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Abstract We analyze correlation functions of SU(k) × SU(2) F flavor currents in a family of three-dimensional N $$ \mathcal{N} $$ = 4 superconformal field theories, combining analytic bootstrap methods with input from supersymmetric localization. Via holographic duality, we extract gluon and graviton scattering amplitudes of M-theory on AdS4 × S 7/ℤ k which contains a ℂ2/ℤ k orbifold singularity. From these results, we derive aspects of the effective description of M-theory on the orbifold singularity beyond its leading low energy limit. We also determine a threshold correction to the holographic correlator from the combined contribution of two-loop gluon and tree-level bulk graviton exchange.

Abstract Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

BackgroundPrevious epidemiological studies have reported an association between Sjögren’s syndrome (SS) and Parkinson’s disease (PD); however, the causality and direction of this relationship remain unclear. In this study, we aimed to investigate the causal relationship between genetically determined SS and the risk of PD using bidirectional Mendelian randomization (MR).MethodsSummary statistics for Sjögren’s syndrome used as exposure were obtained from the FinnGen database, comprising 1,290 cases and 213,145 controls. The outcome dataset for PD was derived from the United Kingdom Biobank database, including 6,998 cases and 415,466 controls. Various MR methods, such as inverse variance weighted (IVW), Mendelian randomization Egger regression (MR-Egger), weighted median (WM), simple mode, weighted mode, MR-pleiotropy residual sum and outlier (MR-PRESSO), and robust adjusted profile score (RAPS), were employed to investigate the causal effects of SS on PD. Instrumental variable strength evaluation and sensitivity analyses were conducted to ensure the reliability of the results. In addition, reverse MR analysis was performed to examine the causal effects of PD on SS.ResultsThe WM, IVW, RAPS and MR-PRESSO methods demonstrated a significant association between genetically predicted SS and reduced risk of PD (odds ratio ORWM = 0.9988, ORIVW = 0.9987, ORRAPS = 0.9987, ORMR-PRESSO = 0.9987, respectively, P < 0.05). None of the MR analyses showed evidence of horizontal pleiotropy (P > 0.05) based on the MR-Egger and MR-PRESSO tests, and there was no statistical heterogeneity in the test results of the MR-Egger and IVW methods. The leave-one-out sensitivity analysis confirmed the robustness of the causal relationship between SS and PD. Furthermore, reverse MR analysis did not support any causal effects of PD on SS.ConclusionOur MR study supports a potential causal association between SS and a reduced risk of PD. Further extensive clinical investigations and comprehensive fundamental research are warranted to elucidate the underlying mechanisms linking SS and PD.

Using electrolytic zero-valent iron-activated sodium hypochlorite (EZVI-NaClO) to pretreat sludge, the capillary suction time (CST) was utilized to evaluate sludge dewaterability. Ammonia nitrogen (NH4-N), dissolved phosphorus, and total phosphorus in the supernatant were used to analyze sludge disintegration. This approach aimed to evaluate the effectiveness of the pretreatment process and its impact on the sludge composition. The migration and transformation of extracellular polymeric substances (EPS), including dissolved EPS (S-EPS), loosely boundEPS, and tightly bound-EPS (TB-EPS), were analyzed by detecting protein and polysaccharide concentrations and three-dimensional fluorescence excitation-emission spectroscopy (3D-EEM). The sludge particle properties, including sludge viscosity and particle size, were also analyzed. The results suggested that the optimal pH value, NaClO dosage, current, and reaction time were 2, 100 mg/gDS (dry sludge), 0.2A, and 30 min, respectively, with a CST reduction of 43%. Protein and polysaccharide contents in TB-EPS were significantly reduced in the EZVI-NaClO group. Conversely, protein and polysaccharides contents in S-EPS increased, suggesting that EZVI-NaClO treatment could disrupt the EPS. Besides, the viscosity of the treated sludge decreased from 195.4 to 54.9 mPa·S, indicating that sludge fluidity became better. ZEVI-NaClO could enhance sludge dewaterability by destructing protein and polysaccharide structure and improving sludge hydrophobicity. HIGHLIGHTS Electrolytic zero-valent iron-activated sodium hypochlorite (EZVI-NaClO)-modified extracellular polymeric substance (EPS) extracted from WAS.; EZVI-NaClO can reduce O = C-NH- that affects protein strength and stiffness.; EZVI-NaClO enhances the flocculation and hydrophobicity of EPS.;

