TTD: Therapeutic Target Database describing target druggability information.

Target discovery is one of the essential steps in modern drug development, and the identification of promising targets is fundamental for developing first-in-class drug. A variety of methods have emerged for target assessment based on druggability analysis, which refers to the likelihood of a target being effectively modulated by drug-like agents. In the therapeutic target database (TTD), nine categories of established druggability characteristics were thus collected for 426 successful, 1014 clinical trial, 212 preclinical/patented, and 1479 literature-reported targets via systematic review. These characteristic categories were classified into three distinct perspectives: molecular interaction/regulation, human system profile and cell-based expression variation. With the rapid progression of technology and concerted effort in drug discovery, TTD and other databases were highly expected to facilitate the explorations of druggability characteristics for the discovery and validation of innovative drug target. TTD is now freely accessible at: https://idrblab.org/ttd/.

TheMarker: a comprehensive database of therapeutic biomarkers.

Distinct from the traditional diagnostic/prognostic biomarker (adopted as the indicator of disease state/process), the therapeutic biomarker (ThMAR) has emerged to be very crucial in the clinical development and clinical practice of all therapies. There are five types of ThMAR that have been found to play indispensable roles in various stages of drug discovery, such as: Pharmacodynamic Biomarker essential for guaranteeing the pharmacological effects of a therapy, Safety Biomarker critical for assessing the extent or likelihood of therapy-induced toxicity, Monitoring Biomarker indispensable for guiding clinical management by serially measuring patients' status, Predictive Biomarker crucial for maximizing the clinical outcome of a therapy for specific individuals, and Surrogate Endpoint fundamental for accelerating the approval of a therapy. However, these data of ThMARs has not been comprehensively described by any of the existing databases. Herein, a database, named 'TheMarker', was therefore constructed to (a) systematically offer all five types of ThMAR used at different stages of drug development, (b) comprehensively describe ThMAR information for the largest number of drugs among available databases, (c) extensively cover the widest disease classes by not just focusing on anticancer therapies. These data in TheMarker are expected to have great implication and significant impact on drug discovery and clinical practice, and it is freely accessible without any login requirement at: https://idrblab.org/themarker.

Altered Dynamics of Brain Spontaneous Activity and Functional Networks Associated With Cognitive Impairment in Patients With Type 2 Diabetes.

BACKGROUND: Cognitive impairment is increasingly recognized as an important comorbidity and complication of type 2 diabetes (T2D), affecting patients' quality of life and diabetes management. Dynamic brain activity indicators can reflect changes in key neural activity patterns of cognition and behavior. PURPOSE: To investigate dynamic functional connectivity (DFC) changes and spontaneous brain activity based on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with T2D, exploring their correlations with clinical features. STUDY TYPE: Retrospective. SUBJECTS: Forty-five healthy controls (HCs) (22 males and 23 females) and 102 patients with T2D (57 males and 45 females). FIELD STRENGTH/SEQUENCE: 3.0 T/T1-weighted imaging and rs-fMRI with gradient-echo planar imaging sequence. ASSESSMENT: Functional networks were created using independent component analysis. DFC states were determined using sliding window approach and k-means clustering. Spontaneous brain activity was assessed using dynamic regional homogeneity (dReHo) variability. STATISTICAL TESTS: One-way analysis of variance and post hoc analysis were used to compare the essential information including demographics, clinical data, and features of DFC and dReHo among groups. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve. P-values <0.05 were taken to indicate statistical significance. RESULTS: T2D group had significantly decreased mean dwell time and fractional windows in state 4 compared to HC. T2D with mild cognitive impairment showed significantly increased dReHo variability in left superior occipital gyrus compared to T2D with normal cognition. Mean dwell time and number of fractional windows of state 4 both showed significant positive correlations with the Montreal cognitive assessment scores (r = 0.309; r = 0.308, respectively) and the coefficient of variation of dReHo was significantly positively correlated with high-density lipoprotein cholesterol (r = 0.266). The integrated index had an area under the curve of 0.693 (95% confidence interval = 0.592-0.794). DATA CONCLUSION: Differences in DFC and dynamic characteristic of spontaneous brain activity associated with T2D-related functional impairment may serve as indicators for predicting symptom progression and assessing cognitive dysfunction. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Self-Powered Pressure-Temperature Bimodal Sensing Based on the Piezo-Pyroelectric Effect for Robotic Perception.

