Uppermost global tree elevations are primarily limited by low temperature or insufficient moisture.

The impact of anthropogenic global warming has induced significant upward dispersal of trees to higher elevations at alpine treelines. Assessing vertical deviation from current uppermost tree distributions to potential treeline positions is crucial for understanding ecosystem responses to evolving global climate. However, due to data resolution constraints and research scale limitation, comprehending the global pattern of alpine treeline elevations and driving factors remains challenging. This study constructed a comprehensive quasi-observational dataset of uppermost tree distribution across global mountains using Google Earth imagery. Validating the isotherm of mean growing-season air temperature at 6.6 ± 0.3°C as the global indicator of thermal treeline, we found that around two-thirds of uppermost tree distribution records significantly deviated from it. Drought conditions constitute the primary driver in 51% of cases, followed by mountain elevation effect which indicates surface heat (27%). Our analyses underscore the multifaceted determinants of global patterns of alpine treeline, explaining divergent treeline responses to climate warming. Moisture, along with temperature and disturbance, plays the most fundamental roles in understanding global variation of alpine treeline elevation and forecasting alpine treeline response to ongoing global warming.

Unveiling community adaptations to extreme heat events using mobile phone location data.

The escalating frequency, duration, and intensity of extreme heat events have posed a significant threat to human society in recent decades. Understanding the dynamic patterns of human mobility under extreme heat will contribute to accurately assessing the risk of extreme heat exposure. This study leverages an emerging geospatial data source, anonymous cell phone location data, to investigate how people in different communities adapt travel behaviors responding to extreme heat events. Taking the Greater Houston Metropolitan Area as an example, we develop two indices, the Mobility Disruption Index (MDI) and the Activity Time Shift Index (ATSI), to quantify diurnal mobility changes and activity time shift patterns at the city and intra-urban scales. The results reveal that human mobility decreases significantly in the daytime of extreme heat events in Houston while the proportion of activity after 8 p.m. is increased, accompanied with a delay in travel time in the evening. Moreover, these mobility-decreasing and activity-delaying effects exhibited substantial spatial heterogeneity across census block groups. Causality analysis using the Geographical Convergent Cross Mapping (GCCM) model combined with correlation analyses indicates that people in areas with a high proportion of minorities and poverty are less able to adopt heat adaptation strategies to avoid the risk of heat exposure. These findings highlight the fact that besides the physical aspect of environmental justice on heat exposure, the inequity lies in the population's capacity and knowledge to adapt to extreme heat. This research is the first of the kind that quantifies multi-level mobility for extreme heat responses, and sheds light on a new facade to plan and implement heat mitigations and adaptation strategies beyond the traditional approaches.

Design, synthesis and bioevaluation of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide derivatives as novel xanthine oxidase inhibitors.

In view of expanding the structure activity relationship of xanthine oxidase inhibitors, a series of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide/carboxylic acid derivatives were designed by molecular docking and synthesized. All the target compounds were evaluated for their in vitro XO inhibition by using febuxostat and allopurinol as the standard controls. Most of the hydrazide derivatives exhibited potency levels in the micromolar range. From the view of docking study, hydrazide derivatives bind to the active site of XO through a novel interaction mode, which is different from that of febuxostat bearing a carboxyl group. The most promising compound 8b was further subjected to kinetic analysis to deduce their modes of inhibition.

[Determination of dimethyl sulfate genotoxic impurities in tertiary amine drugs by ultra-high performance liquid chromatography-tandem mass spectrometry].

Dimethyl sulfate is an important chemical raw material that is widely used in the synthesis of drugs, dyes, spices, and pesticides. The highly toxic and corrosive dimethyl sulfate residue in medicines is harmful to the human body, and hence, the residue level should be strictly controlled. Traditional detection methods use high-purity acetonitrile and anhydrous as the solvents, which limits the choice of detection solvents and degrades the versatility and accuracy of detection. Therefore, a simple and accurate method for the determination of dimethyl sulfate residues is urgently needed. Dimethyl sulfate is usually detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with pyridine as the methylation substrate. In this study, a new method for the detection of dimethyl sulfate was established using tertiary amines such as aminophenazone, which has many advantages over pyridine, as the methylation substrate. For example, the hybrid orbital and electron cloud of the N atom are different, resulting in stronger nucleophilicity of aminophenazone. High temperatures that are detrimental to the stability of dimethyl sulfate are not required when using aminophenazone, and the aliphatic quaternary ammonium salt product is more stable, with good stability, low interference, good ionization properties, and high response. The separation was performed on a Waters Atlantis HILIC C18 column (100 mm×2.1 mm, 3.0 µm) using a mobile phase consisting of 10 mmol/L ammonium acetate solution-0.1% formic acid methanol solution (50∶50, v/v) at a flow rate of 0.3 mL/min. The column temperature was set at 40 ℃, and the sample size was 1 µL. Dimethyl sulfate was determined in the electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM) modes. Dimethyl sulfate showed good linear relationships within the range of 0.9935 to 7.9480 ng/mL (r=0.9997). The limit of detection and limit of quantification for dimethyl sulfate were 0.50 ng/mL and 1.15 ng/mL, respectively. The recoveries (n=3)of dimethyl sulfate were 94.9% to 106.4%. The relative standard deviations (RSDs) were 1.44% to 5.51%. The RSD of the methylated aminophenazone peak area was 4.32%, indicating good stability of the reaction product. Dimethyl sulfate genotoxic impurities were not detected in 9 batches of aminophenazone, caffeine, and tegafur samples, which indicated that the drug manufacturers paid attention to the control of these impurities. The proposed method is advantageous over the existing techniques in terms of the better ion peak shape and higher molecular weight, without interference from other fragments. The method is specific, sensitive, simple, rapid, and accurate, and it can be used for the determination of dimethyl sulfate genotoxic impurities in aminophenazone and other medicines.