Abstract Background How physical activity (PA) and different sleep traits and overall sleep pattern interact in the development of Parkinson’s disease (PD) remain unknown. Objective To prospectively investigate the joint associations of PA and sleep pattern with risk of PD. Methods Included were 339,666 PD-free participants from the UK Biobank. Baseline PA levels were grouped into low (

IntroductionParkinson’s disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≤ 1.5.MethodWe used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≤ 1.5). The models were independently validated using separate datasets.ResultsOur results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≤ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75.ConclusionThe results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment.

Summary: Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan–Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423–1.262) in the azvudine group 0.802 (0.435–1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805–3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546–3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the “National Key R&D Program of China” (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Abstract We study the effect of D-instantons on closed string scattering amplitudes in the two-dimensional type 0B string theory from the worldsheet perspective. We find that the contribution from a pair of D-instanton and anti-D-instanton to the closed string reflection amplitude, with a suitable contour prescription for the integration over the D-instanton moduli space, agrees with the corresponding leading non-perturbative corrections in the proposed dual matrix quantum mechanics. This analysis is further extended to thermal observables defined at finite temperature. The infrared divergence in charged processes is understood through the measure factor for charged D-instantons, and can be treated with spacetime dimensional regularization.

Abstract We study the perturbative S-matrix of closed strings in the two-dimensional type 0B string theory from the worldsheet perspective, by directly integrating correlation functions of N $$ \mathcal{N} $$ = 1 Liouville theory. The latter is computed numerically using recurrence relations for super-Virasoro conformal blocks. We show that the tree level 3- and 4-point amplitudes are in agreement with the proposed dual matrix quantum mechanics. The non-perturbative aspects of the duality will be analyzed in a companion paper.

Abstract We formulate a strategy for computing the complete set of non-perturbative corrections to closed string scattering in c = 1 string theory from the worldsheet perspective. This requires taking into account the effect of multiple ZZ-instantons, including higher instantons constructed from ZZ boundary conditions of type (m, 1), with a careful treatment of the measure and contour in the integration over the instanton moduli space. The only a priori ambiguity in our prescription is a normalization constant N $$ \mathcal{N} $$ m that appears in the integration measure for the (m, 1)-type ZZ instanton, at each positive integer m. We investigate leading corrections to the closed string reflection amplitude at the n-instanton level, i.e. of order e − n / g s $$ {e}^{-n/{g}_s} $$ , and find striking agreement with our recent proposal on the non-perturbative completion of the dual matrix quantum mechanics, which in turn fixes N $$ \mathcal{N} $$ m for all m.

Abstract We study the effect of ZZ instantons in c = 1 string theory, and demonstrate that they give rise to non-perturbative corrections to scattering amplitudes that do not saturate unitarity within the closed string sector. Beyond the leading non-perturbative order, logarithmic divergences are canceled between worldsheet diagrams of different topologies, due to the Fischler-Susskind-Polchinski mechanism. We propose that the closed string vacuum in c = 1 string theory is non-perturbatively dual to a state of the matrix quantum mechanics in which all scattering states up to a given energy with no incoming flux from the “other side” of the potential are occupied by free fermions. Under such a proposal, we find detailed agreement of non-perturbative corrections to closed string amplitudes in the worldsheet description and in the dual matrix model.

Abstract In this paper we give a streamlined derivation of the exact quantization condition (EQC) on the quantum periods of the Schrödinger problem in one dimension with a general polynomial potential, based on Wronskian relations. We further generalize the EQC to potentials with a regular singularity, describing spherical symmetric quantum mechanical systems in a given angular momentum sector. We show that the thermodynamic Bethe ansatz (TBA) equations that govern the quantum periods undergo nontrivial monodromies as the angular momentum is analytically continued between integer values in the complex plane. The TBA equations together with the EQC are checked numerically against Hamiltonian truncation at real angular momenta and couplings, and are used to explore the analytic continuation of the spectrum on the complex angular momentum plane in examples.

