Entangled biphoton generation in the myelin sheath.

Consciousness within the brain hinges on the synchronized activities of millions of neurons, but the mechanism responsible for orchestrating such synchronization remains elusive. In this study we employ cavity quantum electrodynamics to explore entangled biphoton generation through cascade emission in the vibration spectrum of C-H bonds within the lipid molecules' tails. The results indicate that the cylindrical cavity formed by a myelin sheath can facilitate spontaneous photon emission from the vibrational modes and generate a significant number of entangled photon pairs. The abundance of C-H bond vibration units in neurons can therefore serve as a source of quantum entanglement resources for the nervous system. These findings may offer insight into the brain's ability to leverage these resources for quantum information transfer, thereby elucidating a potential source for the synchronized activity of neurons.

Heterogeneous Evolution of Breast Cancer Cells-An Endogenous Molecular-Cellular Network Study.

Breast cancer heterogeneity presents a significant challenge in clinical therapy, such as over-treatment and drug resistance. These challenges are largely due to its obscure normal epithelial origins, evolutionary stability, and transitions on the cancer subtypes. This study aims to elucidate the cellular emergence and maintenance of heterogeneous breast cancer via quantitative bio-process modeling, with potential benefit to therapeutic strategies for the disease. An endogenous molecular-cellular hypothesis posits that both pathological and physiological states are phenotypes evolved from and shaped by interactions among a number of conserved modules and cellular factors within a biological network. We hereby developed a model of core endogenous network for breast cancer in accordance with the theory, quantifying its intrinsic dynamic properties with dynamic modeling. The model spontaneously generates cell states that align with molecular classifications at both the molecular and modular level, replicating four widely recognized molecular subtypes of the cancer and validating against data extracted from the TCGA database. Further analysis shows that topologically, a singular progression gateway from normal breast cells to cancerous states is identified as the Luminal A-type breast cancer. Activated positive feedback loops are found to stabilize cellular states, while negative feedback loops facilitate state transitions. Overall, more routes are revealed on the cellular transition between stable states, and a traceable count explains the origin of breast cancer heterogeneity. Ultimately, the research intended to strength the search for therapeutic targets.

Evolution of Telencephalon Anterior-Posterior Patterning through Core Endogenous Network Bifurcation.

How did the complex structure of the telencephalon evolve? Existing explanations are based on phenomena and lack a first-principles account. The Darwinian dynamics and endogenous network theory-established decades ago-provides a mathematical and theoretical framework and a general constitutive structure for theory-experiment coupling for answering this question from a first-principles perspective. By revisiting a gene network that explains the anterior-posterior patterning of the vertebrate telencephalon, we found that upon increasing the cooperative effect within this network, fixed points gradually evolve, accompanied by the occurrence of two bifurcations. The dynamic behavior of this network is informed by the knowledge obtained from experiments on telencephalic evolution. Our work provides a quantitative explanation for how telencephalon anterior-posterior patterning evolved from the pre-vertebrate chordate to the vertebrate and provides a series of verifiable predictions from a first-principles perspective.

Potential therapeutic targets of gastric cancer explored under endogenous network modeling of clinical data.

Improvement in the survival rate of gastric cancer, a prevalent global malignancy and the leading cause of cancer-related mortality calls for more avenues in molecular therapy. This work aims to comprehend drug resistance and explore multiple-drug combinations for enhanced therapeutic treatment. An endogenous network modeling clinic data with core gastric cancer molecules, functional modules, and pathways is constructed, which is then transformed into dynamics equations for in-silicon studies. Principal component analysis, hierarchical clustering, and K-means clustering are utilized to map the attractor domains of the stochastic model to the normal and pathological phenotypes identified from the clinical data. The analyses demonstrate gastric cancer as a cluster of stable states emerging within the stochastic dynamics and elucidate the cause of resistance to anti-VEGF monotherapy in cancer treatment as the limitation of the single pathway in preventing cancer progression. The feasibility of multiple objectives of therapy targeting specified molecules and/or pathways is explored. This study verifies the rationality of the platform of endogenous network modeling, which contributes to the development of cross-functional multi-target combinations in clinical trials.

Comparison of the One-Step Prone Split-Leg Position to the Traditional Prone Position for Percutaneous Nephrolithotomy: A Single-Center Retrospective Study.

PURPOSE: To evaluate the one-step prone split-leg position compared to the traditional prone position for percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: This study retrospectively analyzed the clinical data for 102 patients with upper urinary tract calculi who underwent PCNL at our hospital from April 2019 to December 2022. All PCNL procedures were performed by the same senior urologist. According to different surgical positions, the patients were divided into a one-step prone split-leg position group (observation group, n = 39) and a traditional bladder lithotomy position followed by prone position group (control group, n = 63). Then, the two groups were compared regarding the time of catheter insertion and channel establishment, channel size, time required for double-J stent placement, total operative time, postoperative hospital stay, stone removal rate, secondary operation rate and postoperative complications. RESULTS: There was no significant difference in the preoperative baseline characteristics of the patients between the two groups (all P > .05). Patients in the observation group had shorter total operative times, higher stone removal rates (76.9% [30/39] vs. 57.1% [36/63], P = .042), and lower secondary operation rates (10.3% [4/39] vs. 28.6% [18/63], P = .029) than those in the control group. There were no significant differences in the time of working channel establishment, channel size, postoperative hospital stay, or postoperative complications between the two groups (all P > .05). CONCLUSION: The one-step prone split-leg position is a safe and reliable surgical posture for treating upper urinary calculi in PCNL patients. It can not only shorten the overall operation time of PCNL but also improve the stone removal rate of the operation, thus reducing the secondary operation rate of multiple renal stones.

Serine-arginine protein kinase 1 (SRPK1) promotes EGFR-TKI resistance by enhancing GSK3ß Ser9 autophosphorylation independent of its kinase activity in non-small-cell lung cancer.

Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a major challenge for clinicians and patients with non-small cell lung cancer (NSCLC). Serine-arginine protein kinase 1 (SRPK1) is a key oncoprotein in the EGFR/AKT pathway that participates in tumorigenesis. We found that high SRPK1 expression was significantly associated with poor progression-free survival (PFS) in patients with advanced NSCLC undergoing gefitinib treatment. Both in vitro and in vivo assays suggested that SRPK1 reduced the ability of gefitinib to induce apoptosis in sensitive NSCLC cells independently of its kinase activity. Moreover, SRPK1 facilitated binding between LEF1, ß-catenin and the EGFR promoter region to increase EGFR expression and promote the accumulation and phosphorylation of membrane EGFR. Furthermore, we verified that the SRPK1 spacer domain bound to GSK3ß and enhanced its autophosphorylation at Ser9 to activate the Wnt pathway, thereby promoting the expression of Wnt target genes such as Bcl-X. The correlation between SRPK1 and EGFR expression was confirmed in patients. In brief, our research suggested that the SRPK1/GSK3ß axis promotes gefitinib resistance by activating the Wnt pathway and may serve as a potential therapeutic target for overcoming gefitinib resistance in NSCLC.

Rational design of heterointerface between MoO2 and N-doped carbon with tunable electromagnetic interference shielding capacity.

Exploring highly efficient electromagnetic interference (EMI) shielding filler is urgently desired for next-generation wireless communication and integrated electronics. In this regard, a series of heterogeneous MoO2/N-doped carbon (MoO2/NC) nanorods with tunable conductivity have been successfully synthesized by regulating the pyrolysis temperature within 600, 700 and 800 °C. Profiting from the rational design of heterointerface and low-dimensional structure, the MoO2/NC powder achieves stronger EMI shielding capacity with the incremental temperature. It is found that the MoO2/NC-800 nanorods exhibit the optimal average EMI shielding effectiveness (SE) of 57.2 dB at a thickness of ∼0.3 mm in the X band. Meanwhile, the corresponding shielding mechanisms of MoO2/NC nanorods are also elaborately explained. More interestingly, the increase of sintering temperature makes an obvious effect on absorption loss but has little influence on reflection loss, demonstrating that adjusting the pyrolysis temperature is an effective strategy to strengthen the electromagnetic energy dissipation.

Topology, vorticity, and limit cycle in a stabilized Kuramoto-Sivashinsky equation.

A noisy stabilized Kuramoto-Sivashinsky equation is analyzed by stochastic decomposition. For values of the control parameter for which periodic stationary patterns exist, the dynamics can be decomposed into diffusive and transverse parts which act on a stochastic potential. The relative positions of stationary states in the stochastic global potential landscape can be obtained from the topology spanned by the low-lying eigenmodes which interconnect them. Numerical simulations confirm the predicted landscape. The transverse component also predicts a universal class of vortex-like circulations around fixed points. These drive nonlinear drifting and limit cycle motion of the underlying periodic structure in certain regions of parameter space. Our findings might be relevant in studies of other nonlinear systems such as deep learning neural networks.

Golgi phosphoprotein 3 induces autophagy and epithelial-mesenchymal transition to promote metastasis in colon cancer.

In this study, we aimed to investigate whether and how Golgi phosphoprotein 3 (GOLPH3) facilitates colon cancer metastasis via the regulation of autophagy and epithelial-mesenchymal transition (EMT). The role GOLPH3 plays in colon cancer metastasis was analyzed using western blotting, immunohistochemistry, transwell, wound-healing, and zebrafish assays. Autophagy and EMT were assessed via RNA-sequencing (RNA-seq) analysis, mRFP-GFP-LC3 reporter assays, and their related markers. Significant associations were found between colon cancer clinical and pathological stages and poor prognosis. GOLPH3 facilitates colon cancer metastasis, both in vitro and in vivo. RNA-seq analysis of GOLPH3-overexpressing and control cell models revealed that GOLPH3 enhances EMT and autophagy. Moreover, examination of autophagic, epithelial, and mesenchymal markers in GOLPH3-overexpressing, -silenced, and control cell lines revealed that GOLPH3 promotes EMT and autophagy. When autophagy was inhibited, GOLPH3-promoted metastasis and EMT were counteracted in vitro and in vivo. Using RNA-seq, PI3K/Akt signaling was identified as the key downstream pathway on which GOLPH3 acts. Mechanistically, we demonstrated that GOLPH3 stimulates autophagy and induces EMT via the suppression of the phosphorylation of protein kinase B (Akt) at Ser473. In summary, GOLPH3 induces autophagy and EMT, promoting metastasis in colon cancer. Beyond this, and in contrast to conventional perspectives, we discovered that GOLPH3 represses the phosphorylation of Akt at Ser473.

Levofloxacin: Is It Still Suitable as an Empirically Used Antibiotic During the Perioperative Period of Flexible Ureteroscopic Lithotripsy? A Single-center Experience with 754 Patients.

PURPOSE: To determine the empirical usage of antibiotics and analyze the pathogen spectrum during the perioperative period of flexible ureteroscopic lithotripsy (FURSL) with a focus on levofloxacin. MATERIALS AND METHODS: This retrospective analysis included 754 patients who underwent FURSL successfully in our hospital from January 2015 to July 2019. All patients were indicated urine cultures and prescribed antibiotics during the perioperative period. Patients with negative preoperative urine cultures were divided into levofloxacin (LVXG) and non-levofloxacin groups (NLVXG) based on the empirical use of antibiotics. Operative time, the length of postoperative hospital stays and total hospital stays, total hospitalization costs, postoperative fever rate and removal rate of stones were compared. Patients with positive urine cultures were analyzed for  pathogen distribution and antibiotic resistance. RESULTS: In the empirical use of antibiotics among 541 cases with negative urine cultures, the prescription rate of levofloxacin was 68.95%. Compared to that in NLVXG, LVXG had a lower cost of antibiotics but higher postoperative fever rate and longer hospital stay. There were no significant differences in operative time, the total hospitalization costs and the removal rate of stones between the two groups. The top two common pathogens were Escherichia coli (36.11%) and Enterococcus faecalis (24.07%), with resistance rates of 74.36% and 71.15% to levofloxacin, respectively. CONCLUSION: Levofloxacin might be no longer suitable as the first-line choice of clinical experience when performing FURSL in our center.

Global potential, topology, and pattern selection in a noisy stabilized Kuramoto-Sivashinsky equation.

We formulate a general method to extend the decomposition of stochastic dynamics developed by Ao et al. [J. Phys. Math. Gen. 37, L25-L30 (2004)] to nonlinear partial differential equations which are nonvariational in nature and construct the global potential or Lyapunov functional for a noisy stabilized Kuramoto-Sivashinsky equation. For values of the control parameter where singly periodic stationary solutions exist, we find a topological network of a web of saddle points of stationary states interconnected by unstable eigenmodes flowing between them. With this topology, a global landscape of the steady states is found. We show how to predict the noise-selected pattern which agrees with those from stochastic simulations. Our formalism and the topology might offer an approach to explore similar systems, such as the Navier Stokes equation.

LncRNA PLAC2 upregulates miR-663 to downregulate TGF-ß1 and suppress bladder cancer cell migration and invasion.

BACKGROUND: The roles of lncRNA PLAC2 in bladder cancer (BC) were explored. METHODS: The expression of PLAC2 in two types of tissue of BC patients was detected by RT-qPCR and the expression data were compared by paired t test. The 56 patients were staged according to the AJCC criteria, and 12, 15, 15 and 14 cases were classified into stage I-IV, respectively. The expression of TGF-ß1 and miR-663 in BC tissues were also detected by RT-qPCR experiments. RESULTS: Our data showed that the expression levels of PLAC2 were significantly lower in BC tissues than that in non-cancer tissues. The expression of PLAC2 was not affect by clinical stages and low expression levels of PLAC2 predicted lower survival rate. The expression of PLAC2 was positively correlated with miR-663 and inversely correlated with TGF-ß1 in BC tissues. In BC cells, downregulated TGF-ß1 and upregulated miR-663 were observed after the overexpression of PLAC2. Overexpression of PLAC2 also resulted in suppressed invasion and migration of BC cells. Overexpression of miR-663 resulted in downregulated TGF-ß1 but did not affect the expression of PLAC2. Overexpression of TGF-ß1 reduced the inhibitory effects of overexpression of PLAC2 and miR-663 on cell migration and invasion. CONCLUSION: PLAC2 can upregulate miR-663 to downregulate TGF-ß1 and suppress BC cell migration and invasion.

Adaptive Landscape Shaped by Core Endogenous Network Coordinates Complex Early Progenitor Fate Commitments in Embryonic Pancreas.

The classical development hierarchy of pancreatic cell fate commitments describes that multipotent progenitors (MPs) first bifurcate into tip cells and trunk cells, and then these cells give rise to acinar cells and endocrine/ductal cells separately. However, lineage tracings reveal that pancreatic progenitors are highly heterogeneous in tip and trunk domains in embryonic pancreas. The progenitor fate commitments from multipotency to unipotency during early pancreas development is insufficiently characterized. In pursuing a mechanistic understanding of the complexity in progenitor fate commitments, we construct a core endogenous network for pancreatic lineage decisions based on genetic regulations and quantified its intrinsic dynamic properties using dynamic modeling. The dynamics reveal a developmental landscape with high complexity that has not been clarified. Not only well-characterized pancreatic cells are reproduced, but also previously unrecognized progenitors-tip progenitor (TiP), trunk progenitor (TrP), later endocrine progenitor (LEP), and acinar progenitors (AciP/AciP2) are predicted. Further analyses show that TrP and LEP mediate endocrine lineage maturation, while TiP, AciP, AciP2 and TrP mediate acinar and ductal lineage maturation. The predicted cell fate commitments are validated by analyzing single-cell RNA sequencing (scRNA-seq) data. Significantly, this is the first time that a redefined hierarchy with detailed early pancreatic progenitor fate commitment is obtained.

CGRP Reduces Apoptosis of DRG Cells Induced by High-Glucose Oxidative Stress Injury through PI3K/AKT Induction of Heme Oxygenase-1 and Nrf-2 Expression.

Dorsal root ganglion (DRG) neurons, which are sensitive to oxidative stress due to their anatomical and structural characteristics, play a complex role in the initiation and progression of diabetic bladder neuropathy. We investigated the hypothesis that the antioxidant and antiapoptotic effects of CGRP may be partly related to the expression of Nrf2 and HO-1, via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, thus reducing apoptosis and oxidative stress responses. This study shows that CGRP activates the PI3K/AKT pathway, thereby inducing increased expression of Nrf2 and HO-1 and resulting in the decrease of reactive oxygen species and malondialdehyde levels and reduced neuronal apoptosis. These effects were suppressed by LY294002, an inhibitor of the PI3K/AKT pathway. Therefore, regulation of Nrf2 and HO-1 expression by the PI3K/AKT pathway plays an important role in the regulation of the antioxidant and antiapoptotic responses in DRG cells in a high-glucose culture model.

Publisher Correction: Potential landscape of high dimensional nonlinear stochastic dynamics with large noise.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Resonant Confinement of an Excitonic Polariton and Ultraefficient Light Harvest in Artificial Photosynthesis.

We uncover a novel phenomenon from a recent artificial light-harvesting experiment [P.-Z. Chen et al., Angew. Chem., Int. Ed. Engl. 55, 2759 (2016)ACIEAY0570-083310.1002/anie.201510503] on organic nanocrystals of self-assembled difluoroboron chromophores. A resonant confinement of a polariton under strong photon-exciton coupling is predicted to exist within the microcavity of the crystal's own natural boundaries. Moreover, the radiative energy of a localized exciton falls into the spectrum of confinement. Hence, in the experiment, the spontaneous emission of an excited pigment would undergo a two-step process. It should first decay to an excitonic polariton trapped by the cavity resonance. The intermediate polariton could then funnel the energy directly to a doped acceptor, leading to the over 90% transfer efficiency observed at less than 1/1000 acceptor/donor ratio. The proposed mechanism is supported by parameter-free analyses entirely based on experiment data. Our finding may imply possible polariton-mediated pathways for energy transfers in biological photosynthesis.

Correction to: 'Dynamical modelling of secondary metabolism and metabolic switches in Streptomyces xiamenensis 318'.

[This corrects the article DOI: 10.1098/rsos.190418.].

Dynamical modelling of secondary metabolism and metabolic switches in Streptomyces xiamenensis 318.

The production of secondary metabolites, while important for bioengineering purposes, presents a paradox in itself. Though widely existing in plants and bacteria, they have no definite physiological roles. Yet in both native habitats and laboratories, their production appears robust and follows apparent metabolic switches. We show in this work that the enzyme-catalysed process may improve the metabolic stability of the cells. The latter can be responsible for the overall metabolic behaviours such as dynamic metabolic landscape, metabolic switches and robustness, which can in turn affect the genetic formation of the organism in question. Mangrove-derived Streptomyces xiamenensis 318, with a relatively compact genome for secondary metabolism, is used as a model organism in our investigation. Integrated studies via kinetic metabolic modelling, transcriptase measurements and metabolic profiling were performed on this strain. Our results demonstrate that the secondary metabolites increase the metabolic fitness of the organism via stabilizing the underlying metabolic network. And the fluxes directing to NADH, NADPH, acetyl-CoA and glutamate provide the key switches for the overall and secondary metabolism. The information may be helpful for improving the xiamenmycin production on the strain.