X-Linked Reticulate Pigmentary Disorder.

This case report describes a child with generalized reticulate hyperpigmentation and recurrent pneumonia, hypohidrosis, photophobia, and diarrhea.

Sound transmission across locally resonant honeycomb sandwich meta-structures with large spatial periodicity.

Honeycomb sandwich structures have been widely used in the field of engineering owing to their outstanding mechanical properties. However, for a honeycomb sandwich structure with large spatial periodicity, there is a low-frequency sound insulation valley. Here, the sound transmission across locally resonant honeycomb sandwich meta-structures was investigated to overcome this sound-insulation valley. An analytical model was developed based on the space-harmonic approach and the low-frequency sound insulation valley was determined analytically and numerically. The results indicate that the resonator distributed at the center of the face panel has a significant impact on the sound transmission performance of the honeycomb sandwich structure, whereas the resonator distributed on the wall of the honeycomb core does not contribute to overcoming this sound-insulation valley. Based on the research results, a design strategy for overcoming this sound-insulation valley was determined by tuning the damping parameter and constructing graded resonators. Moreover, sound transmission under the excitation of oblique incidence sound waves was also investigated. Compared with the method of filling porous materials, the proposed design method is more effective, and more importantly, the mass of the resonator is only 1.23% of that of the porous materials.

Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer.

Breast cancer is the leading cancer in women. Around 20-30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested.

13-Cis Retinoic Acid Induces Neuronal Differentiation in Daoy (Medulloblastoma) Cells Through Epigenetic Regulation of Topoisomerase IIß.

Medulloblastoma (MB) is a malignant tumor of the cerebellum that occurs in children and infants. Abnormal neuronal differentiation can lead to brain tumors, and topoisomerase IIß (Top IIß) plays an important role in neuronal differentiation. The aim of this study was to investigate the molecular mechanism of 13-cis retinoic acid (13-cis RA) promoting the expression of Top IIß and inducing neuronal differentiation in human MB Daoy cells. The results showed that 13-cis RA inhibited the cell proliferation and induced cell cycle arrest in G0/G1 phase. The cells differentiated into a neuronal phenotype, with high expression of the neuronal marker microtubule-associated protein 2 (MAP2) and abundant Top IIß, and obvious neurite growth. Chromatin immunoprecipitation (ChIP) assay showed that histone H3 lysine 27 tri-methylation (H3K27me3) modification in Top IIß promoter decreased after 13-cis RA-induced cell differentiation, while jumonji domain-containing protein 3 (JMJD3) binding in Top IIß promoter increased. These results suggest that H3K27me3 and JMJD3 can regulate the expression of Top IIß gene, which is related to inducing neural differentiation. Our results provide new insights into understanding the regulatory mechanisms of Top IIß during neuronal differentiation and imply the potential application of 13-cis RA in the clinical treatment of MB.

Clinical application status and prospect of the combined anti-tumor strategy of ablation and immunotherapy.

Image-guided tumor ablation eliminates tumor cells by physical or chemical stimulation, which shows less invasive and more precise in local tumor treatment. Tumor ablation provides a treatment option for medically inoperable patients. Currently, clinical ablation techniques are widely used in clinical practice, including cryoablation, radiofrequency ablation (RFA), and microwave ablation (MWA). Previous clinical studies indicated that ablation treatment activated immune responses besides killing tumor cells directly, such as short-term anti-tumor response, immunosuppression reduction, specific and non-specific immune enhancement, and the reduction or disappearance of distant tumor foci. However, tumor ablation transiently induced immune response. The combination of ablation and immunotherapy is expected to achieve better therapeutic results in clinical application. In this paper, we provided a summary of the principle, clinical application status, and immune effects of tumor ablation technologies for tumor treatment. Moreover, we discussed the clinical application of different combination of ablation techniques with immunotherapy and proposed possible solutions for the challenges encountered by combined therapy. It is hoped to provide a new idea and reference for the clinical application of combinate treatment of tumor ablation and immunotherapy.

CXCR4 and TYROBP mediate the development of atrial fibrillation via inflammation.