Abstract We establish the equivalence between two formulations of superstring perturbation theory, one based on integration over the supermoduli space of super Riemann surfaces (SRS), the other based on integration over the bosonic moduli space with insertions of picture changing operators (PCO) on the worldsheet and the vertical integration prescription, by showing how the latter arises from a specific construction of the supermoduli integration contour.

Abstract We illustrate the relation between supermoduli integration and picture changing operators (PCOs) particularly concerning the role of vertical integration, in the context of superstring vacuum amplitudes, by an explicit comparison of different parameterizations of the supermoduli space of genus two super Riemann surfaces.

The cogeneration of hydrogen peroxide (H _2 O _2 ) and power in proton exchange membrane fuel cell (PEMFC) reactors via two-electron oxygen reduction reaction on the cathode is an economical, low-carbon, and green route for the on-site production of H _2 O _2 . However, in practice, the H _2 O _2 that cannot be collected timely will accumulate and self-decompose in the catalyst layer (CL), reducing the H _2 O _2 generation efficiency. Thus, accelerating the mass transport of H _2 O _2 within the cathode CL is critical to efficient H _2 O _2 generation in PEMFC. Herein, we investigated the effects of the membrane electrode assembly (MEA) fabrication process, cathode CL thickness, and cathode carrier water flow rate on H _2 O _2 generation and cell performance in a PEMFC reactor. The results show that the catalyst-coated membrane-type MEA exhibits high power output due to its lower proton transport resistance. However, the formed CL with a dense structure significantly limits H _2 O _2 collection efficiency. The catalyst-coated gas diffusion electrode (GDE)-type MEA formed macroporous structures in the cathode CL, facilitating carrier water entry and H _2 O _2 drainage. In particular, carbon cloth GDE with thin CL could construct rich macroscopic liquid channels, thus maximizing the generation of H _2 O _2 , but will impede fuel cell performance. These results suggest that the construction of a well-connected interface between CL and proton exchange membrane (PEM) in MEA and the establishment of a macroscopic pore structure of the CL are the keys to improve the cell performance and H _2 O _2 collection efficiency.

BackgroundTesticular volume (TV) is an essential parameter for monitoring testicular functions and pathologies. Nevertheless, current measurement tools, including orchidometers and ultrasonography, encounter challenges in obtaining accurate and personalized TV measurements.PurposeBased on magnetic resonance imaging (MRI), this study aimed to establish a deep learning model and evaluate its efficacy in segmenting the testes and measuring TV.Materials and methodsThe study cohort consisted of retrospectively collected patient data (N = 200) and a prospectively collected dataset comprising 10 healthy volunteers. The retrospective dataset was divided into training and independent validation sets, with an 8:2 random distribution. Each of the 10 healthy volunteers underwent 5 scans (forming the testing dataset) to evaluate the measurement reproducibility. A ResUNet algorithm was applied to segment the testes. Volume of each testis was calculated by multiplying the voxel volume by the number of voxels. Manually determined masks by experts were used as ground truth to assess the performance of the deep learning model.ResultsThe deep learning model achieved a mean Dice score of 0.926 ± 0.034 (0.921 ± 0.026 for the left testis and 0.926 ± 0.034 for the right testis) in the validation cohort and a mean Dice score of 0.922 ± 0.02 (0.931 ± 0.019 for the left testis and 0.932 ± 0.022 for the right testis) in the testing cohort. There was strong correlation between the manual and automated TV (R2 ranging from 0.974 to 0.987 in the validation cohort; R2 ranging from 0.936 to 0.973 in the testing cohort). The volume differences between the manual and automated measurements were 0.838 ± 0.991 (0.209 ± 0.665 for LTV and 0.630 ± 0.728 for RTV) in the validation cohort and 0.815 ± 0.824 (0.303 ± 0.664 for LTV and 0.511 ± 0.444 for RTV) in the testing cohort. Additionally, the deep-learning model exhibited excellent reproducibility (intraclass correlation >0.9) in determining TV.ConclusionThe MRI-based deep learning model is an accurate and reliable tool for measuring TV.

Lowering the Pt loading while maintaining high fuel-cell performance is an important but difficult task. Here the authors report modified polymers with intrinsic microporosity as binder for preferential retention of phosphoric acid in the catalyst layer, which offers great opportunities to lower the catalyst loading for high-temperature proton exchange membrane fuel cell.