Multifunctional sensors have played a crucial role in constructing high-integration electronic networks. Most of the current multifunctional sensors rely on multiple materials to simultaneously detect different physical stimuli. Here, we demonstrate the large piezo-pyroelectric effect in ferroelectric Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) single crystals for simultaneous pressure and temperature sensing. The outstanding piezoelectric and pyroelectric properties of PMN-PT result in rapid response speed and high sensitivity, with values of 46 ms and 28.4 nA kPa-1 for pressure sensing, and 1.98 s and 94.66 nC °C-1 for temperature detection, respectively. By leveraging the distinct differences in the response speed of piezoelectric and pyroelectric responses, the piezo-pyroelectric effect of PMN-PT can effectively detect pressure and temperature from mixed-force thermal stimuli, which enables a robotic hand for stimuli classification. With appealing multifunctionality, fast speed, high sensitivity, and compact structure, the proposed self-powered bimodal sensor therefore holds significant potential for high-performance artificial perception.

Uncovering the Nature of Active Sites during Electrocatalytic Reactions by In Situ Synchrotron-Based Spectroscopic Techniques.

Catalysts can effectively accelerate the reaction kinetics process and are recognized as the core to realize the conversion and supply of carbon-free energy. However, the active sites of catalysts, especially nanocatalysts, usually undergo dynamic structural evolution under realistic working conditions, which may be induced by various reaction effects such as the applied voltages, electrolytes, or adsorbed intermediates. Therefore, in-depth and systemic insights into the nature of the active sites involved under the working conditions are prerequisites for correlating structure-performance relationships. However, uncovering and identifying active sites under operation conditions are still formidable scientific and technical challenges, which are severely hindered by the complex physical and chemical processes occurring on the active sites. Meanwhile, complementary and important information could be missed by conducting only the conventionally employed ex situ microscopic and spectroscopic measurements. Accordingly, it is highly desirable for us to develop the ever-increasing in situ synchrotron-based techniques to identify the nature of active sites, which renders the rational design of functional catalysts achievable.In this Account, we elaborately highlight the substantial achievements in cutting-edge in situ X-ray spectroscopy (XAS) techniques by presenting several representative carbon-neutral electrocatalytic examples performed in our group to broadcast the principles and virtues of identifying the active sites and tracing intermediate species during electrocatalytic water splitting and electrocatalytic CO2 reduction (ECR). Specifically, we believe that the interactions between the active sites and the support as well as the adsorption behaviors of intermediates are considered to be the important factors that govern the performance in the water splitting reaction. Meanwhile, the structural rearrangement of alloy catalysts driven by the cathodic potential significantly governs the activity and selectivity toward ECR. More importantly, the directions and suggestions for addressing the current limitations and pitfalls that we may encounter in the course of executing in situ experiments are also provided. Accordingly, it is necessary to use multiple in situ synchrotron-based techniques to obtain the comprehensive details. Furthermore, bridging the gap between the real energy devices and half-reactions could help us to approach the realistic mechanism. Beyond that, developing the rapid time resolution of in situ XAS will overcome the challenge of timescale mismatch to capture the faster structural kinetics of catalysts. Therefore, this Account is aimed to increase the awareness and appreciation of conducting in situ investigations on energy conversion reactions, which would be a guideline for us to explore catalytic scopes that remain challenging.

A comparative study on two methods of ocular surface microbial sampling.

