Phylogenomics and plastomics offer new evolutionary perspectives on Kalanchoideae (Crassulaceae).

BACKGROUND AND AIMS: Kalanchoideae is one of three subfamilies within Crassulaceae and contains four genera. Despite previous efforts, the phylogeny of Kalanchoideae remains inadequately resolved with persistent issues including low support, unstructured topologies and polytomies. This study aimed to address two central objectives: (1) resolving the pending phylogenetic questions within Kalanchoideae by using organelle-scale 'barcodes' (plastomes) and nuclear data; and (2) investigating interspecific diversity patterns among Kalanchoideae plastomes. METHODS: To explore the plastome evolution in Kalanchoideae, we newly sequenced 38 plastomes representing all four constituent genera (Adromischus, Cotyledon, Kalanchoe and Tylecodon). We performed comparative analyses of plastomic features, including GC and gene contents, gene distributions at the IR (inverted repeat) boundaries, nucleotide divergence, plastomic tRNA (pttRNA) structures and codon aversions. Additionally, phylogenetic inferences were inferred using both the plastomic dataset (79 genes) and nuclear dataset (1054 genes). KEY RESULTS: Significant heterogeneities were observed in plastome lengths among Kalanchoideae, strongly correlated with LSC (large single copy) lengths. Informative diversities existed in the gene content at SSC/IRa (small single copy/inverted repeat a), with unique patterns individually identified in Adromischus leucophyllus and one major Kalanchoe clade. The ycf1 gene was assessed as a shared hypervariable region among all four genera, containing nine lineage-specific indels. Three pttRNAs exhibited unique structures specific to Kalanchoideae and the genera Adromischus and Kalanchoe. Moreover, 24 coding sequences revealed a total of 41 lineage-specific unused codons across all four constituent genera. The phyloplastomic inferences clearly depicted internal branching patterns in Kalanchoideae. Most notably, by both plastid- and nuclear-based phylogenies, our research offers the first evidence that Kalanchoe section Eukalanchoe is not monophyletic. CONCLUSIONS: This study conducted comprehensive analyses on 38 newly reported Kalanchoideae plastomes. Importantly, our results not only reconstructed well-resolved phylogenies within Kalanchoideae, but also identified highly informative unique markers at the subfamily, genus and species levels. These findings significantly enhance our understanding of the evolutionary history of Kalanchoideae.

Rogue curves in the Davey-Stewartson I equation.

We report new rogue wave patterns whose wave crests form closed or open curves in the spatial plane, which we call rogue curves, in the Davey-Stewartson I equation. These rogue curves come in various striking shapes, such as rings, double rings, and many others. They emerge from a uniform background (possibly with a few lumps on it), reach high amplitude in such striking shapes, and then disappear into the same background again. We reveal that these rogue curves would arise when an internal parameter in bilinear expressions of the rogue waves is real and large. Analytically, we show that these rogue curves are predicted by root curves of certain types of double-real-variable polynomials. We compare analytical predictions of rogue curves to true solutions and demonstrate good agreement between them.

Machine learning for the micropeptide encoded by LINC02381 regulates ferroptosis through the glucose transporter SLC2A10 in glioblastoma.

Glioblastoma (GBM) is the most common primary intracranial tumor in the central nervous system, and resistance to temozolomide is an important reason for the failure of GBM treatment. We screened out that Solute Carrier Family 2 Member 10 (SLC2A10) is significantly highly expressed in GBM with a poor prognosis, which is also enriched in the NF-E2 p45-related factor 2 (NRF2) signalling pathway. The NRF2 signalling pathway is an important defence mechanism against ferroptosis. SLC2A10 related LINC02381 is highly expressed in GBM, which is localized in the cytoplasm/exosomes, and LINC02381 encoded micropeptides are localized in the exosomes. The micropeptide encoded by LINC02381 may be a potential treatment strategy for GBM, but the underlying mechanism of its function is not precise yet. We put forward the hypothesis: "The micropeptide encoded by LINC02381 regulates ferroptosis through the glucose transporter SLC2A10 in GBM." This study innovatively used machine learning for micropeptide to provide personalized diagnosis and treatment plans for precise treatment of GBM, thereby promoting the development of translational medicine. The study aimed to help find new disease diagnoses and prognostic biomarkers and provide a new strategy for experimental scientists to design the downstream validation experiments.

Lactate-fueled oxidative metabolism drives DNA methyltransferase 1-mediated transcriptional co-activator with PDZ binding domain protein activation.

Activity of transcriptional co-activator with PDZ binding domain (TAZ) protein is strongly implicated in the pathogenesis of human cancer and is influenced by tumor metabolism. High levels of lactate concentration in the tumor microenvironment as a result of metabolic reprogramming are inversely correlated with patient overall survival. Herein, we investigated the role of lactate in the regulation of the activity of TAZ and showed that glycolysis-derived lactate efficiently increased TAZ expression and activity in lung cancer cells. We showed that the reactive oxygen species (ROS) generated by lactate-fueled oxidative phosphorylation (OXPHOS) in mitochondria activated AKT and thereby inhibited glycogen synthase kinase 3 beta/beta-transducin repeat-containing proteins (GSK-3ß/ß-TrCP)-mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1). Upregulation of DNMT1 by lactate caused hypermethylation of TAZ negative regulator of the LATS2 gene promoter, leading to TAZ activation. Moreover, TAZ binds to the promoter of DNMT1 and is necessary for DNMT1 transcription. Our study showed a molecular mechanism of DNMT1 in linking tumor metabolic reprogramming to the Hippo-TAZ pathway and functional significance of the DNMT1-TAZ feedback loop in the migratory and invasive potential of lung cancer cells.

Weakly nonlinear topological gap solitons in Su-Schrieffer-Heeger photonic lattices.

We study both theoretically and experimentally the effect of nonlinearity on topologically protected linear interface modes in a photonic Su-Schrieffer-Heeger (SSH) lattice. It is shown that under either focusing or defocusing nonlinearity, this linear topological mode of the SSH lattice turns into a family of topological gap solitons. These solitons are stable. However, they exhibit only a low amplitude and power and are thus weakly nonlinear, even when the bandgap of the SSH lattice is wide. As a consequence, if the initial beam has modest or high power, it will either delocalize, or evolve into a soliton not belonging to the family of topological gap solitons. These theoretical predictions are observed in our experiments with optically induced SSH-type photorefractive lattices.

Lactate-induced MRP1 expression contributes to metabolism-based etoposide resistance in non-small cell lung cancer cells.

BACKGROUND: Metabolic reprogramming contributes significantly to tumor development and is tightly linked to drug resistance. The chemotherapeutic agent etoposide (VP-16) has been used clinically in the treatment of lung cancer but possess different sensitivity and efficacy towards SCLC and NSCLC. Here, we assessed the impact of etoposide on glycolytic metabolism in SCLC and NSCLC cell lines and investigated the role of metabolic rewiring in mediating etoposide resistance. METHODS: glycolytic differences of drug-treated cancer cells were determined by extracellular acidification rate (ECAR), glucose consumption, lactate production and western blot. DNA damage was evaluated by the comet assay and western blot. Chemoresistant cancer cells were analyzed by viability, apoptosis and western blot. Chromatin immunoprecipitation (ChIP) was used for analysis of DNA-protein interaction. RESULTS: Here we showed that exposure to chemotherapeutic drug etoposide induces an exacerbation of ROS production which activates HIF-1α-mediated the metabolic reprogramming toward increased glycolysis and lactate production in non-small cell lung cancer (NSCLC). We identified lactic acidosis as the key that confers multidrug resistance through upregulation of multidrug resistance-associated protein 1 (MRP1, encoded by ABCC1), a member of ATP-binding cassette (ABC) transporter family. Mechanistically, lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to induce formation of Snail/TAZ/AP-1 complex at the MRP1/ABCC1 promoter. Induction of MRP1 expression inhibits genotoxic and apoptotic effects of chemotherapeutic drugs by increasing drug efflux. Furthermore, titration of lactic acid with NaHCO3 was sufficient to overcome resistance. CONCLUSIONS: The chemotherapeutic drug etoposide induces the shift toward aerobic glycolysis in the NSCLC rather than SCLC cell lines. The increased lactic acid in extracellular environment plays important role in etoposide resistance through upregulation of MRP expression. These data provide first evidence for the increased lactate production, upon drug treatment, contributes to adaptive resistance in NSCLC and reveal potential vulnerabilities of lactate metabolism and/or pathway suitable for therapeutic targeting. Video Abstract The chemotherapeutic drug etoposide induces metabolic reprogramming towards glycolysis in the NSCLC cells. The secreted lactic acid coordinates TGF-ß1/Snail and TAZ/AP-1 pathway to activate the expression of MRP1/ABCC1 protein, thus contributing to chemoresistance in NSCLC.

Classes of non-parity-time-symmetric optical potentials with exceptional-point-free phase transitions.

Paraxial linear propagation of light in an optical waveguide with material gain and loss is governed by a Schrödinger equation with a complex potential. In this Letter, new classes of non-parity-time (PT)-symmetric complex potentials featuring conjugate-pair eigenvalue symmetry are constructed by operator symmetry methods. Due to this eigenvalue symmetry, it is shown that the spectrum of these complex potentials is often all-real. Under parameter tuning in these potentials, a phase transition can also occur, where pairs of complex eigenvalues appear in the spectrum. A distinctive feature of the phase transition here is that the complex eigenvalues may bifurcate out from an interior continuous eigenvalue inside the continuous spectrum; hence, a phase transition takes place without going through an exceptional point. In one spatial dimension, this class of non-PT-symmetric complex potentials is of the form V(x)=h'(x)-h2(x), where h(x) is an arbitrary PT-symmetric complex function. These potentials in two spatial dimensions are also derived. Diffraction patterns in these complex potentials are further examined, and unidirectional propagation behaviors are demonstrated.

[Effects of cigarette smoke on chromatin configuration, DNA methylation and expression of related genes in mice oocytes].

OBJECTIVE: To study the effect of cigarette smoke on chromatin configuration, DNA methylation and expression of related genes in mice oocytes. METHODS: The clean grade ICR female mice were divided into 3 groups, control group, low dose group and high dose group. Animals were placed inside a perspex chamber( 18L) filled up with the smoke produced by 0, 1, 2 cigarettes, one hour a time, twice daily for 4weeks. Nuclear staining with Hoechst 33342, to observe the quality of oocyte and chromatin configuration. Analysis of the DNA methylation patterns by indirect immunofluorescence. The expressions of DNA methyltransferases( DNMT) 1, DNMT3a and DNMT3b mRNA were detected by quantitative real time PCR. RESULTS: With the increase of smoke concentration, the diameter of oocytes was significantly decreased( P <0. 05), the percentage of non surrounded nucleolus( NSN) chromatin configuration was significantly increased( P < 0. 05). In high dose group, the level of DNA methylation wassignificantly lower than that of control group( P < 0. 05). The expression of DNMT1 decreased with the increase of smoke concentration, but the expression level of DNMT3b was significantly decreased( P < 0. 05). CONCLUSION: Cigarette smoke exposure may alter oocyte chromatin configuration, decrease the expression level of DNMTs, resulted in oocytes DNA methylation decreased, so as to decrease the quality of oocytes.

Light localization and nonlinear beam transmission in specular amorphous photonic lattices.

We demonstrate specular photonic "lattices" with random index variations at disordered positions of lattice sites. These amorphous lattice structures, optically induced in a bulk nonlinear crystal, remain invariant during propagation since they are constructed from random components residing on a fixed ring in momentum space. We observe linear spatial localization of a light beam when probing through different "defect" points in such specular lattices, as well as the nonlinear destruction of localized modes. In addition, we illustrate the possibility of image transmission through the disordered lattices, when a self-defocusing nonlinearity is employed.

Nonlinear light behaviors near phase transition in non-parity-time-symmetric complex waveguides.

Many classes of non-parity-time (PT)-symmetric waveguides with arbitrary gain and loss distributions still possess all-real linear spectrum or exhibit phase transition. In this Letter, nonlinear light behaviors in these complex waveguides are probed analytically near a phase transition. Using multi-scale perturbation methods, a nonlinear ordinary differential equation (ODE) is derived for the light's amplitude evolution. This ODE predicts that a single class of these non-PT-symmetric waveguides supports soliton families and amplitude-oscillating solutions both above and below linear phase transition, in close analogy with PT-symmetric systems. For the other classes of waveguides, the light's intensity always amplifies under the effect of nonlinearity, even if the waveguide is below the linear phase transition. These analytical predictions are confirmed by direct computations of the full system.

Symmetry breaking of solitons in one-dimensional parity-time-symmetric optical potentials.

Symmetry breaking of solitons in a class of one-dimensional parity-time (PT) symmetric complex potentials with cubic nonlinearity is reported. In generic PT-symmetric potentials, such symmetry breaking is forbidden. However, in a special class of PT-symmetric potentials V(x)=g(2)(x)+αg(x)+ig'(x), where g(x) is a real and even function and α a real constant, symmetry breaking of solitons can occur. That is, a branch of non-PT-symmetric solitons can bifurcate out from the base branch of PT-symmetric solitons when the base branch's power reaches a certain threshold. At the bifurcation point, the base branch changes stability, and the bifurcated branch can be stable.

Partially PT symmetric optical potentials with all-real spectra and soliton families in multidimensions.

Multidimensional complex optical potentials with partial parity-time (PT) symmetry are proposed. The usual PT symmetry requires that the potential is invariant under complex conjugation and simultaneous reflection in all spatial directions. However, we show that if the potential is only partially PT symmetric, i.e., it is invariant under complex conjugation and reflection in a single spatial direction, then it can also possess all-real spectra and continuous families of solitons. These results are established analytically and corroborated numerically.

Long-term combined blockade of CXCR4 and PD-L1 with in vivo reassembly for intensive tumor interference.

Negative immunoregulatory signal (PD-L1, CXCR4, et al.) and weak immunogenicity elicited immune system failing to detect and destroy cancerous cells. CXCR4 blockade promoted T cell tumor infiltration and increased tumor sensitivity to anti-PD-L1 therapy. Here, pH-responsive reassembled nanomaterials were constructed with anti-PD-L1 peptide and CXCR4 antagonists grafting (APAB), synergized with photothermal therapy for melanoma and breast tumor interference. The self-assembled APAB nanoparticles accumulated in the tumor and rapidly transformed into nanofibers in response to the acidic tumor microenvironment, leading to the exposure of grafted therapeutic agents. APAB enabling to reassemble around tumor cells and remained stable for over 96 h due to the aggregation induced retention (AIR) effect, led to long-term efficiently combined PD-L1 and CXCR4 blockade. Photothermal efficiency (ICG) induced immunogenic cell death (ICD) of tumor cells so as to effectively improve the immunogenicity. The combined therapy (ICG@APAB) could effectively inhibit the growth of primary tumor (∼83.52%) and distant tumor (∼76.24%) in melanoma-bearing mice, and significantly (p < 0.05) prolong the survival time over 42 days. The inhibition assay on tumor metastasis in 4 T1 model mice exhibited ICG@APAB almostly suppressed the occurrence of lung metastases and the expression levels of CD31, MMP-9 and VEGF in tumor decreased by 82.26%, 90.45% and 41.54%, respectively. The in vivo reassembly strategy will offer novel perspectives benefical future immunotherapies and push development of combined therapeutics into clinical settings.

Intraspecific and Intrageneric Genomic Variation across Three Sedum Species (Crassulaceae): A Plastomic Perspective.

Sedum is the largest succulent genus in Crassulaceae. Because of predominant maternal inheritance, little recombination, and slow evolution, plastomes can serve as powerful super barcodes for inter- or intra-species phylogenetic analyses. While previous research has focused on plastomes between Sedum species, intra-species studies are scarce. Here, we sequenced plastomes from three Sedum species (Sedum alfredii, Sedum plumbizincicola, and Sedum japonicum) to understand their evolutionary relationships and plastome structural evolution. Our analyses revealed minimal size and GC content variation across species. However, gene distribution at IR boundaries, repeat structures, and codon usage patterns showed diversity at both inter-specific and intra-specific levels. Notably, an rps19 gene expansion and a bias toward A/T-ending codons were observed. Codon aversion motifs also varied, potentially serving as markers for future studies. Phylogenetic analyses confirmed the non-monophyly of Sedum and divided the Acre clade into two groups. Individuals from the same species clustered together, with strong support for the relationships between S. alfredii, S. tricarpum, and S. plumbizincicola. Additionally, S. japonicum clearly affiliates with the Acre clade. This study provides valuable insights into both intra-specific and intra-generic plastome variation in Sedum, as well as overall plastome evolution within the genus.

Pyramid diffraction in parity-time-symmetric optical lattices.

Nonlinear dynamics of wave packets in two-dimensional parity-time-symmetric optical lattices near the phase transition point are analytically studied. A fourth-order equation is derived for the envelope of these wave packets. A pyramid diffraction pattern is demonstrated in both the linear and nonlinear regimes. Blow-up is also possible in the nonlinear regime for both focusing and defocusing nonlinearities.

The impact of internet use on health status among older adults in China: The mediating role of social support.

Background: With the popularization of the Internet, the use of the Internet is becoming more and more important in the daily life of older adults. However, previous research mainly focuses on Internet use and health in general, and the mechanism of this effect remains to be studied. To bridge this gap, this study aims to explore the mediational effects of social support between Internet use and health among older adults in China. Methods: The data used in this article are from the 2021 Chinese General Social Survey (CGSS). Social support is divided into two aspects and four dimensions: informal social support (relatives support, friends support, neighbors support) and formal social support (social insurance). This article uses the nested multivariate OLS regression models to analyze the impact of Internet use on health. Furthermore, Finally, SPSS macro PROCESS is applied to test their mediation effects. Results: Informal social support positively influenced the health status among older adults, while formal social support did not. Among the three types of informal social support, relatives support and friends support significantly affected health status among Chinese older adults. Regarding social support differences between urban and rural areas, it was found that relatives support is a positively significant factor for rural older adults, while friends support is significant for urban older adults. Conclusions: Since Internet use has many ways of impacting health status, social support only plays a partial mediating role in this study. It recommends that the government should take compelling measures to encourage and promote the use of the Internet among older adults and obtain various social support to improve their health status.

Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis.

Intranasal administration has been widely explored as a potential treatment for allergic rhinitis, and improving intranasal penetration and retention of drugs is a challenging requirement to further improve efficacy. Delivery strategies of nanocarriers that enhance mucosal adhesion or mucus penetration have been proposed to improve nasal drug delivery; however, delivery efficiency remains limited by excessive pulmonary deposition and nonspecific cell phagocytosis. In this work, a "nasal in situ assembly" strategy was presented to construct intranasal morphology transformation nanomedicines with enhanced effective drug concentration for long-term intervention of allergic rhinitis. The polymer-polypeptide nanomedicine (PHCK) with a CCR3 antagonistic peptide (C) and a pH-responsive polyethylene glycol (H) was developed, encapsulating ketotifen (KT). PHCK nanoparticles displayed nasal mucosa permeability and transformed to nanofibers in the acidic environment of the nasal cavity, realizing responsive burst release of KT simultaneously. The fibrotic reassembly reduced the cellular internalization of nanomedicine and increased the CCR3 blockade on the eosinophil (EOS) membranes. Both in vitro and in vivo data indicated that PHCK achieved improved drug accumulation and retention in the nasal cavity and decreased pulmonary deposition, then effectively inhibited mast cell degranulation and EOS chemotaxis. This study demonstrates that the "nasal in situ assembly" strategy can improve drug delivery efficiency upon nasal responsive morphologic transformation, providing exploratory perspectives for nasal delivery platforms establishment and boosting therapeutic effect of allergic rhinitis.

Physical Activity, Screen Time, and Academic Burden: A Cross-Sectional Analysis of Health among Chinese Adolescents.

This paper aims to analyze the effects of physical activity, screen time, and academic burden on adolescent health in China and compare their effects by using the nationally representative sample data from the CEPS (China Educational Panel Survey) cross-section data. This paper first uses regression analysis to examine the relationship between physical activity, screen time, academic burden and health among Chinese adolescents. Then, this paper uses the clustering analysis the influence of physical activity, screen time, and academic burden on the health of Chinese adolescents. The empirical results show that: (1) along with exercise, helping with the housework also has a clear health-promoting effect on adolescents; (2) the time spent surfing the Internet or playing video games, and heavy studying or homework off campus have a negative effect on adolescents' self-rated health and mental health; (3) physical activity has the greatest impact on self-rated health, while screen time has the greatest impact on mental health, and academic burden is not the most important factor affecting adolescent health in China.

Genome evolution of Buchnera aphidicola (Gammaproteobacteria): Insights into strand compositional asymmetry, codon usage bias, and phylogenetic implications.

Taxa of Buchnera aphidicola (hereafter "Buchnera") are mutualistic intracellular symbionts of aphids, known for their remarkable biological traits such as genome reduction, strand compositional asymmetry, and symbiont-host coevolution. With the growing availability of genomic data, we performed a comprehensive analysis of 103 genomes of Buchnera strains from 12 host subfamilies, focusing on the genomic characterizations, codon usage patterns, and phylogenetic implications. Our findings revealed consistent features among all genomes, including small genome sizes, low GC contents, and gene losses. We also identified strong strand compositional asymmetries in all strains at the genome level. Further investigation suggested that mutation pressure may have played a crucial role in shaping codon usage of Buchnera. Moreover, the genomic asymmetries were reflected in asymmetric codon usage preferences within chromosomal genes. Notably, the levels of these asymmetries were varied among strains and were significantly influenced by the degrees of genome shrinkages. Lastly, our phylogenetic analyses presented an alternative topology of Aphididae, based on the Buchnera symbionts, providing robust confirmation of the paraphylies of Eriosomatinae, and Macrosiphini. Our objectives are to further understand the strand compositional asymmetry and codon usage bias of Buchnera taxa, and provide new perspectives for phylogenetic studies of Aphididae.

Nonlinear dynamics of wave packets in parity-time-symmetric optical lattices near the phase transition point.

Nonlinear dynamics of wave packets in parity-time-symmetric optical lattices near the phase-transition point is analytically studied. A nonlinear Klein-Gordon equation is derived for the envelope of these wave packets. A variety of phenomena known to exist in this envelope equation are shown to also exist in the full equation, including wave blowup, periodic bound states, and solitary wave solutions.