Predicting the development trend of the second wave of COVID-19 in five European countries.

The second wave of COVID-19 has caused a dramatic increase in COVID-19 cases and deaths globally. An accurate prediction of its development trend is significant. We predicted the development trend of the second wave of COVID-19 in five European countries, including France, Germany, Italy, Spain, and the UK. We first built models to predict daily numbers of COVID-19 cases and deaths based on the data of the first wave of COVID-19 in these countries. Based on these models, we built new models to predict the development trend of the second wave of COVID-19. We predicted that the second wave of COVID-19 would have peaked around on November 16, 2020, January 10, 2021, December 1, 2020, March 1, 2021, and January 10, 2021, in France, Germany, Italy, Spain, and the UK, respectively. It will be basically under control on April 26, 2021, September 20, 2021, August 1, 2021, September 15, 2021, and August 10, 2021, in these countries, respectively. Their total number of COVID-19 cases will reach around 4,745,000, 7,890,000, 6,852,000, 8,071,000, and 10,198,000, respectively, and total number of COVID-19 deaths will be around 262,000, 262,000, 231,000, 253,000, and 350,000 during the second wave of COVID-19. The COVID-19 mortality rate in the second wave of COVID-19 is predicted to be about 3.4%, 3.5%, 3.4%, 3.4%, and 3.1% in France, Spain, Germany, France, and the UK. The second wave of COVID-19 is expected to cause many more cases and deaths, last for a much longer time, and have a lower COVID-19 mortality rate than the first wave.

Multiple reflections enhanced fiber-optic photoacoustic sensor for gas micro-leakage.

A multiple reflections-enhanced fiber-optic photoacoustic (PA) gas sensor for gas micro-leakage is introduced. Multiple reflections of the excitation laser occur on the inner surface of a reflective ring to enhance the PA signal. The PA signal is obtained by measuring the deflection of the gold-coated poly (phenylene sulfide) (PPS) diaphragm with a Fabry-Perot interferometer (FPI). The second harmonic wavelength modulation spectrum (2f-WMS) technology can essentially eliminate the fundamental frequency noise generated by the wavelength-independent absorption of the reflective ring. Experimental results show that the PA signal can be effectively enhanced 11.7 times by the multiple reflections optical path compare with the double-pass optical path. The minimum detection limit of the system is achieved to be 23.6 ppb. The designed PA gas sensor is suited for remote detection of gas micro-leakage.

Flavone-based natural product agents as new lysine-specific demethylase 1 inhibitors exhibiting cytotoxicity against breast cancer cells in vitro.

Lysine-specific demethylase 1 (LSD1) has recently emerged as a therapeutic target for cancer. However, almost all LSD1 inhibitors developed to date are chemo-synthesised molecules. In this study, the LSD1 inhibitory activity of 12 natural flavones, including four aglycones and their corresponding monoglycosides and diglucosides, was evaluated. Based on the structure-activity relationships, LSD1 inhibition activity was greater for flavonoid monoglycosides than their aglycones lacking the sugar moiety. The effects of isoquercitrin, which exhibited optimal LSD1 inhibitory activity, on cancer cell properties were evaluated. Isoquercitrin induced the expression of key proteins in the mitochondrial-mediated apoptosis pathway and caused apoptosis in LSD1-overexpressing MDA-MB-231 cells via the inhibition of LSD1. These findings suggest that natural LSD1 inhibitors, and particularly isoquercitrin, are promising for cancer treatment.

Identifying cancer subtypes based on embryonic and hematopoietic stem cell signatures in pan-cancer.

PURPOSE: Cancer cells with stem cell-like properties may contribute to cancer development and therapy resistance. The advancement of multi-omics technology has sparked interest in exploring cancer stemness from a multi-omics perspective. However, there is a limited number of studies that have attempted to subtype cancer by combining different types of stem cell signatures. METHODS: In this study, 10,323 cancer specimens from 33 TCGA cancer types were clustered based on the enrichment scores of six stemness gene sets, representing two types of stem cell backgrounds: embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs). RESULTS: We identified four subtypes of pan-cancer, termed StC1, StC2, StC3 and StC4, which displayed distinct molecular and clinical features, including stemness, genome integrity, intratumor heterogeneity, methylation levels, tumor microenvironment, tumor progression, responses to chemotherapy and immunotherapy, and survival prognosis. Importantly, this subtyping method for pan-cancer is reproducible at the protein level. CONCLUSION: Our findings indicate that the ESC signature is an adverse prognostic factor in cancer, while the HSC signature and ratio of HSC/ESC signatures are positive prognostic factors. The subtyping of cancer based on ESC and HSC signatures may provide insights into cancer biology and clinical implications of cancer.

Classification of lung adenocarcinoma based on stemness scores in bulk and single cell transcriptomes.

Tumor stemness is associated with tumor progression and therapy resistance. The recent advances in sequencing, genomics, and computational technologies have facilitated investigation into the tumor stemness cell-like characteristics. We identified subtypes of lung adenocarcinoma (LUAD) in bulk tumors or single cells based on the enrichment scores of 12 stemness signatures by clustering analysis of their transcriptomic profiles. Three stemness subtypes of LUAD were identified: St-H, St-M, and St-L, having high, medium, and low stemness signatures, respectively, consistently in six different datasets. Among the three subtypes, St-H was the most enriched in epithelial-mesenchymal transition, invasion, and metastasis signaling, genomically instable, irresponsive to immunotherapies and targeted therapies, and hence had the worst prognosis. We observed that intratumor heterogeneity was significantly higher in high-stemness than in low-stemness bulk tumors, but significantly lower in high-stemness than in low-stemness single cancer cells. Moreover, tumor immunity was stronger in high-stemness than in low-stemness cancer cells, but weaker in high-stemness than in low-stemness bulk tumors. These differences between bulk tumors and single cancer cells could be attributed to the non-tumor cells in bulk tumors that confounded the results of correlation analysis. Furthermore, pseudotime analysis showed that many St-H cells were at the beginning of the cell evolution trajectory, compared to most St-L cells in the terminal or later phase, suggesting that many low-stemness cells are originated from high-stemness cells. The stemness-based classification of LUAD may provide novel insights into the tumor biology as well as precise clinical management of this disease.

Dissection of Immune Profiles in Microsatellite Stable and Low Microsatellite Instability Colon Adenocarcinoma by Multiomics Data Analysis.

Background: Although microsatellite instability (MSI) is an indicator for active immunotherapy response, only 15% of colon adenocarcinoma (COAD) patients are with MSI. An investigation into the immune profiles in low MSI (MSI-L) and microsatellite stable (MSS) COAD remains lacking, whereas such exploration may provide new insights into COAD immunity. Methods: We hierarchically clustered MSI-L/MSS COAD based on the enrichment levels of 28 immune signatures to identify its immune-specific subtypes. We also comprehensively compared molecular and clinicopathologic profiles among these subtypes. Results: We identified three immune subtypes of MSI-L/MSS COAD (IM-H, IM-M, and IM-L), which had high, medium, and low immune signature scores, respectively. We demonstrated that this subtyping method was reproducible and predictable by analyzing five different datasets, including four bulk tumor datasets and one single-cell dataset. IM-H was characterized by high immunity, high stemness, strong potential of proliferation, invasion and metastasis, epithelial-mesenchymal transition, elevated expression of oncogenic pathways, low tumor purity, low intratumor heterogeneity (ITH), genomic instability, inferior response to chemotherapy, and unfavorable prognosis. IM-M was characterized by the highest ratio of immunostimulatory to immunosuppressive signatures, the best response to chemotherapy, and favorable prognosis. IM-L was characterized by low immunity, high tumor purity, high ITH, and genomic stability. Conclusion: The immune-specific subtyping of MSI-L/MSS COAD may provide new insights into the tumor immunity as well as clinical implications for immunotherapy of the COAD patients who lack MSI.

Aspergichromones A-E, Five Chromone Derivatives with Complicated Polycyclic Architecture from Aspergillus deflectus.

Five unprecedented chromone derivatives involving a 6/6/5/5/5/6 hexacyclic scaffold (1, 2), 6/6/5/6/6/6/6 heptacyclic scaffold (3), and 6/6/6/5/5/6 hexacyclic scaffold (4, 5) were obtained from the fungus Aspergillus deflectus NCC0415. Their structures were identified using comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Except for 3, the other compounds, especially the 6/6/6/5/5/6 hexacyclic derivatives (4 and 5), exhibited potent inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitory activities.

Surface soil metal elements variability affected by environmental and soil properties.

Identifying the factors controlling the spatial variability of soil metal elements could be a challenge task due to the interaction of environmental attributes and human activities. This study aimed to investigate the critical explanatory variables controlling total Ca, Cd, Cr, Cu, Zn, Fe, Mn, Mg, Pb, and Zn variations in the arable topsoil using classical statistics, principal component analysis, and random forest techniques. The work was conducted in the core region of the Three Gorges Reservoir of China. The explanatory variables included soil, topography, climate, vegetation, land use type, and distance-related parameters. Average concentrations of the metal elements were in order of Fe > Mg > Ca > Mn > Zn > Cr > Ni > Pb > Cu > Cd. Soil Cr, Fe, and Pb showed low variability while others presented medium variability. Average concentrations of Cr, Fe, Cd, and Mg exceeded their corresponding background values. There were highly positive correlations between all metal elements except Pb, Cd and Cr. The principal component analysis further demonstrated that the sources of Pb, Cd, and Cr differed with other elements. The results of random forest suggested that soil properties followed by topography were critical parameters affecting the variations of Ca, Mg, Mn, Fe, Ni, Zn, and Cu. Agricultural activities and soil properties were major factors controlling the variations of Pb, Cr, and Cd. Further study should be conducted to understand the relations between the metal elements and soil properties.

Potential ecological and health risk assessment of different kiwifruit orchards in Qianjiang district, Chongqing city, China.

Heavy metal (HM) pollution in orchards is becoming serious in many countries, and some fruit HMs exceed the safety limits. In this study, contents of 8 HMs (Cd, Hg, As, Pb, Cr, Cu, Ni, and Zn) in 5 kiwifruit orchard soils and the tissues (roots, twigs, leaves, fruits) of 4 kiwifruit varieties collected from Qianjiang district, Chongqing city, China, were determined. Seven HMs could meet priority protection class I, except for Cd with slightly poor environmental quality, including 4% and 53% of the samples belonging to the strict control class III and safe utilization class II, respectively. The potential ecological risk index (235.30) indicated that the HMs in the orchard soil were of medium potential ecological risk. The HMs' migration from rock to soil was very obvious. Kiwifruit was easy to accumulate Cu from soil and it had high Zn and Ni translocations to above-ground parts from roots. Compared with other tissues, HMs' concentrations in fruits were the lowest. From the perspective of human health, about 8.3% and 0.83% of the fruit samples for Cr and Cu exceeded the national maximum permissible levels, respectively; fortunately, the health risk index (HRI) values for all the fruit samples were within the safe limits.

Assessing the Healing of Venous Leg Ulcers Using a Noncontact Near-Infrared Optical Imaging Approach.

Objective: Venous leg ulcers (VLUs) are one of the most common complications in lower extremity wounds. To date, clinicians employ visual inspection of the wound site during its healing process by monitoring surface granulation and reduction in wound size across weeks of treatment. In this study, a handheld near-infrared optical scanner (NIROS) has been developed at the Optical Imaging Laboratory to differentiate healing from nonhealing VLUs based on differences in blood flow to the wound and its surroundings. Approach: Noncontact near-infrared (NIR) area imaging of 12 VLUs have been carried out at two podiatric clinics. Diffuse reflectance images of the wounds were used to quantify optical contrasts between the wound and its surroundings. The variability in imaging conditions, analysis, and operator dependency were assessed to determine the robustness of the imaging approach. Results: Optical contrast obtained from diffuse reflectance images of VLUs were distinctly different for healing (positive contrast) and nonhealing (negative contrast) wounds, independent of the varying imaging and data analysis conditions. Innovation: NIR imaging of wounds to differentiate healing from nonhealing VLUs using a noncontact wide-area imager has been demonstrated for the first time. Conclusion: The application of a portable handheld imager to assess the healing or nonhealing nature of VLUs during weekly clinical treatment is significant since physiological changes, as observed using NIROS, manifest before visual reduction in wound size during the healing process.

Critical Review of Noninvasive Optical Technologies for Wound Imaging.

Significance: Noninvasive imaging approaches can provide greater information about a wound than visual inspection during the wound healing and treatment process. This review article focuses on various optical imaging techniques developed to image different wound types (more specifically ulcers). Recent Advances: The noninvasive optical imaging approaches in this review include hyperspectral imaging, multispectral imaging, near-infrared spectroscopy (NIRS), diffuse reflectance spectroscopy, optical coherence tomography, laser Doppler imaging, laser speckle imaging, spatial frequency domain imaging, and fluorescence imaging. The various wounds imaged using these techniques include open wounds, chronic wounds, diabetic foot ulcers, decubitus ulcers, venous leg ulcers, and burns. Preliminary work in the development and implementation of a near-infrared optical scanner for wound imaging as a noncontact hand-held device is briefly described. The technology is based on NIRS and has demonstrated its potential to differentiate a healing from nonhealing wound region. Critical Issues: While most of the optical imaging techniques can penetrate few hundred microns to a 1-2 mm from the wound surface, NIRS has the potential to penetrate deeper, demonstrating the potential to image internal wounds. Future Directions: All the technologies are currently at various stages of translational efforts to the clinic, with NIRS holding a greater promise for physiological assessment of the wounds internal, beyond the gold-standard visual assessment.

High cadmium concentrations in areas with endemic fluorosis: a serious hidden toxin?

Environmental contamination with cadmium (Cd) and fluorine (F) and the associated health impacts on humans have raised significant concerns in the literature, but the additional health risks created by Cd have not been investigated in areas with endemic fluorine intoxication (fluorosis). Here, we report for the first time that naturally occurring Cd in areas where endemic fluorosis is related to coal combustion is a serious hidden toxin. The high Cd levels in rocks and soils of these areas may increase health risks to epidemiological level, irrespective of fluorine levels. We implemented a pilot study in a fluorosis-affected rural area within China's Three Gorges region, and revealed enrichment of Cd in local bedrock (4.48-187 mgkg(-1)), coal (11.5-53.4 mgkg(-1)), and arable soils (1.01-59.7 mgkg(-1)). Cadmium was also observed to concentrate in local food crops (0.58-14.9 mgkg(-1)) and in the urine of local residents (1.7-13.4 microgL(-1)). A routine epidemiological investigation revealed that the two major Cd exposure pathways were through crop consumption and inhalation of emissions from coal combustion. Therefore, the naturally occurring Cd in areas with endemic fluorosis related to coal combustion represents a previously unrecognized toxin that must be addressed as part of efforts to control the endemic problem. The biogeochemical processes of Cd and the associated environmental effects will require additional in-depth study.