Divergent and Multi-Stage Photoisomerization of Four-Coordinated Boron Compounds with a Naphthyl-Pyridyl/Thiazolyl Backbone.

Examination of the photoreactivity of a new class of N,C-chelate organoboron compounds, including a series of unsymmetrically substituted boron molecules, B(naph-pyridyl)(Ar1 )(Ar2 ) and B(naph-thiazolyl)(Ar1 )(Ar2 ), led to the discovery of new and divergent photothermal isomerization phenomena. These include the clean and regioselective photoisomerization by unsymmetrical boron, forming borepin isomers, some of which further isomerize to the corresponding boratanorcaradiene diastereomer pairs as a result of the generation of two chiral centers. Significantly, the boratanorcaradienes involving a 3-thienyl substituent on boron were found to thermally convert to BN-fluoranthene annulated borapentalene via an unprecedented reversible boratacyclopropane-boratacyclopentene rearrangement. Changing the pyridyl donor to a thiazolyl donor on the boron was found to provide the B(naph-thiazolyl)(Mes)2 compounds with a distinct new photoisomerization pathway-instead of borepin, forming new blue fluorescent polycyclic azaborinine species. This work illustrates the richness and complexity of boron photochemistry.

Single-Cell-Derived Tumor-Sphere Formation and Drug-Resistance Assay Using an Integrated Microfluidics.

Considerable evidence points to cancer stem-like cells (CSCs) as responsible for promoting progression, metastasis, and drug resistance. Without damage to the cell biological properties, single-cell-derived tumor-sphere is encouraging options for CSCs identification and studies. Although several single cell-based microfluidic methods have been developed for CSCs studies, clarifying liaison between the biomechanics of cells (such as size and deformability) and stem (such as tumor-sphere formation and drug resistance) remains challenging. Herein, we present a platform of integrated microfluidics for the analysis of single-cell-derived tumor-sphere formation and drug resistance. Tumor-spheres derived from different biomechanics (size and/or deformation) single-cells could be formed efficiently using this device. To demonstrate the microfluidic-platform capability, a proof-of-concept experiment was implemented by evaluating single-cell-derived sphere formation of single glioblastoma cells with different biomechanics. Additionally, a course of chemotherapy to study these single-cell-derived spheres was determined by coculture with vincristine. The results indicate that tumor cell biomechanics is associated with single-cell-derived spheres formation; that is, smaller and/or more deformable tumor cells are more stem-like defined by the formation of single-cell-derived spheres than more prominent and/or lesser deformable tumor cells. Also, tumor-spheres derived from single small and/or more deformable tumor cell have higher drug resistance than more prominent and/or less deformable tumor cells. Our device offers a new approach for single-cell-derived sphere formation according to tumor cell different biomechanical properties. Furthermore, it offers a new method for CSC identification and downstream analysis on a single-cell level.

Constraints on novel word learning in heritage speakers.

Introduction: Recent research on word learning has found that adults can rapidly learn novel words by tracking cross-situational statistics, but learning is greatly influenced by the phonological properties of the words and by the native language of the speakers. Mandarin-native speakers could easily pick up novel words with Mandarin tones after a short exposure, but English-native speakers had specific difficulty with the tonal components. It is, however, unclear how much experience with Mandarin is needed to successfully use the tonal cue in word learning. In this study, we explored this question by focusing on the heritage language population, who typically are exposed to the target language at an early age but then develop and switch to another majority language. Specifically, we investigated whether heritage Mandarin speakers residing in an English-speaking region and speaking English as a dominant language would be able to learn novel Mandarin tonal words from statistical tracking. It helps us understand whether early exposure to the target feature is sufficient to promote the use of that feature in word learning later in life. Methods: We trained 30 heritage Mandarin speakers with Mandarin pseudowords via a cross-situational statistical word learning task (CSWL). Results and discussion: Heritage Mandarin speakers were able to learn the pseudowords across multiple situations, but similar-sounding words (i.e., minimal pairs) were more difficult to identify, and words that contrast only in lexical tones (i.e., Mandarin lexical tone) were distinguished at chance level throughout learning. We also collected information about the participants' heritage language (HL) experience and usage. We did not observe a relationship between HL experience/usage and performance in tonal word learning, suggesting that HL exposure does not necessarily lead to an advantage in learning the target language.

