Two three-dimensional coordination polymers as fluorescence probes for the detection of nitrobenzene, tetracycline, fluazinam and their application in green pepper.

Two coordination polymers (CPs), [Zn5(L)2(phen)5](1) and [Cd2(HL)(2,2-bpy)(H2O)3](2), were synthesized by using 2',3,3',5,5'-Diphenyl ether pentacarboxylic acid (H5L), phenanthroline (phen), and 2,2'-bipyridine (2,2'-bpy) under hydrothermal conditions. The L5- ligand adopts the µ6-к2: к2: к1: к1: к1: к1 mode in 1 and the µ5-к2: к2: к2: к2: к1 mode in 2. Sensing experiments show that 1 and 2 are fluorescence probes with high sensitivity and rapid detection of nitro explosives, antibiotics, and pesticides. In order to verify the ability of 2 to detect FLU in actual samples, we performed a spiked recovery experiment in green pepper water. The spiked recoveries were 97.77-101.18 %. Interestingly, because H5L is not completely deprotonated in 2, there is abundant hydrogen bonding, which makes the fluorescence quenching rate higher and the detection limit lower. The possible fluorescence quenching mechanism of 1 and 2 can be explained by their UV-VIS absorption spectra and orbital energy levels.

Stereo- and Regioselective Installation of Vinyl Sulfonyl Fluoride onto Indoles without Transition-Metal Catalyst.

Herein, we developed a practical method for synthesizing a class of novel and highly valuable indolyl vinyl sulfonyl fluorides. This protocol has carved out a path for constructing a broad range of vinyl sulfonyl fluorinated indoles with exclusive stereo- and regioselectivity through the Friedel-Crafts/elimination reaction without any transition-metal catalyst. This transformation features mild conditions, high efficiency, excellent selectivity, and rich substrate compatibility, highlighting its significant value in medicinal chemistry and many related disciplines.

A portal to highly valuable indole-functionalized vinyl sulfonyl fluorides and allylic sulfonyl fluorides.

A practical and efficient method for the C-3 site selective alkenylation of indoles was developed for constructing novel indole-functionalized vinyl sulfonyl fluorides and indolyl allylic sulfonyl fluorides. The reaction is accomplished with exclusive regio- and stereoselectivity without using transition metal catalysts, providing novel products of great potential value in medicinal chemistry, chemical biology, and drug discovery.

Two complete mitochondrial genomes of Boulenophrys (Anura: Megophryidae: Megophryinae): characteristics and phylogenetic implications.

The Chinese horned toads, Boulenophrys boettgeri (Boulenger, 1899) and Boulenophrys kuatunensis (Pope, 1929), are two captivating species within the family Megophryidae, which inhabit the mountainous streams in the Eastern of China. In this study, two new complete mitochondrial genomes of B. boettgeri and B. kuatunensis were sequenced, assembled, and annotated using next-generation sequencing. The length of mitochondrial genomes of B. boettgeri and B. kuatunensis was 16,597 and 17,921 bp, respectively, with both containing 13 protein coding genes, 22 tRNA genes, two rRNA genes, and one putative control region. Phylogenetic relationships based on protein-coding mitochondrial genes showed that the two Boulenophrys species formed a cluster with other Boulenophrys species. The two new sequences provide valuable insights into the mitochondrial genomes of these two species, offering important data for understanding the phylogenetic relationships of the genus Boulenophrys.

Synthesis of α-Bromo Arylethyl Sulfonyl Fluorides and ß-Arylethenesulfonyl Fluorides via Copper-Catalyzed Meerwein Arylation.

A practical copper-catalyzed process for the synthesis of the ß-arylethenesulfonyl fluorides is described. A series of α-bromo arylethyl sulfonyl fluorides was prepared via Meerwein reaction from arenediazonium tetrafluoroborates and ethenesulfonyl fluoride (ESF) under mild conditions. The following ß-arylethenesulfonyl fluorides were further obtained through a ß-elimination reaction. This protocol features excellent regio- and stereoselectivity and broad substrate scope.

