Period measurement of a periodic structure by using a heterodyne grating interferometer.

This paper proposes an alternative method for grating period measurement based on heterodyne grating interferometry. The optical configurations for measuring the period of reflection/transmission gratings were demonstrated, and four commercially available gratings were used to evaluate the effectiveness of the proposed method. Based on the phase-lock technique, the grating period could be obtained immediately through the phase wrapped/unwrapped process. Under precise measurement conditions, the grating period measurement error of the proposed method was better than 1 nm, and the grating period difference between product specifications was less than 1%. In addition, the measurement results of the proposed method also exhibited high similarity with optical microscopy measurements.

Land use carbon emissions estimation and carbon emissions control strategy effect scenario simulation in Zhejiang province.

Carbon emission control is an important aspect of regional sustainable development. However, there are few studies on predicting the impact of different socio-economic development strategies on carbon emissions under the premise of established government policy objectives, and then evaluating the degree of achievement of policy objectives. In order to research the effect of social and economic development strategies on carbon emissions, remote sensing land use data of Zhejiang Province from 2000 to 2020 were utilized in this paper to quantify carbon emissions, combined with Kaya identity and LMDI decomposition method, and multi-scenario carbon emissions simulation and prediction were carried out under the STIRPAT model framework. The results demonstrate that land use carbon emissions increased by four times in the last 20 years, and increased rapidly between 2000 and 2010, and became stable in recent years. Economic growth is the primary motivator; According to the existing economic development model, carbon emissions will peak and turn around in 2030; If appropriate economic transformation measures are taken to increase the proportion of low-carbon economic components, it is possible to achieve the development model of scenario 2 and scenario 3, and carbon emissions will reach the peak 2-5 years earlier. In general, this study offers a significant conclusion for the investigation of the connection between social and economic growth strategies and carbon emissions, and it can serve as a guide for the formation of government policy.

Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors.

Members of the melanocortin receptor (MCR) family that recognize different melanocortin peptides mediate a broad spectrum of cellular processes including energy homeostasis, inflammation and skin pigmentation through five MCR subtypes (MC1R-MC5R). The structural basis of subtype selectivity of the endogenous agonist γ-MSH and non-selectivity of agonist α-MSH remains elusive, as the two agonists are highly similar with a conserved HFRW motif. Here, we report three cryo-electron microscopy structures of MC3R-Gs in complex with γ-MSH and MC5R-Gs in the presence of α-MSH or a potent synthetic agonist PG-901. The structures reveal that α-MSH and γ-MSH adopt a "U-shape" conformation, penetrate into the wide-open orthosteric pocket and form massive common contacts with MCRs via the HFRW motif. The C-terminus of γ-MSH occupies an MC3R-specific complementary binding groove likely conferring subtype selectivity, whereas that of α-MSH distances itself from the receptor with neglectable contacts. PG-901 achieves the same potency as α-MSH with a shorter length by rebalancing the recognition site and mimicking the intra-peptide salt bridge in α-MSH by cyclization. Solid density confirmed the calcium ion binding in MC3R and MC5R, and the distinct modulation effects of divalent ions were demonstrated. Our results provide insights into ligand recognition and subtype selectivity among MCRs, and expand the knowledge of signal transduction among MCR family members.

Ferula sinkiangensis against gastric cancer: a network pharmacology, molecular docking and cell experiment study.

Background: Ferula sinkiangensis (F. sinkiangensis) is a traditional Chinese medicine that has been used for thousands of years to treat stomach ailments. To identify the main active compounds and explore the mechanisms underlying the therapeutic effect of F. sinkiangensis against gastric cancer (GC) by network pharmacology, molecular docking analysis and cell experiment. Methods: Based on a review of the literature and previous experiments conducted by our research group, the active compounds of F. sinkiangensis were obtained. Active compounds and their target genes were screened from SwissADME, Pubchem, and Pharmmapper databases. GC-related target genes were obtained from GeneCards. The drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.7.2 and STRING database, and the core target genes and core active compounds were identified. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted using the R package clusterProfiler. The core genes with high expression in GC were screened, which correlated with a poor prognosis using the GEPIA, UALCAN, HPA, and KMplotter databases. KEGG signaling pathway analysis was further conducted to predict the mechanism of F. sinkiangensis during the process of GC inhibition. The AutoDock vina 1.1.2 program was used to verify the molecular docking of the core active compounds and core target genes. MTT, Transwell, and Wound healing assay were used to detect the effects of ethyl acetate extract of F. sinkiangensis on the proliferation, invasion, and apoptosis of GC cells. Results: Final results indicated that the active compounds include Farnesiferol C, Assafoetidin, Lehmannolone, Badrakemone, etc. The identified core target genes were GPI, TKT, GLYCTK, ERBB2, GAPDH, etc. The Glycolysis/Gluconeogenesis pathway and the Pentose Phosphate pathway might play important roles in the treatment of GC with F. sinkiangensis. The data from the study showed that F. sinkiangensis was able to inhibit the proliferation of GC cells. Meanwhile, F. sinkiangensis remarkedly repressed the invasion and migration of GC cells in in vitro experiment. Conclusions: This study revealed that F. sinkiangensis has an antitumor effect in in vitro experiment, and that the mechanism of F. sinkiangensis in GC treatment shows characteristics of multi-components, multi-targets, and multi-pathways, which provides a theoretical basis for its clinical application and subsequent experimental verification.

