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According to the requirements of the "Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions", this health technology assessment provides an evidence-based basis for drug selection and rational clinical use of glucagon-like peptide-1 receptor agonist drugs in medical institutions.We consult the drug instructions, clinical treatment guidelines and search relevant documents in databases such as China national knowledge infrastructure, Wanfang, PubMed, and government websites such as National Medical Products Administration, Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency to collect and sort out the relevant information of the indications, pharmacological effects, guideline recommendations, drug prices and other information of glucagon-like peptide-1 receptor agonists, using a percentile system systematically evaluate the five dimensions of glucagon-like peptide-1 receptor agonists in terms of pharmaceutical properties, efficacy, safety, economy, and other attributes.The final scores of the evaluation results from high to low are semaglutide (71.00 points), dulaglutide (68.75 points), liraglutide (67.50 points), exenatide (67.00 points), lixisenatide (63.50 points), polyethylene glycol loxenatide (58.00 points) and benaglutide (49.00 points).In clinical practice, semaglutide and dulaglutide are the top two drugs that can be used as recommended drugs. This health technology assessment can provide an evidence-based basis for hospital selection and rational use of glucagon-like peptide-1 receptor agonists. Clinicians can rationally choose and use drugs according to the patient's conditions and needs.

Jinjian Li,1,* Kun Yang,2,* Xinghui Pan,1 Hui Peng,1 Chenting Hou,1 Jie Xiao,1 Qing Wang1 1Ophthalmology, Affiliated Hospital of Qingdao University, Qingdao, 266500, People’s Republic of China; 2Medical Research Center, Affiliated Hospital of Qingdao University, Qingdao, 266500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Wang, Ophthalmology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266500, People’s Republic of China, Tel +86 17853290636, Fax +86 532 82911747, Email wangqing6836@sina.comPurpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs).Methods: HCECs were cultured in 70– 120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-1β and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed.Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-1β, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-1β and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs.Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.Keywords: myocardial infarction-associated transcript, dry eye, pyroptosis, apoptosis

Aiming at the comparison and optimization of comprehensive evaluation methods, this paper proposes an optimization strategy of comprehensive evaluation method and constructs a relative excellence measure of the comprehensive evaluation method based on the deviation of rating value and Spearman grade correlation coefficient. On the basis of the relative excellence measure, combined with the compatibility test, the optimization strategy of the comprehensive evaluation method is given to realize the optimization of the comprehensive evaluation method. Finally, the feasibility of this strategy is verified by a case.

As the theoretical upper bound of evapotranspiration (ET) or water use by ecosystems, potential ET (PET) has always been widely used as a variable linking a variety of disciplines, such as climatology, ecology, hydrology, and agronomy. However, substantial uncertainties exist in the current PET methods (e.g., empiric models and single-layer models) and datasets, because of unrealistic configurations of land surface and unreasonable parameterizations. Therefore, this study comprehensively considered interspecific differences in various vegetation-related parameters (e.g., plant stomatal resistance and CO2 effects on stomatal resistance) to calibrate and parametrize the Shuttleworth-Wallace (SW) model for forests, shrubland, grassland and cropland. We derived the parameters using identified daily ET observations with no water stress (i.e., PET) at 96 eddy covariance (EC) sites across the globe. Model validations suggest that the calibrated model could be transferable from known observations to any location. Based on four popular meteorological datasets, relatively realistic canopy height and time-varying land use/land cover and Leaf Area Index, we generated a global 5 km ensemble mean monthly PET dataset that includes two components of potential transpiration (PT) and soil evaporation (PE) for the 1982–2015 time period. Using this new dataset, the climatological characteristics of PET partitioning and the spatio-temporal changes in PET, PE and PT were investigated. The global mean annual PET was 1200 mm with PT/PET of 40 % and PE/PET of 60 %, and moreover controlled by PT and PE over 43 % and 57 % of the globe, respectively. Globally, the annual PET and PT significantly (phttps://doi.org/10.11888/Terre.tpdc.300193 (Sun et al., 2023).

