Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

Morphological and Phylogenetic Analyses Reveal Three New Species of Entomopathogenic Fungi Belonging to Clavicipitaceae (Hypocreales, Ascomycota).

This study aims to report three new species of Conoideocrella and Moelleriella from Yunnan Province, Southwestern China. Species of Conoideocrella and Moelleriella parasitize scale insects (Coccidae and Lecaniidae, Hemiptera) and whiteflies (Aleyrodidae, Hemiptera). Based on the phylogenetic analyses of the three-gene nrLSU, tef-1α, and rpb1, it showed one new record species (Conoideocrella tenuis) and one new species (Conoideocrella fenshuilingensis sp. nov.) in the genus Conoideocrella, and two new species, i.e., Moelleriella longzhuensis sp. nov. and Moelleriella jinuoana sp. nov. in the genus Moelleriella. The three new species were each clustered into separate clades that distinguished themselves from one another. All of them were distinguishable from their allied species based on their morphology. Morphological descriptions, illustrations, and comparisons of the allied taxa of the four species are provided in the present paper. In addition, calculations of intraspecific and interspecific genetic distances were performed for Moelleriella and Conoideocrella.

The G932C mutation of chitin synthase 1 gene (CHS1) mediates buprofezin resistance as confirmed by CRISPR/Cas9-mediated knock-in approach in the brown planthopper, Nilaparvata lugens.

The brown planthopper (Nilaparvata lugens) is a major destructive rice pest in Asia. High levels of insecticide resistance have been frequently reported, and the G932C mutation in the chitin synthase 1 (CHS1) gene has been found to mediate buprofezin resistance. However, there has been no direct evidence to confirm the functional significance of the single G932C substitution mutation leading to buprofezin resistance in N. lugens. Here, we successfully constructed a knock-in homozygous strain (Nl-G932C) of N. lugens using CRISPR/Cas9 coupled with homology-directed repair (HDR). Compared with the background strain susceptible to buprofezin (Nl-SS), the knock-in strain (Nl-G932C) showed a 94.9-fold resistance to buprofezin. Furthermore, resistant strains (Nl-932C) isolated from the field exhibited a 2078.8-fold resistance to buprofezin, indicating that there are other mechanisms contributing to buprofezin resistance in the field. Inheritance analysis showed that the resistance trait is incomplete dominance. In addition, the Nl-G932C strain had a relative fitness of 0.33 with a substantially decreased survival rate, emergence rate, and fecundity. This study provided in vivo functional evidence for the causality of G932C substitution mutation of CHS1 with buprofezin resistance and valuable information for facilitating the development of resistance management strategies in N. lugens. This is the first example of using CRISPR/Cas9 gene-editing technology in a hemipteran insect to directly confirm the role of a candidate target site mutation in insecticide resistance.

Research of the dynamic regulatory mechanism of Compound Danshen Dripping Pills on myocardial infarction based on metabolic trajectory analysis.

BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely. PURPOSE: It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process. METHODS: The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology. RESULTS: CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids. CONCLUSION: The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.

Synthesis and Preclinical Evaluation of Novel 68Ga-DOTA-RBB as Potential PET Radiotracer for Imaging CDK4/6 in Tumors.

Many malignant tumors, including breast cancer, exhibit amplification and overexpression of cyclin-dependent kinase 4 and 6 (CDK4/6). Ribociclib, approved and used in clinical treatment, acts as a highly selective CDK4/6 inhibitor for ER+/HER2- breast cancer. By modifying ribociclib with the chelator DOTA, we designed and synthesized a novel CDK4/6-positive PET imaging agent, which was radiolabeled by 68Ga for radioactive tagging. The radiotracer demonstrates high radiochemical purity, excellent stability in vitro and in vivo, and favorable pharmacokinetic characteristics. Cell uptake experiments using MCF-7 cells indicate that an excess of ribociclib (RBB) can inhibit cellular uptake of 68Ga-DOTA-RBB. Imaging and biodistribution experiments in MCF-7 tumor-bearing nude mice show significant radioactive accumulation in the tumor. However, preadministration of excess ribociclib results in a substantial reduction in radioactive accumulation within the tumor. On the basis of our explorations, 68Ga-DOTA-RBB, as a targeted imaging agent for CDK4/6-positive tumors, holds significant potential application values.