Self-assembly formation of CuI hybrid micron phosphors with tunable emission for multifunctional applications.

Low-cost and eco-friendly CuI hybrid compounds with various structures have recently attracted increasing attention due to their excellent optical properties and promising phosphor applications. However, the poor solubility and solution processability of bulk powders with agglomerated particle limited their practical applications greatly. In this work, we reported the self-assembly formation of CuI hybrid micron phosphors via the aqueous PVP micelle-assisted assembly route. Seven CuI hybrid micron phosphors with the emission from blue 450 nm to red 636 nm have been successfully synthesized. Among them, CuI-pyridine hybrid micron phosphors can be obtained via the reaction of CuI with various pyridines. PVP limits the size growth of the phosphors efficiently and it also plays an important role in controlling the distinct crystal phase formation. Whereas, micron phosphors based on bidentate ligands including 2-propylpyrazine, 5-bromopyrimidine or 4,4'-bipyridine need to be prepared via ligand exchange reaction. The micron phosphors present excellent stability in water and can be dispersed in the aqueous solution of PVP or PVA to form homogenous luminescent composites. The luminescent composites based on PVP are easy to use for fabricating anti-counterfeiting patterns via brush-painting or screen-printing. On the other hand, PVA composites can be applied for preparing free standing monochromatic or multichromatic emitting films as color convertor for display backlight. The PVA composites also exhibit the promising phosphor application for light-emitting diode (LED). Especially, the white LED can be directly realized via optimizing the mixing ratio of blue and orange phosphors.

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), as a severe form of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. The pathogenesis of NASH is complex and multifactorial, obesity and type 2 diabetes mellitus (T2DM) have been implicated as major risk factors. Glucagon-like peptide-1 receptor (GLP-1R) is one of the most successful drug targets of T2DM and obesity, and its peptidic ligands have been proposed as potential therapeutic agents for NASH. In this article we provide an overview of the pathophysiology and management of NASH, with a special focus on the pharmacological effects and possible mechanisms of GLP-1 mimetics in treating NAFLD/NASH, including dual and triple agonists at GLP-1R, glucose-dependent insulinotropic polypeptide receptor or glucagon receptor.

Layer-Tunable Nonlinear Optical Characteristics and Photocarrier Dynamics of 2D PdSe2 in Broadband Spectra.

Layered 2D transition metal dichalcogenides (TMDCs) exhibited fascinating nonlinear optical (NLO) properties for constructing varied promising optoelectronics. However, exploring the desired 2D materials with both superior nonlinear absorption and ultrafast response in broadband spectra remain the key challenges to harvest their greatest potential. Here, based on synthesizing 2D PdSe2 films with the controlled layer number, the authors systematically demonstrated the broadband giant NLO performance and ultrafast excited carrier dynamics of this emerging material under femtosecond visible-to-near-infrared laser-pulse excitation (400-1550 nm). Layer-dependent and wavelength-dependent evolution of optical bandgap, nonlinear absorption, and photocarrier dynamics in the obtained 2D PdSe2 are clearly revealed. Specially, the transition from semiconducting to semimetallic PdSe2 induced dramatic changes of their interband absorption-relaxation process. This work makes 2D PdSe2 more competitive for future ultrafast photonics and also opens up a new avenue for the optical performance optimization of various 2D materials by rational design of these materials.

Design and fabrication of a downlight luminaire with a dual frusto-conical reflector.

