Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat.

OBJECTIVE: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL). MATERIALS AND METHODS: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment. RESULTS: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05). CONCLUSIONS: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Anthropogenic and climate impacts on carbon stocks of grassland ecosystems in Inner Mongolia and adjacent region.

Up to date, most studies reported that degradation is worsened in the grassland ecosystems of Inner Mongolia and adjacent regions as a result of intensified grazing. This seems to be scientific when considering the total forage or total above-ground biomass as a degradation indicator, but it does not hold true in terms of soil organic carbon density (SOCD). In this study, we quantified the changes of grassland ecosystem carbon stock in Inner Mongolia and adjacent regions from the 1980s to 2000s and identified the major drivers influencing these variations, using the National Grassland Resource Inventory and Soil Survey Dataset in 1980s and the Inventory data during 2002 to 2009 covering 624 sampling plots concerned vegetal traits and edaphic properties across the study region. The result indicated that the above-, below-ground and total vegetation biomass declined from the 1980s to 2000s by ∼ 10 %. However, total forage production increased by 6.72 % when considering livestock intake. SOCD remained stable despite a 67 % increase in grazing intensity. A generalized linear model (GLIM) analysis suggested that an increase in grazing intensity from the 1980s to 2000s could only explain 1.04 % of the total biomass change, while changes in precipitation and temperature explained 17.7 % (p < 0.05) of total vegetation biomass (TVB) change. Meanwhile, SOCD change during 1980s - 2000s could be explained 10.08 % by the soil texture (p < 0.05) and <1.6 % by changes in climate and livestock. This implies that the impacts of climate change on grassland biomass are more significant than those of grazing utilization, and SOCD was resistant to both climate change and intensified grazing. Overall, intensified grazing did not result in significant negative impacts on the grassland carbon stocks in the study region during the 1980s and 2000s. The grassland ecosystems possess a mechanism to adjust their root-shoot ratio, enabling them to maintain resilience against grazing utilization.

Sensors on Internet of Things Systems for the Sustainable Development of Smart Cities: A Systematic Literature Review.

The Internet of Things (IoT) is a critical component of smart cities and a key contributor to the achievement of the United Nations Sustainable Development Goal (UNSDG) 11: Sustainable Cities and Communities. The IoT is an infrastructure that enables devices to communicate with each other over the Internet, providing critical components for smart cities, such as data collection, generation, processing, analysis, and application handling. IoT-based applications can promote sustainable urban development. Many studies demonstrate how the IoT can improve smart cities' sustainable development. This systematic literature review provides valuable insights into the utilization of the IoT in the context of smart cities, with a particular focus on its implications for sustainable urban development. Based on an analysis of 73 publications, we discuss the role of IoT in the sustainable development of smart cities, focusing on smart communities, smart transportation, disaster management, privacy and security, and emerging applications. In each domain, we have detailed the attributes of IoT sensors. In addition, we have examined various communication technologies and protocols suitable for transmitting sensor-generated data. We have also presented the methods for analyzing and integrating these data within the IoT application layer. Finally, we identify research gaps in the literature, highlighting areas that require further investigation.

Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.

Sensors on the Internet of Things Systems for Urban Disaster Management: A Systematic Literature Review.

The occurrence of disasters has the potential to impede the progress of sustainable urban development. For instance, it has the potential to result in significant human casualties and substantial economic repercussions. Sustainable cities, as outlined in the United Nations Sustainable Development Goal 12, prioritize the objective of disaster risk reduction. According to the Gesi Smarter 2030, the Internet of Things (IoT) assumes a pivotal role in the context of smart cities, particularly in domains including smart grids, smart waste management, and smart transportation. IoT has emerged as a crucial facilitator for the management of disasters, contributing to the development of cities that are both resilient and sustainable. This systematic literature analysis seeks to demonstrate the sensors utilized in IoT for the purpose of urban catastrophe management. The review encompasses both the pre-disaster and post-disaster stages, drawing from a total of 72 articles. During each stage, we presented the characteristics of sensors employed in IoT. Additionally, we engaged in a discourse regarding the various communication technologies and protocols that can be utilized for the purpose of transmitting the data obtained from sensors. Furthermore, we have demonstrated the methodology for analyzing and implementing the data within the application layer of IoT. In conclusion, this study addresses the existing research deficiencies within the literature and presents potential avenues for future exploration in the realm of IoT-enabled urban catastrophe management, drawing upon the findings of the evaluated publications.

Associations of executive function and age of first use of methamphetamine with methamphetamine relapse.

Background and aims: Methamphetamine (MA) is a psychostimulant associated with a high relapse rate among patients with MA use disorder (MUD). Long-term use of MA is associated with mental disorders, executive dysfunction, aggressive behaviors, and impulsivity among patients with MUD. However, identifying which factors may be more closely associated with relapse has not been investigated. Thus, we aimed to investigate the psychological factors and the history of MA use that may influence MA relapse. Methods: This cross-sectional study included 168 male MUD patients (MUD group) and 65 healthy male residents (control group). Each patient was evaluated with self-report measures of executive dysfunction, psychopathological symptoms, impulsiveness, aggressiveness, and history of MA use. Data were analyzed with t-tests, analyses of variance, and correlation and regression analyses. Results: The MUD group reported greater executive dysfunction, psychopathological symptoms, impulsivity, and aggression than the control group. Lower age of first MA use was associated both with having relapsed one or more times and with having relapsed two or more times; greater executive dysfunction was associated only with having relapsed two or more times. Conclusion: Patients with MUD reported worse executive function and mental health. Current results also suggest that lower age of first MA use may influence relapse rate in general, while executive dysfunction may influence repeated relapse in particular. The present results add to the literature concerning factors that may increase the risk of relapse in individuals with MUD.

High-frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces drug craving and improves decision-making ability in methamphetamine use disorder.

Methamphetamine abuse is escalating worldwide. Its strong and irreversible neurotoxicity generally causes structural and functional changes in the brain. Repetitive transcranial magnetic stimulation (rTMS) as a non-invasive tool can be used to modulate neuronal activity, cortical excitability, and dopaminergic neurotransmission. This study aims to explore the efficacy of high-frequency rTMS in reducing drug craving and increasing decision-making ability for methamphetamine use disorder patients. Sixty-four methamphetamine use disorder patients were randomized to sham rTMS group and 10-Hz rTMS group. Visual analog scale (VAS) and Iowa game test (IGT) were used to evaluate drug craving and cognitive decision-making ability before and after treatment. Before the treatment, the two groups had no differences in the scores of VAS and IGT. After the intervention, VAS scores of 10-Hz rTMS group were significantly lower than that of sham rTMS group. In addition, the two groups had significant differences in the net score of IGT on block 4 and block 5, which favoured the 10-Hz rTMS group. Taken together, the present results suggest that High-frequency rTMS can be used to reduce drug craving and improve decision-making function for methamphetamine use disorder.

Mesenchymal Stem Cell-Derived Neuron-Like Cell Transplantation Combined with Electroacupuncture Improves Synaptic Plasticity in Rats with Intracerebral Hemorrhage via mTOR/p70S6K Signaling.

Previous studies have shown that the combination of mesenchymal stem cell (MSC) transplantation and electroacupuncture (EA) stimulation is a neuroprotective strategy for treating intracerebral hemorrhage (ICH). However, the underlying mechanisms by which the combined treatment promotes neuroprotection remain unclear. This study was designed to investigate the effects of the combined treatment on synaptic plasticity and elucidate their underlying mechanisms. Therefore, rat ICH models were established by injecting collagenase and heparin, and the animals were randomly divided into model control (MC), EA stimulation (EA), MSC-derived neuron-like cell transplantation (MSC-dNLCs), and MSC-dNLC transplantation combined with EA stimulation (MSC-dNLCs+EA) groups. We observed the ultrastructure of the brain and measured the brain water content (BWC) and the levels of the microtubule-associated protein 2 (MAP2), galactocerebrosidase (GALC), and glial fibrillary acidic protein (GFAP) proteins. We also measured the levels of the phosphorylated mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (p70S6K) proteins, as well as the expression of synapse-related proteins. The BWC increased in rats after ICH and decreased significantly in ICH rats treated with MSC-dNLC transplantation, EA stimulation, or combined therapy. Meanwhile, after ICH, the number of blood vessels increased more evidently, but only the combined treatment reduced the number of blood vessels among rats receiving the three treatments. Moreover, the levels of MAP2, GALC, postsynaptic density 95 (PSD95), and synaptophysin (SYP) proteins, as well as the levels of the phosphorylated mTOR and p70S6k proteins, increased in the MSC-dNLCs+EA group compared with those in the MSC-dNLCs and EA groups. Compared with the MC group, GFAP expression was significantly reduced in the MSC-dNLCs, EA, and MSC-dNLCs+EA groups, but the differences among the three treatment groups were not significant. In addition, the number of synapses increased only in the MSC-dNLCs+EA group compared to the MC group. Based on these data, the combination of MSC-dNLC transplantation and EA stimulation exerts a synergistic effect on improving the consequences of ICH by relieving cerebral edema and glial scarring, promoting the survival of neurons and oligodendrocytes, and activating mTOR/p70S6K signaling to enhance synaptic plasticity.