High percentage of bone marrow CD8+ tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia.

Tissue-resident memory T (TRM) cells infiltrating solid tumors could influence tumor progression and the response to immune therapies. However, the proportion and prognostic value of TRM cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) are unclear. In this study, we used flow cytometry to assay the phenotype of 49 BM samples from patients newly diagnosed with AML (ND-AML). We found that the BM CD8+ effector memory (TEM) cells highly expressed CD69 (CD8+ TRM-like T cells), and their percentage was significantly increased in patients with ND-AML compared with that in healthy individuals (HI). The high percentage of CD8+ TRM-like subset was associated with poor overall survival in our ND-AML cohort. The Kaplan-Meier Plotter database verified a significantly reduced survival rate among patients with high expression of CD8+ TRM-like T cell characteristic genes (CD8A, CD69, and TOX), especially the M4 and M5 subtypes. Phenotypic analysis revealed that the BM CD8+ TRM-like subpopulation exhibited exhausted T cell characteristics, but its high expression of CD27 and CD28 and low expression of CD57 suggested its high proliferative potential. The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8+ T cells in the BM of patients with AML and verified the high expression of immune checkpoints and costimulatory molecules. In conclusion, we found that the accumulation of BM CD8+ TRM-like cells could be an immune-related survival prediction marker for patients with AML.

Treatment of Morganella morganii-Associated Non-healing Diabetic Foot Ulcer With Vaporous Hyperoxia Therapy: A Case Report.

Diabetic foot ulcers represent a significant complication of diabetes mellitus, characterized by mechanical changes of bony architecture often leading to chronic wounds with increased risk of infection and impaired healing. Morganella morganii, a Gram-negative bacterium, is one of the pathogens found in infected diabetic foot ulcers. It is a human gastrointestinal commensal organism that may cause widespread deadly infections. This report discusses the case of a 76-year-old male with diabetes mellitus who presented with M. morganii diabetic foot ulcer to an in-patient rehabilitation facility. Despite conventional wound care and antibiotic therapy, the ulcer failed to improve. The management approach for this patient consisted of a rehabilitation modality called Vaporox, a machine that utilizes vaporous hyperoxia therapy (VHT), as it combines ultrasonic mist and high concentration of oxygen to fasten revascularization and healing. This case highlights the potential efficacy of VHT as an adjunctive therapy for the management of diabetic foot ulcers, particularly those complicated by pathogens, such as M. morganii.

Pd(II)/N,N'-Disulfonyl Bisimidazoline-Catalyzed Enantioselective Synthesis of Cyclic Quaternary Centers and Mechanistic Investigations.

A Pd(II)/N,N'-disulfonyl bisimidazoline-catalyzed asymmetric 1,4-conjugate addition reaction of low-cost arylboronic acids with readily available ß-substituted cyclic enones is described, providing a straightforward way of constructing cyclic all-carbon quaternary stereocenters with high enantioselectivity, in which ≥96% ee was obtained in most cases. The reaction proceeded without the protection of inert gas, making the operation process simple. Theoretical calculations have been applied to understand the origins of enantioselectivity.

[Spatio-temporal Evolution and Prediction of Carbon Storage in Huaibei City Based on InVEST-PLUS Model].

This study aimed to investigate the impact of spatiotemporal changes in land use on ecosystem carbon storage. The study analyzed the spatiotemporal changes in carbon storage in the study area based on land use data from five periods (1985, 1995, 2005, 2015, and 2020) using the InVEST model. The PLUS model was used to predict land use changes in the study area under four different scenarios (natural development, farmland protection, ecological protection, and double protection of farmland and ecology) in 2035, and the ecosystem carbon storage under different scenarios was estimated. The results of the study indicated that the farmland in the area under investigation had been decreasing consistently from 1985 to 2020, with a more rapid rate of change observed between 2015 and 2020. During this period, the overall dynamic attitude towards land use reached 34.62 %. Additionally, the carbon storage in the area showed a decreasing trend over the years, with a decrease of 1.55×105 t from 1985 to 2020. Between 2005 and 2015, the carbon storage showed a decrease of 1.22×105 t, with an average annual decrease of 1.22×104 t. The areas with higher carbon storage were located in the eastern part of the study area, whereas areas with lower carbon storage were found in the central and northwestern parts. Although the proportion of carbon storage in farmland decreased from 66.89 % to 57.73 %, farmland remained the most important carbon pool in the study area. The conversion of other land use types to grassland and forestland was advantageous for increasing ecosystem carbon storage. Finally, the study projected that by 2035, the carbon storage in the natural development scenario, the farmland protection scenario, the ecological protection scenario, and the dual protection scenario would be 81.77×105, 82.45×105, 82.82×105, and 82.51×105 t, respectively.

BiU-net: A dual-branch structure based on two-stage fusion strategy for biomedical image segmentation.

BACKGROUND AND OBJECTIVE: Computer-based biomedical image segmentation plays a crucial role in planning of assisted diagnostics and therapy. However, due to the variable size and irregular shape of the segmentation target, it is still a challenge to construct an effective medical image segmentation structure. Recently, hybrid architectures based on convolutional neural networks (CNNs) and transformers were proposed. However, most current backbones directly replace one or all convolutional layers with transformer blocks, regardless of the semantic gap between features. Thus, how to sufficiently and effectively eliminate the semantic gap as well as combine the global and local information is a critical challenge. METHODS: To address the challenge, we propose a novel structure, called BiU-Net, which integrates CNNs and transformers with a two-stage fusion strategy. In the first fusion stage, called Single-Scale Fusion (SSF) stage, the encoding layers of the CNNs and transformers are coupled, with both having the same feature map size. The SSF stage aims to reconstruct local features based on CNNs and long-range information based on transformers in each encoding block. In the second stage, Multi-Scale Fusion (MSF), BiU-Net interacts with multi-scale features from various encoding layers to eliminate the semantic gap between deep and shallow layers. Furthermore, a Context-Aware Block (CAB) is embedded in the bottleneck to reinforce multi-scale features in the decoder. RESULTS: Experiments on four public datasets were conducted. On the BUSI dataset, our BiU-Net achieved 85.50 % on Dice coefficient (Dice), 76.73 % on intersection over union (IoU), and 97.23 % on accuracy (ACC). Compared to the state-of-the-art method, BiU-Net improves Dice by 1.17 %. For the Monuseg dataset, the proposed method attained the highest scores, reaching 80.27 % and 67.22 % for Dice and IoU. The BiU-Net achieves 95.33 % and 81.22 % Dice on the PH2 and DRIVE datasets. CONCLUSIONS: The results of our experiments showed that BiU-Net transcends existing state-of-the-art methods on four publicly available biomedical datasets. Due to the powerful multi-scale feature extraction ability, our proposed BiU-Net is a versatile medical image segmentation framework for various types of medical images. The source code is released on (https://github.com/ZYLandy/BiU-Net).

AdaDFKD: Exploring adaptive inter-sample relationship in data-free knowledge distillation.

In scenarios like privacy protection or large-scale data transmission, data-free knowledge distillation (DFKD) methods are proposed to learn Knowledge Distillation (KD) when data is not accessible. They generate pseudo samples by extracting the knowledge from teacher model, and utilize above pseudo samples for KD. The challenge in previous DFKD methods lies in the static nature of their target distributions and they focus on learning the instance-level distributions, causing its reliance on the pretrained teacher model. To address above concerns, our study introduces a novel DFKD approach known as AdaDFKD, designed to establish and utilize relationships among pseudo samples, which is adaptive to the student model, and finally effectively mitigates the aforementioned risk. We achieve this by generating from "easy-to-discriminate" samples to "hard-to-discriminate" samples as human does. We design a relationship refinement module (R2M) to optimize the generation process, wherein we learn a progressive conditional distribution of negative samples and maximize the log-likelihood of inter-sample similarity of pseudosamples. Theoretically, we discover that such design of AdaDFKD both minimize the divergence and maximize the mutual information between the distribution of teacher and student models. Above results demonstrate the superiority of our approach over state-of-the-art (SOTA) DFKD methods across various benchmarks, teacher-student pairs, and evaluation metrics, as well as robustness and fast convergence.

AMPA receptor potentiation alleviates NLRP3 knockout-induced fear generalization in mice.

Genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome enhances the extinction of contextual fear memory, which is attributed to its role in neuronal and synaptic dysregulation, concurrent with neurotransmitter function disturbances. This study aimed to determine whether NLRP3 plays a role in generalizing fear via the inflammatory axis. We established the NLRP3 KO mice model, followed by behavioral and biochemical analyses. The NLRP3 KO mice displayed impaired fear generalization, lower neuroinflammation levels, and dysregulated neurotransmitter function. Additionally, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not the inhibition of NMDA or 5-HT2C receptors, resulted in fear generalization in NLRP3 KO mice because TAT-GluA2 3Y, but not SB242084 and D-cycloserine, treated blocked NLRP3 deprivation effects on fear generalization. Thus, global knockout of NLRP3 is associated with aberrant fear generalization, possibly through AMPA receptor signaling.

An unexpected role of EasDaf: catalyzing the conversion of chanoclavine aldehyde to chanoclavine acid.

Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasDaf or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasDaf not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. KEY POINTS: • EAs possess complicated skeletons and are widely used in several clinical diseases • EasDaf belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid • The catalytic mechanism of EasDaf for dehydrogenation was analyzed by molecular docking and site mutations.

In Situ Species Analysis of a Lithium-Ion Battery Electrolyte Containing LiTFSI and Propylene Carbonate.

In this study, we analyzed the species in a model electrolyte consisting of a lithium salt, lithium bis(trifluoromethane sulfone)imide (LiTFSI), and a widely used neutral solvent propylene carbonate (PC) with excess infrared (IR) spectroscopy, ab initio molecular dynamics simulations (AIMD), and quantum chemical calculations. Complexing species including the charged ones [Li+(PC)4, TFSI-, TFSI-(PC), TFSI-(PC)2, and Li(TFSI)2-] are identified in the electrolyte. Quantum chemical calculations show strong Li+···O(PC) interaction, which suggests that Li+ would transport in the mode of solvation-carriage. However, the interaction energy of each hydrogen bond in TFSI-(PC) is very weak, suggesting that TFSI- would transport in hopping mode. In addition, the concentration dependences of the relative population of the species were also derived, providing a scenario for the dissolving process of the salt in PC. These in-depth studies provide physical insights into the structural and interactive properties of the electrolyte of lithium-ion batteries.

Green and Efficient Extraction of Phenolic Components from Plants with Supramolecular Solvents: Experimental and Theoretical Studies.

The supramolecular solvent (SUPRAS) has garnered significant attention as an innovative, efficient, and environmentally friendly solvent for the effective extraction and separation of bioactive compounds from natural resources. However, research on the use of a SUPRAS for the extraction of phenolic compounds from plants, which are highly valued in food products due to their exceptional antioxidant properties, remains scarce. The present study developed a green, ultra-sound-assisted SUPRAS method for the simultaneous determination of three phenolic acids in Prunella vulgaris using high-performance liquid chromatography (HPLC). The experimental parameters were meticulously optimized. The efficiency and antioxidant properties of the phenolic compounds obtained using different extraction methods were also compared. Under optimal conditions, the extraction efficiency of the SUPRAS, prepared with octanoic acid reverse micelles dispersed in ethanol-water, significantly exceeded that of conventional organic solvents. Moreover, the SUPRAS method demonstrated greater antioxidant capacity. Confocal laser scanning microscopy (CLSM) images revealed the spherical droplet structure of the SUPRAS, characterized by a well-defined circular fluorescence position, which coincided with the position of the phenolic acids. The phenolic acids were encapsulated within the SUPRAS droplets, indicating their efficient extraction capacity. Furthermore, molecular dynamics simulations combined with CLSM supported the proposed method's mechanism and theoretically demonstrated the superior extraction performance of the SUPRAS. In contrast to conventional methods, the higher extraction efficiency of the SUPRAS can be attributed to the larger solvent contact surface area, the formation of more types of hydrogen bonds between the extractants and the supramolecular solvents, and stronger, more stable interaction forces. The results of the theoretical studies corroborate the experimental outcomes.

The relevance and accuracy of an AI algorithm-based descriptor on 23 facial attributes in a diverse female US population.

BACKGROUND: The response of AI in situations that mimic real life scenarios is poorly explored in populations of high diversity. OBJECTIVE: To assess the accuracy and validate the relevance of an automated, algorithm-based analysis geared toward facial attributes devoted to the adornment routines of women. METHODS: In a cross-sectional study, two diversified groups presenting similar distributions such as age, ancestry, skin phototype, and geographical location was created from the selfie images of 1041 female in a US population. 521 images were analyzed as part of a new training dataset aimed to improve the original algorithm and 520 were aimed to validate the performance of the AI. From a total 23 facial attributes (16 continuous and 7 categorical), all images were analyzed by 24 make-up experts and by the automated descriptor tool. RESULTS: For all facial attributes, the new and the original automated tool both surpassed the grading of the experts on a diverse population of women. For the 16 continuous attributes, the gradings obtained by the new system strongly correlated with the assessment made by make-up experts (r ≥ 0.80; p < 0.0001) and supported by a low error rate. For the seven categorical attributes, the overall accuracy of the AI-facial descriptor was improved via enrichment of the training dataset. However, some weaker performance in spotting specific facial attributes were noted. CONCLUSION: In conclusion, the AI-automatic facial descriptor tool was deemed accurate for analysis of facial attributes for diverse women although some skin complexion, eye color, and hair features required some further finetuning.

Progress of Clinical Studies Targeting Claudin18.2 for the Treatment of Gastric Cancer.

Claudin18.2 is a tight junction protein, highly selective, generally expressed only in normal gastric mucosal epithelial cells, which can effectively maintain the polarity of epithelial and endothelial cells, thus effectively regulating the permeability and conductance of the paracellular pathway. Abnormal expression of Claudin18.2 can occur in various primary malignant tumors, especially gastrointestinal tumors, and even in metastatic foci. It regulates its expression by activating the aPKC/MAPK/AP-1 pathway, and therefore, the Claudin18.2 protein is a pan-cancer target expressed in primary and metastatic lesions in human cancer types. Zolbetuximab (IMAB362), an antibody specific for Claudin18.2, has been successfully tested in a phase III clinical trial, and the results of the study showed that combining Zolbetuximab with chemotherapy notably extends patients' survival and is expected to be a potential first-line treatment for patients with Claudin18.2(+)/HER-2(-) gastric cancer. Here, we systematically describe the biological properties and oncogenic effects of Claudin18.2, centering on its clinical-pathological aspects and the progress of drug studies in gastric cancer, which can help to further explore its clinical value.

Catalytic (4+2) Annulation via Regio- and Enantioselective Interception of in-situ Generated Alkylgold Intermediate.

A regio- and stereoselective stepwise (4+2) annulation of N-propargylamides and α,ß-unsaturated imines/ketones has been accomplished with synergetic catalysis by a combination of a gold-complex and a chiral quinine-derived squaramide (QN-SQA), leading to highly functionalized chiral tetrahydropyridines/dihydropyrans in good to high yields with generally excellent enantioselectivity. Mechanistic studies and DFT calculations indicate that the in-situ formed alkylgold species is the key intermediate in this transformation, and the amide group served as a traceless directing group in this highly selective transformation. This method complements the enantioselective (4+2) annulation of allene reagents, providing the formal internal C-C π-bond cycloaddition products, which is challenging and remains elusive.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma: A case report.

BACKGROUND: Multiple primary carcinomas (MPCs) are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual. Synchronous MPCs are rarer than solitary cancers or metachronous MPCs. Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases. CASE SUMMARY: A 64-year-old patient presented with dysphagia, without obvious cause. A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results. After multi-disciplinary consultations, combination chemotherapy (a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14) and esophageal cancer radiotherapy were initiated. Based on the results of genetic testing, we switched to a regimen of leucovorin + fluorouracil + oxaliplatin and cetuximab regimen for 8 cycles. Subsequently, capecitabine and bevacizumab were administered until the most recent follow-up, at which the tumor remained stable. CONCLUSION: Successful cetuximab chemotherapy treatment provides a reference for the non-operative and homogeneous treatment of different pathological types of synchronous MCPs.

Desulfurdioxidative N-N Coupling of N-Arylhydroxylamines and N-Sulfinylanilines: Reaction Development and Mechanism.

A highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N-N coupling is developed. This metal free protocol employs readily accessible N-arylhydroxylamines and N-sulfinylanilines to provide highly valuable hydrazine products with good reaction yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O-sulfenylated arylhydroxylamine intermediate undergoes a retro-[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N-N bond and release SO2.