The short and scare record limits to understand the history of the hydroclimate change in east-central China. In this study, we developed a 225-year tree-ring width chronology (STD) for Chinese pine originating from the Shiren Mountain in Henan Province, east-central China. We analysed the correlation between the STD and different climatic factors and then reconstructed the May–June moisture variation, which is one of the longest moisture variation reconstruction based on tree-ring width in this region. Further, the results of the spatial analysis between our reconstruction and actual moisture variation revealed that our reconstruction is representative of large-scale May–June self-calibrating Palmer Drought Severity Index (scPDSI) in east-central China. Additionally, the reconstruction showed five relatively dry and five relatively wet epochs over the past 225 years. It also showed that the moisture variation in the study area is similar to those corresponding to other nearby sites and could be validated by historical documents; these findings demonstrate the reliability of our reconstruction back in time. Furthermore, we detected the reason for the coherent May–June moisture change in east-central China. It showed that the actual scPDSI showed significantly positive correlations with concurrent precipitation. Additionally, regression analyses showed that precipitation is largely determined by the frontal system, which is also responsible for the coherent May–June moisture pattern observed in east-central China. In addition, the result of spectral analysis and correlation patterns of the reconstructed scPDSI with global sea surface temperatures indicated that the El Nino-Southern Oscillations might be the forcing mechanism for regional moisture variability.

Cerebral ischemia is one of the major global health problems, but the treatment for it is currently very limited. A tissue plasminogen activator, the only drug effective in the treatment of cerebral ischemia, has a narrow time window and strict contraindications, resulting in only a small percentage of patients benefiting from it. Apigenin (APG) is a natural phytoestrogen flavonoid, widely found in vegetables and fruits including parsley, Chinese celery and chamomile. APG has shown good neuroprotective effects in animal models of many neurological diseases. For the first time, we report a review of the neuroprotective effects of APG in cerebral ischemia. We came to the conclusion that APG can exert various protective effects against cerebral ischemia, including anti-oxidative stress, anti-inflammatory, anti-autophagic, anti-apoptotic and other neuroprotective effects. Moreover, APG has shown a highly promising ability to prevent cerebral ischemia in terms of regulating blood glucose, blood pressure, lipids and gut microbes. The aspect that is of particular importance is the potential of APG to prevent cerebral ischemia in postmenopausal women, who are more likely to suffer from cerebral ischemia and have a much higher mortality rate than men of the same age. This review has provided evidence on the therapeutic and preventive effects of APG in cerebral ischemia, suggesting the potential values of APG as a candidate medication in future.

BackgroundTo compare the postoperative safety, efficacy, predictability, visual quality and biomechanics after implantation of Artisan vs. Artiflex phakic intraocular lenses (PIOLs).MethodsPubmed, Embase, Cochrane Library were conducted up from January 2000 to February 2020. Comparative clinical studies reporting in accordance with the eligibility criteria were included in this meta-analysis. The pooled weighted mean differences (WMDs) and odds ratios (ORs) with corresponding 95% confidence intervals were calculated.ResultsComparative trials with myopia patients were selected in this review. The pooled WMD and OR estimates statistical significance in terms of postoperative best corrected visual acuity (BCVA), efficacy, postoperative spherical equivalence (SE), predictability, contrast sensitivity and mean intraocular higher-order aberrations (HOA) (mm) for a 6-mm pupil, manifesting that Artiflex PIOL showed evident beneficial effect for correcting myopia compared to Artisan PIOL. There was no significant difference in the incidence of complications between the two groups.ConclusionBoth of two techniques were safe and effective for myopia and compared to Artisan PIOL, Artiflex PIOL had significant improvement in efficacy, predictability, contrast sensitivityand HOA, except safety and complications in the treatment of moderate to high myopia.

Aims: This article aimed to assess the changes of subfoveal choroidal thickness (SFCT) in different follow-up durations for myopic children under the treatment of orthokeratology and give a reference for further studies.Method: Relevant publications were comprehensively retrieved through different databases, such as PubMed, Web of Science, Cochrane Library and Chinese database of Wan Fang and Wei Pu. Retrieval time was from the inception to February 2022. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were selected as the effect for calculating and analyzing the changes of choroidal thickness in myopic children with orthokeratology.Result: A total of eight articles of 371 Patients (371 eyes) met our inclusion criteria. During the first month of wearing orthokeratology, choroidal thickness dramatically increased by 21.09 μ m (95%CI: 25.64, 16.7; PConclusion: This meta-analysis demonstrated that in the first month with orthokeratology, choroidal thickness presented an obvious increase, after that it became stable or got a slightly rise for the longer following-up treatment.

Global warming has a significant impact on the ecosystem of the high-altitude areas of the Tibetan Plateau, such as land degradation and the rapid retreat of glaciers. It is important to understand the effects of global warming occurring over hundreds or thousands of years. However, the long-term reconstruction of temperature is still lacking for the region of Western Sichuan Plateau (WSP). In this study, we reconstructed summer (June–July) temperatures back to 1383 for the WSP region based on a significant positive correlation between the standard chronology and summer temperature. The reconstruction passed statistical tests and explained 55.4% of the climatic variance in the period for which data are available (1962 to 2005). There have been five periods with warm summers and five with cold summers during the past 623 years. Warm periods occurred in 1383–1445, 1525–1590, 1700–1724, 1825–1870, and 1930–1960, while relatively cold periods occurred in 1446–1524, 1591–1675, 1725–1824, 1900–1929, and 1961–1990. A comparison with observed data and regional temperature reconstruction series shows that the reconstruction has a high degree of consistency and is indicative and reliability. The spatial correlation was analyzed with Climatic Research Unit gridded data to detect the spatial representativeness of the reconstruction, confirming that the reconstruction has a strong regional temperature signal for the WSP. Furthermore, ensemble empirical mode decomposition indicates quasi-oscillations of 2.8–3.3 years, 6.4–8.3 years, 11.1–14.2 years, 25–38.4 years, 89 years, and 138 years in the reconstructed temperature time series during the past 623 years. El Niño Southern Oscillation cycles, solar activity, and Atlantic multi-decadal oscillation can potentially be the primary forcing factors. Meanwhile, the coordinated action of temperature-induced drought stress with a late growing season related to delayed snowmelt can potentially be attributed to the divergence problem (observed around 2005).

In the context of global warming, climate change in river headwater regions and its drivers have attracted increasing attention. In this study, tree-ring width (TRW) chronology was constructed using tree-ring samples of fir (Abies faxoniana) in Dadu River Basin in the central part of the western Sichuan Plateau, China. Correlation analysis with climatic factors implies that the radial growth of trees in the region is mainly limited by temperature and has the highest correlation with the mean minimum temperature in summer (June and July) (R = 0.602, p < 0.001). On this basis, the TRW chronology was adopted to reconstruct variations in the mean minimum temperatures in summer from 1733 to 2010 in the upper reaches of Dadu River. The reconstruction equation was stable and reliable and offered a variance explanation rate of 36.2% in the observed period (1962~2010). In the past 278 years, the region experienced nine warm periods and ten cold periods. The warmest and coldest years occurred in 2010 and 1798, respectively, with values of 13.6 °C and 11.0 °C. The reconstruction was highly spatiotemporally representative and verified by temperatures reconstructed using other tree-ring data in surrounding areas. A significant warming trend was found in the last few decades. Moreover, the multi-taper method (MTM) analysis indicated significant periodic changes in quasi-2-year and 21–35-year periods, for which the El Niño Southern Oscillation (ENSO) and the Pacific decadal oscillation (PDO) could be the key controlling factors.

We proposed a novel torsion sensor based on the Lyot filter with the twisted polarization-maintaining fiber (PMF) acting as the birefringence medium. Lyot filter is formed by two linear polarizers and a piece of PMF. Based on the high birefringence of the PMF, the output polarization rotates with a rate equal to the twisting rate applied on the PMF, and the sensor realizes a high sensitivity of 90.072 dB/rad. The proposed sensor also demonstrated a low strain sensitivity of 2 .32 × 1 0 - 6 rad/μɛ. On the other hand, based on the phase hits of the polarization interference, the wavelength sensitivity reaches 15.477 nm/rad. The monitoring range of the wavelength demodulation is complementary with the intensity demodulation in one cycle, making the valid sensing range of the proposed sensor expand. The proposed highly sensitive compact torsion sensor, with large sensing range and low crosstalk, has potential applications in many fields such as manufacturing industry, civil engineering, aerospace industry and modern smart structure monitoring.

Secondary organic aerosols (SOA) constitute a large fraction of atmospheric aerosols, yet our knowledge of the formation and aging processes of SOA in megacities of China is still limited. In this work, the formation and aging processes of SOA in winter in Beijing was investigated using a high-resolution aerosol mass spectrometer (AMS) and an oxidation flow reactor (OFR). Our results showed that the OA enhancement from OH aging peaked at ∼3.9 equivalent days with an average enhancement of 0.9 (±0.3) μg m

We propose a method for generating bottle-hollow (BH) beams by tailoring the polarization state of the incident field in a tightly focused system. An optical BH field can be generated in the vicinity of the focus by tailoring azimuthal and radial polarization indices of the incident field. Calculations show that the length and diameter are mainly affected by the radial polarization index. While for the azimuthal index, it affects the width of the hollow greatly. As a result, an all-optical controlled tunable BH beam is achieved. The generated BH beam may find application in optical tweezers.

Inorganic nitrogen (IN) and organic nitrogen (ON) molecules constitute a significant part of atmospheric aerosol. Unlike IN, the total ON quantity remains largely unquantified due to a lack of a simple and direct measurement method. This analytical deficiency hinders the quantitative assessment of the various environmental and health effect impacts by aerosol ON. In this work, we developed an analyzer system that utilizes programmed thermal evolution of carbonaceous and nitrogenous aerosols and chemiluminescence detection coupled with the multivariate curve resolution data treatment to achieve simultaneous quantification of IN and ON. The system is capable of detecting IN and ON as low as 96 ng N per sample on a small filter aliquot (1 cm2) without any pretreatment. This method breakthrough opens the door to quantifying an important pool of aerosol N that was analytically inaccessible in the past and holds the promise to quantifying IN and ON in other environmental samples. As a demonstration, quantification of aerosol ON at an urban site in Hong Kong, China, in samples spanning over a year reveals ON constituting a significant fraction (9-52%) of the total aerosol nitrogen and having major source origins in both secondary formation and primary emissions.

Bovine serum albumin (BSA) label-free concentration sensor based on silica corrosion quantitative monitoring system (SCQMS) has been proposed. Anti-resonance of hollow cylindrical waveguide (HCW) in SCQMS is simulated and investigated for monitoring corrosion rate quantitatively. Hydrofluoric acid (HF) samples with different concentrations are studied respectively, and the corrosion rate is obtained by demodulating the corresponding anti-resonance dips shift and free spectral range (FSR). Therefore, a high-precision SQCMS was prepared successfully. On this basis, a highly sensitive concentration sensor based on hole-assisted dual-core fiber (HADF) is prepared. The BSA samples with concentration from 0.2 mg/mL to 0.7 mg/mL are detected. The sensor has a high sensitivity of 30.04 nm/(mg/mL) and ultra-low limit of detection (LOD) of 0.05 mg/mL for the assisted core exposed to the target solution directly. We have demonstrated the SCQMS that can be a feasible tool for precise and quantitative corrosion of silicon structure safely. In addition, the concentration sensor structure has a wide application for ultra-low LOD, simple preparation process and high integration.

Additional file 1.

The health effects of atmospheric particulate matter (PM) have become a major environmental concern in urban areas. Most PM studies are mainly designed to measure the “ambient” or “emitted” concentrations of PM. Some studies are specifically designed to address exposure to PM for pedestrians and/or commuters on-board vehicles or at bus stops, but less attention is paid to the exposure during physical exercise such as jogging. To this end, concentrations of both fine particulate matter (PM2.5) and black carbon (BC) were measured along three jogging trails in the densely populated city Macau in China. The three jogging trails include the campus of University of Macau (UM), Guia Municipal Park (GP), and Saivan Lake (SL). In our measurements, PM2.5 and BC ranged from 2.9 to 84.1 and 0.4–19.5 μg/m³, respectively. BC/PM2.5 ratio ranged from 0.016 to 0.448. Among all three jogging trails, the highest BC concentration was found at SL (19.5 μg/m³), and the highest PM2.5 concentration was found at UM (84.1 μg/m³). On the contrary, the BC and PM2.5 concentrations at the elevated (about 50 m above sea level) GP trail were lower than those at the other two jogging trails. BC and PM2.5 concentrations were generally lower in the night loops (21:30–23:00) than those in the morning loops (07:30–09:00), which coincide with morning rush hours, with only a few exceptions. The difference in geographical locations also affects the BC and PM2.5 concentrations measured, with locations near bus terminals, busy roads, or with congested street canyons having higher concentrations. Doses of BC and PM2.5 after 60 min of exposure during typical jogging exercise are also estimated to evaluate the exposure to PM pollution at these three jogging trails when exercising. The results from the current studies provide information both on personal choice for the time/venue for jogging exercise and on future abatement policy to mitigate such risks of exposure to BC and PM2.5.

With intensifying climate change, droughts over Southwest China (SWC) are drawing increasing interest. The droughts of 2009–2011 have attracted special concern. However, the roles of atmospheric evaporative demand [reflected by reference evapotranspiration (ET0)] and precipitation (P) anomalies in drought evolutions are still unclear. To that end, we revisited the evolution of the 2009–2011 SWC meteorological droughts quantitatively and comprehensively by quantifying the ET0 and P impacts. In terms of three drought parameters [i.e., drought intensity (DI), area (DA), and duration (DD)], SWC experienced the second most severe drought of the 1961–2012 period in 2009. Evident differences existed among the drought conditions in different months, i.e., more severe droughts occurred in February–March 2009, September 2009 to March 2010, and June–October 2011. Based on the annual means over drought regions, the 2009 and 2011 DI (DA) could be attributed to lower P, but the P and ET0 impacts [P, ET0, and P-and-ET0 (which reflects drought occurrence due to their combined impacts only)] were comparable in 2010. In addition, P reduction was responsible for DD during 2009–2011. Except in January–March, which were dominated mostly by P, DI (DA) was generally dominated by ET0 (ET0 or P-and-ET0) over the three years. While P dominated spatially and temporally for the majority of the 36 months for DI (DD), some areas were mainly affected by ET0 (ET0 or P-and-ET0). Therefore, to better understand drought evolutions and improve drought monitoring and forecasting, the impacts of ET0 anomalies should be fully considered. The results of this study provide an important reference framework for comprehensively understanding the underlying mechanisms of droughts not only in SWC but also in other regions around the world.

A simple method is proposed to manipulate the transverse energy flow in the focal plane of a tightly focused azimuthally polarized beam. Using the Richards–Wolf formulas, we obtain explicit expressions for all components of the electromagnetic field and the Poynting vector near focus of the tightly focused input field with azimuthal polarization and optical vortex. Further, the redistributions of the transverse energy flow by designing phase masks, including traditional and annular vortex phase masks are explored. Transverse energy flow in the shape of a regular polygon is achieved. As a result, transport absorptive particles can be transported along more flexible paths, which might be help in optical tweezers manipulations.

Glioma accounts for nearly 80% of all intracranial malignant tumors. It is a major challenge to society as it is causes to impaired brain function in many patients. Currently, gliomas are mainly treated with surgery, postoperative radiotherapy, and chemotherapy. However, the curative effects of these treatments are not satisfactory. Oncolytic virus (OV) is a novel treatment which works by activating the immune functions and inducing apoptosis of tumor cells. The OV propagates indefinitely in the host cell, eventually leading to the death of host cell. Subsequently, a large number of antigens and signal molecules are released which exert antitumor immunity. Several preclinical and clinical studies have shown that G207, DNX2401, Zika and other viruses have important roles in malignant tumors. For example, these viruses can reduce the growth of tumor cells without causing severe complications. However, the known OVs have not been clearly classified. Herein, we divided OVs into neurotropic and non-neurophilic OVs based on whether the OVs are naturally neurotropic or not. The therapeutic effects of each group were compared. Finally, challenges encountered in the clinical application of OVs in the treatment of malignant gliomas were summarized.

Traffic flow measurement is very important for traffic management systems. However, the existing traditional measurement approaches are highly time-consuming and expensive to continuously gather the required data and to maintain the corresponding equipment, such as loop detectors and video cameras. On the other hand, many services on the web propose to estimate automobile travel time taking into account traffic conditions thanks to crowd sourced data (Floating Car Data). This work proposes to reconstruct, from estimated travel time, traffic flows using machine learning method. In particular, we evaluate the capacity of Gaussian Process Regressor (GPR) to address this issue. After obtaining estimated travel time on a given route, a clustering process shows that travel duration profiles in each day can be associated to different “types of day”. Then, different regressors are trained in order to estimate traffic flows from travel duration. In the “multi-model” variant, we trained a Regressor for each type of day. Conversely, in the “single model” variant, only one Regressor is trained (the type of day is not taken into account). This is an innovative work to estimate and reconstruct the traffic flow in transportation networks with machine learning method from aggregated Floating Car Data (FCD). A series of experiments are conducted to compare the estimated traffic flows, obtained by the proposed single model and multi-model, and the real ones from actual sensors. The obtained results show that both single model and multi-models can capture the tendency of real traffic flows. Furthermore, the performance can be improved by regulating parameters in GPR machine learning model, such as half width of sample window and sample size (a whole week or only weekdays), and multi-models can highly increase the performance compared with the single model. Therefore, the proposed GPR machine learning and FCD based new method can replace those traditional loop detectors for the measurement of traffic flow.

Analyzing the correlation between carbon metabolism and urban form could provide new insight for low-carbon city design. The paper analyzed the spatial changes of urban carbon metabolism and also of the urban form from 1990 to 2010, using a combination of GIS method and landscape indices. The study showed that urban center in 2010 increase to 2.2 times that in 1990, which caused the expansion and extension of high carbon emission area in the southeast plain. The evolution of suburbs and outer suburbs was influenced by urban center and fell behind urban center, which caused the opposite change of the medium and low carbon emission area in the periphery of southeast center. The spatial distribution of carbon sequestration was affected by the policies during urbanization, which caused the shrink and fragmentation before 2000 and the recovery of the high carbon sequestration area after 2000. The study could be quite useful for regional land use planning for providing quantitative evaluation.

Hyperosmolarity is pro-inflammatory stress to the ocular surface epithelium associated with dry eye disease (DED). Astaxanthin (AST) is a kind of carotene, which exists in seafood and plays important roles in the amelioration of inflammatory diseases like arteriosclerosis, inflammatory bowel disease, sepsis, rheumatoid arthritis, gastric inflammation, brain inflammatory diseases. The aim of this study was to characterize the protective effect and potential mechanism of AST on DED in vitro and in vivo. Mouse models and human corneal epithelial cell (HCEC) cultures were exposed to hyperosmotic saline solution (HOSS) in in vitro and in vivo experiments, respectively. Experimental subjects were first pretreated with AST, and then the effect of the compound was assessed with clinical evaluation, real-time PCR (RT-PCR), western blot and immunofluorescent staining. We further investigated the possible mechanism of AST in DED by pre-treating with phosphoinositide 3-kinase inhibitor (LY294002). The addition of AST significantly reduced the expression of High-mobility group box 1 (HMGB1), as well as significantly inhibited the increases of TNF-α, IL-1β in a dose-dependent manner, but promoted the expression of phospho-Akt (p-Akt). BALB/c mice in DE group pretreated with AST showed significantly decreased corneal fluorescein staining scores. Moreover, pretreatment with LY294002 could eliminate the effects of AST preconditioning on the decrease of HMGB1. Our study provides evidence that AST could ameliorate DED which may be related to the inhibition of HMGB1, TNF-α, IL-1β, while PI3K/Akt signaling pathway may be involved in the expression of HMGB1 and the protective effect of AST preconditioning.

During 1961–2012, the regional average annual potential evapotranspiration (PET) of Southwest China (SWC) and the four subregions (named as SR1, SR2, SR3, and SR4) showed different decreases (excluding SR3); while the breakpoint analysis suggested that PET changes (i.e., sign and magnitude) have shifted. Based on a group of sensitivity experiments with Penman-Monteith equation and a new separating method, the contributions of each climate factor alone (i.e., net radiation, Rn; mean temperature, Tave; wind speed, Wnd; and vapor pressure deficit, Vpd) to PET changes were calculated. Results showed that declined Wnd in SR1, reduced Rn in SR2, SR4, and SWC, and increased Vpd in SR3 were responsible for the PET changes during 1961–2012. However, the determinant factor for each subregion and SWC varied in different segmented periods, which were identified using the breakpoint analysis. The impacts of PET shifts on SWC dryness/wetness (reflected by the 3 month Standardized Precipitation-Evapotranspiration index, SPEI-3) during 1961–2012 were then quantified. Briefly, SPEI-3 changes in SR3, SR4, and SWC had the determinant factor of PET in the first one or two period(s), and precipitation in the last period; while they were attributed to PET (precipitation) in SR1 (SR2) for each segmented period. It is found that PET and precipitation had comparable contributions to the variations in SWC dryness/wetness. Our findings have suggested that more attentions should be paid to the impacts of PET changes and shifts in future studies of dryness/wetness or drought.