Abstract We explore the analytic structure of the non-perturbative S-matrix in arguably the simplest family of massive non-integrable quantum field theories: the Ising field theory (IFT) in two dimensions, which may be viewed as the Ising CFT deformed by its two relevant operators, or equivalently, the scaling limit of the Ising model in a magnetic field. Our strategy is that of collider physics: we employ Hamiltonian truncation method (TFFSA) to extract the scattering phase of the lightest particles in the elastic regime, and combine it with S-matrix bootstrap methods based on unitarity and analyticity assumptions to determine the analytic continuation of the 2 → 2 S-matrix element to the complex s-plane. Focusing primarily on the “high temperature” regime in which the IFT interpolates between that of a weakly coupled massive fermion and the E 8 affine Toda theory, we will numerically determine 3-particle amplitudes, follow the evolution of poles and certain resonances of the S-matrix, and exclude the possibility of unknown wide resonances up to reasonably high energies.

Abstract We study U(N) Chern-Simons theory coupled to massive fundamental fermions in the lightcone Hamiltonian formalism. Focusing on the planar limit, we introduce a consistent regularization scheme, identify the counter terms needed to restore relativistic invariance, and formulate scattering theory in terms of unambiguously defined asymptotic states. We determine the 2 → 2 planar S-matrix element in the singlet channel by solving the Lippmann-Schwinger equation to all orders, establishing a result previously conjectured in the literature.

Abstract The gene encoding beta2-adrenergic receptor (β2-AR), adrenoceptor beta 2 (ADRB2), has been reported to closely associated with various cancers. However, its role in lung adenocarcinoma (LUAD) remains controversial. This research shed light on the prognostic value of ADRB2 in LUAD and further explored its association with immune cell infiltration. ADRB2 was significantly decreased in LUAD. ADRB2 expression in LUAD was significantly correlated with gender, smoking status, T classification, and pathologic stage. Patients in the low ADRB2 expression group presented with significantly poorer overall survival (OS) and disease-specific survival (DSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) results showed that ADRB2 participates in immune response. The expression of ADRB2 was positively correlated with the infiltration level of most immune cells. Notably, ADRB2 is involved in LUAD progression partly by regulating the immune microenvironment, which may potentially serve as a significant prognostic biomarker as well as a potential drug target.

Abstract Background To investigate hypothalamic-pituitary-thyroid function in children of different ages, nutritional phases, and genotypes that were diagnosed with Prader-Willi syndrome (PWS), as well as the effects of recombinant human growth hormone (rhGH) treatment on thyroid hormones in PWS patients. Methods One hundred and thirty PWS patients (87 boys and 43 girls) aged from newborn to 15 years (y) (median 1.25 y, mean, SD: 2.95 ± 3.45 y), were surveyed in this study. Serum thyroid hormone levels were examined at least once per3-6 months during the 2 years follow-up study. Central hypothyroidism (C-HT) was identified as low/normal thyroid-stimulating hormone (TSH) and low free thyroxine 4 (FT4). Results All study participants had normal neonatal TSH screening test results. The prevalence of C-HT is 36.2% (47/130). No C-HT cases were diagnosed in PWS either below 1 month (m) or above 12 y. The prevalence of C-TH would be increased with age before 3 y until reaching the peak, followed by a gradual decline over the years. The prevalence of C-HT varies significantly at different ages (Pearson's χ2 = 19.915; p

PurposeVitamin D-dependent rickets type 1A (VDDR1A) is a rare autosomal recessive disorder caused by deficiency of the CYP27B1 gene. This study aims to investigate the phenotypic and genotypic features of VDDR1A children in southern China and evaluate the long-term therapeutic effects.MethodsTwelve children from southern China with VDDR1A were enrolled in this study. Their clinical, radiological, biochemical, and molecular findings were analyzed retrospectively. The rickets severity score (RSS), biochemical parameters, and height standard deviation score (HtSDS) were used to evaluate clinical outcomes.ResultsSix males and six females were included in this VDDR1A cohort. The age of onset was from 6 months to 1.8 years, and the age at diagnosis was 2.1 ± 0.8 years. The most common clinical symptoms at diagnosis were delayed walking (10/12) and severe growth retardation (9/12). HtSDS at diagnosis was negatively associated with age (p