Effect of baicalin on renal function in patients with diabetic nephropathy and its therapeutic mechanism.

The present study observed the effect of baicalin on blood glucose and renal function in patients with diabetic nephropathy and explored its mechanism of action. A total of 95 patients diagnosed with diabetic nephropathy by clinical and laboratory examinations were selected and randomly divided into a control and treatment group. The control group included 45 patients who were treated with routine symptomatic treatment. The remaining 50 patients in the treatment group received baicalin, in addition to routine symptomatic treatment. The treatment course was 6 months. Following this, the changes of indicators such as fasting plasma glucose (FPG), glycosylated hemoglobin (HBA1c), aldose reductase (AR) activity, 24-h urinary microalbumin, urinary ß2-microglobulin (ß2-MG) and urinary albumin excretion rate (UAER) were compared before and after treatment; at the same time, the variations of indexes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-px), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) were detected. Compared with those in the control group, baicalin had little effect on the treatment group's FPG and HBA1c, but it clearly reduced the AR activity and the difference was significant (P<0.05). Baicalin visibly decreased the 24-h urinary microalbumin, urinary ß2-MG and UAER (P<0.05) and had notable effect on improving renal function. Following treatment, compared with those in the control group, baicalin distinctly increased the levels of SOD and GSH-px (P<0.05) and decreased the content of NF-κB and VEGF (P<0.05), however, its impact on the expression of TGF-ß1 was not statistically significant (P>0.05). The results showed that baicalin may improve the renal function in patients with diabetic nephropathy and delay the progression of diabetic nephropathy through various ways, including anti-inflammation and anti-oxidation.

Environmental benefits of electronic commerce over the conventional retail trade? A case study in Shenzhen, China.

Electronic commerce has been becoming the new driver of the retail industry. The large-scale expansion of electronic commerce with additional packaging certainly increases stress on the environment. However, a comparative analysis of environmental impacts of electronic commerce and conventional retail trade channels is unavailable. In this study, an Average Package Difference Model (APDM) was developed to evaluate CO2 emissions difference via the two retail channels in Shenzhen, China based on a life-cycle perspective. In the meanwhile, the national emission was estimated by the above results. Our results suggest that conventional retail has a higher environmental cost than that of electronic commerce, especially during shopping trips. Specifically, average CO2 emission difference per package in terms of product returns, packaging, buildings and transportation were 0.14 ±â€¯0.03, 0.84 ±â€¯0.08, 0.67 ±â€¯0.04, 1.3 ±â€¯0.26 kg, respectively. CO2 is mainly emitted from buildings and consumer trips in conventional retail trade, whereas packaging is mainly responsible for CO2 emission in e-commerce. In China, the total CO2 emission difference between conventional retail and electronic commerce was 124 million tons in 2016. Growth of the proportion of electronic commerce will contribute to lower CO2 emissions induced by the entire retail industry. Actually, carbon emissions can be reduced in both conventional retail and electronic commerce, such as the reusable packaging, opening shopping centers in dense population zones and promoting the usage of public transportation.

Design, synthesis and bioevaluation of 2-mercapto-6-phenylpyrimidine-4-carboxylic acid derivatives as potent xanthine oxidase inhibitors.

A series of 2-mercapto-6-phenylpyrimidine-4-carboxylic acid derivatives (7a‒c, 8a‒e, 9a‒e and 10a‒e) as novel xanthine oxidase inhibitors were designed based on molecular docking, and synthesized by a new method using ketoenol acids and thiourea as the starting materials. In vitro activity assay indicated that most of the designed compounds displayed submicromolar inhibitory potency. Specifically, compound 9b had the most potent enzyme inhibitory activity with the IC50 at 0.132 µM. Steady-state enzyme kinetics indicated that 9b behaved as a mixed-type inhibitor for XO.