Atrial fibrillation (AF) is a rapid supraventricular arrhythmia. However, the pathogenesis of atrial fibrillation remains controversial. We obtained transcriptome expression profiles GSE41177, GSE115574 and GSE79768 from GEO database. WGCNA was performed, DEGs were screened, PPI network was constructed using STRING database. CTD database was used to identify the reference score of hub genes associated with cardiovascular diseases. Prediction of miRNAs of hub genes was performed by TargetScan. DIANA-miRPath v3.0 was applied to make functional annotation of miRNA. The animal model of atrial fibrillation was constructed, RT-PCR was used to verify the expression of hub genes. Immunofluorescence assay for THBS2 and VCAN was made to identify molecular. Design of BP neural network was made to explore the prediction relationship of CXCR4 and TYROBP on AF. The merged datasets contained 104 up-regulated and 34 down-regulated genes. GO and KEGG enrichment analysis results of DEGs showed they were mainly enriched in 'regulation of release of sequestered calcium ion into cytosol', 'actin cytoskeleton organization' and 'focal adhesion'. The hub genes were CXCR4, SNAI2, S100A4, IGFBP3, CSNK2A1, CHGB, VCAN, APOE, C1QC and TYROBP, which were up-regulated expression in the AF compared with control tissues. There was strong correlation among the CXCR4, TYROBP and AF based on the BP neural network. Through training, best training performance is 9.6474e-05 at epoch 14, and the relativity was 0.99998. CXCR4 and TYROBP might be involved in the development of atrial fibrillation by affecting inflammation-related signalling pathways and may serve as targets for early diagnosis and preventive treatment.

Bioassay-guided isolation of cytotoxic constituents from the flowers of Aquilaria sinensis.

Bioassay-guided fractionation of the EtOH extract from the flowers of Aquilaria sinensis (Lour.) Spreng. (Thymelaeaceae) led to the isolation of a new cucurbitane-type triterpenoid, aquilarolide A (1), along with five known compounds (2-6). The structure of 1 was elucidated by extensive 1D and 2D nuclear magnetic resonance (NMR) experiments and mass spectrometry (MS) data and theoretical calculations of its electronic circular dichroism (ECD) spectra. Aquilarolide A, cucurbitacin E (3), cucurbitacin B (4), and 7-hydroxy-6-methoxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one (6) showed significant cytotoxicity against human lung adenocarcinoma SPC-A-1, human lung squamous cell carcinoma NCI-H520, human lung adenocarcinoma A549, and paclitaxel-resistant A549 (A549/Taxol) cell lines. All four active compounds, with IC50 values ranging from 0.002 to 0.91 µM, had better inhibitory activities against A549/Taxol cells than paclitaxel (IC50 = 1.80 µM). Among them, cucurbitacin E (IC50 = 0.002 µM) is the most active. Further studies are needed to evaluate their in vivo antitumor activities and to clarify their mechanisms.

[Characteristics and Source Analysis of Water-soluble Inorganic Pollution in PM2.5 During Summer in Central China].

In order to investigate the pollution characteristics and sources of water-soluble ions in atmospheric PM2.5 in different regions of central China during summer, Wuhan, Suizhou, and Pingdingshan were selected as urban, suburban, and rural monitoring stations, respectively, to collect PM2.5 samples, and the mass concentration of PM2.5 in the atmosphere and the contents of eight water-soluble ions were analyzed. The results showed that ρ(water-soluble ions) at the three sites showed obvious spatial distribution characteristics, with Pingdingshan[(36.29±9.82) µg·m-3] > Wuhan[(32.55±10.05) µg·m-3] > Suizhou[(26.10±6.23) µg·m-3], accounting for 52.47%, 51.32%, and 48.61% of the PM2.5 mass concentration, respectively. In the Pingdingshan station, the proportion of water-soluble ions was the largest due to biomass combustion in the rural area. Additionally, SNA (SO42-, NO3-, and NH4+) were the main ionic components, accounting for 95.65%, 96.12%, and 97.33% of the total water-soluble ions, respectively. The mean values of SOR of the Wuhan (0.64) and Suizhou (0.63) stations were higher than that of the Pingdingshan station (0.50), whereas the NOR values of the Wuhan (0.18) and Pingdingshan (0.19) stations were higher than that of the Suizhou station (0.15). The difference in SOR and NOR among stations was affected by the secondary conversion mechanism, the ammonia-rich environment, and the surrounding traffic sources, respectively. The PM2.5 at the Wuhan and Pingdingshan stations was in general alkaline, whereas at the Suizhou station it was neutral or weakly acidic, which was mainly caused by differences in NH4+. NH4+ mainly existed in the form of (NH4)2SO4 and NH4NO3 at the Wuhan and Pingdingshan stations, whereas at the Suizhou station it mainly existed in the form of (NH4)2SO4 or (NH4)HSO4. PCA-MLR analysis revealed that the Wuhan (89.27%) and Suizhou (67.38%) stations were the most affected by secondary conversion sources, whereas the Wuhan station was also affected by industrial sources (8.54%) and coal sources (2.27%). The pollution sources of the Suizhou station also included biomass combustion (24.42%) and dust sources (8.25%). The Pingdingshan station was most affected by biomass combustion (58.37%), followed by dust and combustion sources (38.05%) and traffic sources (3.58%). The analysis of potential sources of SNA (PSCF) showed that the main potential source areas of Wuhan were the boundary of Hubei, Henan, and Anhui and the southwest area of Anhui. Suizhou and Pingdingshan were affected by long-distance transport, and the main potential source regions were distributed in Shanghai, Jiangsu, and Anhui provinces from the east coast to the west.

