The calcium-dependent protein kinase CPK16 regulates hypoxia-induced ROS production by phosphorylating the NADPH oxidase RBOHD in Arabidopsis.

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N terminus of RBOHD at four serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16-RBOHD module shapes ROS production during hypoxia and reoxygenation in Arabidopsis.

Effect of vinegar supplementation on patients with esophageal lesions lightly stained with Lugol's iodine solution: Prospective single-centre trial.

BACKGROUND: Esophageal chromoendoscopy with iodine solution is important for detecting early esophageal cancer. The effect of routine treatment for lesions lightly stained with Lugol's iodine solution is limited, and the addition of natural substances to a regular diet is becoming increasingly common. Vinegar has antitumor effects as reported in previous studies. AIM: To evaluate whether vinegar supplementation could improve the prognosis of patients with lightly stained esophageal lesions. METHODS: This prospective single-centre trial included consecutive patients with lightly stained lesions between June 2020 and April 2022. Patients in the experimental group received increased amounts of vinegar for 6 months. The primary outcome of the study was the clinical therapeutic effect. Complications related to vinegar ingestion and adverse events were also recorded in detail. RESULTS: A total of 166 patients were included in the final analysis. There was no significant difference in the baseline data between the two groups. Intention-to-treat (ITT) analysis demonstrated that the rates at which endoscopic characteristics improved were 33.72% in the experimental group and 20.00% in the conventional group (P = 0.007); and the rates at which biopsy pathology improved were 19.77% and 8.75%, respectively (P = 0.011). Additional vinegar consumption had a statistically protective effect on the rate at which endoscopic characteristics improved [hazard ratio (HR) ITT = 2.183, 95%CI: 1.183-4.028; HRper-protocol (PP) = 2.307, 95%CI: 1.202-4.426] and biopsy pathology improved (HRITT = 2.931, 95%CI: 1.212-7.089; HRPP = 3.320, 95%CI: 1.295-8.507). No statistically significant effect of increased vinegar consumption on preventing high-grade intraepithelial neoplasia or early cancer was observed (HRITT = 0.382, 95%CI: 0.079-1.846; HRPP = 0.382, 95%CI: 0.079-1.846). The subgroup analyses indicated that the overall therapeutic improvement of endoscopic characteristics and biopsy pathology seemed more obvious in older (age > 60) male patients with small lesions (lesion size ≤ 0.5 cm). Three patients in the experimental group reported acid regurgitation and heartburn. No adverse event during gastroscopy were recorded during follow-up. CONCLUSION: A moderately increased ingestion of vinegar could not directly reduce the risk of esophageal cancer in the mucosa dysplasia population, but it improved the endoscopic characteristics and ameliorated the biopsy pathology to a certain extent. Further research is needed to verify the effect of nutritional intervention on precancerous esophageal lesions.

Toward Real Chemical Accuracy on Current Quantum Hardware Through the Transcorrelated Method.

Quantum computing is emerging as a new computational paradigm with the potential to transform several research fields including quantum chemistry. However, current hardware limitations (including limited coherence times, gate infidelities, and connectivity) hamper the implementation of most quantum algorithms and call for more noise-resilient solutions. We propose an explicitly correlated Ansatz based on the transcorrelated (TC) approach to target these major roadblocks directly. This method transfers, without any approximation, correlations from the wave function directly into the Hamiltonian, thus reducing the resources needed to achieve accurate results with noisy quantum devices. We show that the TC approach allows for shallower circuits and improves the convergence toward the complete basis set limit, providing energies within chemical accuracy to experiment with smaller basis sets and, thus, fewer qubits. We demonstrate our method by computing bond lengths, dissociation energies, and vibrational frequencies close to experimental results for the hydrogen dimer and lithium hydride using two and four qubits, respectively. To demonstrate our approach's current and near-term potential, we perform hardware experiments, where our results confirm that the TC method paves the way toward accurate quantum chemistry calculations already on today's quantum hardware.

Dapagliflozin ameliorates myocardial infarction injury through AMPKα-dependent regulation of oxidative stress and apoptosis.

Dapagliflozin (DAPA) has been demonstrated to reduce cardiovascular mortality and heart failure hospitalization rates in diabetic patients. However, the mechanism underlying its cardio-protective effect in non-diabetic patients remains unclear. Our study aimed to explore the cardio-protective impact of DAPA on myocardial infarction in non-diabetic mice. We induced myocardial infarction in C57BL/6 mice by ligating the descending branch of the left coronary artery. After surgery, the animals were randomly treated with either saline or DAPA. We employed echocardiography, Western blot analysis, and tissue staining to assess post-infarction myocardial injury. Additionally, we investigated the mechanism of action through cell experiments. Compared to the myocardial infarction group, DAPA treatment significantly attenuated ventricular remodeling and improved cardiac function. By mitigating myocardial oxidative stress and apoptosis, DAPA may activate the AMPKα signaling pathway, thereby exerting a protective effect. These findings suggest that DAPA could serve as a novel therapeutic approach for patients with cardiac infarction.

Karyotype and LTR-RTs analysis provide insights into oak genomic evolution.

BACKGROUND: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. RESULTS: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. CONCLUSION: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs.

Effect of Negative Online Reviews and Physician Responses on Health Consumers' Choice: Experimental Study.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of online medical services. Although some researchers have investigated how numerical ratings affect consumer choice, limited studies have focused on the effect of negative reviews that most concern physicians. OBJECTIVE: This study aimed to investigate how negative review features, including proportion (low/high), claim type (evaluative/factual), and physician response (absence/presence), influence consumers' physician evaluation process under conditions in which a physician's overall rating is high. METHODS: Using a 2×2×2 between-subject decision-controlled experiment, this study examined participants' judgment on physicians with different textual reviews. Collected data were analyzed using the t test and partial least squares-structural equation modeling. RESULTS: Negative reviews decreased consumers' physician selection intention. The negative review proportion (ß=-0.371, P<.001) and claim type (ß=-0.343, P<.001) had a greater effect on consumers' physician selection intention compared to the physician response (ß=0.194, P<.001). A high negative review proportion, factual negative reviews, and the absence of a physician response significantly reduced consumers' physician selection intention compared to their counterparts. Consumers' locus attributions on the negative reviews affected their evaluation process. Physician attribution mediated the effects of review proportion (ß=-0.150, P<.001), review claim type (ß=-0.068, P=.01), and physician response (ß=0.167, P<.001) on consumer choice. Reviewer attribution also mediated the effects of review proportion (ß=-0.071, P<.001), review claim type (ß=-0.025, P=.01), and physician response (ß=0.096, P<.001) on consumer choice. The moderating effects of the physician response on the relationship between review proportion and physician attribution (ß=-0.185, P<.001), review proportion and reviewer attribution (ß=-0.110, P<.001), claim type and physician attribution (ß=-0.123, P=.003), and claim type and reviewer attribution (ß=-0.074, P=.04) were all significant. CONCLUSIONS: Negative review features and the physician response significantly influence consumer choice through the causal attribution to physicians and reviewers. Physician attribution has a greater effect on consumers' physician selection intention than reviewer attribution does. The presence of a physician response decreases the influence of negative reviews through direct and moderating effects. We propose some practical implications for physicians, health care providers, and online medical service platforms.

Advances in MiRNAs Involved in Endometrial Carcinoma.

Endometrial carcinoma (EC) is a common malignancy worldwide. Existing evidence has revealed that EC could be associated with abnormal gene expression. Meantime, evidence supports that miRNAs act as critical regulators in gene expression through the binding to the 3'- untranslated region (3'-UTR). Accordingly, this review concludes some recent studies focusing on miRNAs that influence EC, aiming at understanding the association between miRNAs and EC more clearly and providing a reference for further studies on miRNA-related drugs treating EC.

Black phosphorus-based nanoparticles induce liver cancer cell mitochondrial apoptosis and immune cell tumor infiltration for enhancing dendritic cell therapy.

Cellular immunotherapy is a crucial aspect of current tumor immunotherapy, though it presents several challenges such as immune cell dysfunction, limited recognition of neoantigens, and inadequate lymphocyte infiltration into the tumor microenvironment. This study proposes a novel approach utilizing a combination of dendritic cell (DC)-based cellular immunotherapy and a photothermal nanoadjuvant black phosphorus (BP) nanoparticles to overcome these challenges. A new platform called PLGA@BP-R848, which consists of modifying poly-(lactic-co-glycolic acid) (PLGA) onto BP nanosheets loading the immune adjuvant R848. The PLGA@BP-R848 nanoparticles demonstrated exceptional drug delivery and release capabilities, as well as a photothermal effect, biocompatibility, and the ability to activate the mitochondrial apoptotic pathway Blc-2-Bax-Cytochrome c-caspase-3 and inhibit the PI3K-AKT-mTOR signaling pathway. In a hepatocellular carcinoma mouse model, the binding of PLGA@BP-R848 nanoparticles and dendritic cells primed with GPC3 peptides, successfully induced a systemic anti-tumor immune response. PLGA@BP-R848 nanoparticles bolster immune cell infiltration into tumors and induce cancer cell apoptosis. The synergistic therapy involving dendritic cells and photothermal nanoadjuvant effectively suppressed tumor growth, and facilitated the formation of tertiary lymphatic structures (TLS) in tumors. This study presents a novel approach in using photothermal nanoadjuvants to advance antitumor effect of cellular immunotherapy, such as DCs therapy.

The Effect of Sensory Reweighting on Postural Control and Cortical Activity in Parkinson's Disease.

Aims: Balance requires the cortical control of visual, somatosensory, and vestibular inputs. The aim of this cross-sectional study was to compare the contributions of each of these systems on postural control and cortical activity using a sensory reweighting approach between participants with Parkinson's disease (PD) and controls. Methods: Ten participants with PD (age: 72 ± 9; 3 women; Hoehn & Yahr: 2 [1.5 - 2.50]) and 11 controls (age: 70 ± 3; 4 women) completed a sensory organization test in virtual reality (VR-SOT) while cortical activity was being recorded using electroencephalography (EEG). Conditions 1 to 3 were completed on a stable platform; conditions 4 to 6 on a foam. Conditions 1 and 4 were done with eyes open; conditions 2 and 5 in a darkened VR environment; and conditions 3 and 6 in a moving VR environment. Linear mixed models were used to evaluate changes in center of pressure (COP) displacement and EEG alpha and theta/beta ratio power between the two groups across the postural control conditions. Condition 1 was used as reference in all analyses. Results: Participants with PD showed greater COP displacement than controls in the anteroposterior (AP) direction when relying on vestibular input (condition 5; p<0.0001). The mediolateral (ML) COP sway was greater in PD than in controls when relying on the somatosensory (condition 2; p = 0.03), visual (condition 4; p = 0.002), and vestibular (condition 5; p < 0.0001) systems. Participants with PD exhibited greater alpha power compared to controls when relying on visual input (condition 2; p = 0.003) and greater theta/beta ratio power when relying on somatosensory input (condition 4; p = 0.001). Conclusions: PD affects reweighting of postural control, exemplified by greater COP displacement and increased cortical activity. Further research is needed to establish the temporal dynamics between cortical activity and COP displacement.

Facile fabrication of carbon nanotube hollow microspheres as a fiber coating for ultrasensitive solid-phase microextraction of phthalic acid esters in tea beverages.

The efficient extraction of phthalic acid esters (PAEs) is challenging due to their extremely low concentration, complicated matrices and hydrophilicity. Herein, hollow microspheres, as an ideal coating, possess significant potential for solid-phase microextraction (SPME) due to their fascinating properties. In this study, multiwalled carbon nanotube hollow microspheres (MWCNT-HMs) were utilized as a fiber coating for the SPME of PAEs from tea beverages. MWCNT-HMs were obtained by dissolving the polystyrene (PS) cores with organic solvents. Interestingly, MWCNT-HMs well maintain the morphology of the MWCNTs@PS precursors. The layer-by-layer (LBL) assembly of MWCNTs on PS microsphere templates was achieved through electrostatic interactions. Six PAEs, di-ethyl phthalate (DEP), di-iso-butyl phthalate (DIBP), di-n-butyl phthalate (DBP), benzyl butyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and di-n-octyl phthalate (DOP), were selected as target analytes for assessing the efficiency of the coating for SPME. The stirring rate, sample solution pH and extraction time were optimized by using the Box-Behnken design. Under optimal working conditions, the proposed MWCNT-HMs/SPME was coupled with gas chromatography-tandem mass spectrometry (GC-MS/MS) to achieve high enrichment factors (118-2137), wide linearity (0.0004-10 µg L-1), low limits of detection (0.00011-0.0026 µg L-1) and acceptable recovery (80.2-108.5%) for the detection of PAEs. Therefore, the MWCNT-HM coated fibers are promising alternatives in the SPME method for the sensitive detection of PAEs at trace levels in tea beverages.

Block2: A comprehensive open source framework to develop and apply state-of-the-art DMRG algorithms in electronic structure and beyond.

block2 is an open source framework to implement and perform density matrix renormalization group and matrix product state algorithms. Out-of-the-box it supports the eigenstate, time-dependent, response, and finite-temperature algorithms. In addition, it carries special optimizations for ab initio electronic structure Hamiltonians and implements many quantum chemistry extensions to the density matrix renormalization group, such as dynamical correlation theories. The code is designed with an emphasis on flexibility, extensibility, and efficiency and to support integration with external numerical packages. Here, we explain the design principles and currently supported features and present numerical examples in a range of applications.

Therapeutic effect of umbilical cord blood cells on spinal cord injury.

Spinal cord injury (SCI) is a nervous system disease characterized by sensory and motor dysfunction, axonal apoptosis, decreased vascular density, and inflammation. At present, surgical treatment, drug treatment, and cell therapy can be used. Surgical treatment can improve motor and independent function scores, and drug treatment can promote the recovery of neurons in the spinal cord, but only improve symptoms. Complete recovery of SCI has not yet been achieved. However, the differentiation of stem cells brings hope for the treatment of SCI. Umbilical cord blood cells (UCBs) are ethically readily available and can repair neuronal damage. However, it is still unclear how they can improve symptoms and repair nerve severity. In this paper, the role of UCBs in the treatment of SCI is described in detail from different aspects such as behavior, morphology, and molecular expression changes, so as to provide new ideas and theoretical directions for future research.

Discovery of a Superconductor Bi5 O4 S3 Cl Containing the Unique BiS3 Layer.

The BiS2 -based layered superconductors with structures similar to those of cuprates and iron-based superconductors have stimulated much research interest. Here, a new quaternary compound is reported, Bi5 O4 S3 Cl, which crystalizes in a tetragonal structure with P4/mmm (No. 123) space group having alternately stacking unique BiS3 layers and Bi2 O2 layers along the c-axis with a Cl atom located at the center of the unit cell. A superconducting transition above 3 K is observed for both electrical transport and magnetic measurements. Hall resistivity measurements show its multiband character with a conduction dominated by electron-like charge carriers. The first-principles calculations exhibit that the semiconducting parent phase Bi5 O4 S3 Cl becomes metallic when sulfur vacancies are introduced, which hints the origin of superconductivity in Bi5 O4 S3 Cl. The findings will inspire the exploration of new BiS-based superconductors.

Newt A1 cell-derived extracellular vesicles promote mammalian nerve growth.

Newts have the extraordinary ability to fully regenerate lost or damaged cardiac, neural and retinal tissues, and even amputated limbs. In contrast, mammals lack these broad regenerative capabilities. While the molecular basis of newts' regenerative ability is the subject of active study, the underlying paracrine signaling factors involved remain largely uncharacterized. Extracellular vesicles (EVs) play an important role in cell-to-cell communication via EV cargo-mediated regulation of gene expression patterns within the recipient cells. Here, we report that newt myogenic precursor (A1) cells secrete EVs (A1EVs) that contain messenger RNAs associated with early embryonic development, neuronal differentiation, and cell survival. Exposure of rat primary superior cervical ganglion (SCG) neurons to A1EVs increased neurite outgrowth, facilitated by increases in mitochondrial respiration. Canonical pathway analysis pinpointed activation of NGF/ERK5 signaling in SCG neurons exposed to A1EV, which was validated experimentally. Thus, newt EVs drive neurite growth and complexity in mammalian primary neurons.

[Cigarette Smoke Induces Gefitinib Resistance in NSCLC Cells 
via ROS/Sirt3/SOD2 Pathway].

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutations are the most common driver mutations in non-small cell lung cancer (NSCLC). To prolong the survival of the patients, EGFR tyrosine kinase inhibitors (TKIs) resistance in NSCLC is a major challenge that needs to be addressed urgently, and this study focuses on investigating the mechanism of cigarette smoke (CS) induced Gefitinib resistance in NSCLC. METHODS: PC-9 and A549 cells were cultured in vitro and treated with 1 µmol/L Gefitinib for 4 h and 10% cigarette smoke extract (CSE) for 48 h. Western blot was used to detect Sirtuin 3 (Sirt3) and superoxide dismutase 2 (SOD2) protein expressions; DCFH-DA probe was used to detect intracellular reactive oxygen species (ROS); CCK-8 kit was used to detect cell activity, and EdU was used to detect cell proliferation ability. Sirt3 overexpression plasmid (OV-Sirt3) was transfected in PC-9 and A549 cells and treated with 1 µmol/L Gefitinib for 4 h and 10% CSE for 48 h after N-acetylcysteine (NAC) action. The expressions of Sirt3 and SOD2 were detected by Western blot; the ROS level in the cells was detected by DCFH-DA probe, and the cell activity was detected by CCK-8. RESULTS: CSE induced an increase in the 50% inhibitory concentration (IC50) of both PC-9 and A549 cells to Gefitinib (P<0.01) and enhanced the proliferation of PC-9 and A549 cells, suggesting that CS induced Gefitinib resistance in NSCLC. ROS was involved in CSE-induced Gefitinib resistance (P<0.05). CSE induced low expressions of Sirt3 and SOD2 (P<0.01), and Sirt3/SOD2 was associated with poor prognosis in lung cancer patients (P<0.05). OV-Sirt3 in PC-9 and A549 cells reversed CSE-induced Gefitinib resistance (P<0.05) and significantly reduced ROS production. NAC reversed CSE-induced Gefitinib resistance in PC-9 and A549 cells (P<0.05). CONCLUSIONS: The ROS/Sirt3/SOD2 pathway is involved in CS-induced Gefitinib resistance in NSCLC.

Photoredox Cleavage of a Csp3-Csp3 Bond in Aromatic Hydrocarbons.

Functionalizing molecules through the selective cleavage of carbon-carbon bonds is an attractive approach in synthetic chemistry. Despite recent advances in both transition-metal catalysis and radical chemistry, the selective cleavage of inert Csp3-Csp3 bonds in hydrocarbon feedstocks remains challenging. Examples reported in the literature typically involve substrates containing redox functional groups or highly strained molecules. In this article, we present a straightforward protocol for the cleavage and functionalization of Csp3-Csp3 bonds in alkylbenzenes using photoredox catalysis. Our method employs two distinct bond scission pathways. For substrates with tertiary benzylic substituents, a carbocation-coupled electron transfer mechanism is prevalent. For substrates with primary or secondary benzylic substituents, a triple single-electron oxidation cascade is applicable. Our strategy offers a practical means of cleaving inert Csp3-Csp3 bonds in molecules without any heteroatoms, resulting in primary, secondary, tertiary, and benzylic radical species.

Calcium-dependent activation of CPK12 facilitates its cytoplasm-to-nucleus translocation to potentiate plant hypoxia sensing by phosphorylating ERF-VII transcription factors.

Calcium-dependent protein kinases (CDPKs/CPKs) are key regulators of plant stress signaling that translate calcium signals into cellular responses by phosphorylating diverse substrate proteins. However, the molecular mechanism by which plant cells relay calcium signals in response to hypoxia remains elusive. Here, we show that one member of the CDPK family in Arabidopsis thaliana, CPK12, is rapidly activated during hypoxia through calcium-dependent phosphorylation of its Ser-186 residue. Phosphorylated CPK12 shuttles from the cytoplasm to the nucleus, where it interacts with and phosphorylates the group VII ethylene-responsive transcription factors (ERF-VII) that are core regulators of plant hypoxia sensing, to enhance their stabilities. Consistently, CPK12 knockdown lines show attenuated tolerance of hypoxia, whereas transgenic plants overexpressing CPK12 display improved hypoxia tolerance. Nonethelss, loss of function of five ERF-VII proteins in an erf-vii pentuple mutant could partially suppress the enhanced hypoxia-tolerance phenotype of CPK12-overexpressing lines. Moreover, we also discovered that phosphatidic acid and 14-3-3κ protein serve as positive and negative modulators of the CPK12 cytoplasm-to-nucleus translocation, respectively. Taken together, these findings uncover a CPK12-ERF-VII regulatory module that is key to transducing calcium signals from the cytoplasm into the nucleus to potentiate hypoxia sensing in plants.

Cigarette smoke induces the ROS accumulation and iNOS activation through deactivation of Nrf-2/SIRT3 axis to mediate the human bronchial epithelium ferroptosis.

Cigarette smoke (CS)-induced oxidative stress drives the pathogenesis of respiratory diseases, in which the activation and accumulation of reactive oxygen species (ROS) play an important role. Ferroptosis, a regulated cell death induced by Fe2+-dependent, lipid peroxidation, and ROS, is closely related to CS-induced airway injury disease, but its mechanism remains unclear. We found that bronchial epithelial ferroptosis and expression of iNOS in smoking patients were significantly higher than that in non-smokers. The iNOS, induced by CS exposure, was involved in bronchial epithelial cell ferroptosis, whereas genetic depletion or pharmacologic inactivation of iNOS attenuated the CS-induced ferroptosis and mitochondrial dysfunction. Our mechanistic studies found that SIRT3 directly bound to and negatively regulated iNOS to mediate ferroptosis. Moreover, we found that the Nrf-2/SIRT3 signal was deactivated by cigarette smoke extract (CSE)-induced ROS. Collectively, these results linked CS to human bronchial epithelial cell ferroptosis through ROS deactivation of the Nrf-2/SIRT3 signal to promote iNOS expression. Our study provides new insights into the pathogenesis of CS-induced tracheal injury diseases such as chronic bronchitis, emphysema, and chronic obstructive pulmonary disease.

Density Matrix Renormalization Group for Transcorrelated Hamiltonians: Ground and Excited States in Molecules.

We present the theory of a density matrix renormalization group (DMRG) algorithm which can solve for both the ground and excited states of non-Hermitian transcorrelated Hamiltonians and show applications in molecular systems. Transcorrelation (TC) accelerates the basis set convergence rate by including known physics (such as, but not limited to, the electron-electron cusp) in the Jastrow factor used for the similarity transformation. It also improves the accuracy of approximate methods such as coupled cluster singles and doubles (CCSD) as shown by recent studies. However, the non-Hermiticity of the TC Hamiltonians poses challenges for variational methods like DMRG. Imaginary-time evolution on the matrix product state (MPS) in the DMRG framework has been proposed to circumvent this problem, but this is currently limited to treating the ground state and has lower efficiency than the time-independent DMRG (TI-DMRG) due to the need to eliminate Trotter errors. In this work, we show that with minimal changes to the existing TI-DMRG algorithm, namely, replacing the original Davidson solver with the general Davidson solver to solve the non-Hermitian effective Hamiltonians at each site for a few low-lying right eigenstates, and following the rest of the original DMRG recipe, one can find the ground and excited states with improved efficiency compared to the original DMRG when extrapolating to the infinite bond dimension limit in the same basis set. An accelerated basis set convergence rate is also observed, as expected, within the TC framework.

SERS spectroscopy with machine learning to analyze human plasma derived sEVs for coronary artery disease diagnosis and prognosis.

Coronary artery disease (CAD) is one of the major cardiovascular diseases and represents the leading causes of global mortality. Developing new diagnostic and therapeutic approaches for CAD treatment are critically needed, especially for an early accurate CAD detection and further timely intervention. In this study, we successfully isolated human plasma small extracellular vesicles (sEVs) from four stages of CAD patients, that is, healthy control, stable plaque, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction. Surface-enhanced Raman scattering (SERS) measurement in conjunction with five machine learning approaches, including Quadratic Discriminant Analysis, Support Vector Machine (SVM), K-Nearest Neighbor, Artificial Neural network, were then applied for the classification and prediction of the sEV samples. Among these five approaches, the overall accuracy of SVM shows the best predication results on both early CAD detection (86.4%) and overall prediction (92.3%). SVM also possesses the highest sensitivity (97.69%) and specificity (95.7%). Thus, our study demonstrates a promising strategy for noninvasive, safe, and high accurate diagnosis for CAD early detection.