BackgroundTransient Receptor Potential (TRP) channel is a kind of channel protein widely distributed in peripheral and central nervous system. They can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role and function of the TRP family genes in tumours remain unclear.MethodsGene alterations (mutation, copy number, methylation), expression, clinical features, and prognostic value of the TRP family genes were evaluated in pan-cancer using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. TRP score was calculated by the ssGSEA function of the R package “GSVA”. The association of TRP score and the tumour microenvironment (TME), especially the tumour immune microenvironment (TIME), along with immunotherapy response were explored in-depth.ResultsTRP family genes were involved in tumour progression and highly associated with poor prognosis in a variety of cancers. TRP score was positively associated with malignant pathways in pan-cancer, such as IL6–JAK–STAT3 signalling, interferon-gamma response, and inflammatory response. All pathways were closely associated with TIME. Elevated TRP score also correlated with multiple immune-related characteristics of the TIME in pan-cancer. Moreover, the TRP score was a predictive biomarker for immune checkpoint inhibitor (ICI) treatments in patients with tumours.ConclusionsTRP family genes play a key role in pan-cancer and are closely associated with TME. Patients with high TRP scores have excellent immune-activated TIME and immunotherapy sensitivity. Therefore, the TRP score could be a potential biomarker for patients with tumours treated with ICI.

There is limited data on the impact of extracorporeal membrane oxygenation (ECMO) on pulmonary physiology and imaging in adult patients. The current study sought to evaluate the serial changes in oxygenation and pulmonary opacities after ECMO initiation.

Allylation of N-unsubstituted isatin N,N′-cyclic azomethine imines with Morita-Baylis-Hillman carbonates in the presence of 1–10 mol% DABCO in DCM at room temperature, rapidly gave N-allylated and N, β-diallylated isatin N,N′-cyclic azomethine imine 1,3-dipoles in moderate to high yields. The reaction features mild reaction conditions, easily practical operation, and short reaction times in most cases. Furthermore, the alkylated products were transformed into novel bicyclic spiropyrrolidine oxoindole derivatives through the [3+2] or [3+3]-cycloaddition with maleimides or Knoevenagel adducts.

Abstract We treat RR flux backgrounds of type II string theory in the framework of closed superstring field theory based on the NSR formalism, focusing on two examples: (1) the pp-wave background supported by 5-form flux, and (2) AdS3 × S 3 × M 4 supported by mixed 3-form fluxes. In both cases, we analyze the classical string field solution perturbatively, and compute the correction to the dispersion relation of string states to quadratic order in the RR flux. In the first example, our result is in a delicate way consistent with that obtained from lightcone quantization of the Green-Schwarz string. In the second example, we will obtain numerically the mass corrections to pulsating type IIB strings in AdS3 × S 3 × M 4. Our results, valid at finite AdS radius, agree with previously known answers in the semiclassical limit and in the BMN limit respectively.

Parkinson’s disease (PD) is a common neurodegenerative disease, and the mechanism underlying PD pathogenesis is not completely understood. Increasing evidence indicates that microRNAs (miRNAs) play a critical regulatory role in the pathogenesis of PD. This study aimed to explore the miRNA-mRNA regulatory network for PD. The differentially expressed miRNAs (DEmis) and genes (DEGs) between PD patients and healthy donors were screened from the miRNA dataset GSE16658 and mRNA dataset GSE100054 downloaded from the Gene Expression Omnibus (GEO) database. Target genes of the DEmis were selected when they were predicted by three or four online databases and overlapped with DEGs from GSE100054. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were then conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Metascape analytic tools. The correlation between the screened genes and PD was evaluated with the online tool Comparative Toxicogenomics Database (CTD), and protein-protein interaction (PPI) networks were built by the STRING platform. We further investigated the expression of genes in the miRNA-mRNA regulatory network in blood samples collected from PD patients and healthy donors via qRT-PCR. We identified 1505 upregulated and 1302 downregulated DEGs, and 77 upregulated and 112 downregulated DEmis were preliminarily screened from the GEO database. Further functional enrichment analysis identified 10 PD-related hub genes, including RAC1, IRS2, LEPR, PPARGC1A, CAMKK2, RAB10, RAB13, RAB27B, RAB11A, and JAK2, which were mainly involved in Rab protein signaling transduction, AMPK signaling pathway, and signaling by Leptin. A miRNA-mRNA regulatory network was then constructed with 10 hub genes, and their interacting miRNAs overlapped with DEmis, including miR-30e-5p, miR-142-3p, miR-101-3p, miR-32-3p, miR-508-5p, miR-642a-5p, miR-19a-3p, and miR-21-5p. Analysis of clinical samples verified significant upregulation of LEPR and downregulation of miR-101-3p and miR-30e-5p in PD patients as compared with healthy donors. Thus, the miRNA-mRNA regulatory network was initially constructed and has the potential to provide novel insights into the pathogenesis and treatment of PD.