[Pollution and Potential Ecological Risk Assessment of Heavy Metals in Surface Sediments of Tangxun Lake].

In order to understand the pollution characteristics, spatial distribution, potential sources, and ecological risk of heavy metals in the sediments of Tangxun Lake, the contents of heavy metals (As, Hg, Cd, Cr, Cu, Pb, Zn, and Ni) in the surface sediments of Tangxun Lake were analyzed, and the pollution status and potential ecological risk degree of heavy metals in the sediments were evaluated using the geo-accumulation index and potential ecological risk index. The potential sources of heavy metal pollutants were analyzed by correlation and principal component analysis. The results showed that except for Cr, the contents of other heavy metals were higher than their background values. The contents of Hg, Cd, Zn, and Cu were higher in the southwest and northeast corners of the lake, which may come from the combined pollution of sewage discharge, fisheries, and surrounding industrial and agricultural activities. The geo-accumulation index and potential ecological risk showed that Hg and Cd were in moderate pollution; Cu, Pb, and Zn were in non-light pollution; and As, Cr, and Ni were in non-pollution. Except for Hg and Cd, there were serious and serious potential ecological risks, and the other elements were at a low risk level. The heavy metals in the surface sediments of Tangxun Lake showed a high ecological risk level.

[Characteristics and Origin Analysis of Air Pollution During the Spring Festival in Linfen, Fenwei Plain].

In recent years, frequent haze episodes have resulted in the deterioration of air quality of the Fenwei Plain during winter and holidays. Besides coal combustion and industrial emissions, the topography and climate of the Fenwei Plain were also the main causes of the haze. The samples were collected in Linfen of Fenwei Plain during the Spring Festival from February 2 to February 13, 2019. The 13 elements(Li, Be, Ti, Rb, Sc, Y, La, Ce, Zr, V, Tl, U, and Sn) in PM2.5 were determined by inductively coupled plasma mass spectrometry(ICP-MS). Combined with the meteorological data, the spatial and temporal distribution of pollutants and potential source analysis were evaluated by cluster analysis and backward trajectory. The average concentration of SO2 was 58.39 µg·m-3 during the sampling period, which exceeded the 24 h average mass concentration limit(50.00 µg·m-3) of national ambient air quality standard(GB 3095-2012). The average concentrations of O3, NO2, and CO was 52.15 µg·m-3, 29.02 µg·m-3, and 2.29 mg·m-3, respectively. The results showed that SO2 was the dominated pollutant. NO2 and CO were mainly affected by diffusion from urban areas. The backward trajectory analysis indicated that the basin topography of the Fenwei Plain may be the main cause of the haze. The analysis of potential source contribution function(PSCF) of soil sources showed that the potential dominated areas included Northern Shaanxi, southern Gansu and Southern Ningxia., which were mainly affected by the monsoon climate.

[Characteristics and Health Risk Assessment of Heavy Metals in PM2.5 Under Winter Haze Conditions in Central China: A Case Study of Huanggang, Hubei Province].