A design method and corresponding fabrication procedures are proposed for a dual frusto-conical reflector of a downlight luminaire. The profile of the dual frusto-conical reflector consists of two flat-slant reflective surfaces with slightly different slopes. The optimum dual frusto-conical reflector can be obtained with the proposed design method. The finished product of the dual frusto-conical reflector is fabricated by a 3D printer and followed by surface polishing and reflection paint spraying. The measurement results show that luminaires exhibited 70% optimum illuminance confined within an illumination area of 1.8m2, and the optimum illumination intensity is at 252 lux. The optimum efficiency of the proposed luminaire can reach 158 lm/W for normal-white light-emitting diode (LED) and 119 lm/W for warm-white LED, respectively.

Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor.

Cholecystokinin A receptor (CCKAR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with a sulfated ligand and to couple with divergent G-protein subtypes, including Gs, Gi and Gq. However, the basis for G-protein coupling promiscuity and ligand recognition by CCKAR remains unknown. Here, we present three cryo-electron microscopy structures of sulfated CCK-8-activated CCKAR in complex with Gs, Gi and Gq heterotrimers, respectively. CCKAR presents a similar conformation in the three structures, whereas conformational differences in the 'wavy hook' of the Gα subunits and ICL3 of the receptor serve as determinants in G-protein coupling selectivity. Our findings provide a framework for understanding G-protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8.

Molecular basis for kinin selectivity and activation of the human bradykinin receptors.

Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain control. Des-Arg10-kallidin, the carboxy-terminal des-Arg metabolite of kallidin, and bradykinin selectively activate two G protein-coupled receptors, type 1 and type 2 bradykinin receptors (B1R and B2R), respectively. The hyperactivation of bradykinin receptors, termed 'bradykinin storm', is associated with pulmonary edema in COVID-19 patients, suggesting that bradykinin receptors are important targets for COVID-19 intervention. Here we report two G protein-coupled complex structures of human B1R and B2R bound to des-Arg10-kallidin and bradykinin, respectively. Combined with functional analysis, our structures reveal the mechanism of ligand selectivity and specific activation of the bradykinin receptor. These findings also provide a framework for guiding drug design targeting bradykinin receptors for the treatment of inflammation, cardiovascular disorders and COVID-19.

Molecular insights into differentiated ligand recognition of the human parathyroid hormone receptor 2.

The parathyroid hormone receptor 2 (PTH2R) is a class B1 G protein-coupled receptor (GPCR) involved in the regulation of calcium transport, nociception mediation, and wound healing. Naturally occurring mutations in PTH2R were reported to cause hereditary diseases, including syndromic short stature. Here, we report the cryogenic electron microscopy structure of PTH2R bound to its endogenous ligand, tuberoinfundibular peptide (TIP39), and a heterotrimeric Gs protein at a global resolution of 2.8 Å. The structure reveals that TIP39 adopts a unique loop conformation at the N terminus and deeply inserts into the orthosteric ligand-binding pocket in the transmembrane domain. Molecular dynamics simulation and site-directed mutagenesis studies uncover the basis of ligand specificity relative to three PTH2R agonists, TIP39, PTH, and PTH-related peptide. We also compare the action of TIP39 with an antagonist lacking six residues from the peptide N terminus, TIP(7-39), which underscores the indispensable role of the N terminus of TIP39 in PTH2R activation. Additionally, we unveil that a disease-associated mutation G258D significantly diminished cAMP accumulation induced by TIP39. Together, these results not only provide structural insights into ligand specificity and receptor activation of class B1 GPCRs but also offer a foundation to systematically rationalize the available pharmacological data to develop therapies for various disorders associated with PTH2R.

Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor.

The glucagon-like peptide-1 (GLP-1) receptor is a validated drug target for metabolic disorders. Ago-allosteric modulators are capable of acting both as agonists on their own and as efficacy enhancers of orthosteric ligands. However, the molecular details of ago-allosterism remain elusive. Here, we report three cryo-electron microscopy structures of GLP-1R bound to (i) compound 2 (an ago-allosteric modulator); (ii) compound 2 and GLP-1; and (iii) compound 2 and LY3502970 (a small molecule agonist), all in complex with heterotrimeric Gs. The structures reveal that compound 2 is covalently bonded to C347 at the cytoplasmic end of TM6 and triggers its outward movement in cooperation with the ECD whose N terminus penetrates into the GLP-1 binding site. This allows compound 2 to execute positive allosteric modulation through enhancement of both agonist binding and G protein coupling. Our findings offer insights into the structural basis of ago-allosterism at GLP-1R and may aid the design of better therapeutics.

Venlafaxine Inhibits the Apoptosis of SHSY-5Y Cells Through Active Wnt/ß-Catenin Signaling Pathway.

OBJECTIVE: This study aimed to explore the mechanism of venlafaxine in regulating the apoptosis of SHSY-5Y cells induced by hypoxia. METHODS: The CoCl2-induced neuronal hypoxia model was established based on SHSY-5Y cells. The morphology and related protein expression of SHSY-5Y cells were detected by qPCR, ELISA and Western blot. RESULTS: Under the condition of hypoxia-induced by CoCl2, the expression of HIF-1α in SHSY-5Y cells was up-regulated and the expression of ß-catenin was down-regulated. After adding siRNA targeting HIF-1 α to the culture cell system, down-regulation of ß -catenin expression in SHSY-5Y cells was restored. This confirmed the existence of the "hypoxia-HIF-1α-Wnt/ß-catenin-depression" axis. Further studies have shown that venlafaxine can alleviate neuronal apoptosis induced by hypoxia by upregulating the Wnt/ß-catenin signaling pathway. CONCLUSION: Venlafaxine regulates apoptosis induced by hypoxia through the Wnt/ß-catenin signaling pathway, which provides a new theoretical basis for the treatment of depression.

Characterization of a naturally occurring mutation V368M in the human glucagon receptor and its association with metabolic disorders.

Glucagon is a peptide hormone secreted by islet α cells. It plays crucial roles in glucose homeostasis and metabolism by activating its cognate glucagon receptor (GCGR). A naturally occurring deleterious mutation V368M in the human GCGR leads to reduced ligand binding and down-regulation of glucagon signaling. To examine the association between this mutation and metabolic disorders, a knock-in mouse model bearing homozygous V369M substitution (equivalent to human V368M) in GCGR was made using CRISPR-Cas9 technology. These GcgrV369M+/+ mice displayed lower fasting blood glucose levels with improved glucose tolerance compared with wild-type controls. They also exhibited hyperglucagonemia, pancreas enlargement and α cell hyperplasia with a lean phenotype. Additionally, V369M mutation resulted in a reduction in adiposity with normal body weight and food intake. Our findings suggest a key role of V369M/V368M mutation in GCGR-mediated glucose homeostasis and pancreatic functions, thereby pointing to a possible interplay between GCGR defect and metabolic disorders.

Factors associated with loss to follow-up of outpatients with depression in general hospitals.

OBJECTIVE: We aimed to understand the reasons behind outpatient loss to follow-up and the views of Chinese patients with depression regarding disease diagnosis and antidepressant therapy. METHODS: Consecutive outpatients with newly diagnosed depressive disorder between September 2012 and August 2013 at the Shanghai First People's Hospital (a tertiary hospital) were categorized into follow-up and lost-to-follow-up groups. We collected information on demographics, the Hamilton depression (HAMD) scale, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale, and Symptom Checklist-90. Patients were routinely followed at 2, 4, 8, and 12 weeks. Any missed appointment was considered lost to follow-up. RESULTS: After 12 weeks of treatment, only 42.2% (70/166) of patients were continuing follow-up. Patients lost to follow-up were significantly younger (median, 42.5 vs. 56.5 years), had different marital status, higher education level, higher SDS score (43.8 ± 10.8 vs. 40.2 ± 10.9), and higher HAMD score (median, 21 vs. 19). Age (odds ratio (OR) = 0.97, 95% confidence interval (CI): 0.95-0.997), and HAMD score (OR = 1.14, 95% CI: 1.01-1.29) were independently associated with loss to follow-up. CONCLUSION: Young age, higher HAMD score, and poor knowledge of depression and treatment were the main factors associated with loss to follow-up during depression management among our Chinese patients.

Hierarchical mesoporous silica nanoparticles for tailorable drug release.

In order to modulate the drug release profiles, the hierarchical mesoporous silica nanoparticles (HMSNs) are fabricated by a two-step synthetic process. The HMSNs exhibit uniform spherical morphology with nanoscaled size, well mono-dispersed size distribution, and smooth surface. Because of the hierarchical pore structures with different mesoporous sizes and morphologies (partial open and partial blocked pores), the HMSNs can release the loaded drug in a controlled manner. The hierarchical mesoporous structures directed drug release profiles suggest a feasible strategy to tailor drug release behaviors. Meanwhile, the HMSNs exhibit good biocompatibility. Therefore, the HMSNs having tailorable drug release capacity would be a potential candidate to improve their therapeutic efficiency for drug delivery systems.

Treatment Effect of Antipsychotics in Combination with Horticultural Therapy on Patients with Schizophrenia: A Randomized, Double-blind, Placebo-controlled Study.

BACKGROUND: As a newly developed treatment method for schizophrenia, horticultural therapy is gaining more attention. However, there is as of now little research investigating this topic as well as a general lack of studies adopting into standard treatment plans. AIMS: Investigate treatment effect of horticultural therapy on patients with schizophrenia and its possibility of standardized application in psychiatric hospitals. METHODS: 110 patients with schizophrenia who met the inclusion criteria and provided informed consent were selected from the rehabilitation ward of the Minhang District Mental Health Center from September 2015 to December 2015. We used random-number methods to classify patients into either the intervention group or the control group. While the two groups both received normal medications, the intervention group also attended horticultural therapy. Patients in the intervention group were led by a rehabilitation therapist who had obtained the level II psychological counselor qualification (the standard qualification for counselors in China). The treatment period lasted for 12 weeks. Treatment was held 3 times every week and each session lasted for 90 minutes. The specific contents included ridging, planting, watering, fertilizing and pruning of flowers; plowing, sowing, watering, fertilizing, weeding and catching pests for gardens; appreciating, collecting vegetables, cooking and tasting for flowers and grasses. During the final 10 minutes of every session, patients mutually expressed their thoughts and experiences and the rehabilitation therapist concluded the session. The two groups were measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, the end of the 4th week and the end of the 12th week. RESULTS: There was no statistically significant difference in gender, age, course of disease, marital status, mean dosage of antipsychotic medications and PANSS score before the intervention among two groups. The PANSS score in the intervention group was statistically significant lower than in the control group both at the end of the 4th week (t=-4.03, p<0.001) and at the end of the 12th week (t=-5.57, p<0.001). There were statistically significant differences before and after intervention in the intervention group (F=253.03, p<0.001); there was statistically significant differences before and after intervention in the control group (F=67.66, p<0.001). There was statistically significant difference in the positive scale score among the two groups both at the end of the 4th week (t=-3.69, p<0.001) and the end of the 12th week (t=-3.55, p<0.001); there was a statistically significant difference in the general psychopathology scale score among the two groups both at the end of the 4th week (t=-3.67, p<0.001) and the end of the 12th week (t=-3.34, p<0.001). Likewise, there were statistically significant differences in the positive scale scores at baseline, end of the 4th week and the end of the 12th week both among the intervention group (F=13.76, p<0.001) and the control group (F=5.12, p=0.02); there were statistically significant differences in the general psychopathology scale scores at the baseline, the end of the 4th weekand the end of the 12th week both among the intervention group (F=156.40, p<0.001) and the control group (F=56.72, p<0.001). There was statistically significant differences in the negative scale score at the end of the 12th week among the two groups (t=-2.76, p<0.001). There were statistically significant differences in the positive scale scores at the baseline, the end of the 4th week and the end of the 12th week both among the intervention group (F=103.94, p<0.001) and the control group (F=34.03, p<0.001). CONCLUSIONS: Although antipsychotic medications can alleviate the psychiatric symptoms of patients with schizophrenia, the treatment effect for both positive and negative symptoms would be even more effective if it is combined with horticultural therapy.

Panic attacks 10 years after heart transplantation successfully treated with low-dose citalopram: a case report.

Panic attacks are common among patients who have undergone heart transplantation, but there are no clinical guidelines for the treatment of panic attacks in this group of patients. This report describes a 22-year-old woman who experienced panic attacks 10 years after heart transplant surgery. The attacks started after she discovered that the average post-transplantation survival is 10 years. Treated with citalopram 10 mg/d, her symptoms improved significantly after 2 weeks and had completely resolved after 8 weeks. A positive physician-patient relationship with the doctors who regularly followed her medical condition was crucial to encouraging her to adhere to the treatment with citalopram. She continued taking the citalopram for 7 months without any adverse effects. When followed up 3 months after stopping the citalopram, she had had no recurrence of the panic attacks.