Abstract We systematically analyze the effective action on the moduli space of (2, 0) superconformal field theories in six dimensions, as well as their toroidal compactification to maximally supersymmetric Yang-Mills theories in five and four dimensions. We present a streamlined approach to non-renormalization theorems that constrain this effective action. The first several orders in its derivative expansion are determined by a one-loop calculation in five-dimensional Yang-Mills theory. This fixes the leading higher-derivative operators that describe the renormalization group flow into theories residing at singular points on the moduli space of the compactified (2, 0) theories. This understanding allows us to compute the a-type Weyl anomaly for all (2, 0) superconformal theories. We show that it decreases along every renormalization group flow that preserves (2, 0) supersymmetry, thereby establishing the a-theorem for this class of theories. Along the way, we encounter various field-theoretic arguments for the ADE classification of (2, 0) theories.

Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety.

Abstract We implement the Rayleigh-Ritz method in supersymmetric quantum mechanics with flat directions, and extract the S-matrix and metastable resonances. The effectiveness of the method is demonstrated in two strongly coupled systems: an N $$ \mathcal{N} $$ = 1 toy supermembrane model, and an N $$ \mathcal{N} $$ = 4 model with a U(1) gauge multiplet and a charged chiral multiplet.

Abstract We revisit the perturbative S-matrix of c = 1 string theory from the worldsheet perspective. We clarify the origin of the leg pole factors, the non-analyticity of the string amplitudes, and the validity as well as limitations of earlier computations based on resonance momenta. We compute the tree level 4-point amplitude and the genus one 2-point reflection amplitude by numerically integrating Virasoro conformal blocks with DOZZ structure constants on the sphere and on the torus, with sufficiently generic complex Liouville momenta, and find agreement with known answers from the c = 1 matrix model.

Abstract We study the Virasoro conformal block decomposition of the genus two partition function of a two-dimensional CFT by expanding around a ℤ3-invariant Riemann surface that is a three-fold cover of the Riemann sphere branched at four points, and explore constraints from genus two modular invariance and unitarity. In particular, we find “critical surfaces” that constrain the structure constants of a CFT beyond what is accessible via the crossing equation on the sphere.

Abstract We derive recursive representations in the internal weights of N -point Virasoro conformal blocks in the sphere linear channel and the torus necklace channel, and recursive representations in the central charge of arbitrary Virasoro conformal blocks on the sphere, the torus, and higher genus Riemann surfaces in the plumbing frame.

Abstract We study the scattering of long strings in c = 1 string theory, both in the worldsheet description and in the non-singlet sector of the dual matrix quantum mechanics. From the worldsheet perspective, the scattering amplitudes of long strings are obtained from a decoupling limit of open strings amplitudes on FZZT branes, which we compute by integrating Virasoro conformal blocks along with structure constants of boundary Liouville theory. In particular, we study the tree level amplitudes of (1) a long string decaying by emitting a closed string, and (2) the scattering of a pair of long strings. We show that they are indeed well defined as limits of open string amplitudes, and that our results are in striking numerical agreement with computations in the adjoint and bi-adjoint sectors of the dual matrix model (based on proposals of Maldacena and solutions due to Fidkowski), thereby providing strong evidence of the duality.

