PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior.

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function. Synaptic abnormalities, such as defects in the density and morphology of postsynaptic dendritic spines, underlie the pathology of various neuropsychiatric disorders. Protocadherin 17 (PCDH17) is associated with major mood disorders, including bipolar disorder and depression. However, the molecular mechanisms by which PCDH17 regulates spine number, morphology, and behavior remain elusive. In this study, we found that PCDH17 functions at postsynaptic sites, restricting the number and size of dendritic spines in excitatory neurons. Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety- and depression-like behaviors in mice. Mechanistically, PCDH17 interacts with actin-relevant proteins and regulates actin filament (F-actin) organization. Specifically, PCDH17 binds to ROCK2, increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3 (Ser3). Inhibition of ROCK2 activity with belumosudil (KD025) ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression, suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development. Hence, these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior, providing pathological insights into the neurobiological basis of mood disorders.

Identification of agricultural surface source pollution in plain river network areas based on 3D-EEMs and convolutional neural networks.

Agricultural non-point sources, as major sources of organic pollution, continue to flow into the river network area of the Jiangnan Plain, posing a serious threat to the quality of water bodies, the ecological environment, and human health. Therefore, there is an urgent need for a method that can accurately identify various types of agricultural organic pollution to prevent the water ecosystems in the region from significant organic pollution. In this study, a network model called RA-GoogLeNet is proposed for accurately identifying agricultural organic pollution in the river network area of the Jiangnan Plain. RA-GoogLeNet uses fluorescence spectral data of agricultural non-point source water quality in Changzhou Changdang Lake Basin, based on GoogLeNet architecture, and adds an efficient channel attention (ECA) mechanism to its A-Inception module, which enables the model to automatically learn the importance of independent channel features. ResNet are used to connect each A-Reception module. The experimental results show that RA-GoogLeNet performs well in fluorescence spectral classification of water quality, with an accuracy of 96.3%, which is 1.2% higher than the baseline model, and has good recall and F1 score. This study provides powerful technical support for the traceability of agricultural organic pollution.

Research progress on the correlation between platelet aggregation and tumor progression.

Platelets are generally considered as the main functional unit of the coagulation system. However, more and more studies have confirmed that platelets also have an important relationship with tumor progression. Tumor cells can utilize platelets to promote their own infiltration and hematogenous metastasis, and platelets are activated and aggregated in this process. Therefore, platelet aggregation may be a concomitant marker of tumor progression. This is of great significance for predicting tumor metastasis before timely treatments.

A facile synthesis of highly efficient In2S3 photocatalysts for the removal of cationic dyes with size-dependent photocatalysis.

In this study, a 3D thornball-like hierarchical ß-In2S3, displaying extremely rapid photodegradation of cationic dyes, was synthesized by a facile method. The formation of a uniform thornball-like structure depended on the microwave reaction method and citric acid as the pH regulator. The size of In2S3 was easily adjusted by changing the microwave irradiation time from 5 min to 15 min. The morphology, structure, composition, energy level, charge separation, and surface properties of different-sized In2S3 were characterized. The results showed that In2S3 synthesized in 10 min (In2S3-10) displayed optimal interface property for the electron-hole separation, maximum hydrophilia with most surface negative charges for the surface adsorption, contributing to the complete photodegradation of rhodamine B (RhB) in just 25 minutes of visible light illumination. The photodegradation path of RhB was speculated with four possible paths, including the processes of de-ethylation, open-ring of xanthene, and rupture of carbon-carbon bonds up to the decomposition into small molecules. Finally, the reusability of In2S3-10 was tested, obtaining nearly 96% photodegradation efficiency after sequential 5 cycles.

Successful Neoadjuvant Chemotherapy for Small-Cell Neuroendocrine Carcinoma of the Pancreas: A Case Report.

Neoadjuvant therapy for pancreatic neuroendocrine tumors may potentially aid downstaging, increase the possibility of radical surgery. We herein report a case of a 63-year-old man who had been diagnosed with locally advanced small-cell neuroendocrine carcinomas of the pancreas according to the diagnostic biopsy. The patient received 6 courses of etoposide and cisplatin as neoadjuvant therapy in an attempt to stop tumor progression, which promoted obvious tumor shrinkage without adverse effects and allowed subsequent Appleby procedure, the distal pancreatectomy with celiac artery resection. The patient showed no recurrence in the follow-up of a contrast-enhanced computed tomographic scan, which is 8 months after surgery. To the best of our knowledge, this is a rare case to report etoposide and cisplatin administration before surgery for unresectable pancreatic neuroendocrine carcinoma promoted a pathological partial response and finally achieved a radical surgery, providing a novel therapeutic option for patients with locally advanced pancreatic neuroendocrine carcinoma.

Pancreatic ductal adenocarcinoma immune microenvironment and immunotherapy prospects.

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.

2,7-Dibromo-9,9-dimethyl-9H-fluorene.

The title mol-ecule, C(15)H(15)Br(2), has crystallographic m2m site symmetry. As a result, all atoms, except for those of the methyl groups, are exactly coplanar. In the crystal structure, there are weak π-π inter-actions with a centroid-centroid distance of 3.8409 (15) Šbetween symmetry-related mol-ecules, which stack along the c axis.

1-O-vinyl glycosides via Tebbe olefination, their use as chiral auxiliaries and monomers.

A series of anomerically pure 1-O-formyl glycosides 1 was prepared and converted into the corresponding 1-O-vinyl glycosides 2 by Tebbe olefination. The unsubstituted vinyl glycosides were obtained as anomerically pure compounds in good yields, and the method of preparation was compatible with the presence of a variety of functional groups. Remarkably, the anomeric formate group was regioselectively converted into the corresponding olefin in the presence of acetate and benzoate protecting groups. With the perspective to use the 1-O-vinyl glycosides as monomers for the preparation of glycosylated poly(vinyl alcohol) derivatives with controlled tacticity, their scope as chiral auxiliaries for a stereodifferentiation in addition reactions to the olefin function was investigated by using the [2+2] cycloaddition to dichloroketene as a model reaction. In particular, vinyl 2,3,4,6-tetra-O-benzoyl-alpha-d-mannopyranoside (2i) exhibited excellent diastereoselectivity. Finally, the 1-O-vinyl glycosides were successfully subjected to radical homopolymerization in bulk or used as electron-rich comonomers in radical copolymerizations with maleic anhydride, yielding alternating, glycosylated poly(vinyl alcohol-alt-maleic anhydride).