Reversible Local Protonation-Deprotonation: Tuning Stimuli-Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti-Counterfeiting and Encryption.

Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli-responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)-C12H16N2)ZnBr4 ((R/S-LH2)ZnBr4) and monoprotonated ((R/S)-C12H15N2)2ZnBr4 ((R/S-LH1)2ZnBr4), derived from the chiral organic amine (R/S)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine ((R/S)-C12H14N2). These compounds showcase luminescent properties; the zero-dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo-layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation-deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation-deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli-responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications in information storage, anti-counterfeiting, and information encryption.

Altered tumor microenvironment heterogeneity of penile cancer during progression from non-lymphatic to lymphatic metastasis.

BACKGROUND: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. METHODS: In this study, using single-cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. RESULTS: The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial-mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. CONCLUSIONS: This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non-lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Predicting distant metastasis in nasopharyngeal carcinoma using gradient boosting tree model based on detailed magnetic resonance imaging reports.

BACKGROUND: Development of distant metastasis (DM) is a major concern during treatment of nasopharyngeal carcinoma (NPC). However, studies have demonstrated improved distant control and survival in patients with advanced NPC with the addition of chemotherapy to concomitant chemoradiotherapy. Therefore, precise prediction of metastasis in patients with NPC is crucial. AIM: To develop a predictive model for metastasis in NPC using detailed magnetic resonance imaging (MRI) reports. METHODS: This retrospective study included 792 patients with non-distant metastatic NPC. A total of 469 imaging variables were obtained from detailed MRI reports. Data were stratified and randomly split into training (50%) and testing sets. Gradient boosting tree (GBT) models were built and used to select variables for predicting DM. A full model comprising all variables and a reduced model with the top-five variables were built. Model performance was assessed by area under the curve (AUC). RESULTS: Among the 792 patients, 94 developed DM during follow-up. The number of metastatic cervical nodes (30.9%), tumor invasion in the posterior half of the nasal cavity (9.7%), two sides of the pharyngeal recess (6.2%), tubal torus (3.3%), and single side of the parapharyngeal space (2.7%) were the top-five contributors for predicting DM, based on their relative importance in GBT models. The testing AUC of the full model was 0.75 (95% confidence interval [CI]: 0.69-0.82). The testing AUC of the reduced model was 0.75 (95%CI: 0.68-0.82). For the whole dataset, the full (AUC = 0.76, 95%CI: 0.72-0.82) and reduced models (AUC = 0.76, 95%CI: 0.71-0.81) outperformed the tumor node-staging system (AUC = 0.67, 95%CI: 0.61-0.73). CONCLUSION: The GBT model outperformed the tumor node-staging system in predicting metastasis in NPC. The number of metastatic cervical nodes was identified as the principal contributing variable.

Netrin-1 Is an Important Mediator in Microglia Migration.

Microglia migrate to the cerebral cortex during early embryonic stages. However, the precise mechanisms underlying microglia migration remain incompletely understood. As an extracellular matrix protein, Netrin-1 is involved in modulating the motility of diverse cells. In this paper, we found that Netrin-1 promoted microglial BV2 cell migration in vitro. Mechanism studies indicated that the activation of GSK3ß activity contributed to Netrin-1-mediated microglia migration. Furthermore, Integrin α6/ß1 might be the relevant receptor. Single-cell data analysis revealed the higher expression of Integrin α6 subunit and ß1 subunit in microglia in comparison with classical receptors, including Dcc, Neo1, Unc5a, Unc5b, Unc5c, Unc5d, and Dscam. Microscale thermophoresis (MST) measurement confirmed the high binding affinity between Integrin α6/ß1 and Netrin-1. Importantly, activation of Integrin α6/ß1 with IKVAV peptides mirrored the microglia migration and GSK3 activation induced by Netrin-1. Finally, conditional knockout (CKO) of Netrin-1 in radial glial cells and their progeny led to a reduction in microglia population in the cerebral cortex at early developmental stages. Together, our findings highlight the role of Netrin-1 in microglia migration and underscore its therapeutic potential in microglia-related brain diseases.

Synthesis of highly sensitive and multi-response Eu-MOF, fluorescence sensing properties and anti-counterfeiting applications.

A new Europium metal-organic framework (Eu-MOF), namely [Eu(dpa) (H2O)]·0.5(bpy)·4H2O}n (H4dpa = 5-(3,4-dicarboxyphenoxy) isophenic acid, bpy = protonated 4,4'-bipyridine) was synthesized and structurally characterized by elemental analyses, infrared spectroscopy, and X-ray single-crystal diffraction analyses. Eu-MOF shows a three-dimensional network structure based on EuIII ions and (dpa)4- ligands via µ4: η1, η2, η2, η2 coordination mode. Fluorescence analysis shows that Eu-MOF has excellent fluorescence sensing characteristics, which can efficiently and sensitively detect various pollutants in water: the limit of detection (LOD) of ratiometric fluorescence detection of ANI in water was 42.9 nM, which was better than the single-peak detection limit. In addition, the peak detection limits of Eu-MOF for Flu, ORN and NB were 120 nM, 27 nM and 94 nM, respectively. In addition, XPS, LUMO orbital energy level, fluorescence lifetime, ultraviolet absorption and other principles are used to explore the mechanism of fluorescence quenching. Surprisingly, Eu-MOF not only has excellent anti- counterfeiting ability and stability, can be used as anti-counterfeiting material in life, but also has good selectivity to Flu. Eu-MOF has obvious fluorescence quenching effect on Flu on paper under ultraviolet light, which can be used for rapid in situ imaging test paper of pesticide residues.

Rapid Selection of Patients Suitable for Deep Inspiration Breath-Hold Using an Automatic Delineating System and RapidPlan Model in Patients With Left Breast Cancer Undergoing Adjuvant Radiation Therapy With IMRT.

PURPOSE: This study aimed to determine whether radiation therapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH) in patients with left breast cancer. METHODS AND MATERIALS: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104 of 136 plans were selected for RP model training. A total of 32 of 136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. RESULTS: Two RP models were established for post-breast-conserving surgery (BCS) and post-modified radical mastectomy. There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the 2 plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < .05) and moderately correlated in patients after postmodified radical mastectomy (0.46 ≤ r ≤ 0.58, P <.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the 2 surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. CONCLUSIONS: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH.

A protocol for hydrogenation of aldehydes and ketones to alcohols in aqueous media at room temperature in high yields and purity.

In this paper, the hydrogenation of aldehydes and ketones using the RANEY® nickel catalyst was successfully applied for the synthesis of alcohol compounds without additional column chromatographic purification. This synthetic strategy features a wide range of substrates, excellent atom economy, high chemical discrimination and the use of a ligand-free catalytic system. Reactions were performed at room temperature in water providing alcohols in high yields and purity.

A fluorescent terbium-metal-organic framework material for high-sensitivity detection of vomitoxin and oxytetracycline hydrochloride in water.

A unique luminescent lanthanide metal-organic framework (LnMOF)-based fluorescence detection platform was utilized to achieve sensitive detection of vomitoxin (VT) and oxytetracycline hydrochloride (OTC-HCL) without the use of antibodies or biomolecular modifications. The sensor had a fluorescence quenching constant of 9.74 × 106 M-1 and a low detection limit of 0.68 nM for vomitoxin. Notably, this is the first example of a Tb-MOF sensor for fluorescence detection of vomitoxin. We further investigated its response to two mycotoxins, aflatoxin B1 and ochratoxin A, and found that their Stern-Volmer fluorescence quenching constants were lower than those of VT. In addition, the fluorescence sensor realized sensitive detection of OTC-HCL with a detection limit of 0.039 µM. In conclusion, the method has great potential as a sensitive and simple technique to detect VT and OTC-HCL in water.

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

Comparative study of reactive oxygen species and tetracycline degradation pathways in catalytic peroxodisulfate activation by asymmetric mesoporous TiO2 and the corresponding controlled-release materials.