A Spatiotemporally Controlled and Mitochondria-Targeted Prodrug of Hydrogen Sulfide Enables Mild Mitochondrial Uncoupling for the Prevention of Lipid Deposition.

Mild mitochondrial uncoupling offers therapeutic benefits for various diseases like obesity by regulating cellular energy metabolism. However, effective chemical intervention tools for inducing mild mitochondria-targeted uncoupling are limited. Herein, we have developed a mitochondria-targeted H2S prodrug M1 with a unique property of on-demand photoactivated generation of H2S accompanied by self-reporting fluorescence for real-time tracking. Upon photoirradiation, M1 decomposes in mitochondria to generate H2S and a turn-on fluorescent coumarin derivative for the visualization and quantification of H2S. M1 is confirmed to induce reactive oxygen species (ROS)-dependent mild mitochondrial uncoupling, activating mitochondria-associated adenosine monophosphate-activated protein kinase (AMPK) to suppress palmitic acid (PA)-induced lipid deposition in hepatocytes. The uncoupling functions induced by M1 are strictly controlled in mitochondria, representing a fresh strategy to prevent lipid deposition and improve metabolic syndrome by increasing cellular energy expenditure.

The hippocampal salt-inducible kinase 2-CREB-regulated transcription co-activator 1 system mediates the antidepressant actions of paroxetine in mice.

The hippocampal salt-inducible kinase 2 (SIK2)-CREB-regulated transcription co-activator 1 (CRTC1) system has been demonstrated to participate in not only the pathogenesis of depression but also the antidepressant mechanisms of several antidepressant medications including fluoxetine, paroxetine, and mirtazapine. Like fluoxetine, paroxetine is also a widely used selective serotonin (5-HT) reuptake inhibitor (SSRI). Recent studies have indicated that paroxetine also modulates several pharmacological targets other than the 5-HT system. Here, we speculate that paroxetine regulates the hippocampal SIK2-CRTC1 system. Chronic stress models of depression, various behavioral tests, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription PCR, and genetic knockdown were used together in the present study. Our results show that the antidepressant actions of paroxetine in mice models of depression were accompanied by its preventing effects against chronic stress on hippocampal SIK2, CRTC1, and CRTC1-CREB binding. In contrast, genetic knockdown of hippocampal CRTC1 notably abrogated the antidepressant effects of paroxetine in mice. In summary, regulating hippocampal SIK2 and CRTC1 participates in the antidepressant mechanism of paroxetine, extending the knowledge of its pharmacological targets.

Case report: Near-fatal hypermagnesemia resulting from the use of Epsom salts in a patient with normal renal function.

Hypermagnesemia commonly occurs in patients with renal dysfunction. Diagnosing hypermagnesemia represents a challenge due to its rarity and the absence of routine monitoring of magnesium levels. Furthermore, the lack of awareness among clinicians regarding this uncommon condition frequently leads to delayed diagnoses. Few patients survive with a serum magnesium level exceeding 7 mmol/L. This article presents a case study of near-fatal hypermagnesemia resulting from the oral administration of Epsom salts in a patient with normal renal function. A 60-year-old female presented to the gastroenterology department on Oct. 6, 2023, with a 3-day history of black stools. She underwent subtotal gastrectomy in 2005 and has a stable history of nephrotic syndrome. To investigate the cause of her bleeding, electronic gastroscopy and colonoscopy were scheduled for Oct. 11, 2023. She experienced a sudden loss of consciousness 30 min after the ingestion of Epsom salts. The attending physician suspected a severe magnesium poisoning. She was promptly administered calcium gluconate, underwent tracheal intubation with ambu bag ventilation, and received early continuous renal replacement therapy (CRRT). Swift diagnosis and CRRT contributed to a reduction in her serum magnesium levels from an initial 8.71 mmol/L to 1.35 mmol/L, leading to a remarkable improvement in the toxic symptoms associated with hypermagnesemia. Subsequently, she was managed in the gastroenterology department, with gastroscopy revealing bleeding from the gastrointestinal anastomotic ulcer. Following conservative treatments including acid suppression, stomach protection, and hemostasis, her symptoms improved, and she was successfully discharged. This study aims to alert clinicians to the possibility of hypermagnesemia in individuals with normal renal function. Physicians should exercise caution when prescribing Epsom salts to patients with underlying gastrointestinal conditions. If necessary, alternative drug therapies may be considered to mitigate the risk of hypermagnesemia. Timely intervention is pivotal in averting life-threatening complications linked to hypermagnesemia.

Stable Cu/Cu2O/CuN3@NC Catalysts for Aqueous Phase Reforming of Methanol.

Aqueous-phase reforming of methanol represents a promising avenue for hydrogen (H2) production. However, developing highly efficient and low-cost nonprecious catalysts remains challenging. Here, we report the synthesis of Cu-based catalysts with Cu, Cu2O, and CuN3 nanoparticles anchored on the nitrogen-doped carbon, forming Cu0/Cu+/Cu-N3 active sites. This catalyst achieves a H2 production rate of 140.1 µmol/gcat/s at 210 °C, which is several times to 2 orders of magnitude higher than that of Cu-, Ni-, even Pt-based catalysts, demonstrating excellent long-term stability over 350 h at 210 °C. A mechanism investigation reveals that the Cu-N3 site facilitates water dissociation into *OH and improves *CO and *OH conversion, leading to enhanced CO conversion and H2 production kinetics.

Single-cell epigenomics and spatiotemporal transcriptomics reveal human cerebellar development.

Human cerebellar development is orchestrated by molecular regulatory networks to achieve cytoarchitecture and coordinate motor and cognitive functions. Here, we combined single-cell transcriptomics, spatial transcriptomics and single cell chromatin accessibility states to systematically depict an integrative spatiotemporal landscape of human fetal cerebellar development. We revealed that combinations of transcription factors and cis-regulatory elements (CREs) play roles in governing progenitor differentiation and cell fate determination along trajectories in a hierarchical manner, providing a gene expression regulatory map of cell fate and spatial information for these cells. We also illustrated that granule cells located in different regions of the cerebellar cortex showed distinct molecular signatures regulated by different signals during development. Finally, we mapped single-nucleotide polymorphisms (SNPs) of disorders related to cerebellar dysfunction and discovered that several disorder-associated genes showed spatiotemporal and cell type-specific expression patterns only in humans, indicating the cellular basis and possible mechanisms of the pathogenesis of neuropsychiatric disorders.

Influence of Case Management Model Combined with Continuous Nursing Care on Compliance Behavior and Adverse Emotions in Elderly Patients with Lung Cancer: A Prospective Single-Center Case-Control Study.

Aims: To ask lots of questions about finding the truth about the influence of the case management model combined with continuous nursing care on following the law behavior and negative feelings of love, hate, fear, etc. in old patients with lung scale-like cell cancer. Materials and Methods: One hundred and forty-three elderly patients with squamous cell carcinoma of the lung were selected for this prospective study, 10 cases were shed due to epidemic and transfer, and finally 68 cases were in the control group and 65 cases in the observation group. The differences in anxiety and depression scores, quality of life, and compliance behavior between the two groups were observed and compared. Results: After nursing, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of the observation group were lower than those of the control group, while the social support score was significantly higher than that of the control group. The scores of psychological behavior, exercise status, drug taking, and balanced diet of the two groups were significantly improved, and the observation group was significantly improved. The scores of medical compliance behavior in the observation group were significantly higher than those in the control group, and the mental vitality score, social interaction score, emotional restriction score, and mental status of the patients in the observation group were significantly higher than those in the control group, and the above statistics showed that the difference was statistically significant (P < 0.05). Conclusion: The use of a case management model combined with extended care significantly improved the compliance behavior and anxiety and depression of elderly patients with squamous cell carcinoma of the lung and improved the quality of life and social support.

Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans.

Whether adult hippocampal neurogenesis (AHN) persists in adult and aged humans continues to be extensively debated. A major question is whether the markers identified in rodents are reliable enough to reveal new neurons and the neurogenic trajectory in primates. Here, to provide a better understanding of AHN in primates and to reveal more novel markers for distinct cell types, droplet-based single-nucleus RNA sequencing (snRNA-seq) is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans. All of the major cell types in the hippocampus and their expression profiles were identified. The dynamics of the neurogenic lineage was revealed and the diversity of astrocytes and microglia was delineated. In the neurogenic lineage, the regulatory continuum from adult neural stem cells (NSCs) to immature and mature granule cells was investigated. A group of primate-specific markers were identified. We validated ETNPPL as a primate-specific NSC marker and verified STMN1 and STMN2 as immature neuron markers in primates. Furthermore, we illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples. The interaction analysis and the comparative investigation on published datasets and ours imply that astrocytes provide signals inducing the proliferation, quiescence and inflammation of adult NSCs at different stages and that the proinflammatory status of astrocytes probably contributes to the decrease and variability of AHN in adults and elderly individuals.

Satellite Cells are Activated in a Rat Model of Radiation-Induced Muscle Fibrosis.

Radiation-induced muscle fibrosis is a long-term side effect of radiotherapy that significantly affects the quality of life and even reduces the survival of cancer patients. We have demonstrated that radiation induces satellite cell (SC) activation at the molecular level; however, cellular evidence in a rat model of radiation-induced muscle fibrosis was lacking. In this study, we evaluated SC activation in vivo and investigated whether radiation affects the proliferation and differentiation potential of SCs in vitro. For in vivo studies, Sprague-Dawley rats were randomly divided into six groups (n = 6 per group): non-irradiated controls, 90 Gy/1 week-, 90 Gy/2 weeks-, 90 Gy/4 weeks-, 90 Gy/12 weeks- and 90 Gy/24 weeks-postirradiation groups. Rats received a single dose of radiation in the left groin area and rectus femoris tissues were collected in the indicated weeks. Fibrosis, apoptosis, and autophagy were evaluated by Masson's trichrome staining, TUNEL staining, and electron microscopy, respectively. SC activation and central nuclear muscle fibers were evaluated by immunofluorescence staining and hematoxylin and eosin staining. IL-1ß concentrations in serum and irradiated muscle tissue samples were determined by ELISA. For in vitro studies, SCs were isolated from rats with radiation-induced muscle fibrosis and their proliferation and differentiation were evaluated by immunofluorescence staining. In vivo, fibrosis increased over time postirradiation. Apoptosis and autophagy levels, IL-1ß concentrations in serum and irradiated skin tissues, and the numbers of SCs and central nuclear muscle fibers were increased in the irradiated groups when compared with the control group. In vitro, cultured SCs from irradiated muscle were positive for the proliferation marker Pax7, and differentiated SCs were positive for the myogenic differentiation marker MyHC. This study provided cellular evidence of SC activation and proliferation in rats with radiation-induced muscle fibrosis.

Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages.

Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.

Multistep Photoisomerization of Dimesitylboron-Functionalized Stilbene Analogues.

Dimesitylboron-functionalized stilbene derivatives have been found to undergo an unusual regioselective photoisomerization upon irradiation at 365 nm. Using NMR to follow the photoreaction, the structures of key reaction intermediates and the final products were established. This photoisomerization occurs in four steps: trans-cis isomerization, Diels-Alder reaction, di-π-methane rearrangement, and ring opening with [1,3]-H migration. This results in the formation of a rare structure with three fused five-membered rings and a six-membered one.

Image-guided high-dose-rate interstitial brachytherapy - a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer.

PURPOSE: To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). CASE REPORT: This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive (131)I, the lesion expanded as 3.7 × 3.0 × 2.3 cm(3) and 2.0 × 1.5 × 1.5 cm(3). The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. RESULTS: Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. CONCLUSIONS: The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC.