Pan-transcriptomic analysis reveals alternative splicing control of cold tolerance in rice.

Plants have evolved complex mechanisms to adapt to harsh environmental conditions. Rice (Oryza sativa) is a staple food crop that is sensitive to low temperatures. However, its cold stress responses remain poorly understood, thus limiting possibilities for crop engineering to achieve greater cold tolerance. In this study, we constructed a rice pan-transcriptome and characterized its transcriptional regulatory landscape in response to cold stress. We performed Iso-Seq and RNA-Seq of 11 rice cultivars subjected to a time-course cold treatment. Our analyses revealed that alternative splicing-regulated gene expression plays a significant role in the cold stress response. Moreover, we identified CATALASE C (OsCATC) and Os03g0701200 as candidate genes for engineering enhanced cold tolerance. Importantly, we uncovered central roles for the 2 serine-arginine-rich proteins OsRS33 and OsRS2Z38 in cold tolerance. Our analysis of cold tolerance and resequencing data from a diverse collection of 165 rice cultivars suggested that OsRS2Z38 may be a key selection gene in japonica domestication for cold adaptation, associated with the adaptive evolution of rice. This study systematically investigated the distribution, dynamic changes, and regulatory mechanisms of alternative splicing in rice under cold stress. Overall, our work generates a rich resource with broad implications for understanding the genetic basis of cold response mechanisms in plants.

Polycomb-Dependent Chromatin Looping Contributes to Gene Silencing during Drosophila Development.

Interphase chromatin is organized into topologically associating domains (TADs). Within TADs, chromatin looping interactions are formed between DNA regulatory elements, but their functional importance for the establishment of the 3D genome organization and gene regulation during development is unclear. Using high-resolution Hi-C experiments, we analyze higher order 3D chromatin organization during Drosophila embryogenesis and identify active and repressive chromatin loops that are established with different kinetics and depend on distinct factors: Zelda-dependent active loops are formed before the midblastula transition between transcribed genes over long distances. Repressive loops within polycomb domains are formed after the midblastula transition between polycomb response elements by the action of GAGA factor and polycomb proteins. Perturbation of PRE function by CRISPR/Cas9 genome engineering affects polycomb domain formation and destabilizes polycomb-mediated silencing. Preventing loop formation without removal of polycomb components also decreases silencing efficiency, suggesting that chromatin architecture can play instructive roles in gene regulation during development. VIDEO ABSTRACT.

Ectopic expression of a bacterial thiamin monophosphate kinase enhances vitamin B1 biosynthesis in plants.

Plants and bacteria have distinct pathways to synthesize the bioactive vitamin B1 thiamin diphosphate (TDP). In plants, thiamin monophosphate (TMP) synthesized in the TDP biosynthetic pathway is first converted to thiamin by a phosphatase, which is then pyrophosphorylated to TDP. In contrast, bacteria use a TMP kinase encoded by ThiL to phosphorylate TMP to TDP directly. The Arabidopsis THIAMIN REQUIRING2 (TH2)-encoded phosphatase is involved in TDP biosynthesis. The chlorotic th2 mutants have high TMP and low thiamin and TDP. Ectopic expression of Escherichia coli ThiL and ThiL-GFP rescued the th2-3 mutant, suggesting that the bacterial TMP kinase could directly convert TMP into TDP in Arabidopsis. These results provide direct evidence that the chlorotic phenotype of th2-3 is caused by TDP rather than thiamin deficiency. Transgenic Arabidopsis harboring engineered ThiL-GFP targeting to the cytosol, chloroplast, mitochondrion, or nucleus accumulated higher TDP than the wild type (WT). Ectopic expression of E. coli ThiL driven by the UBIQUITIN (UBI) promoter or an endosperm-specific GLUTELIN1 (GT1) promoter also enhanced TDP biosynthesis in rice. The pUBI:ThiL transgenic rice accumulated more TDP and total vitamin B1 in the leaves, and the pGT1:ThiL transgenic lines had higher TDP and total vitamin B1 in the seeds than the WT. Total vitamin B1 only increased by approximately 25-30% in the polished and unpolished seeds of the pGT1:ThiL transgenic rice compared to the WT. Nevertheless, these results suggest that genetic engineering of a bacterial vitamin B1 biosynthetic gene downstream of TMP can enhance vitamin B1 production in rice.

Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma.

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.

Systematic analysis of IGF2BP family members in non-small-cell lung cancer.

BACKGROUND: The insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, and IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, and cancer immunity in various human cancers, including non-small cell lung cancer (NSCLC). However, the literature on NSCLC largely omits the specific context of lung squamous cell carcinoma (LUSC), an oversight we aim to address. METHODS: Our study evaluated the differential expression of IGF2BP family members in tumors and normal tissues. Meta-analyses were conducted to assess the prognostic value of IGF2BPs in lung adenocarcinoma (LUAD) and LUSC. Additionally, correlations between IGF2BPs and tumor immune cell infiltration, mutation characteristics, chemotherapy sensitivity, and tumor mutation burden (TMB) were investigated. GSEA was utilized to delineate biological processes and pathways associated with IGF2BPs. RESULTS: IGF2BP2 and IGF2BP3 expression were found to be upregulated in LUSC patients. IGF2BP2 mRNA levels were correlated with cancer immunity in both LUSC and LUAD patients. A higher frequency of gene mutations was observed in different IGF2BP1/2/3 expression groups in LUAD compared to LUSC. Meta-analyses revealed a significant negative correlation between overall survival (OS) and IGF2BP2/3 expression in LUAD patients but not in LUSC patients. GSEA indicated a positive association between VEGF and IGF2BP family genes in LUAD, while matrix metallopeptidase activity was inversely correlated with IGF2BP family genes in LUSC. Several chemotherapy drugs showed significantly lower IC50 values in high IGF2BP expression groups in both LUAD and LUSC. CONCLUSION: Our findings indicated that IGF2BPs play different roles in LUAD and LUSC. This divergence highlights the need for tailored therapeutic strategies and prognostic tools, cognizant of the unique molecular profiles of LUAD and LUSC.

PGD: Shared gene linking polycystic ovary syndrome and endometrial cancer, influencing proliferation and migration through glycometabolism.

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.

The high electron mobility for spin-down channel of two-dimensional spin-polarized half-metallic ferromagnetic EuSi2N4 monolayer.

The two-dimensional (2D) monolayer material MoSi2N4 was successfully synthesized in 2020[Hong et al., Science 369, 670, (2020)], exhibiting a plethora of new phenomena and unusual properties, with good stability at room temperature. However, MA2Z4 family monolayer materials involve primarily transition metal substitutions for M atoms. In order to address the research gap on lanthanide and actinide MA2Z4 materials, this work conducts electronic structure calculations on novel 2D MSi2N4 (M = La, Eu) monolayer materials by employing first-principles methods and CASTEP. High carrier mobility is discovered in the indirect bandgap semiconductor 2D LaSi2N4 monolayer (~5400 cm2 V-1 s-1) and in the spin (spin-down channel) carrier mobility of the half-metallic ferromagnetic EuSi2N4 monolayer (~2800 cm2 V-1 s-1). EuSi2N4 monolayer supplements research on spin carrier mobility in half-metallic ferromagnetic monolayer materials at room temperature and possesses a magnetic moment of 5 µB, which should not be underestimated. Furthermore, due to the unique electronic band structure of EuSi2N4 monolayer (with the spin-up channel exhibiting metallic properties and the spin-down channel exhibiting semiconductor properties), it demonstrates a 100% spin polarization rate, presenting significant potential applications in fields such as magnetic storage, magnetic sensing, and spintronics.

Aromatic and magnetic properties in a series of heavy rare earth-doped Ge6 cluster anions.

A series of pentagonal bipyramidal anionic germanium clusters doped with heavy rare earth elements, REGe 6 - (RE = Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu), have been identified at the PBE0/def2-TZVP level using density functional theory (DFT). Our findings reveal that the centrally doped pentagonal ring structure demonstrates enhanced stability and heightened aromaticity due to its uniform bonding characteristics and a larger charge transfer region. Through natural population analysis and spin density diagrams, we observed a monotonic decrease in the magnetic moment from Gd to Yb. This is attributed to the decreasing number of unpaired electrons in the 4f orbitals of the heavy rare earth atoms. Interestingly, the system doped with Er atoms showed lower stability and anti-aromaticity, likely due to the involvement of the 4f orbitals in bonding. Conversely, the systems doped with Gd and Tb atoms stood out for their high magnetism and stability, making them potential building blocks for rare earth-doped semiconductor materials.

In Situ Constructing of Rigid-Soft Coupling Solid-Electrolyte Interphase on Silicon Electrode toward High-Performance Lithium Ion Batteries.

The application of Si anodes is hindered by some critical issues such as large volume changes of bare Si and fragile solid-electrolyte interface (SEI), resulting in low coulombic efficiency and rapid capacity decay. Herein, a multifunctional SEI film with high content of LiF is in situ constructed via the surface grafting of carbon-fluorine functionalized groups on silicon nanoparticles (SiNPs) during cycling. Mechanical study demonstrates that the incorporation of LiF with high modulus and unbroken carbon-fluorine groups with highly elastic guarantee the rigid-soft coupling SEI film on Si electrode. Furthermore, it is demonstrated that the rigid-soft coupling SEI film can effectively accommodate the volume expansion of Si nanoparticles during lithiation process, with the electrode expanding rate of only 114.16% after 100 cycles (263.87% for bare Si without surface modification). Afterward, with the aid of well-designed rigid-soft coupling SEI, the initial Coulomb efficiency of 89.8% is achieved, showing a reversible capacity of 1477 mAh g-1 after 200 cycles at 1.2 A g-1 . This work provides a simple and efficient solution that can potentially facilitate the practical application of Si anodes.

Machine learning for accurate detection of small airway dysfunction-related respiratory changes: an observational study.

BACKGROUND: The use of machine learning(ML) methods would improve the diagnosis of small airway dysfunction(SAD) in subjects with chronic respiratory symptoms and preserved pulmonary function(PPF). This paper evaluated the performance of several ML algorithms associated with the impulse oscillometry(IOS) analysis to aid in the diagnostic of respiratory changes in SAD. We also find out the best configuration for this task. METHODS: IOS and spirometry were measured in 280 subjects, including a healthy control group (n = 78), a group with normal spirometry (n = 158) and a group with abnormal spirometry (n = 44). Various supervised machine learning (ML) algorithms and feature selection strategies were examined, such as Support Vector Machines (SVM), Random Forests (RF), Adaptive Boosting (ADABOOST), Navie Bayesian (BAYES), and K-Nearest Neighbors (KNN). RESULTS: The first experiment of this study demonstrated that the best oscillometric parameter (BOP) was R5, with an AUC value of 0.642, when comparing a healthy control group(CG) with patients in the group without lung volume-defined SAD(PPFN). The AUC value of BOP in the control group was 0.769 compared with patients with spirometry defined SAD(PPFA) in the PPF population. In the second experiment, the ML technique was used. In CGvsPPFN, RF and ADABOOST had the best diagnostic results (AUC = 0.914, 0.915), with significantly higher accuracy compared to BOP (p < 0.01). In CGvsPPFA, RF and ADABOOST had the best diagnostic results (AUC = 0.951, 0.971) and significantly higher diagnostic accuracy (p < 0.01). In the third, fourth and fifth experiments, different feature selection techniques allowed us to find the best IOS parameters (R5, (R5-R20)/R5 and Fres). The results demonstrate that the performance of ADABOOST remained essentially unaltered following the application of the feature selector, whereas the diagnostic accuracy of the remaining four classifiers (RF, SVM, BAYES, and KNN) is marginally enhanced. CONCLUSIONS: IOS combined with ML algorithms provide a new method for diagnosing SAD in subjects with chronic respiratory symptoms and PPF. The present study's findings provide evidence that this combination may help in the early diagnosis of respiratory changes in these patients.

Transition-Metal-Free Radical Relay Cascade Annulation of Amides: Access to Antitumor Active Benzo[b]azepine and Oxindole Derivatives.

Efficient transition-metal-free synthesis of benzo[b]azepines and oxindoles is achieved via a radical relay cascade strategy employing halogen atom transfer (XAT) for aryl radical generation followed by intramolecular hydrogen atom transfer (HAT). Optimization yielded moderate to substantial yields under visible light irradiation. Preliminary biological assessments revealed promising anti-tumor activity for select compounds. This study underscores the potential of XAT-mediated radical relay cascades in medicinal chemistry and anticancer drug discovery.

Transcriptomic and physiological analysis provide new insight into seed shattering mechanism in Pennisetum alopecuroides 'Liqiu'.

KEY MESSAGE: Through the histological, physiological, and transcriptome-level identification of the abscission zone of Pennisetum alopecuroides 'Liqiu', we explored the structure and the genes related to seed shattering, ultimately revealing the regulatory network of seed shattering in P. alopecuroides. Pennisetum alopecuroides is one of the most representative ornamental grass species of Pennisetum genus. It has unique inflorescence, elegant appearance, and strong stress tolerance. However, the shattering of seeds not only reduces the ornamental effect, but also hinders the seed production. In order to understand the potential mechanisms of seed shattering in P. alopecuroides, we conducted morphological, histological, physiological, and transcriptomic analyses on P. alopecuroides cv. 'Liqiu'. According to histological findings, the seed shattering of 'Liqiu' was determined by the abscission zone at the base of the pedicel. Correlation analysis showed that seed shattering was significantly correlated with cellulase, lignin, auxin, gibberellin, cytokinin and jasmonic acid. Through a combination of histological and physiological analyses, we observed the accumulation of cellulase and lignin during 'Liqiu' seed abscission. We used PacBio full-length transcriptome sequencing (SMRT) combined with next-generation sequencing (NGS) transcriptome technology to improve the transcriptome data of 'Liqiu'. Transcriptomics further identified many differential genes involved in cellulase, lignin and plant hormone-related pathways. This study will provide new insights into the research on the shattering mechanism of P. alopecuroides.

Serum CXCL13 level is related to treatment response and predicts disease prognosis in Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a type of B-cell lymphoma that produces IgM. Our study aimed to investigate the role of CXCL13, a chemokine essential for B lymphocytes, in the evaluation of treatment response and prognosis in WM. We collected serum samples and clinical data from 72 WM patients, with 69 patients receiving systemic therapy and 3 patients opting not to receive treatment. Serum CXCL13 levels at baseline and after six months of treatments were measured by enzyme-linked immunosorbent assay. The median serum level of CXCL13 was 1 539.2 pg/ml (range 10.0-21 389.9) at baseline and significantly decreased to 123.1 pg/ml (range 0.0-6 741.5) after 6 months of treatments. At baseline, higher CXCL13 levels were associated with lower hemoglobin levels (p = 0.001), higher ß2-microglobulin levels (p = 0.001), lower albumin levels (p = 0.046), and higher IPSS-WM scores (p = 0.013). After 6 months of treatment, patients who achieved PR/VGPR had significantly lower CXCL13 levels compared to those with SD (70.2 pg/ml vs 798.6 pg/ml, p = 0.002). The median follow-up period was 40 months (range 4.2-188). Eight patients died during the follow-up period. Overall survival differed based on CXCL13 levels. When grouped by baseline CXCL13 levels, the median OS was 60.0 months in patients with serum CXCL13 > 2 000 pg/ml, while it was not reached in patients with low CXCL13 levels (p < 0.001). Based on CXCL13 levels after the treatments, the median OS was 74.0 months in patients with serum CXCL13 > 200 pg/ml, while it was not reached in patients with CXCL13 ≤ 200 pg/ml. In a subgroup of 28 patients with a series of serum samples, the increase of serum CXCL13 level was associated with disease progression or the start of next-line therapy (p < 0.001). Our study concludes that serum CXCL13 levels decrease in WM patients treated with various regimens and correlate with treatment response. Detecting serum CXCL13 at baseline or after treatment help in predicting prognosis.

Characteristic activation pattern and network connectivity of prefrontal cortex in patients with type 2 diabetes mellitus and major depressive disorder during a verbal fluency task: A functional near-infrared spectroscopy study based on network-based statistic prediction.

INTRODUCTION: Type 2 diabetes (T2DM) and major depressive disorder (MDD) together occur frequently among the elderly population. However, the inconsistency in assessments and limited medical resources in the community make it challenging to identify depression in patients with T2DM. This cross-sectional study aimed to investigate the activation pattern and network connectivity of prefrontal cortex (PFC) during a verbal fluency task (VFT) in patients with T2DM and MDD using functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with MDD group, T2DM group, and healthy group) with 100 participants in each group were included in the study. Recruitment took place from August 1, 2020, to December 31, 2023. Due to the close association between the PFC and depressive emotions, fNIRS was used to monitor brain activation and network connectivity of PFC in all participants during a task of Chinese-language phonological VFT. Network-based statistic prediction (NBS-predict) was adopted as data analysis method. RESULTS: Patients in the T2DM with MDD group showed characteristic activation pattern and network connectivity in contrast with patients with T2MD and healthy controls, including decreased activation in PFC, and decreased network connectivity of right dorsolateral prefrontal cortex (DLPFC). Furthermore, the network connectivity of the right DLPFC in patients with T2DM and MDD was negatively correlated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: There was a distinctive activation pattern and network connectivity of the prefrontal cortex in patients with T2DM and MDD. The right DLPFC could serve as a potential target for the diagnosis and intervention of MDD in patients with T2DM.

Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Rodent model of metabolic dysfunction-associated fatty liver disease: a systematic review.

Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease.

Discovering SnB7-: a half-sandwich structure with double aromaticity and pathways to molecular machines.

Numerous boron-based molecular fluxional models, such as the Wankel motor, tank treads B11- and B10C, and the Earth-Moon system Be6B11-, have been widely recognized for their potential to develop molecular machines. From a series of tin-doped boron clusters SnBn- (n = 5-14), the half-sandwich structure SnB7- is found to possess high relative energy stability, and a HOMO-LUMO gap of 4.33 eV. This structure exhibits valence electron orbitals reminiscent of σ-π double aromatic compounds. The incorporation of tin effectively fills the doubly vacant π orbitals of its parent triplet B7-, thereby enhancing both magnetic shielding capabilities and range. Thermal bath tests demonstrate its significant dynamic stability, as the kinetic energy provided by thermal baths below 3800 K remains insufficient to disrupt its inherent elasticity. Additionally, transition state searches and intrinsic reaction coordinate analyses confirm that the tin atom migrates from the centre to the edge of the boron ligand surface, a phenomenon that can be observed in high-temperature thermal bath simulations. This fluxional behaviour provides insights for constructing novel molecular machine models.

Exploring the stability and aromaticity of rare earth doped tin cluster MSn16- (M = Sc, Y, La).

Rare earth elements have high chemical reactivity, and doping them into semiconductor clusters can induce novel physicochemical properties. The study of the physicochemical mechanisms of interactions between rare earth and tin atoms will enhance our understanding of rare earth functional materials from a microscopic perspective. Hence, the structure, electronic characteristics, stability, and aromaticity of endohedral cages MSn16- (M = Sc, Y, La) have been investigated using a combination of the hybrid PBE0 functional, stochastic kicking, and artificial bee colony global search technology. By comparing the simulated results with experimental photoelectron spectra, it is determined that the most stable structure of these clusters is the Frank-Kasper polyhedron. The doping of atoms has a minimal influence on density of states of the pure tin system, except for causing a widening of the energy gap. Various methods such as ab initio molecular dynamics simulations, the spherical jellium model, adaptive natural density partitioning, localized orbital locator, and electron density difference are employed to analyze the stability of these clusters. The aromaticity of the clusters is examined using iso-chemical shielding surfaces and the gauge-including magnetically induced currents. This study demonstrates that the stability and aromaticity of a tin cage can be systematically adjusted through doping.

Probing the Structural and Electronic Properties of the Anionic and Neutral Tellurium-Doped Boron Clusters TeBnq (n = 3-16, q = 0, -1).

In this study, we employ density functional theory along with the artificial bee colony algorithm for cluster global optimization to explore the low-lying structures of TeBnq (n = 3-16, q = 0, -1). The primary focus is on reporting the structural properties of these clusters. The results reveal a consistent doping pattern of the tellurium atom onto the in-plane edges of planar or quasi-planar boron clusters in the most energetically stable isomers. Additionally, we simulate the photoelectron spectra of the cluster anions. Through relative stability analysis, we identify three clusters with magic numbers -TeB7-, TeB10, and TeB12. The aromaticity of these clusters is elucidated using adaptive natural density partitioning (AdNDP) and magnetic properties analysis. Notably, TeB7- exhibits a perfect σ-π doubly aromatic structure, while TeB12 demonstrates strong island aromaticity. These findings significantly contribute to our understanding of the structural and electronic properties of these clusters.

Activation of the PERK-CHOP signaling pathway during endoplasmic reticulum stress contributes to olanzapine-induced dyslipidemia.

Olanzapine (OLZ) is a widely prescribed antipsychotic drug with a relatively ideal effect in the treatment of schizophrenia (SCZ). However, its severe metabolic side effects often deteriorate clinical therapeutic compliance and mental rehabilitation. The peripheral mechanism of OLZ-induced metabolic disorders remains abstruse for its muti-target activities. Endoplasmic reticulum (ER) stress is implicated in cellular energy metabolism and the progression of psychiatric disorders. In this study, we investigated the role of ER stress in the development of OLZ-induced dyslipidemia. A cohort of 146 SCZ patients receiving OLZ monotherapy was recruited, and blood samples and clinical data were collected at baseline, and in the 4th week, 12th week, and 24th week of the treatment. This case-control study revealed that OLZ treatment significantly elevated serum levels of endoplasmic reticulum (ER) stress markers GRP78, ATF4, and CHOP in SCZ patients with dyslipidemia. In HepG2 cells, treatment with OLZ (25, 50 µM) dose-dependently enhanced hepatic de novo lipogenesis accompanied by SREBPs activation, and simultaneously triggered ER stress. Inhibition of ER stress by tauroursodeoxycholate (TUDCA) and 4-phenyl butyric acid (4-PBA) attenuated OLZ-induced lipid dysregulation in vitro and in vivo. Moreover, we demonstrated that activation of PERK-CHOP signaling during ER stress was a major contributor to OLZ-triggered abnormal lipid metabolism in the liver, suggesting that PERK could be a potential target for ameliorating the development of OLZ-mediated lipid dysfunction. Taken together, ER stress inhibitors could be a potentially effective intervention against OLZ-induced dyslipidemia in SCZ.