PURPOSE: To compare the effect of traditional conjunctival sac swab sampling (A) with aerosolization ocular surface microorganism sampling (B),a novel microbial sampling method, in detecting ocular microbial infection. METHODS: The study included 61 participants (122 eyes) enrolled at the Eye Hospital, Wenzhou Medical University from December, 2021 to March, 2023. Each eye of the participants underwent sampling first with method A then B.Before aerosolization sampling, the air environment was disinfected and sampled as blank air control sample. Subsequently, the air pulses impinging the ocular surface causes dehiscence of the tear film covering the ocular surface and aerosols are formed.The microorganisms from the ocular surface attach to the aerosols generated as aerosolization ocular surface microorganism and be sampled as subject sample by bio-aerosol sampler.The samples were collected and incubated at 25℃ for 3-5 days and 37℃ for 24-48 h.The colonies were counted and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: The accuracy in Group B was higher than that in Group A (45.8% vs. 38.3%, P = 0.289). There was a slight level of agreement between the results from both the sampling methods (k = 0.031, P = 0.730). The sensitivity in Group B was higher than that in Group A (57.1% vs. 35.7%, P = 0.453). The specificity results in Group B was higher than that in Group A (44.3% vs. 38.7%, P = 0.480). There were 12 and 37 types of microbes detected in Groups A and B, respectively. CONCLUSIONS: Compared with traditional swab sampling, the novel aerosolization sampling method shows higher accuracy and more comprehensive detection of microbes; however, it cannot completely replace swab sampling. The novel method can be a novel conducive strategy and supplement swab sampling to auxiliary diagnose ocular surface infection.

Understanding Synergistic Catalysis on Cu-Se Dual Atom Sites via Operando X-ray Absorption Spectroscopy in Oxygen Reduction Reaction.

The construction and understanding of synergy in well-defined dual-atom active sites is an available avenue to promote multistep tandem catalytic reactions. Herein, we construct a dual-hetero-atom catalyst that comprises adjacent Cu-N4 and Se-C3 active sites for efficient oxygen reduction reaction (ORR) activity. Operando X-ray absorption spectroscopy coupled with theoretical calculations provide in-depth insights into this dual-atom synergy mechanism for ORR under realistic device operation conditions. The heteroatom Se modulator can efficiently polarize the charge distribution around symmetrical Cu-N4 moieties, and serve as synergistic site to facilitate the second oxygen reduction step simultaneously, in which the key OOH*-(Cu1 -N4 ) transforms to O*-(Se1 -C2 ) intermediate on the dual-atom sites. Therefore, this designed catalyst achieves satisfied alkaline ORR activity with a half-wave potential of 0.905 V vs. RHE and a maximum power density of 206.5 mW cm-2 in Zn-air battery.

Associations of 3-monochloropropane-1,2-diol and glycidol with prevalence of metabolic syndrome: Findings from Lanxi Nutrition and Safety Study.

In this study, we investigated the association of 2,3-dihydroxypropyl mercapturic acid (DHPMA), a urinary biomarker of environmental and dietary exposure to 3-monochloropropane-1,2-diol and glycidol, with prevalent MetS in a Chinese middle-aged and elderly population. The urinary DHPMA concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis and further calibrated by the urinary creatinine content. MetS cases were defined by the Adult Treatment Panel III criteria for Asian-Americans of National Cholesterol Education Program (NCEP/ATPIII). Multivariate-adjusted modified Poisson regression models were used to analyze the associations between the urinary DHPMA concentrations and MetS prevalence. Of the 1613 participants aged 45-75 years, we documented 552 (34.2%) MetS cases. After adjustment for potential risk factors, the relative risks (95% confidence intervals) of MetS prevalence across the increasing quartiles of DHPMA concentrations were 1.14 (0.93-1.39), 1.29 (1.06-1.56), and 1.50 (1.25-1.80), respectively, compared with the lowest quartile. We also observed strong positive association between urinary DHPMA concentrations and hypertriglyceridemia prevalence (P < 0.001 for trend). These positive associations remained unchanged in the subgroups stratified by general demographic, dietary and behavioral risk factors. These results suggested that urinary DHPMA was associated with higher prevalence of MetS among Chinese elderly people.

Preparation, in vitro and in vivo evaluation of pinocembrin-loaded TPGS modified liposomes with enhanced bioavailability and antihyperglycemic activity.

PURPOSE: To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity. SIGNIFICANCE: The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research. METHODS: Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation. RESULTS: PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about -26.650 mV), high drug encapsulation efficiency (87.32 ± 1.34%) and good storage (at 4 or 25 °C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the Cmax, MRT0-t, and T1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·mL-1, 12.695 ± 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment. CONCLUSION: These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings.

Synergistic Modulation at Atomically Dispersed Fe/Au Interface for Selective CO2 Electroreduction.

The electrocatalytic carbon dioxide reduction reaction (CO2RR) offers an attractive route to fuels and feedstocks from renewable energy. Gold is active for the electrochemical CO2RR to CO, while the competing hydrogen evolution reaction is unavoidable. Here, we report a synergistic strategy, via introducing atomically dispersed Fe to tune the electronic structure of the Au nanoparticle, to improve the CO selectivity. By using operando X-ray absorption and infrared spectroscopies, we reveal the dynamic structural evolution and the adsorption of reactant intermediates at the single-atom Fe1/Au interface. During the reaction, the interaction between Fe and Au atoms becomes stronger, and the Fe1/Au synergies affect the adsorption of reaction intermediates, thus improving the selectivity of CO up to 96.3% with a mass activity of 399 mA mg-1. These results highlight the significant importance of synergistic modulation for advancing the single-atom decorated nanoparticle catalysis.

Pinocembrin polymeric micellar drug delivery system: preparation, characterisation and anti-hyperuricemic activity evaluation.

Aim: Hydrophobic pinocembrin (PCB) was incorporated into a new nano-drug delivery system to enhance solubility, bioavailability and anti-hyperuricemic activity of the drug.Methods: We fabricated PCB loaded polymeric micelles (PCB-FPM) by thin film dispersion method and appropriately determined their physical characteristics. The oral relative bioavailability and anti-hyperuricemic activity of PCB-FPM and free PCB were observed.Results: The optimum particle size of the micelles was 19.90 ± 0.93 nm. PCB-FPM exhibited great stability within 18 days, coupled with lower cytotoxicity and higher biocompatibility. Moreover, the percent cumulative release of PCB-FPM was much higher than free PCB in the dissolution media. The oral bioavailability of PCB-FPM was increased by 2.61 times compared with free PCB. Uric acid (UA) level of rats was reduced in PCB-FPM group (200 mg/kg) by 78.82% comparable to the model control.Conclusion: PCB-FPM may become an ideal strategy to increase oral in-vivo availability and anti-hyperuricemic activity of PCB.

Hyperoside-loaded TPGs/mPEG-PDLLA self-assembled polymeric micelles: preparation, characterization and in vitro/in vivo evaluation.

Hyperoside (Hyp) self-assembled polymeric micelles (Hyp-PMs) were purposely developed to enhance aqueous solubility, in vivo availability and anti-oxidative effect of Hyp. In preparing Hyp-PMs, we employed the thin film dispersion method with the micelles consisting of TPGs and mPEG2000-PDLLA3000. The particle size, polydispersity index and zeta potential of Hyp-PMs were 67.42 ± 1.44 nm, 0.229 ± 0.015 and -18.67 ± 0.576 mV, respectively, coupled with high encapsulation efficiency （EE）of 90.63 ± 1.45% and drug loading (DL) of 6.97 ± 1.56%. Furthermore, the value of critical micelle concentration (CMC) was quite low, which indicated good stability and improved self-assembly ability of Hyp-PMs. Also, trend of in vitro Hyp release from Hyp-PMs demonstrated enhanced solubility of Hyp. Similarly, in comparison with free Hyp, oral bioavailability of Hyp-PMs was improved (about 8 folds) whilst half-life of Hyp-PMs was extended (about 3 folds). In vitro anti-oxidative effect showed obvious strong scavenging DPPH capability of Hyp-PMs, which may be attributed to its smaller size and better solubility. Altogether, Hyp-PMs may serve as a possible strategy to potentially enhance aqueous solubility, bioavailability and anti-oxidative effect of Hyp, which may play a key role in Hyp application in the pharmaceutical industries.

Preparation of Pinocembrin-Loaded F127/MPEG-PDLLA Polymer Micelles and Anti-Osteoporotic Activity.

Pinocembrin (PCB) is 5,7-dihydroxyl flavanone and has multiple pharmacological activities, namely, anti-inflammation, anti-osteoporotic, and so on. However, low water solubility and bioavailability have hindered its application. Herein, we aimed to increase its bioavailability through preparation of F127/MPEG-PDLLA polymer micelles (PCB-M). We characterized the micelles through appropriate attributes such as analysis of particle size (PS), polydispersity (PDI), transmission electron microscopic (TEM) image, stability test, and evaluation of in vitro release of drug. After physical characterization, the respective PS, PDI, and entrapment efficiency (EE) of PCB-M were estimated to be 27.63 ± 0.17 nm, 0.055 ± 0.02, and 90.53 ± 0.01%. Fluorescence probe method was employed to measure critical micelle concentration (CMC) of PCB-M, we observed CMC was low, thereby suggesting that PCB-M had good stability. In vitro release analysis indicated that the rate of cumulative PCB release from PCB-M was greater than 90% in each medium compared with free PCB, which was less than 40%, thus pointing to a significantly improved solubility of PCB. In vivo pharmacokinetic results showed that oral biological availability of PCB-M increased 5.3 folds comparable to free PCB. The effects of PCB on osteoblasts and ALP activities were investigated; subsequently, zebrafish osteoporotic model was established with prednisolone to study the anti-osteoporotic effects of PCB and PCB-M. The results showed that PCB improved osteoporosis with PCB-M being more effective than free PCB. Finally, PCB-M can be used as a promising method to improve the solubility of PCB, while the bioavailability and anti-osteoporotic effect of PCB could be improved, thus laying a foundation for clinical use in the future.

Atomically Precise Dinuclear Site Active toward Electrocatalytic CO2 Reduction.

The development of atomically precise dinuclear heterogeneous catalysts is promising to achieve efficient catalytic performance and is also helpful to the atomic-level understanding on the synergy mechanism under reaction conditions. Here, we report a Ni2(dppm)2Cl3 dinuclear-cluster-derived strategy to a uniform atomically precise Ni2 site, consisting of two Ni1-N4 moieties shared with two nitrogen atoms, anchored on a N-doped carbon. By using operando synchrotron X-ray absorption spectroscopy, we identify the dynamically catalytic dinuclear Ni2 structure under electrochemical CO2 reduction reaction, revealing an oxygen-bridge adsorption on the Ni2-N6 site to form an O-Ni2-N6 structure with enhanced Ni-Ni interaction. Theoretical simulations demonstrate that the key O-Ni2-N6 structure can significantly lower the energy barrier for CO2 activation. As a result, the dinuclear Ni2 catalyst exhibits >94% Faradaic efficiency for efficient carbon monoxide production. This work provides bottom-up target synthesis approaches and evidences the identity of dinuclear sites active toward catalytic reactions.

Biomass-Derived Carbon Materials: Controllable Preparation and Versatile Applications.

Biomass-derived carbon materials (BCMs) are encountering the most flourishing moment because of their versatile properties and wide potential applications. Numerous BCMs, including 0D carbon spheres and dots, 1D carbon fibers and tubes, 2D carbon sheets, 3D carbon aerogel, and hierarchical carbon materials have been prepared. At the same time, their structure-property relationship and applications have been widely studied. This paper aims to present a review on the recent advances in the controllable preparation and potential applications of BCMs, providing a reference for future work. First, the chemical compositions of typical biomass and their thermal degradation mechanisms are presented. Then, the typical preparation methods of BCMs are summarized and the relevant structural management rules are discussed. Besides, the strategies for improving the structural diversity of BCMs are also presented and discussed. Furthermore, the applications of BCMs in energy, sensing, environment, and other areas are reviewed. Finally, the remaining challenges and opportunities in the field of BCMs are discussed.

Dynamic Surface Reconstruction of Single-Atom Bimetallic Alloy under Operando Electrochemical Conditions.

The atomic-level understanding of the dynamic evolution of the surface structure of bimetallic nanoparticles under industrially relevant operando conditions provides a key guide for improving their catalytic performance. Here, we exploit operando X-ray absorption fine structure spectroscopy to determine the dynamic surface reconstruction of Cu/Au bimetallic alloy where single-atom Cu was embedded on the Au nanoparticle, under electrocatalytic conditions. We identify the migration of isolated Cu atoms from the vertex position of the Au nanoparticle to the stable (100) plane of the Au first atom layer, when the reduction potential is applied. Density functional theory calculations reveal that the surface atom migration would significantly modulate the Au electronic structure, thus serving as the real active site for the catalytic performance. These findings demonstrate the real structural change under electrochemical conditions and provide guidance for the rational design of high-activity bimetallic nanocatalysts.

The role of P2Y6 receptors in the maintenance of neuropathic pain and its improvement of oxidative stress in rats.

AIM: To explore the role of P2Y6 receptors in the maintenance of neuropathic pain and progression of oxidative stress, we investigated the efficacy of the selective P2Y6 receptors antagonist MRS2578 on the antiallodynic effects and improvement of pathological neuropathic pain-induced oxidative stress, thereby finding a potential therapeutic target in neurological disease. MATERIALS AND METHODS: The mechanical allodynia in the ipsilateral spinal dorsal horn (SDH) of rats was observed in rats after chronic constriction injury (CCI). Meanwhile, the messenger RNA (mRNA) levels of biological parameters, including superoxide dismutase (SOD), glutathione (GSH), and heme oxygenase-1 (HO-1) in the SDH of rats were measured by real-time polymerase chain reaction (RT-PCR). In addition, the mRNA expression and protein levels of P2Y6 were measured by RT-PCR and Western blot assay, respectively. Next, the rats subjected to CCI were intrathecally infused with MRS2578 to block the expression of P2Y6 receptors. The positive expression of P2Y6 receptors was examined by immunohistochemistry. RESULTS: In the present study, the results revealed that the P2Y6 expression in the ipsilateral SDH of CCI rats was significantly upregulated. In addition, inhibition of the P2Y6 receptor in SDH increased CCI-induced tactile allodynia. Furthermore, the levels of SOD, GSH, and HO-1 which were correlated with oxidative stress produced by CCI were also decreased. CONCLUSION: The results demonstrated that inhibition of the P2Y6 receptor can generate antiallodynic effects and improved the pathological neuropathic pain-induced oxidative stress. Thus, this study provides a potential approach for the therapy of neurological disease.

Long-Term Spatiotemporal Variations in Soil Moisture in North East China Based on 1-km Resolution Downscaled Passive Microwave Soil Moisture Products.

It is very important to analyze and monitor agricultural drought to obtain high temporal-spatial resolution soil moisture products. To overcome the deficiencies of passive microwave soil moisture products with low resolution, we construct a spatial fusion downscaling model (SFDM) using Moderate Resolution Imaging Spectroradiometer (MODIS) data. To eliminate the inconsistencies in soil depth and time among different microwave soil moisture products (Advanced Microwave Scanning Radiometer on the Earth Observing System (AMSR-E) and its successor (AMSR2) and the Soil Moisture Ocean Salinity (SMOS)), a time series reconstruction of the difference decomposition (TSRDD) method is developed to create long-term multisensor soil moisture datasets. Overall, the downscaled soil moisture (SM) products were consistent with the in situ measurements (R > 0.78) and exhibited a low root mean square error (RMSE < 0.10 m3/m3), which indicates good accuracy throughout the time series. The downscaled SM data at a 1-km spatial resolution were used to analyze the spatiotemporal patterns and monitor abnormal conditions in the soil water content across North East China (NEC) between 2002 and 2018. The results showed that droughts frequently appeared in western North East China and southwest of the Greater Khingan Range, while drought centers appeared in central North East China. Waterlogging commonly appeared in low-terrain areas, such as the Songnen Plain. Seasonal precipitation and temperature exhibited distinct interdecadal characteristics that were closely related to the occurrence of extreme climatic events. Abnormal SM levels were often accompanied by large meteorological and natural disasters (e.g., the droughts of 2008, 2015, and 2018 and the flooding events of 2003 and 2013). The spatial distribution of drought in this region during the growing season shows that the drought-affected area is larger in the west than in the east and that the semiarid boundary extends eastward and southward.

Activation of Pedunculopontine Glutamate Neurons Is Reinforcing.

Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice. We used anatomical, electrophysiological, and behavioral assays to determine their patterns of connectivity and ascribe functional roles in reinforcement. We found that photoactivation of PPTg glutamate cell bodies could serve as a direct positive reinforcer on intracranial self-photostimulation assays. Further, PPTg glutamate neurons directly innervate VTA; photostimulation of this pathway preferentially excites VTA dopamine neurons and is sufficient to induce behavioral reinforcement. These results demonstrate that ascending PPTg glutamate projections can drive motivated behavior, and PPTg to VTA synapses may represent an important target relevant to drug addiction and other mental health disorders. SIGNIFICANCE STATEMENT: Uncovering brain circuits underlying reward-seeking is an important step toward understanding the circuit bases of drug addiction and other psychiatric disorders. The dopaminergic system emanating from the ventral tegmental area (VTA) plays a key role in regulating reward-seeking behaviors. We used optogenetics to demonstrate that the pedunculopontine tegmental nucleus sends glutamatergic projections to VTA dopamine neurons, and that stimulation of this circuit promotes behavioral reinforcement. The findings support a critical role for pedunculopontine tegmental nucleus glutamate neurotransmission in modulating VTA dopamine neuron activity and behavioral reinforcement.

An algorithm for retrieving land surface temperatures using VIIRS data in combination with multi-sensors.

A practical algorithm was proposed to retrieve land surface temperature (LST) from Visible Infrared Imager Radiometer Suite (VIIRS) data in mid-latitude regions. The key parameter transmittance is generally computed from water vapor content, while water vapor channel is absent in VIIRS data. In order to overcome this shortcoming, the water vapor content was obtained from Moderate Resolution Imaging Spectroradiometer (MODIS) data in this study. The analyses on the estimation errors of vapor content and emissivity indicate that when the water vapor errors are within the range of ±0.5 , the mean retrieval error of the present algorithm is 0.634 K; while the land surface emissivity errors range from -0.005 to +0.005, the mean retrieval error is less than 1.0 K. Validation with the standard atmospheric simulation shows the average LST retrieval error for the twenty-three land types is 0.734 K, with a standard deviation value of 0.575 K. The comparison between the ground station LST data indicates the retrieval mean accuracy is -0.395 K, and the standard deviation value is 1.490 K in the regions with vegetation and water cover. Besides, the retrieval results of the test data have also been compared with the results measured by the National Oceanic and Atmospheric Administration (NOAA) VIIRS LST products, and the results indicate that 82.63% of the difference values are within the range of -1 to 1 K, and 17.37% of the difference values are within the range of ±2 to ±1 K. In a conclusion, with the advantages of multi-sensors taken fully exploited, more accurate results can be achieved in the retrieval of land surface temperature.