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With the ever-growing development of information technology, the education sector has adopted advanced technologies to improve this field. Different procedures based on human-computer interaction (HCI) can be applied to the efficient interaction between humans and computers to enhance the productivity of computers in various fields, especially in education. Active learning is one of the major technological fields that improves the usability of active learning. With the implementation of HCI approaches such as project-based learning (PBL), active learning classrooms (ALCs), and multi-user virtual environments (MUVE), students’ learning capabilities and teachers’ teaching skills are improved and education becomes more effective. After studying different applications of HCI in active learning, the study proposed to extract common features and select the most efficient ones from them. For the evaluation process, we presented two techniques named Criteria Importance Through Inter Correlation (CRITIC) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) in order to select the most effective HCI approach among various options. We choose nine criteria along with ten alternatives and rank them based on their performance scores. For assigning weights to criteria, we utilized the CRITIC strategy, while the TOPSIS technique is applied for ranking the alternatives. In the proposed study, it is identified that the alternative with the highest performance score is kept in first place, while the alternative with the worst performance score is kept at the bottom. The study concluded that the efficient and effective approach was selected among various options, and it can be employed as a suggestion for decision-related issues and future directions.

The city of Lhasa is located in the central Tibetan Plateau and is the most densely populated area. As the first continuous monitoring of atmospheric mercury (Hg) species in a city in the Tibetan Plateau, our monitoring in Lhasa showed that the concentrations of gaseous elemental Hg (GEM), gaseous oxidized Hg (GOM), and particle-bound Hg (PBM) during the subsequent Indian summer monsoon (S-ISM) period were 2.73 ± 1.48 ng m−3, 38.4 ± 62.7 pg m−3, and 59.1 ± 181.0 pg m−3, respectively. During the westerly circulation (WEC) period, the GEM, GOM, and PBM concentrations were 2.11 ± 2.09 ng m−3, 35.8 ± 43.3 pg m−3, and 52.9 ± 90.1 pg m−3, respectively. The GOM and PBM concentrations were higher than those of previous monitoring in the Tibetan Plateau and other provincial capitals in China. Typical high-value occurrence processes were studied to investigate random events with high atmospheric Hg concentrations in Lhasa. Combustion events nearby or further away may be the main contributor of the high-concentration events. The lowest GEM concentrations occurred in the afternoon, and persistently high concentrations were observed at night. The changes in GEM concentrations were consistent with the trends of other pollutant concentrations and contradictory to those of the wind speed. The high GEM concentrations at night can be attributed to the lower boundary layer height and lower wind speed. For both GOM and PBM, higher GOM concentrations occurred during the day and PBM during the night. The results of the principal component analysis indicated that local sources and wind speed are important factors influencing atmospheric Hg concentrations in Lhasa. The trajectory simulation showed that the source of the GEM in Lhasa gradually shifted from the south to the west of Lhasa from the S-ISM to the WEC periods, while both the southern and western sources were important in the late WEC period. The concentrations and change patterns of Hg species in Lhasa were significantly different than those at other monitoring sites in the Tibetan Plateau. Monitoring Hg species in Lhasa shows the possible maximum anthropogenic influences in the Tibetan Plateau and demonstrates the dramatic effect of wind on changes in urban atmospheric Hg concentrations.

High-Mountain Asia (HMA) is a global hotspot of stratospheric intrusion, and elevated surface ozone were observed at ground monitoring sites. Still, links between the variability of surface ozone and stratospheric intrusion at regional scale remain unclear. This study synthesized ground measurements of surface ozone over the HMA and analyzed their seasonal variations. The monthly mean surface ozone concentrations peaked earlier in the south in April and later in the north in July over the HMA. The migration of monthly surface ozone peaks was coupled with the synchronous movement of tropopause folding and westerly jet that created a conducive conditions for stratospheric ozone intrusion. Such intrusion contributed ~65 % of surface ozone at three typical sites across the HMA. We demonstrated that surface ozone over the HMA is mainly controlled by stratospheric intrusion, which warrants a proper consideration in understanding atmospheric chemistry and impacts of ozone over this highland region and beyond.

Ground-based observational characterization of atmosphere aerosols over Central Asia is very limited. This study investigated the columnar aerosol characteristics over Issyk-Kul, Kyrgyzstan, a background site in Central Asia using the long-term (∼14 years: August 2007-November 2021) data acquired with the Cimel sunphotometer. The mean aerosol optical depth (AOD) and Ångström exponent (AE) during the observation period were 0.14 ± 0.10 and 1.19 ± 0.41, respectively. Both AOD and AE varied across seasons, with highest AOD in spring (0.17 ± 0.17). Regarding the aerosol types, clean continental aerosols were dominant type (65%), followed by mixed aerosols (∼19%), clean marine aerosols (∼14%), dust (0.8%), and urban/industrial and biomass burning aerosol (0.7%). The aerosol volume size distribution was bimodal indicating the influence of both anthropogenic and natural aerosols with clear dominance of coarse mode during the spring season. Mainly dust and mixed aerosols were present during high aerosol episodes while the coarse mode aerosol volume concentration was 7.5 (strong episodes) and ∼19 (extreme episodes) times higher than the whole period average. Aerosol over this background sites were from local and regional sources with some contribution of long-range transport.

This study investigated the simulated solar light disinfection of Escherichia coli CGMCC 1.1595, a multidrug-resistant (MDR) strain resistant to tetracycline and ampicillin. With the increase of light intensity, the maximum inactivation efficiency reached 0.74 log in 60 min following visible light irradiation with an intensity of 115.8 mW/cm2 and following UVA–visible light irradiation, using a 98% UVA-ray contribution at 6.5 mW/cm2 and 95% contribution at 20.0 mW/cm2, the inactivation efficiency was up to 6.09 log. The inactivated MDR E. coli did not regrow after light irradiation or in the dark after 24 or 48 h after visible light disinfection, demonstrating that visible light disinfection can prevent MDR E. coli self-repair. The MDR E. coli plasmid electrophoresis band gradually went dark with increase of the light irradiation time and could be completely eliminated by high UVA light intensity treatment, however, simulated sunlight irradiation had minimal influence on both tetracycline and ampicillin resistance of the MDR E. coli strain.

Measurements of land-air mercury (Hg) exchanges over vegetated surfaces are needed to further constrain Hg fluxes over vegetated terrestrial surfaces. Yet, knowledge of land-air Hg dynamics in alpine grasslands remains poor. Hg fluxes over an alpine meadow were measured throughout a full vegetation period in the central Tibetan Plateau (TP). This TP grassland served as a small source of atmospheric total gaseous Hg (TGM) during vegetation period (0.92 μg m

Background Krüppel-like factor 9 (KLF9) is one of the most important members of the KLF family, and is abnormally expressed in many tumors. However, the detailed function of KLF9 in endometrial cancer (EC) was barely investigated. Methods In this study, a total of 52 paired EC tissues were recruited to detect the KLF9 expression. Then a serial of phenotypic experiments and mechanism researches were performed. Results The results showed that KLF9 expression was decreased in EC tissues, and the reduced expression of KLF9 is associated with highly metastatic capacity of EC cells. KLF9 could inhibit the proliferation and invasion of EC cells by inhibiting the Wnt/β-catenin signaling pathway. Progesterone receptor (PR) could bind to KLF9 promoter and a positive correlation between KLF9 and PR expression was witnessed. Conclusions Taken together, the reduction of KLF9 induced by PR might participate in the development of EC and targeting KLF9 may provide a novel strategy for EC management.

China experiences severe particulate matter (PM) pollution. Although a monitoring network for PM2.5 (diameter

Introduction Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy, a condition risking the health of both the mother and the baby. Naringenin (NGN) has been demonstrated to have multiple therapeutic functions, while it is also considered to exhibit antidiabetic properties. The present study aimed to investigate the protective effects of NGN in pregnant diabetic rats. Methods GDM was induced by feeding the rats with a high-fat diet for 5 weeks, followed by intraperitoneal injection of streptozotocin (35 mg/kg). The fasting blood glucose were determined with a glucometer and the 24-h urine protein (24-UPro) were determined by the sulfonyl salicylic acid method. The pathological morphological changes and apoptosis of glomeruli cells of kidney tissue using hematoxylin and eosin (H&E) staining and TUNEL analysis. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the serum T-AOC, the activity of SOD, the levels of GSH-Px, CAT and MDA, TNF-α, IL-6, TGF-β, ICAM-1.The expression of related genes were measured by RT-qPCR and Western blot analyses. Results In the NGN-treated group, it was observed that the general status of the rats was improved, while the levels of blood glucose and 24-UPro were significantly decreased. In addition, the histopathological changes in renal tissues and renal cell apoptosis were significantly improved upon treatment with NGN. The expression levels of oxidative stress and inflammation-associated factors also differed signifigcantly between the model and NGN-treated groups. Upon treatment with NGN, the levels of peroxisome proliferator-activated receptor α were significantly increased, while the activity of enzymes involved in the oxidative metabolism of fatty acids was significantly decreased. Conclusion These preliminary experimental findings demonstrate that NGN has a certain renoprotective effect on GDM, which provides a novel therapeutic option for this condition.

The Tibetan Plateau is generally considered to be a significantly clean area owing to its high altitude; however, the transport of atmospheric pollutants from the Indian subcontinent to the Tibetan Plateau has influenced the Tibetan environments. Nyingchi is located at the end of an important water vapor channel. In this study, continuous monitoring of gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and particle-bound mercury (PBM) was conducted in Nyingchi from 30 March to 3 September 2019, to study the influence of the Indian summer monsoon (ISM) on the origin, transport, and behavior of Hg. The GEM and PBM during the preceding Indian summer monsoon (PISM) period (1.20±0.35 ng m−3 and 11.4±4.8 pg m−3 for GEM and PBM, respectively) were significantly higher than those during the ISM period (0.95±0.21 ng m−3, and 8.8±6.0 pg m−3); the GOM during the PISM period (13.5±7.3 pg m−3) was almost at the same level as that during the ISM period (12.7±14.3 pg m−3). The average GEM concentration in the Nyingchi region, obtained using passive sampler, was 1.12±0.28 ng m−3 (from 4 April 2019 to 31 March 2020). The GEM concentration showed that the sampling area was very clean compared to other high-altitude sites. The GEM has several patterns of diurnal variation during different periods. Stable high GEM concentrations occur at night and low concentrations occur in the afternoon during PISM, which may be related to the nocturnal boundary layer structure. High values occurring in the late afternoon during the ISM may be related to long-range transport. Low concentrations of GEM observed during the morning in the ISM may originate from vegetation effects. The results of the trajectory model demonstrate that the sources of pollutants at Nyingchi are different with different circulation patterns. During westerly circulation in the PISM period, pollutants mainly originate from central India, northeastern India, and central Tibet. During the ISM period, the pollutants mainly originate from the southern part of the SET site. The strong precipitation and vegetation effects on Hg species during the ISM resulted in low Hg concentrations transmitted to Nyingchi during this period. Further, principal component analysis showed that long-distance transport, local emissions, meteorological factors, and snowmelt factors are the main factors affecting the local Hg concentration in Nyingchi. Long-distance transport factor dominates during PISM and ISM3, while local emissions is the major contributor between PISM and ISM3. Our results reveal the Hg species distribution and possible sources of the most important water vapor channel in the Tibetan Plateau and could serve as a basis for further transboundary transport flux calculations.

The location of Central Asia, almost at the center of the global dust belt region, makes it susceptible for dust events. The studies on atmospheric impact of dust over the region are very limited despite the large area occupied by the region and its proximity to the mountain regions (Tianshan, Hindu Kush-Karakoram-Himalayas, and Tibetan Plateau). In this study, we analyse and explain the modification in aerosols’ physical, optical and radiative properties during various levels of aerosol loading observed over Central Asia utilizing the data collected during 2010–2018 at the AERONET station in Dushanbe, Tajikistan. Aerosol episodes were classified as strong anthropogenic, strong dust and extreme dust. The mean aerosol optical depth (AOD) during these three types of events was observed a factor of ~3, 3.5 and 6.6, respectively, higher than the mean AOD for the period 2010–2018. The corresponding mean fine-mode fraction was 0.94, 0.20 and 0.16, respectively, clearly indicating the dominance of fine-mode anthropogenic aerosol during the first type of events, whereas coarse-mode dust aerosol dominated during the other two types of events. This was corroborated by the relationships among various aerosol parameters (AOD vs. AE, and EAE vs. AAE, SSA and RRI). The mean aerosol radiative forcing (ARF) at the top of the atmosphere (ARFTOA), the bottom of the atmosphere (ARFBOA), and in the atmosphere (ARFATM) were −35 ± 7, −73 ± 16, and 38 ± 17 Wm−2 during strong anthropogenic events, −48 ± 12, −85 ± 24, and 37 ± 15 Wm−2 during strong dust event, and −68 ± 19, −117 ± 38, and 49 ± 21 Wm−2 during extreme dust events. Increase in aerosol loading enhanced the aerosol-induced atmospheric heating rate to 0.5–1.6 K day−1 (strong anthropogenic events), 0.4–1.9 K day−1 (strong dust events) and 0.8–2.7 K day−1 (extreme dust events). The source regions of air masses to Dushanbe during the onset of such events are also identified. Our study contributes to the understanding of dust and anthropogenic aerosols, in particular the extreme events and their disproportionally high radiative impacts over Central Asia.

Air pollutants can be transported to the pristine regions such as the Tibetan Plateau, by monsoon and stratospheric intrusion. The Tibetan Plateau region has limited local anthropogenic emissions, while this region is influenced strongly by transport of heavy emissions mainly from South Asia. We conducted a comprehensive study on various air pollutants (PM2.5, total gaseous mercury, and surface ozone) at Nam Co Station in the inland Tibetan Plateau. Monthly mean PM2.5 concentration at Nam Co peaked in April before monsoon season, and decreased during the whole monsoon season (June–September). Monthly mean total gaseous mercury concentrations at Nam Co peaked in July and were in high levels during monsoon season. The Indian summer monsoon acted as a facilitator for transporting gaseous pollutants (total gaseous mercury) but a suppressor for particulate pollutants (PM2.5) during the monsoon season. Different from both PM2.5 and total gaseous mercury variabilities, surface ozone concentrations at Nam Co are primarily attributed to stratospheric intrusion of ozone and peaked in May. The effects of the Indian summer monsoon and stratospheric intrusion on air pollutants in the inland Tibetan Plateau are complex and require further studies.

The Tibetan Plateau is generally considered to be a significantly clean area owing to its high altitude; however, the transport of atmospheric pollutants from the Indian subcontinent to the Tibetan Plateau has infected the Tibetan environments. Nyingchi is located at the end of an important water vapor channel. In this study, continuous monitoring of gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and particle-bound mercury (PBM) was conducted in Nyingchi from March 30 to September 3, 2019, to study the influence of the Indian summer monsoon (ISM) on the origin, transport and behavior of mercury. The atmospheric Hg concentrations during the preceding Indian summer monsoon (PISM) period (1.20 ± 0.35 ng m−3, 13.5 ± 7.3 pg m−3, and 11.4 ± 4.8 pg m−3 for GEM, GOM, and PBM, respectively) were relatively higher than those during the ISM period (0.95 ± 0.21 ng m−3, 12.7 ± 14.3 pg m−3 and 8.8 ± 6.0 pg m−3). The average annual total gaseous mercury concentration in the Nyingchi region was obtained using a passive sampler as 1.12 ± 0.28 ng m−3. The GEM concentration showed that the sampling area was very clean. The GEM has several patterns of daily variation during different periods. Stable high GEM concentrations occur at night during PISM, which may be related to the nocturnal boundary layer. High values occurring in the late afternoon during the ISM may be related to long-range transport. The results of the trajectory model demonstrate that the sources of pollutants at Nyingchi are different under the control of different airflow fields. During westerly circulation, pollutants mainly originate from northeast India or Nepal. During the ISM period, the pollutants mainly originate from northeast India, or the Bay of Bengal, and the Indian Ocean. The strong precipitation and vegetation effects on Hg during the ISM resulted in low Hg concentrations transmitted to Nyingchi during this period. Further, principal component analysis showed that long-distance transport, local emissions, meteorological factors, and snowmelt factors are the main factors affecting the local Hg concentration in Nyingchi.

Indoor air pollution (IAP) is one of the leading risk factors for various adverse health outcomes including premature deaths globally. Even though research related to IAP has been carried out, bibliometric studies with particular emphasis on this topic have been lacking. Here, we investigated IAP research from 1990 to 2019 retrieved from the Web of Science database through a comprehensive and systematic scientometric analysis using the CiteSpace 5.7.R2, a powerful tool for visualizing structural, temporal patterns and trends of a scientific field. There was an exponential increase in publications, however, with a stark difference between developed and developing countries. The journals publishing IAP related research had multiple disciplines; 'Indoor Air' journal that focuses solely on IAP issues ranked fifth among top-cited journals. The terms like 'global burden', 'comparative risk assessment,' 'household air pollution (HAP)', 'ventilation', 'respiratory health', 'emission factor', 'impact,' 'energy', 'household', 'India' were the current topical subject where author Kirk R. Smith was identified with a significant contribution. Research related to rural, fossil-fuel toxicity, IAP, and exposure-assessment had the highest citation burst signifying the particular attention of scientific communities to these subjects. Overall, this study examined the evolution of IAP research, identified the gaps and provided future research directions.

Seawater is a valuable water resource in coastal regions. However, during seawater chlorination, a group of halophenols (HPs) may be formed. These HPs have lower odor and taste detection thresholds than other disinfection by-products (DBPs), however these are usually more toxic than most of the abundantly detected DBPs. Hence, an effective approach for control of HP formation during seawater chlorination is required to minimize highly toxic HP formation. Pretreatment using TiO2 photocatalysis was applied in this study to assess its ability for removal of HP precursors. Seawater samples with external addition of 1 mg/L phenol were spiked with TiO2 from 0.1 to 10.0 g/L and exposed under UV light for 2 to 120 min. The UV absorbance at 254 nm and the excitation–emission matrix fluorescence of dissolved organic matter were measured for each treated sample. It was observed that the optimal treatment condition to achieve the highest UV254 removal was 4.0 g/L TiO2 with UV exposure of 30 min. By pretreatment using this method and stated dose and exposure, only two types of HPs were detected during chlorination, compared with four types of HPs formed in the untreated samples. Moreover, the pretreatment greatly reduced the concentration of 2,4,6-TBP from more than 400 μg/L to less than 1 μg/L. The significance of this research study is to identify the effectiveness of UV/TiO2 in reducing DBP formation by analyzing the mechanisms during the process, which indicates the use of UV/TiO2 pretreatment for control of HP formation in seawater during chlorination.

The extensive use of antibiotics has resulted in the development of antibiotic-resistant bacteria (ARB), which may not be completely removed by traditional wastewater treatment processes. More effective approaches to disinfection are needed to prevent the release of ARB into the surface water. The metal-free photocatalyst graphitic carbon nitride (g-C3N4) has aroused great interest as a possible agent for water and wastewater treatment, due to its low cytotoxicity and photoactivity with visible light. In this study, the efficacy of g-C3N4 was assessed as a possible means to enhance ARB inactivation by irradiation. ARB were isolated and purified from secondary effluents in 4 municipal wastewater treatment plants. Of these, 4 typical multi-drug ARB isolates, belonging to Enterobacteriaceae, were selected for irradiation experiments. Inactivation was seen to increase with irradiation time. At 60 min, the inactivation of the 4 ARB isolates by light at > 300 nm and > 400 nm was in the range of 0.25–0.39 log and 0.16–0.19 log, respectively. The use of g-C3N4-mediated photocatalysis at the same wavelengths significantly enhanced that to 0.64–1.26 log and 0.31–0.41 log, respectively. The antibiotic susceptibility of the ARB isolates remained unchanged either prior to or after irradiation and was independent of photon fluence, reaction time, and the presence of g-C3N4. This study establishes a baseline for understanding the effectiveness of g-C3N4 photocatalysis on inactivation of ARB in wastewaters and lays the foundation for further improvement in the use of photocatalysis for wastewater treatment.

Information about the long-term trends of wet mercury (Hg) deposition is important for assessing the impact of atmospheric pollution on environmental health. As the most populated and capital city of Tibet, Lhasa is isolated far away from the heavily-polluted urban clusters in China. In this study, a 10-year observation was conducted in Lhasa to establish the long-term trend of wet Hg deposition and investigate the possible causes of this variation trend. Our study showed no significant increase in wet Hg deposition while Lhasa has achieved rapid population and economic growth during the study period. The contrasting changes in long-term wet Hg deposition and socioeconomic development (e.g., GDP growth) could be greatly attributed to the efforts in preventing and controlling air pollution at regional and local levels. This trend in Lhasa differs greatly from those observed by a rapid increase of Hg trend in the remote areas of the Tibetan Plateau. Our findings indicate that the remote cryospheric areas over the Tibetan Plateau are prone to be affected by transboundary Hg pollution, and more attention should be paid to its environmental and health effects for future study.

Black carbon (BC) aerosol impacts the air quality, public health, agricultural productivity, weather, monsoon, cryosphere, and climate system from the local to the global scale. However, its distribution over vast Central Asia is poorly known, because it is one of the poorly sampled regions of the world. BC in the soil can be resuspended into the atmosphere and transported to downwind regions with sensitive ecosystems and vulnerable populations, such as from Central Asian countries to the cryospheric regions in the Tianshan Mountain and the Tibetan Plateau, which could accelerate the melting of the snowfields and glaciers. We report the distribution of BC and total organic carbon (TOC) in surface soil with samples collected at multiple sites, for the first time, over three countries in Central Asia (Uzbekistan, Tajikistan, and Kyrgyzstan). The mean BC (TOC) concentrations over three countries were 0.06 ± 0.06 (11.86 ± 4.84) mg g−1, 0.15 ± 0.21 (20.35 ± 10.96) mg g−1, and 0.32 ± 0.29 (26.45 ± 20.38) mg g−1, respectively. They were found to be originated from the same or similar sources, at least over Tajikistan and Kyrgyzstan, as indicated by their high and significant correlation (R2 > 0.6, p

This paper presents the results of the study on columnar aerosol optical and physical properties and radiative effects directly observed over Dushanbe, the capital city of Tajikistan, a NASA AERONET site (equipped with a CIMEL sunphotometer) in Central Asia. The average aerosol optical depth (AOD) and Angstrom exponent (AE) during the observation period from July 2010 to April 2018 were found to be 0.28 ± 0.20 and 0.82 ± 0.40, respectively. The highest seasonal AOD (0.32 ± 0.24), accompanied by the lowest average AE (0.61 ± 0.25) and fine-mode fraction in AOD (0.39), was observed during summer due to the influence of coarse particles like dust from arid regions. Fine particles were found in significant amounts during winter. The ‘mixed aerosol’ was identified as the dominant aerosol type with presence of ‘dust aerosol’ during summer and autumn seasons. Aerosol properties like volume size distribution, single scattering albedo, asymmetry parameter and refractive index suggested the influence of coarse particles (during summer and autumn). Most of the air masses reaching this site transported local and regional emissions, including from beyond Central Asia, explaining the presence of various aerosol types in Dushanbe’s atmosphere. The seasonal aerosol radiative forcing efficiency (ARFE) in the atmosphere was found high (>100 Wm−2) and consistent throughout the year. Consequently, this resulted in similar seasonally coherent high atmospheric solar heating rate (HR) of 1.5 K day−1 during summer-autumn-winter, and ca. 0.9 K day−1 during spring season. High ARFE and HR values indicate that atmospheric aerosols could exert significant implications to regional air quality, climate and cryosphere over the central Asian region and downwind Tianshan and Himalaya-Tibetan Plateau mountain regions with sensitive ecosystems.

Accurately measuring reactive gaseous mercury (RGM) concentrations in the atmosphere is important to improve our understanding of the global mercury (Hg) cycle. In this study, we compared the RGM collection efficiencies of four sampling methods, including a 14 cm long KCl-coated denuder, a KCl-coated glass fiber filter, a KCl-coated quartz sand tube, and a cation exchange membrane. Both laboratory studies and field RGM monitoring were performed in environments with low humidity [relative humidity (RH) of ∼20%], medium humidity (RH of 50–70%), and high humidity (RH of ∼100%). Laboratory results showed that in environments with

Long-term (2004–2015) satellite data over three adjacent yet contrasting regions: Indo-Gangetic Plain, Himalayas and Tibetan Plateau (TP) were used to study the spatiotemporal distribution of total...

// Jian Chen 1, 2, * , Qitian Mu 1, 2, 3, * , Xia Li 1, 2, * , Xiufeng Yin 1, 2 , Mengxia Yu 1, 2 , Jing Jin 1, 2 , Chenying Li 1, 2 , Yile Zhou 1, 2 , Jiani Zhou 1, 2, 4 , Shanshan Suo 1, 2 , Demin Lu 1, 2 and Jie Jin 1, 2 1 Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 2 Institute of Hematology, Zhejiang University, Hangzhou, China 3 Laboratory of Stem Cell Transplantation, Ningbo First Hospital, Zhejiang, China 4 Hematology Department of Ningbo Medical Center Lihuili Estern Hospital, Ningbo, China * These authors contributed equally to this work Correspondence to: Jie Jin, email: zjuhematology@163.com Keywords: homoharringtonine, smad3, TGF-β, acute myeloid leukemia Received: April 04, 2016 Accepted: March 29, 2017 Published: April 08, 2017 ABSTRACT Homoharringtonine (HHT) has long and widely been used in China for the treatment of acute myeloid leukemia (AML), the clinical therapeutic effect is significant but the working mechanism is poorly understood. The purpose of this study is to screen the possible target for HHT with virtual screening and verify the findings by cell experiments. Software including Autodock, Python, and MGL tools were used, with HHT being the ligand and proteins from PI3K-Akt pathway, Jak-stat pathway, TGF-β pathway and NK-κB pathway as the receptors. Human AML cell lines including U937, KG-1, THP-1 were cultured and used as the experiment cell lines. MTT assay was used for proliferation detection, flowcytometry was used to detect apoptosis and cell cycle arrest upon HHT functioning, western blotting was used to detect the protein level changes, viral shRNA transfection was used to suppress the expression level of the target protein candidate, and viral mRNA transfection was used for over-expression. Virtual screening revealed that smad3 from TGF-β pathway might be the candidate for HHT binding. In AML cell line U937 and KG-1, HHT can induce the Ser423/425 phosphorylation of smad3, and this phosphorylation can subsequently activate the TGF-β pathway, causing cell cycle arrest at G1 phase in U937 cells and apoptosis in KG-1 cells, knockdown of smad3 can impair the sensitivity of U937 cell to HHT, and over-expression of smad3 can re-establish the sensitivity in both cell lines. We conclude that smad3 is the probable target protein of HHT and plays an important role in the functioning mechanism of HHT.

// Xia Li 1, 2, * , Xiufeng Yin 1, 2, * , Huafeng Wang 1, 2 , Jiansong Huang 1, 2 , Mengxia Yu 1, 2 , Zhixin Ma 1, 2 , Chenying Li 1, 2 , Yile Zhou 1, 2 , Xiao Yan 1, 2 , ShuJuan Huang 1, 2 , Jie Jin 1, 2, 3 1 Department of Hematology, The First Affiliated Hospital of Zhejiang University, Hangzhou, People’s Republic of China 2 Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China 3 Key Lab of Hematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China * These authors contributed equally to this work and share first authorship Correspondence to: Jie Jin, email: zjuhematology@163.com Keywords: acute myeloid leukemia, FLT3-ITD, homoharringtonine, ibrutinib Received: February 25, 2016 Accepted: December 25, 2016 Published: January 03, 2017 ABSTRACT Acute myeloid leukemia (AML) is a highly heterogeneous disease and internal tandem duplication mutation in FMS-like tyrosine-kinase-3 (FLT3-ITD) has a negative impact on outcome. Finding effective treatment regimens is desperately needed. In this study, we explored the inhibitory effect and mechanism of homoharringtonine (HHT) in combination with ibrutinib on FLT3-ITD mutant AML cells. Consequently, we observed a synergistic inhibitory effect when ibrutinib was combined with HHT to inhibit cell proliferation, induce apoptosis and arrest cell cycle at G0/G1 phase in MV4-11 and MOLM-13 leukemia cells. Our results indicate that the mechanisms of the combination effect are mainly via regulating the STAT5/Pim-2/C-Myc pathway, AKT pathway and Bcl-2 family, activating p21WAF1/CIP1 and inhibiting CCND/CDK complex protein. Interestingly, synergistic cytotoxicity of ibrutinib and HHT was dependent on both FLT3 and BTK. Here we provide a novel effective therapeutic approach for the treatment of AML patients with FLT3-ITD mutation.

Microplastics (MPs) are ubiquitously spread in water environment and have raised global concerns due to their adverse effect to biological and ecological systems. Wastewater treatment plants have been reported to be an important route of releasing MPs into the environment. As a great source of MPs in number in wastewater, the characteristics of microbeads have hardly been studied. In this study, the variation of the characteristics of microbeads prior to and after incubating in wastewater samples has been identified. Reported digestion methods of acid, alkaline, enzymatic, and wet preoxidation digestion were subsequently applied to assess their efficacy for digesting microbeads from the wastewater, and enzymatic digestion has shown the optimal efficacy. Finally, enzymatic digestion was applied to evaluate microbeads and other MPs in real wastewater treatment plant samples. It is shown that the sequential treatment of fine screen, grit chamber, and improved sequencing batch reactor activated sludge processes were able to remove 72% pellets in number and 43% MPs in total, while a large portion was still remaining after the secondary treatment. This study set a base for understanding the characteristics and occurrence of MPs, especially microbeads in wastewater samples.

In recent decades, most big cities in China have experienced severe air pollution accompanied by rapid economic and social development. Analysis of measurements of air pollutants form a fundamental basis for understanding the characteristics of air pollution and are important references for policy-making. In this study, five-year measurements of air pollutants at 6 sites in Lhasa, a typical high altitude big city in southwestern China, were analyzed from January 2013 to December 2017. Air pollutants at all the 6 sites in Lhasa generally displayed similar patterns of both diurnal and monthly variations, indicating the mixed atmospheric environment and the overall effect of the meteorological conditions in the city. Spatially, the air pollutant concentrations at the 6 sites were generally characterized by high concentrations of SO2, NO2, CO, PM10 and PM2.5 at urban sites and high O3 concentrations at suburban sites. In comparison with other provincial capital cities in China, Lhasa has low concentrations of air pollutants, except for O3, and thus, better air quality. Although Lhasa has experienced rapid urbanization and economic development, air pollution conditions have remained rather stable and even decreased slightly in term of particular air pollutants. We suggested that the relatively isolated location, low air pollutant emissions associated with its industrial structure and renewable energy consumption, and effective air pollution control measures, collectively contributed to the synchronous improvement of the economy and air quality in Lhasa. Such "Lhasa pattern" may serve as a positive example for other regional hub cities in China and beyond that experience socioeconomic development and simultaneously seek to improve air quality.

The extensive use of antibiotics has resulted in the development of antibiotic-resistant bacteria (ARB), which may not be completely removed by traditional wastewater treatment processes. More effective approaches to disinfection are needed to prevent the release of ARB into the surface water. The metal-free photocatalyst graphitic carbon nitride (g-C

To understand the characteristics of particulate matter (PM) and other air pollutants in Xinjiang, a region with one of the largest sand-shifting deserts in the world and significant natural dust emissions, the concentrations of six air pollutants monitored in 16 cities were analyzed for the period January 2013–June 2019. The annual mean PM2.5, PM10, SO2, NO2, CO, and O3 concentrations ranged from 51.44 to 59.54 μg m−3, 128.43–155.28 μg m−3, 10.99–17.99 μg m−3, 26.27–31.71 μg m−3, 1.04–1.32 mg m−3, and 55.27–65.26 μg m−3, respectively. The highest PM concentrations were recorded in cities surrounding the Taklimakan Desert during the spring season and caused by higher amounts of wind-blown dust from the desert. Coarse PM (PM10-2.5) was predominant, particularly during the spring and summer seasons. The highest PM2.5/PM10 ratio was recorded in most cities during the winter months, indicating the influence of anthropogenic emissions in winters. The annual mean PM2.5 (PM10) concentrations in the study area exceeded the annual mean guidelines recommended by the World Health Organization (WHO) by a factor of ca. ∼5–6 (∼7–8). Very high ambient PM concentrations were recorded during March 19–22, 2019, that gradually influenced the air quality across four different cities, with daily mean PM2.5 (PM10) concentrations ∼8–54 (∼26–115) times higher than the WHO guidelines for daily mean concentrations, and the daily mean coarse PM concentration reaching 4.4 mg m−3. Such high PM2.5 and PM10 concentrations pose a significant risk to public health. These findings call for the formulation of various policies and action plans, including controlling the land degradation and desertification and reducing the concentrations of PM and other air pollutants in the region.

Background Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) by providing patients with long-term survival. Although most patients who receive TKI treatment have shown satisfactory tolerance, second malignancies (SMs) should not be ignored because of lifetime treatment. We designed a retrospective study to evaluate the incidence and possible risk factors of SMs in CML patients treated with TKIs. Patients and Methods Records of 223 patients with Philadelphia chromosome-positive CML treated with imatinib were reviewed to investigate frequencies and characteristics of SMs. The data of SMs were compared with the number expected from the National Central Cancer Registry. The possible risk factors of SM in CML patients treated with TKIs were also evaluated using Poisson regression in this study. Results After a median follow-up of 64 months (range, 4-253 months) from CML diagnosis, 7 patients (3.14%) developed 6 different SMs including colon, stomach, breast, kidney, cervical, and lymphonodus tissue. The risk of second cancer was higher than expected (observed-to-expected ratio, 2.45; 95% confidence interval, 1.17-5.14; P = .018). No associated elements were found in terms of influencing the incidence of SM in CML patients treated with TKIs. Conclusion We found patients with CML treated with TKIs had a higher relative incidence of SM compared with the expected incidence among the general Chinese population. However, the correlations between second cancer and the potential risk factors including the length of exposure and cumulative dose of TKIs were not found in this study.

Hourly speciated measurements of atmospheric mercury made in a remote, high-altitude site in the Tibetan Plateau revealed the first field observations of the reduction of reactive mercury in the presence of sunlight in the atmosphere. Measurements were collected over four winter months on the shore of Nam Co Lake in the inland Tibetan Plateau. The data was analyzed to identify sources and atmospheric transformations of the speciated mercury compounds. The absence of local anthropogenic sources provided a unique opportunity to examine chemical transformations of mercury. An optimization algorithm was used to determine the parameters of a chemical box model that would match the measured reactive mercury concentrations. This required the presence of a photolytic reduction reaction previously observed in laboratory studies and in power plant plumes. In addition, the model estimated the role of vertical mixing in diluting reactive gaseous mercury during the day, and the role of bromine chemistry in oxidizing gaseous elemental mercury to produce reactive gaseous mercury. This work provides further evidence of the need to add the photolytic reduction reaction of oxidized mercury into atmospheric transport models in order to better simulate mercury deposition.

Homoharringtonine (HHT) is a natural alkaloid isolated from various Cephalotaxus species. HHT has been used to treat acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), chronic lymphocyte leukaemia and myelodysplastic syndromes. Although HHT inhibits protein synthesis and promotes apoptosis of leukaemia cells in preclinical studies, its molecular target proteins remain unknown. The aim of this study was to identify target proteins of HHT.We have synthesized a biotinylated affinity column and used it to identify targets of HHT and confirmed the results by MS and Western blots. We also examined the effects of HHT on the target protein and determined roles of the target protein in anti-leukaemia activities of HHT through Western blots, flow cytometry and retrovirus transfection.Myosin-9, a member of the myosin super-family, was identified as a direct interactor of HHT. Furthermore, HHT up-regulated the expression level of myosin-9 in both AML and CML cell lines in a time-dependent manner. Thus, HHT-induced apoptosis of leukaemia cells begins in 6 h and continues to increase for 24 h. There is a positive correlation between up-regulated myosin-9 expression level and increased percentage of apoptotic cells mediated by HHT. Overexpression of myosin-9 could increase the sensitivity of the leukaemia cells to the cytotoxicity of HHT and arrest cells in S and G2/M phases.Our results indicated that myosin-9 was the target protein of HHT and played an important role in the HHT-induced apoptosis of leukaemia cells.

One year of online total gaseous mercury (TGM) measurements were carried out for the first time in Lanzhou, a city in northwest China that was once seriously polluted. Measurements were made from October 2016 to October 2017 using the Tekran 2537B instrument, and the annual mean concentration of TGM in Lanzhou was 4.48 ± 2.32 ng m−3 (mean ± standard deviation). TGM concentrations decreased during the measurement period, with autumn 2017 average concentrations 2.87 ng m−3 lower than autumn 2016 average concentrations. Similar diurnal variations of TGM were obtained in different seasons with low concentrations observed in the afternoon and high concentrations at night. The principal component analysis and conditional probability function results revealed that the sources of mercury were similar to the other atmospheric pollutants such as SO2, CO, NO2 and PM2.5, and were mainly from industrial combustion plants in urban districts. Concentration weighted trajectory analysis using backward trajectories demonstrated that higher mercury concentrations were related to air masses from adjacent regions, indicating the importance of influences from local-to-regional scale sources. A synthesis of multi-decadal atmospheric mercury measurements in Lanzhou and other Chinese megacities revealed that atmospheric mercury concentrations were either generally stable or experienced a slight decrease, during a time when China implemented control measures on atmospheric pollution. Long-term atmospheric mercury observations in urban and background sites in China are warranted to assess mercury pollution and the effectiveness of China's mercury control policies.