Earliest systematic coal exploitation for fuel extended to ~3600 B.P.

Coal has long fueled human civilizations. The history of systematic coal fuel exploitation has been traced back to the late third millennium before present (post-2500 B.P.). Although sporadic combustion of coal for fuel was reported in some prehistoric archaeological sites, evidence for the systematic exploitation of coal for fuel before 2500 B.P. remains lacking. Here, we report comprehensive understanding for the earliest systematic exploitation of coal for fuel at the Jirentaigoukou site in Xinjiang, northwestern China, at ~3600 B.P. The main body of the site witnessed systematic exploitation of bituminous coals, illustrating a complete chaîne opératoire with selective mining, planned storage, and extensive combustion. Our results transform the knowledge of energy history by extending the upper limit of the systematic exploitation of coal for fuel by approximately a millennium, and provide a precedent of energy transition under intense conflict between social demand and environmental deterioration.

Arnicolide D Inhibits Oxidative Stress-Induced Breast Cancer Cell Growth And Invasion Through Apoptosis, Ferroptosis, And Parthanatos.

BACKGROUND: Breast cancer is the most common malignant tumor in women, and its pathogenesis is very complicated. More and more studies have found that Traditional Chinese Medicine plays an important role in tumor prevention. OBJECTIVE: To investigate the mechanism of arnicolide D isolated from Centipeda minima in breast cancer. METHODS: Cell Counting Kit-8 (CCK-8), western blot, RT-qPCR, ELISA, flow cytometry, and Transwell were used to detect the effect of arnicolide D on the biological function of breast cancer cells. RESULTS: Arnicolide D promoted reactive oxygen species (ROS) production and induced a decrease in mitochondrial membrane potential in breast cancer cells, thereby inhibiting cell viability and increasing lactate dehydrogenase (LDH) release. Arnicolide D activated the classical apoptosis pathway to induce cell apoptosis; it significantly promoted PARP-1 expression, enhanced the nuclear translocation of apoptosis-inducing factor (AIF), and reduced the expression of AIF in mitochondria, indicating that it can induce the occurrence of parthanatos in a ROS dependent manner. In addition, arnicolide D down-regulated glutathione peroxidase 4 (GPX4) expression and increased the accumulation of Fe2+ and malondialdehyde (MDA), thereby activating ferroptosis. Apoptosis inhibitor, ferroptosis inhibitor, PARP inhibitor, PARP-1 siRNA, AIF siRNA and GPX4 overexpression vector significantly attenuated the inhibitory effect of arnicolide D on cell viability and reduced LDH release, which indicates that arnicolide D inhibits breast cancer cell growth by inducing apoptosis, parthanatos and ferroptosis. Arnicolide D also reduced breast cancer cell invasion and inhibited the expression of matrix metallopeptidase (MMP)-2 and MMP-9. CONCLUSION: Arnicolide D can activate a variety of cell death modes by inducing oxidative stress, thereby inhibiting the growth and invasion of breast cancer cells, indicating that arnicolide D has a good anti-tumor effect.

Infection microenvironment-activated core-shell nanoassemblies for photothermal/chemodynamic synergistic wound therapy and multimodal imaging.

The development of intelligent designs of new antibacterial modalities for diagnosing and treating chronic multidrug-resistant bacterial infections is an urgent need, but achieving the precisive theranostic in response to specific inflammatory microenvironments remains a great challenge. This paper describes our work designing and demonstrating infection microenvironment-activated core-shell Gd-doped Bi2S3@Cu(II) boron imidazolate framework (Bi2S3:Gd@Cu-BIF) nanoassemblies. Upon exposure to a single beam of 808 nm laser, Bi2S3:Gd@Cu-BIF nanoassemblies showed exceptional photothermal conversion (η = 52.6%) and produced several cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, by depleting the intracellular glutathione and in-situ catalyzing the decomposition of endogenous hydrogen peroxide in the inflammatory microenvironment. The broad-spectrum antibacterial properties of nanoassemblies were confirmed to be effective against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition rate of 99.99% in vitro. Additionally, in vivo wound-healing studies revealed that Bi2S3:Gd@Cu-BIF nanoassemblies could serve as an effective wound spray to accelerate healing following MRSA infections via photothermal/chemodynamic (PTT/CDT) synergistic therapy. The effective wound healing rate in the synergistic treatment group was 99.8%, which is higher than the 69.5% wound healing rate in the control group. Furthermore, magnetic resonance and computed tomography dual-modal imaging mediated by Bi2S3:Gd@Cu-BIF nanoassemblies also exhibits promising potential as an integrated diagnostic nanoplatform. Overall, this work provides useful insights for developing all-in-one theranostic nanoplatforms for clinical treatment of drug-resistant bacterial infections. STATEMENT OF SIGNIFICANCE: New treatments and effective diagnostic strategies are critical for fighting drug-resistant bacterial infections. Infection microenvironment-activated Bi2S3@Cu-BIF nanoassemblies can simultaneously increase eigen temperature and generate cytotoxic reactive oxygen species, such as singlet oxygen and hydroxyl radicals, under near-infrared laser irradiation, achieving the synergistic effect of photothermal and chemodynamic therapy, which has been proven to be highly effective for inhibiting bacterial activity and speeding wound healing from methicillin-resistant Staphylococcus aureus infection. More importantly, the nanoassemblies could enable early precise visualized detection of bacterial abscess using magnetic resonance/computed tomography dual-modal bio-imaging techniques.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Diagnosing Hepatocellular Carcinoma: Diagnostic Performance and Interobserver Agreement.

OBJECTIVES: To determine the diagnostic performance and inter-reader agreement of the contrast-enhanced ultrasound liver imaging reporting and data system (CEUS-LI-RADS) for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. METHODS: In this prospective study, CEUS-LI-RADS categories (LR-5 for predicting HCC) were assigned by six blinded readers and compared to the definitive HCC diagnosis in patients with liver cirrhosis per the 2017 China Liver Cancer Guidelines (CLCG). CEUS features were recorded in 96 patients with 96 histology-proven lesions. The diagnostic performance of LR-5 was described by the sensitivity, specificity and accuracy. Multi-reader agreement was assessed by using intraclass correlation coefficients (ICC). RESULTS: In cirrhotic patients, the specificity of LR-5 (range: 92.7-100.0 %) was statistically higher than that of CLCG for each reader (range: 28.6-64.3 %). However, the sensitivity (range: 38.6-63.6 %) and accuracy (range: 53.4-70.7 %) were statistically lower in CEUS-LIRADS than in CLCG (sensitivity range: 88.6-100.0 %; accuracy range: 77.6-86.2 %). Only fair to moderate inter-reader agreement was achieved for the CEUS-LI-RADS category (ICC = 0.595) and washout appearance (ICC range: 0.338 to 0.555). Neither nodule-in-nodule nor mosaic architecture was observed more often in HCC (all P > 0.05), with poor inter-reader consistency for both (both ICC < 0.20). CONCLUSION: CEUS-LI-RADS category 5 has a high specificity but a low accuracy for identifying HCC in high-risk patients. Inter-reader agreement is not satisfactory concerning CEUS-LIRADS category and washout appearance. Moreover, the clinical value of ancillary features favoring HCC is quite limited.

Ancient genomes reveal tropical bovid species in the Tibetan Plateau contributed to the prevalence of hunting game until the late Neolithic.

Local wild bovids have been determined to be important prey on the northeastern Tibetan Plateau (NETP), where hunting game was a major subsistence strategy until the late Neolithic, when farming lifestyles dominated in the neighboring Loess Plateau. However, the species affiliation and population ecology of these prehistoric wild bovids in the prehistoric NETP remain unknown. Ancient DNA (aDNA) analysis is highly informative in decoding this puzzle. Here, we applied aDNA analysis to fragmented bovid and rhinoceros specimens dating ∼5,200 y B.P. from the Neolithic site of Shannashuzha located in the marginal area of the NETP. Utilizing both whole genomes and mitochondrial DNA, our results demonstrate that the range of the present-day tropical gaur (Bos gaurus) extended as far north as the margins of the NETP during the late Neolithic from ∼29°N to ∼34°N. Furthermore, comparative analysis with zooarchaeological and paleoclimatic evidence indicated that a high summer temperature in the late Neolithic might have facilitated the northward expansion of tropical animals (at least gaur and Sumatran-like rhinoceros) to the NETP. This enriched the diversity of wildlife, thus providing abundant hunting resources for humans and facilitating the exploration of the Tibetan Plateau as one of the last habitats for hunting game in East Asia.

A Janus upconverting nanoplatform with biodegradability for glutathione depletion, near-infrared light induced photodynamic therapy and accelerated excretion.

The major limitations of photodynamic therapy (PDT) are the poor tissue penetration of excitation light and the neutralization of reactive oxygen species (ROS) generated by overexpressed glutathione (GSH) in cancer cells. Despite tremendous efforts to design nanoplatforms, PDT still suffers from unsatisfactory effects. Furthermore, the residual of nanomaterials in the body has restricted their clinical application. To address these issues, Janus nanocomposites containing an Yb/Er codoped NaYF4 upconverting nanocrystal head and a disulfide-bridged mesoporous organosilicon body (UCN/MON) with loaded chlorin e6 (Ce6) were designed. On one hand, the upconverting nanocrystal head can convert near-infrared (NIR) light into visible light to activate Ce6 to release ROS. On the other hand, the silica body can be degraded though a redox reaction with GSH, to not only improve the tumor selectivity of the photosensitizer by redox- and pH-triggered Ce6 release, but also diminish the concentration of GSH in cancer cells to reduce the depletion of ROS. Thereby, an enhanced PDT triggered by NIR irradiation was achieved. Furthermore, UCN/MONs showed a higher clearance rate after therapeutic actions than nonbiodegradable UCN/MSNs due to their biocompatibility. Taken together, this work revealed the potential of UCN/MONs for highly efficient and NIR-induced PDT, highlighting the prospects of UCN/MONs in the clinic.

Evaluation of thyroid nodules with coexistent Hashimoto's thyroiditis according to various ultrasound-based risk stratification systems：A retrospective research.

PURPOSES: To investigate the efficiency of Thyroid Imaging Reporting and Data System (TI-RADS) proposed by KWAK, the American College of Radiology, and the 2015 American Thyroid Association (ATA) guidelines for thyroid nodules with Hashimoto's thyroiditis (HT) and to determine whether HT influence the diagnostic performance of these risk-stratification systems. METHODS: A total of 101 nodules with HT and 101 nodules with non-HT were retrospectively analyzed by ultrasound-based diagnostic classifications and compared with histopathological results. The areas under the receiver operating characteristic curve (AUCs) were calculated for comparative analysis. RESULTS: In the HT group, KWAK TI-RADS has the best sensitivity (91.67%), while ACR TI-RADS has the highest specificity (82.93%) and accuracy (81.19%). The AUCs of ACR TI-RADS, ATA guidelines, and KWAK TI-RADS were 0.844, 0.782, and 0.830, respectively. In the non-HT group, the sensitivity and specificity of three risk-stratification systems had no significant difference. The AUCs of ACR TI-RADS, ATA guidelines, and KWAK TI-RADS were 0.872, 0.839, and 0.874, respectively. No significant difference was found in diagnostic effectiveness of the same systems with both contexts. CONCLUSIONS: ACR TI-RADS performed the most effective for thyroid nodules in HT, whereas KWAK TI-RADS was the best for those in non-HT. Both of TI-RADS (ACR and KWAK) provided higher diagnostic effectiveness than ATA guidelines in HT or in non-HT. Moreover, HT could not affect the diagnostic performance of these risk-stratification systems.

Diagnostic Performance Evaluation of Practice Guidelines, Elastography and Their Combined Results for Thyroid Nodules: A Multicenter Study.

The purpose of this multicenter study was to compare the differential diagnostic value of the 2015 American Thyroid Association (ATA) and 2017 American College of Radiology (ACR) practice guidelines and elastography in thyroid nodules. This study also investigated whether the diagnostic value of practice guidelines can be improved, and the unnecessary biopsy rate decreased in combination with elastography. A total of 498 thyroid nodules were evaluated using the ATA and the ACR guidelines. Strain elastography, acoustic radiation force impulse imaging and point-shear wave elastography were used to assess the nodules. The suspicious levels were downgraded or upgraded after combination and unnecessary biopsy rates were calculated, respectively. The diagnostic performance of the practice guidelines was better than that of elastography. The ACR guidelines had a lower unnecessary biopsy rate and similar diagnostic performance compared with the ATA guidelines. The unnecessary biopsy rates significantly decreased when the ACR guidelines were combined with elastography, but the rates did not decrease when the ATA guidelines were combined with elastography.

Virtual Touch Tissue Imaging and Quantification (VTIQ) combined with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for malignancy risk stratification of thyroid nodules.

OBJECTIVE: This study was conducted to investigate the diagnostic performance of Virtual Touch Tissue Imaging and Quantification (VTIQ), combined with the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) in differentiating malignant and benign thyroid nodules. METHODS: A total of 130 thyroid nodules in 128 patients were included. The diagnostic performance of conventional ultrasound (US), VTIQ, and the combination of these two techniques was calculated and compared according to the area under the receiver operating characteristic curve (AUROC), for sensitivity, specificity, and accuracy. RESULTS: The sensitivity and specificity for the ACR TI-RADS were 98.6% (72/73) and 24.6% (14/57), respectively. There was a strong agreement with ACR TI-RADS categories of thyroid nodules (all ICCs > 0.60). With an optimal cutoff value of 2.46 m/s, the sensitivity and specificity of the minimal shear wave velocity (SWVmin) were 87.7% (64/73) and 70.2% (40/57). By applying this value to downgrade or upgrade ACR TI-RADS, the specificity significantly increased from 24.6% (14/57) to 47.4% (27/57; P < 0.05) and the sensitivity remained at 98.6% (72/73). CONCLUSIONS: VTIQ combined with ACR TI-RADS could improve the specificity of the differential diagnosis of thyroid nodules without a loss of sensitivity.

Pre-operative Conventional Ultrasound and Sonoelastography Evaluation for Predicting Axillary Lymph Node Metastasis in Patients with Malignant Breast Lesions.

The objective of our study was to evaluate the association between the sonoelastography features of breast tumor and axillary lymph node metastasis (ALNM) in patients with breast cancer. In a cohort of 106 women with breast cancer, the conventional ultrasound features and elasticity parameters by elasticity imaging and Virtual Touch Tissue Imaging & Quantification (VTIQ) were retrospectively analyzed. Ultrasound and elastography findings were compared with pathologic axillary lymph node status. Receiver operating characteristic curve analysis was used to evaluate diagnostic performance. Pathologically, the overall incidence of ALNM was 39.6% (42/106) in the final analysis. ALNM was significantly more frequent in tumors with elasticity imaging scores >4.5, maximal shear wave velocity values (Smax) >6.42 m/s and mean shear wave velocity values (Smean) >5.66 m/s, respectively. The sensitivity, specificity and accuracy were 78.6%, 54.7% and 64.2% for elasticity imaging score; 85.7%, 54.7% and 67.0% for Smax; and 59.5%, 79.7% and 71.7% for Smean, respectively Elastography features, including elasticity imaging score and VTIQ, can be used to supplement conventional ultrasound to predict ALNM in patients with breast cancers.

A Modified Thyroid Imaging Reporting and Data System (mTI-RADS) For Thyroid Nodules in Coexisting Hashimoto's Thyroiditis.

To develop a conventional ultrasound (US) modified Thyroid Imaging Reporting and Data System (mTI-RADS) to stratify the malignancy risk of thyroid nodule in coexisting Hashimoto's thyroiditis (HT). The study included 138 malignant and 292 benign thyroid nodules confirmed by cytological or histopathological results. The risk score (RS) for each significant US feature was estimated by multiplying corresponding regression coefficient and the total score for each nodule was defined as the sum of these individual scores. The mTI-RADS was established according to the total RS and divided into category 3, 4a, 4b, 4c and 5. Marked hypoechogenicity, taller-than-wide shape, poorly-defined margin, microcalcification or macrocalcification and halo sign absence were statistically significant US features in prediction of thyroid malignancy (all p < 0.05). The total RS for each nodule was defined as following: RS = 2.1× (if marked hypoechogenicity) + 1.2× (if taller-than-wide shape) + 1.7× (if no halo sign) + 0.6× (if poorly-defined margin) + 1.2× (if microcalcification or macrocalcification). The malignancy rates in mTI-RADS category 3, 4a, 4b, 4c and 5 nodules were 3.7%, 19.3%, 38.1%, 62.7% and 94.1%, respectively, with significant differences among different categories (P < 0.001). The mTI-RADS category may facilitate subsequent treatment management in HT patients.

Shear Wave Velocity: A New Quantitative Index to Estimate the Status of Thyroid in Diffuse Thyroid Disease.

Objective. The purpose of the study was to assess the application value of VTQ in DTD. Research Design and Methods. Thirty healthy subjects and 74 DTD patients were involved. The thyroid stiffness, which was expressed by SWV, was measured by VTQ and compared between the patients and healthy people. The relationship between SWV and thyroid serological indexes was also analyzed. Results. The thyroid SWVs of DTD patients were higher than those of the healthy (2.56 ± 1.33 m/s versus 1.74 ± 0.16 m/s, P = 0.011). There was no significant difference between the thyroid SWVs in GD and HT patients (P = 0.168). The SWVs in patients with GD and HT were both higher than those of the healthy (P < 0.05). The area under the ROC curve was 0.938 for SWV to distinguish between DTD and healthy thyroid. With a cutoff value of 2.02 m/s, the sensitivity and specificity were 81.12% and 100.00%, respectively. Additionally, we found a positive liner correlation between thyroid SWV and TSH in DTD patients (P < 0.001). Conclusion. SWV is a good indicator of the thyroid tissue stiffness, which might be considered helpful in screening DTD. What is more, SWV might have a potential in assessing the thyroid function.