To explore the pollution characteristics and potential health risks of heavy metals in PM2.5 on haze days in Central China, PM2.5 samples were collected from the Huanggang monitoring station, a regional observation point in Central China, between January 13 and 24, 2018. The contents of Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Sn, and Pb in PM2.5 were analyzed by inductively coupled plasma mass spectrometry(ICP-MS), and the enrichment factor method was used to determine the potential risk based on the exposure model recommended by the Environmental Protection Administration(EPA). The results showed that during the observation period, the concentrations of Zn in PM2.5 were highest, and the concentrations of the carcinogens As and Cd were higher than the secondary standard limits of China's ambient air quality standard(GB 3095-2012), with 70% of these elemental concentrations accounting for the largest proportion in the middle haze period. The enrichment factor analysis showed that Cd, Sn, Co, Pb, and Zn were the most abundant elements, especially during the middle haze period, and were mostly derived from transportation and coal combustion. The results of the human health risk assessment showed that exposure via hand-mouth feeding was the main non-carcinogenic risk, and the exposure and non-carcinogenic risks of children were significantly higher than those of adults. Pb poses a non-carcinogenic risk to children, while heavy metals in PM2.5 pose no non-carcinogenic risks to adults and carcinogenic heavy metals pose no carcinogenic risks.

MYBPC2 and MYL1 as Significant Gene Markers for Rhabdomyosarcoma.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue tumor in children. Rhabdomyosarcoma commonly results in pain and bleeding caused by tumor compression and is prone to early metastasis and recurrence, which can seriously affect the therapeutic outcomes and long-term prognosis. Up to 37.7% of rhabdomyosarcomas may metastasize. Therefore, the molecular mechanisms underlying rhabdomyosarcoma must be explored to identify an effective target for its early diagnosis and specific treatment. METHODS: A dataset of 18 rhabdomyosarcoma tissue samples and 6 healthy skeletal muscle samples was downloaded. Differentially expressed genes between rhabdomyosarcoma and healthy tissue samples were identified by GEO2R. Kyoto Encyclopedia of Genes and Genomes and gene ontology pathway enrichment analyses were performed. A protein-protein interaction network was constructed, and hub genes were identified. Expression and survival analyses of hub genes were performed. Additionally, 30 patients with rhabdomyosarcoma were recruited, and overall survival information and samples were collected. Reverse transcription quantitative real-time polymerase chain reaction assays were performed to verify the expression of MYBPC2 and MYL1 in rhabdomyosarcoma tumor tissues. The Kaplan-Meier method was used to explore overall survival based on our clinical data. RESULTS: In total, 164 genes were up-regulated and 394 were down-regulated in rhabdomyosarcoma tumor tissues. Gene ontology analysis revealed that variations were predominantly enriched in the cell cycle, muscle contraction, muscle system processes, cytoskeleton, nucleotide binding, and cytoskeletal protein binding. The protein-protein interaction network revealed 3274 edges, and 441 nodes were constructed. Ten hub genes were identified; of these, MYBPC2 and MYL1 were significantly up-regulated in rhabdomyosarcoma. Compared with the healthy group, patients with rhabdomyosarcoma exhibiting high expression of MYBPC2 and MYL1 exhibited significantly worse overall survival. CONCLUSIONS: We found differentially expressed genes between rhabdomyosarcoma and healthy tissue samples. MYBPC2 and MYL1 may be involved in the pathogenesis of rhabdomyosarcoma and therefore deserve further exploration.

Erastin-induced ferroptosis is a regulator for the growth and function of human pancreatic islet-like cell clusters.

Ferroptosis is a newly identified and novel form of cell death, which is characterized by an iron- and reactive oxygen species (ROS)-dependent manner. Potential utility of ferroptotic cell death has been recently proposed for cancer treatment. Meanwhile, ROS generation and apoptosis are inherently consequent to cell apoptosis and dysfunction during islet cell preparation and transplantation. Whether ferroptosis induction is a regulator for cell viability and function in human pancreatic islet-cell clusters (ICCs) derived from pancreatic progenitor cells (PPCs) remains elusive. We thus sought to induce ferroptosis in our established cell culture system of human PPCs/ICCs, examine the effects of ferroptosis on ICCs, and explore the potential regulatory pathways involved. Our results showed that ICCs were prone to the use of ferroptosis-inducing and inhibiting agents under our culture conditions. Erastin, a ferroptosis inducer, was found to trigger ferroptosis in ICCs, without the apparent detection of other types of cell death involved, such as apoptosis and autophagy. In corroboration, the use of ferroptosis inhibitor, ferrostatin-1 (Fer-1), was found to enhance the cell viability of ICCs and prevent them from ferroptosis as well as improve its function. Mechanistically, the erastin-induced ferroptosis in ICCs was probably mediated via activation of JNK/P38/MAPK pathways and upregulation of NOX4 expression. Together, our findings may provide a scientific basis of ferroptosis inhibition as a potential for the amelioration of ICC survival and functionality during islet transplantation in diabetic patients.

Neural Circuit Mechanisms That Underlie Parental Care.

In mammals, parental care is essential for the survival of the young; therefore, it is vitally important to the propagation of the species. These behaviors, differing between the two sexes, are innate, stereotyped, and are also modified by an individual's reproductive experience. These characteristics suggest that neural mechanisms underlying parental behaviors are genetically hardwired, evolutionarily conserved as well as sexually differentiated and malleable to experiential changes. Classical lesion studies on neural control of parental behaviors, mostly done in rats, date back to the 1950s. Recent developments of new methods and tools in neuroscience, which allow precise targeting and activation/inhibition of specific populations of neurons and their projections to different brain structures, have afforded fresh opportunities to dissect and delineate the detailed neural circuit mechanisms that govern distinct components of parental behaviors in the genetically tractably organism, the laboratory mouse (Mus musculus). In this review, we summarize recent discoveries using modern neurobiological tools within the context of traditional lesion studies. In addition, we discuss interesting cross talk between neural circuits that govern parent care with those that regulate other innate behaviors such as feeding and mating.

Isolation and identification of two new compounds from the Penicillium sp. SYPF7381.

Two new compounds, (7R, 2E, 5E)-3,5,7-trimethyl-2,5-octadienedioic-8-methyl ester (1) and neovasipyridone G (3), together with a new natural product compound (7R,2E,5E)-3,5,7-trimethyl-2,5-octadienedioic acid (2), and six known compounds (4-9) were isolated from Penicillium sp. SYPF7381. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 2 were determined by optical rotation. The absolute configuration of compound 3 was determined by means of electronic circular dichroism (ECD) calculation. In addition, the in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. Furthermore, the structure-antiinflammation activity relationships for these isolated compounds were summarized based on the experimental as well as the docking results.

Fibroblast growth factor 21 protects against lipotoxicity-induced pancreatic ß-cell dysfunction via regulation of AMPK signaling and lipid metabolism.

Fibroblast growth factor 21 (FGF21) is known as a potent metabolic regulator but its protective mechanisms against lipotoxicity-induced ß-cell dysfunction and apoptosis remain elusive. Here, we aimed to examine the regulatory pathways whereby FGF21 mediates islet lipid metabolism in lipotoxicity-treated cells and animal models. Rat ß-cell line (INS-1E cells) and islets isolated from C57/BL6J mice were exposed to palmitic acid (PA) with/without FGF21, mimicking lipotoxic conditions. Resultant insulin secretion and intracellular signaling were analyzed with Western blotting and RNA-seq. C57/BL6J and global FGF21 knockout (KO) mice were fed with a high-fat diet (HFD) to induce lipotoxicity and given with a long-acting mimetic of FGF21. Insulin resistance and ß-cell function were then assessed using homeostasis model assessment of insulin resistance (HOMA-IR) and insulinogenic index. FGF21 ameliorated PA-induced lipid accumulation, reversed cell apoptosis, and enhanced glucose-stimulated insulin secretion (GSIS) as impaired by lipotoxicity in islet ß-cells. Mechanistically, FGF21 exerted its beneficial effects through activation of AMPK-ACC (acetyl-CoA carboxylase) pathway and peroxisome proliferation-activated receptors (PPARs) δ/γ signaling, thus increasing the levels of carnitine palmitoyltransferase-1A (CPT1A) and leading to increased fatty acid (FA) oxidation and reduced lipid deposition in ß-cells. Interestingly, FGF21 reduced PA-induced cell death via restoration of the expression of apoptosis inhibitor Birc3. In vivo studies further showed that FGF21 is critical for islet insulinogenic capacity and normal function in the context of HFD-treated animals. FGF21 down-regulates islet cell lipid accumulation, probably via activation of AMPK-ACC and PPARδ/γ signaling, and reduces cell death under lipotoxicity, indicating that FGF21 is protective against lipotoxicity-induced ß-cell dysfunction and apoptosis.

Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promote the Proliferation and Differentiation of Pancreatic Progenitor Cells and the Engraftment Function of Islet-Like Cell Clusters.

Pancreatic progenitor cells (PPCs) are the primary source for all pancreatic cells, including beta-cells, and thus the proliferation and differentiation of PPCs into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Meanwhile, mesenchymal stem cells (MSCs) can enhance the development and function of different cell types of interest, but their role on PPCs remains unknown. We aimed to explore the mechanism-of-action whereby MSCs induce the in vitro and in vivo PPC/ICC development by means of our established co-culture system of human PPCs with human fetal bone marrow-derived MSCs. We examined the effect of MSC-conditioned medium on PPC proliferation and survival. Meanwhile, we studied the effect of MSC co-culture enhanced PPC/ICC function in vitro and in vivo co-/transplantation. Furthermore, we identified IGF1 as a critical factor responsible for the MSC effects on PPC differentiation and proliferation via IGF1-PI3K/Akt and IGF1-MEK/ERK1/2, respectively. In conclusion, our data indicate that MSCs stimulated the differentiation and proliferation of human PPCs via IGF1 signaling, and more importantly, promoted the in vivo engraftment function of ICCs. Taken together, our protocol may provide a mechanism-driven basis for the proliferation and differentiation of PPCs into clinically transplantable islets.

Morphologies Transformation of BODIPY-Based Main Chain Supramolecular Polymers Amphiphiles: From Helical Nanowires to Nanosheets.

The aggregate morphologies of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) main chain supramolecular polymer amphiphiles (SPA) are tunable by a fine balance of different non-covalent interactions. When the BODIPY segments and sodium cholate are mixed in aqueous solution, they form SPA by electrostatic attraction and hydrogen-bonds. This SPA displays helical nanowires' morphology. After the third component dimeric ß-cyclodextrin (ß-CD-C) is added, the hydrogen bonds between the cholate are substituted by the host-guest interaction between cholate and ß-CD-C. Therefore, these SPA transform their aggregate morphologies into nanosheets' architecture. Therefore, a simple and effective way to regulate self-assembly by non-covalent forces is developed. This supramolecular method may provide an effective way to prepare various nanostructures in aqueous solution and show promising application in the future.

The bis-dimethylfluoreneaniline organic dye sensitizers for solar cells: A theoretical study and design.

Development of novel dye sensitizers with suitable optoelectronic properties is effective to improve the power conversion efficiency of dye-sensitized solar cells (DSSCs). Considering the effectiveness of conjugate bridges in modification of optoelectronic properties, based on the dye sensitizers C201, C203, C204 and C205, five kinds of organic dye sensitizers are designed with different thiophene-based moieties and the functionalized graphene flakes (GFs) as conjugate bridges. The performances of these dye sensitizers are analyzed in terms of the calculated geometries, electronic structures and excitation properties. The transition configurations and molecular orbitals of dye sensitizers suggest that bis-dimethylfluoreneaniline is effective electron donor, and the transitions of optical absorption in visible region are charge transfer excitations. The conjugate lengths, energy level alignments, light harvesting capabilities, excitation character, and transition properties, as well as the free energy variations for electron injection and dye regeneration support that the designed dye sensitizers are effective to be applied in DSSCs. Particularly, introducing the functionalized GF into conjugate bridges significantly elongate conjugate length, reduce orbital energy gap, lead to denser distribution of orbital energy, generate red-shift of absorption spectra, enhance light harvesting capability, increase absorption bands and coefficients. Therefore, introducing the functionalized GF into conjugate bridges is effective, and the designed panchromatic dye sensitizer C20x-GF-BTD must be better than other designed dye sensitizers for DSSCs.

AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building.

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.