Electroacupuncture Enhance Therapeutic Efficacy of Mesenchymal Stem Cells Transplantation in Rats With Intracerebral Hemorrhage.

BACKGROUND: Previous studies have showed the beneficial effects of mesenchymal stem cells (MSCs) on experimental intracerebral hemorrhage (ICH) animal. Enhancement of the treatment efficacy of MSCs in ICH is essential, considering the diseases association with high rates of disability and mortality. Some auxiliary methods to enhance the beneficial efficacy of MSCs have been introduced. However, the effect of electroacupuncture (EA) on the therapeutic efficacy of MSCs transplantation in hemorrhagic stroke and its potential mechanism is not explored. METHODS: ICH rat models were established using collagenase and heparin. 48 h after ICH induction, the rats were randomly divided into model control (MC), MSCs transplantation (MSCs), EA stimulation (EA) and MSCs transplantation combined with EA stimulation (MSCs + EA) groups. We used mNSS test and gait analysis to assess neurological function of rats, and PET/CT to evaluate the volume of hemorrhage focus and level of glucose uptake. The concentrations of MDA, SOD, NSE, S100B and MBP in serum or plasma were examined with ELISA. Neural differentiation of MSCs, and the expressions of Bcl-2, Bax, Arg-1 and iNOS proteins around hematoma were detected by immunofluorescence and immunohistochemistry staining respectively. Western blot was carried out to analyze the expression levels of COX4, OGDH, PDH-E1α, Bcl-2 and Bax proteins. TUNEL staining was used to estimate cell apoptosis and transmission electron microscopy (TEM) was used to observe the ultrastructure and number of mitochondria. RESULTS: Our data showed that EA promoted neuron-like differentiation of transplanted MSCs and the expressions of BDNF and NGF proteins in ICH rats. The score of mNSS and the gait analysis showed that the recovery of the neurological function in the MSCs + EA group was better than that in the MSCs and EA groups. EA improved the structure of brain tissue, and alleviated brain injury further after MSCs transplantation in ICH rats. When compared with the MSCs and EA groups, the level of glucose uptake and numbers of mitochondria and Arg-1 positive cells in MSCs + EA group increased significantly, but the numbers of apoptotic cells and iNOS positive cells and volume of hemorrhage focus reduced. The expressional levels of COX4, OGDH, PDH-E1α and Bcl-2 proteins increased, while the expressional level of Bax protein decreased compared with those in the MSCs and EA groups. CONCLUSIONS: Our results reveal that EA improve therapeutic efficacy of MSCs transplantation in ICH rats.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Mesenchymal stem cells ameliorate renal fibrosis by galectin-3/Akt/GSK3ß/Snail signaling pathway in adenine-induced nephropathy rat.

BACKGROUND: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. METHODS: TIF model was induced by adenine gavage. Bone marrow-derived MSCs was injected by tail vein after modeling. Renal function and fibrosis related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. Further possible mechanism was explored by transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with lentiviral vector. RESULTS: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-ß1, Kim-1, p-Smad2/3, IL-6, IL-1ß, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-ß1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt, p-GSK3ß and snail in TGF-ß1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3ß and snail. CONCLUSION: The mechanism of MSCs anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3ß/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.

Therapeutic Effects of Low-Intensity Pulsed Ultrasound on Premature Ovarian Insufficiency.

We explored the therapeutic effects of low-intensity pulsed ultrasound (LIPUS) on a rat model of ovarian damage induced by cyclophosphamide. A total of 44 female rats with premature ovarian insufficiency induced by cyclophosphamide were randomly divided into two groups (an ultrasound group and a control group); 22 normal rats without premature ovarian insufficiency were also included as a third group. The ultrasound group was treated with LIPUS, while the other two groups received the same treatment but without any power output. We monitored the estrous cycles of all rats. Seven days after treatment, 21 rats were selected to mate with male rats. We then recorded the pregnancy rate along with the number and weight of newborn rats per nest. We collected samples of blood, uterus and ovaries from the remaining 45 rats before they were sacrificed. Compared with the normal group, the control group exhibited disordered estrous cycles, more atretic follicles (p < 0.01), higher levels of serum follicle-stimulating hormone (p < 0.01), fewer other follicles (p < 0.01) and lower serum levels of E2 and anti-Müllerian hormone (p < 0.01). Compared with the control group, the ultrasound group had normal estrous cycles with fewer atretic follicles (p < 0.01), lower levels of serum follicle-stimulating hormone (p < 0.01), more other follicles (p < 0.01) and higher levels of serum E2 (p < 0.01). No significant difference in the levels of serum anti-Müllerian hormone was noted between the control group and the ultrasound group. No significant differences were observed between the three groups with respect to pregnancy rate or the number and weight of newborns per nest (p > 0.05). In conclusion, our data indicate that LIPUS could improve some ovarian functions of rats with premature ovarian insufficiency.

Therapeutic Effects of Focused Ultrasound on Expression of Notch1, C-Fos and Transforming Growth Factor-ß3 in Vulvar Skin of SD Rats with Vulvar Lichen Simplex Chronicus.

The purpose of this study was to investigate the therapeutic effects of focused ultrasound on the expression of notch1, c-fos and transforming growth factor-ß3 (TGF-ß3) in genital skin of SD rats with vulvar lichen simplex chronicus (LSC). Fifty-six female SD rats with LSC were randomly divided into therapy and sham groups. The therapy group was exposed to focused ultrasound. The sham group received the same therapy with an instrument that had no power output. Four wk after a singly focused ultrasound therapy, histologic analyses revealed that recovered SD rats accounted for 75% of SD rats in the therapy group and 10.7% in the sham group. Total collagen fiber density in the superficial layer of dermis in the therapy group was significantly lower than that in the sham group. Notch1 and c-fos protein expression in the therapy group was significantly lower than that in the sham group, with the opposite effect present for TGF-ß3. Focused ultrasound therapy may inhibit superficial collagen fibrosis in the dermis by affecting expression of notch1, c-fos and TGF-ß3 in vulvar skin tissue and consequently reduce the recurrence rate of LSC.

Imaging Chemical Kinetics of Radical Polymerization with an Ultrafast Coherent Raman Microscope.

Numerous mechanisms have been proposed for polymerization to provide qualitative and quantitative prediction of how monomers spatially and temporally arrange into the polymeric chains. However, less is known about this process at the molecular level because the ultrafast chemical reaction is inaccessible for any form of microscope so far. Here, to address this unmet challenge, a stimulated Raman scattering microscope based on collinear multiple beams (COMB-SRS) is demonstrated, which allows label-free molecular imaging of polymer synthesis in action at speed of 2000 frames per second. The field of view of the developed 2 kHz SRS microscope is 30 × 28 µm2 with 50 × 46 pixels and 7 µs dwell time. By catching up the speed of chemical reaction, COMB-SRS is able to quantitatively visualize the ultrafast dynamics of molecular vibrations with submicron spatial resolution and sub-millisecond temporal resolution. The propagating polymer waves driven by reaction rate and persistent UV initiation are observed in situ. This methodology is expected to permit the development of novel functional polymers, controllable photoresists, 3D printing, and other new polymerization technologies.

Polydiacetylene-based ultrastrong bioorthogonal Raman probes for targeted live-cell Raman imaging.

Live-cell Raman imaging based on bioorthogonal Raman probes with distinct signals in the cellular Raman-silent region (1800-2800 cm-1) has attracted great interest in recent years. We report here a class of water-soluble and biocompatible polydiacetylenes with intrinsic ultrastrong alkyne Raman signals that locate in this region for organelle-targeting live-cell Raman imaging. Using a host-guest topochemical polymerization strategy, we have synthesized a water-soluble and functionalizable master polydiacetylene, namely poly(deca-4,6-diynedioic acid) (PDDA), which possesses significantly enhanced (up to ~104 fold) alkyne vibration compared to conventional alkyne Raman probes. In addition, PDDA can be used as a general platform for multi-functional ultrastrong Raman probes. We achieve high quality live-cell stimulated Raman scattering imaging on the basis of modified PDDA. The polydiacetylene-based Raman probes represent ultrastrong intrinsic Raman imaging agents in the Raman-silent region (without any Raman enhancer), and the flexible functionalization of this material holds great promise for its potential diverse applications.

Spatiotemporal patterns and drivers of ecosystem service supply and demand across the conterminous United States: A multiscale analysis.

Land-use and land-cover changes associated with urbanization have significantly influenced biodiversity and ecosystem functions, as well as the supply and demand of ecosystem services (ESs). Assessing ESs and exploring their drivers are critical for regional land-use planning and ecological sustainability. In this study, the supply-demand matrix approach was used to quantify ES supply, demand, and their gap at multiple scales across the conterminous United States from 1940 to 2011. A new integrated measurement framework was proposed to offset ES deficits by identifying an optimal land-use conversion strategy. We focused on exploring the scale and spatial effects of the impacts of various drivers on ESs using ordination and regression analysis. The results showed that the expansion of developed land led to decreased ES supply and increased ES demand during the past seven decades, generating growing ES deficits at different scales, especially in highly urbanized metropolitan areas. To alleviate or offset ES deficits, promoting the intensive utilization of developed land and converting cropland, pasture, and barren land into forests would be the optimal land use strategies. Moreover, the drivers of ESs exhibited not only scale dependence but also spatial heterogeneity. The smaller the scale, the more diverse the drivers. The natural and socioeconomic drivers explained less variation at the metropolitan scale than at the state scale. Economic factors were key drivers for ESs at the state scale, while social factors were key drivers at the metropolitan scale. The regression coefficients for the drivers of ESs in the geographically weighted regression (GWR) model showed remarkable spatial heterogeneity. The GWR coefficients might have important implications for decision making in ES management. Localized and efficient land-use strategies and management policies are needed to reduce the ecological footprints of urban areas and thus achieve regional sustainability.

Coherent Raman Scattering Unravelling Mechanisms Underlying Skull Optical Clearing for Through-Skull Brain Imaging.

Optical access of a mouse brain using microscopes is the key to study brain structures and functions in vivo. However, the opaque skull of a mouse has to be either opened or thinned in an invasive way to attain an adequate imaging depth in the brain. Mild skull optical clearing is highly desired, but its chemical mechanism is far from being understood. Here, we unraveled the molecular process underlying optical clearing of the mouse skull by label-free hyperspectral stimulated Raman scattering (SRS) microscopy, thereby discovering the optimal clearing strategy to turn a turbid skull into a transparent skull window. Furthermore, we demonstrated in vivo three-photon imaging of vascular structures as deep as 850 µm in the cortex of the mouse brain. Coherent Raman based microspectroscopy holds great promise to advance skull and tissue clearing methods in the future.

[Establishment of a rat model of dimethylbenzanthracene-induced vulvar squamous intraepithelial lesions].

OBJECTIVE: To establish a SD rat model of vulvar squamous intraepithelial lesions. METHODS: Seventy female SD rats were randomized into 4 groups, namely the blank control group (n=10), mechanical irritation group (n=10), acetone solution group (n=10), and mechanical irritation with DMBA acetone solution group (n=40, model group), and the corresponding treatments were administered 3 times a week for 14 weeks. The changes of the vulvar skin of the rats were observed regularly until the 18th week. The expression of mutant p53 (mtp53) and vascular endothelial growth factor (VEGF) proteins were detected using immunohistochemistry and Western blotting, and the expressions of mtp53 and VEGF mRNA were detected with qRT- PCR in the blank control group and model group. RESULTS: No significant differences were found in the morphological or histopathological changes of the skin among the blank control group, mechanical irritation group and acetone solution group. In the model group, low-grade squamous intraepithelial lesions (LSIL) occurred in 28 rats (70%) and high-grade squamous intraepithelial lesions (HSIL) in 11 rats (27.5%) at 14 weeks, with a success rate of 97.5% in inducing vulvar squamous intraepithelial lesions. Compared with the blank control group, the rats in the model group showed significantly increased expressions of mtp53 and VEGF at both the protein level (P < 0.05) and the mRNA level (P < 0.05). CONCLUSIONS: DMBA in acetone solution combined with mechanical irritation can induce vulvar squamous intraepithelial lesions in female SD rats.