The removal of trace amounts of antibiotics from water environments while simultaneously avoiding potential environmental hazards during the treatment is still a challenge. In this work, green, harmless, and novel asymmetric mesoporous TiO2 (A-mTiO2) was combined with peroxodisulfate (PDS) as active components in a controlled-release material (CRM) system for the degradation of tetracycline (TC) in the dark. The formation of reactive oxygen species (ROS) and the degradation pathways of TC during catalytic PDS activation by A-mTiO2 powder catalysts and the CRMs were thoroughly studied. Due to its asymmetric mesoporous structure, there were abundant Ti3+/Ti4+ couples and oxygen vacancies in A-mTiO2, resulting in excellent activity in the activation of PDS for TC degradation, with a mineralization rate of 78.6%. In CRMs, ROS could first form during PDS activation by A-mTiO2 and subsequently dissolve from the CRMs to degrade TC in groundwater. Due to the excellent performance and good stability of A-mTiO2, the resulting constructed CRMs could effectively degrade TC in simulated groundwater over a long period (more than 20 days). From electron paramagnetic resonance analysis and TC degradation experiments, it was interesting to find that the ROS formed during PDS activation by A-mTiO2 powder catalysts and CRMs were different, but the degradation pathways for TC were indeed similar in the two systems. In PDS activation by A-mTiO2, besides the free hydroxyl radical (·OH), singlet oxygen (1O2) worked as a major ROS participating in TC degradation. For CRMs, the immobilization of A-mTiO2 inside CRMs made it difficult to capture superoxide radicals (·O2-), and continuously generate 1O2. In addition, the formation of sulfate radicals (·SO4-), and ·OH during the release process of CRMs was consistent with PDS activation by the A-mTiO2 powder catalyst. The eco-friendly CRMs had a promising potential for practical application in the remediation of organic pollutants from groundwater.

A mild protocol for efficient preparation of functional molecules containing triazole.

The construction of a class of novel triazole molecules containing sulfonyl fluoride functionalities was achieved through Cu-catalyzed click chemistry in good to excellent yields. The sulfonyl fluoride moieties were cleaved completely under base conditions to produce N-unsubstituted triazoles quantitatively, which provides a strategy to combine SuFEx click chemistry with Cu-catalyzed click chemistry ingeniously.

PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.

[Trametenolic acid inhibits migration and invasion of hepatocellular carcinoma HepG2.2.15 cells via RhoC/ROCK1 pathway].

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.

The Segmentation of Multiple Types of Uterine Lesions in Magnetic Resonance Images Using a Sequential Deep Learning Method with Image-Level Annotations.

Fully supervised medical image segmentation methods use pixel-level labels to achieve good results, but obtaining such large-scale, high-quality labels is cumbersome and time consuming. This study aimed to develop a weakly supervised model that only used image-level labels to achieve automatic segmentation of four types of uterine lesions and three types of normal tissues on magnetic resonance images. The MRI data of the patients were retrospectively collected from the database of our institution, and the T2-weighted sequence images were selected and only image-level annotations were made. The proposed two-stage model can be divided into four sequential parts: the pixel correlation module, the class re-activation map module, the inter-pixel relation network module, and the Deeplab v3 + module. The dice similarity coefficient (DSC), the Hausdorff distance (HD), and the average symmetric surface distance (ASSD) were employed to evaluate the performance of the model. The original dataset consisted of 85,730 images from 316 patients with four different types of lesions (i.e., endometrial cancer, uterine leiomyoma, endometrial polyps, and atypical hyperplasia of endometrium). A total number of 196, 57, and 63 patients were randomly selected for model training, validation, and testing. After being trained from scratch, the proposed model showed a good segmentation performance with an average DSC of 83.5%, HD of 29.3 mm, and ASSD of 8.83 mm, respectively. As far as the weakly supervised methods using only image-level labels are concerned, the performance of the proposed model is equivalent to the state-of-the-art weakly supervised methods.