Abstract We consider topological defect lines (TDLs) in two-dimensional conformal field theories. Generalizing and encompassing both global symmetries and Verlinde lines, TDLs together with their attached defect operators provide models of fusion categories without braiding. We study the crossing relations of TDLs, discuss their relation to the ’t Hooft anomaly, and use them to constrain renormalization group flows to either conformal critical points or topological quantum field theories (TQFTs). We show that if certain non-invertible TDLs are preserved along a RG flow, then the vacuum cannot be a non-degenerate gapped state. For various massive flows, we determine the infrared TQFTs completely from the consideration of TDLs together with modular invariance.

Background The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. Methods Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. Results The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. Conclusion TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.

Introduction. Patients receiving chemotherapy for breast cancer may be at risk of developing cardiac dysfunction and electrophysiological abnormalities. The aim of this study is to evaluate alterations in electrocardiographic (ECG) parameters in breast cancer patients receiving chemotherapy. Materials and Methods. This was a prospective single-center cohort study conducted in the Fourth Hospital of Hebei Medical University, China. Participants with breast cancer referred for chemotherapy from May 1, 2019, to October 1, 2019, were invited to participate in the study. Standard 12-lead ECG and echocardiography were performed at baseline or before chemotherapy (prechemotherapy) (T0), after 1 cycle (T1), after 3 cycles (T2), and at the end of chemotherapy (T3). Results. A total of 64 patients with diagnosed breast cancer undergoing chemotherapy were included. Echocardiographic parameters showed no significant variation during the entire procedure (all P>0.05). The incidence of abnormal ECG increased from 43.75% at baseline to 65.63% at the end of chemotherapy, of which only the prevalence of fragmented QRS (fQRS) was significantly increased after the drug regimen (26.56% to 53.13%). At the end of the treatment, heart rate, P-wave dispersion, corrected QT interval, T-peak to T-end, RR, SV1, RV5, Sokolow–Lyon index (SLI), and index of cardioelectrophysiological balance deteriorated markedly (all P

Abstract We constrain the spectrum of two-dimensional unitary, compact conformal field theories with central charge c > 1 using modular bootstrap. Upper bounds on the gap in the dimension of primary operators of any spin, as well as in the dimension of scalar primaries, are computed numerically as functions of the central charge using semi-definite programming. Our bounds refine those of Hellerman and Friedan-Keller, and are in some cases saturated by known CFTs. In particular, we show that unitary CFTs with c < 8 must admit relevant deformations, and that a nontrivial bound on the gap of scalar primaries exists for c < 25. We also study bounds on the dimension gap in the presence of twist gaps, bounds on the degeneracy of operators, and demonstrate how “extremal spectra” which maximize the degeneracy at the gap can be determined numerically.

Abstract We introduce spectral functions that capture the distribution of OPE coefficients and density of states in two-dimensional conformal field theories, and show that nontrivial upper and lower bounds on the spectral function can be obtained from semidefinite programming. We find substantial numerical evidence indicating that OPEs involving only scalar Virasoro primaries in a c > 1 CFT are necessarily governed by the structure constants of Liouville theory. Combining this with analytic results in modular bootstrap, we conjecture that Liouville theory is the unique unitary c > 1 CFT whose primaries have bounded spins. We also use the spectral function method to study modular constraints on CFT spectra, and discuss some implications of our results on CFTs of large c and large gap, in particular, to what extent the BTZ spectral density is universal.

Abstract We show that by studying the flat spacetime limit of the Mellin amplitude associated with the four-point correlation function of scalar operators in the stress tensor multiplet of ABJM theory, one can produce the momentum expansion of the M-theory four-graviton S-matrix elements. Using CFT data previously obtained from the supersymmetric localization method, we carry out this procedure explicitly to the second nontrivial order in the momentum expansion, and recover precisely the known R 4 contribution to the scattering amplitude of super-gravitons in M-theory in eleven dimensions.

Abstract Membrane proteins are an important kind of proteins embedded in the membranes of cells and play crucial roles in living organisms, such as ion channels, transporters, receptors. Because it is difficult to determinate the membrane protein’s structure by wet-lab experiments, accurate and fast amino acid sequence-based computational methods are highly desired. In this paper, we report an online prediction tool called MemBrain, whose input is the amino acid sequence. MemBrain consists of specialized modules for predicting transmembrane helices, residue–residue contacts and relative accessible surface area of α-helical membrane proteins. MemBrain achieves a prediction accuracy of 97.9% of A TMH, 87.1% of A P, 3.2 ± 3.0 of N-score, 3.1 ± 2.8 of C-score. MemBrain-Contact obtains 62%/64.1% prediction accuracy on training and independent dataset on top L/5 contact prediction, respectively. And MemBrain-Rasa achieves Pearson correlation coefficient of 0.733 and its mean absolute error of 13.593. These prediction results provide valuable hints for revealing the structure and function of membrane proteins. MemBrain web server is free for academic use and available at www.csbio.sjtu.edu.cn/bioinf/MemBrain/ .

Abstract We find a simple relation between two-dimensional BPS N = 2 $$ \mathcal{N}=2 $$ superconformal blocks and bosonic Virasoro conformal blocks, which allows us to analyze the crossing equations for BPS 4-point functions in unitary (2, 2) superconformal theories numerically with semidefinite programming. We constrain gaps in the non-BPS spectrum through the operator product expansion of BPS operators, in ways that depend on the moduli of exactly marginal deformations through chiral ring coefficients. In some cases, our bounds on the spectral gaps are observed to be saturated by free theories, by N = 2 $$ \mathcal{N}=2 $$ Liouville theory, and by certain Landau-Ginzburg models.

Abstract We study two-dimensional (4, 4) superconformal field theories of central charge c = 6, corresponding to nonlinear sigma models on K3 surfaces, using the superconformal bootstrap. This is made possible through a surprising relation between the BPS N $$ \mathcal{N} $$ = 4 superconformal blocks with c = 6 and bosonic Virasoro conformal blocks with c = 28, and an exact result on the moduli dependence of a certain integrated BPS 4-point function. Nontrivial bounds on the non-BPS spectrum in the K3 CFT are obtained as functions of the CFT moduli, that interpolate between the free orbifold points and singular CFT points. We observe directly from the CFT perspective the signature of a continuous spectrum above a gap at the singular moduli, and find numerically an upper bound on this gap that is saturated by the A 1 N $$ \mathcal{N} $$ = 4 cigar CFT. We also derive an analytic upper bound on the first nonzero eigenvalue of the scalar Laplacian on K3 in the large volume regime, that depends on the K3 moduli data. As two byproducts, we find an exact equivalence between a class of BPS N $$ \mathcal{N} $$ = 2 superconformal blocks and Virasoro conformal blocks in two dimensions, and an upper bound on the four-point functions of operators of sufficiently low scaling dimension in three and four dimensional CFTs.

Background: Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected. Methods: A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out. Results: Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found. Conclusions: We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.

Background: Dermatomyositis (DM) and polymyositis (PM) are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations. Responding to a wide range of exogenous and endogenous microbial or sterile stimuli, NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1, which processes the pro-inflammatory cytokines pro-interleukin (IL)-1β and pro-IL-18 into active and secreted IL-1β and IL-18. The NLRP3 inflammasome is implicated in infectious and sterile inflammatory diseases. However, it remains unclear whether it is involved in the pathogenesis of DM/PM, which we aim to address in our research. Methods: In this study, 22 DM/PM patients and 24 controls were recruited. The protein and RNA expression of IL-1β, IL-18, NLRP3, and caspase-1 in serum and muscle samples were tested and compared between the two groups. Results: The serum IL-1β and IL-18 levels were significantly higher in DM/PM patients than those in the controls by enzyme linked immunosorbent assay (ELISA, DM vs. control, 25.02 ± 8.29 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001; PM vs. control, 26.49 ± 7.79 ng/ml vs. 16.49 ± 3.30 ng/ml,P < 0.001). Moreover, the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed that DM/PM patients exhibited higher RNA expression of IL-1β, IL-18, and NLRP3 in the muscle (for IL-1β, DM vs. control, P= 0.0012, PM vs. control, P= 0.0021; for IL-18, DM vs. control, P= 0.0045, PM vs. control, P= 0.0031; for NLRP3, DM vs. control, P= 0.0017, PM vs. control, P= 0.0006). Moreover, the protein expression of NLRP3 and caspase-1 in muscle samples of DM/PM patients were also significantly elevated compared to that in the muscles of the controls. