enhancing the escape of tumor cells from apoptosis in vivo and in vitro. Double staining with Annexin V-APC and 7-AAD showed that the proportions of apoptotic cells in 95D-Nrf2 cells were gradually increased after the addition of 3-MA. Importently, Nrf2 induced autophagosome formation and enhanced autophagic activity, which subsequently inhibits NSCLC cell apoptosis. In conclusion, our present study demonstrates that Nrf2 promotes progression of non-small cell lung cancer through activating autophagy. It provides novel insights into Nrf2-mediated of cell proliferation in NSCLC and may facilitate therapeutic development against NSCLC.

•The inhabitants of cliff tomb from the southern China were genetically homogeneity with ancient populations from the northern China, which is striking distinct from previously published ancient genomes from southern China.•We provide concrete evidence, for the first time, that the inhabitants of cliff tombs were originated from the Central Plains of China, rejecting either the local origin hypothesis or the exotic origin hypothesis.•By combing genomic data with anthropological evidence, we find that these individuals that buried together share a first-degree relationship with each other, suggesting that the cliff tombs were specifically designed for family burials and that genetic kinship played a significant role in burial customs during the Eastern Han Dynasty in the Sichuan Basin.

Background: Novel biomarkers for personalizing anticoagulation remain undetermined. We aimed to investigate the association of plasma miRNAs with pharmacokinetic–pharmacodynamic (PK-PD) profiles of rivaroxaban. Methods: This is a multicenter, exploratory study of miRNAs in a Chinese population. Healthy volunteers and patients receiving rivaroxaban were enrolled in the study. The area under the plasma concentration–time curve from time 0-t h (AUC0-t) and anti-Xa activity at 3 h (AXA3h) were measured in healthy volunteers, and AXA3hwas measured in patients. MiRNAs were detected by miRNA microarray in 26 healthy volunteers with 20 mg rivaroxaban, and quantitative reverse transcription polymerase chain reaction was used to exclude undetectable ones. MiR-320a-3p and miR-483-5p were then quantified in 65 healthy volunteers and 71 patients. MiRNA levels at 3 h were compared between high and low AXA3hor AUC0-tsubjects and in matched patients with or without bleeding during follow-up. The miRNA targets were predicted by TargetScan, miRTarBase, and miRDB. Validated genes were included in GO enrichment and KEGG analyses. The protein–protein interaction network was established by STRING and visualized by Cytoscape. Results: A total of 136 Chinese subjects completed the study. In healthy volunteers taking 15 mg rivaroxaban, the miR-320a level at 3 h was significantly positively correlated with AXA3hand AUC0-t(r= 0.359, p= 0.025; r= 0.370, p= 0.02, respectively). A positive correlation was also observed between miR-483 and AXA3hor AUC0-t(r= 0.372, p= 0.02; r= 0.523, p= 0.001, respectively). MiR-320a and miR-483 levels at 3 h in the higher AUC0-tgroup were significantly higher than those at 0 h. MiR-483 levels at 3 h may distinguish healthy volunteers with high or low AXA3hor AUC0-t. In the 10 mg fed subgroup, higher 3 h mir-483 levels were also observed compared with the control group. No significant differences were found in the comparisons among patients. Bioinformatic analysis showed that these miRNAs may play a regulatory role by targeting ABCG2, ITGB3, PTEN, MAPK1/3, etc. Conclusions: MiR-320a and miR-483 levels were found to be associated with PK and PD profiles of rivaroxaban in healthy Chinese subjects. Further studies are required to verify these findings and explore the mechanisms.

Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. No explicit consensus can be achieved to date due to sparse clinical data, potentially compromising the outcomes of patients. In this comprehensive review from a clinician’s perspective, the epidemiology and prognosis are described, diagnosis based on manifestations, pathology, and medical imaging are discussed, and both traditional and emerging therapeutics are addressed as well. Turin consensus remains the mainstay diagnostic criteria for PDTC, and individualized assessments are decisive for treatment option. The prognosis is optimal if complete resection is performed at early stage but dismal in nearly half of patients with locally advanced and/or distant metastatic diseases, in which adjuvant therapies such as 131I therapy, external beam radiation therapy, and chemotherapy should be incorporated. Emerging therapeutics including molecular targeted therapy, differentiation therapy, and immunotherapy deserve further investigations to improve the prognosis of PDTC patients with advanced disease.

It has been reported that Golgi protein-73 (GP73), glypican-3 (GPC3), and des-γ-carboxy prothrombin (DCP) could serve as serum markers for the early detection of hepatocellular carcinoma (HCC). This study aimed to evaluate a panel of immunostaining markers (including GP73, GPC3, DCP, CD34, and CD31) as well as reticulin staining to distinguish HCC from the mimickers. Our results revealed that CD34 immunostaining and reticulin staining were highly sensitive for the diagnosis of HCC. A special immunoreaction pattern of GP73—a diffuse coarse-block pattern in a perinuclear region or a concentrated cluster-like or cord-like pattern in a certain part of the cytoplasm—was observed in HCC cells, in contrast to the cytoplasmic fine-granular pattern in surrounding non-tumor cells and non-malignant nodules. This coarse-block pattern correlated significantly with less differentiated HCC. In comparison, GPC3 displayed a good advantage in diagnosing well-differentiated HCC. In our study, DCP and CD31 showed little diagnostic value for HCC as an immunostaining marker. When GP73, GPC3, and CD34 were combined, the specificity improved to 96.6%. Our findings demonstrate for the first time that the immunohistochemical panel of GP73, GPC3, and CD34 as well as reticulin staining is highly specific for the pathological diagnosis of HCC.

A form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In conclusion, IgG4 Hashimoto's thyroiditis presents histopathological features quite distinct from its non-IgG4 counterpart.

A form of Hashimoto’s thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto’s thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto’s thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto’s thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto’s thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto’s thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto’s thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto’s thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In conclusion, IgG4 Hashimoto’s thyroiditis presents histopathological features quite distinct from its non-IgG4 counterpart.

In high growth economies, continuous rural to urban migration has put forth a large challenge for the housing planners. In particular, China has witnessed much higher rate of rural to urban migration and hence provides an interesting case for research. In India, rural to urban migrants are at great dis-advantage with regard to housing and access to basic services. This article is a comparative research on housing conditions and mobility of the migrants in urban areas in China and India, based on data collected from one city each in each country—Surat in India and Dongguan in China. The article focuses on identifying the housing sub-markets accessed by the migrants in both the cities and the process of access to the same, studying the living conditions of the migrants in both the cities and discussing the policy implications of the existing situation.

Graubert: Calico: Research Funding; Janssen: Research Funding; astrazeneca: Research Funding.

This paper argues that although the construction of smart cities in China has followed other countries closely, the popularization of concepts, the construction mechanisms and achievements are still behind the advanced countries. The pilot and demonstration pattern in the Chinese construction of smart cities has several advantages, such as wide coverage of cities, large investment funds, diversity of applications and good coordination among different agents. Utilizing this pattern is conducive to exploring a suitable way to construct China's smart cities, and narrow the gap between China and the advanced countries. The paper summarizes eight barriers in the construction of smart cities in China, and offers some proposals on promoting the levels of construction regarding several aspects, such as forming the construction pattern, expanding the application system, strengthening the investment on R&D, providing the support of the industry, and integrating pilot projects.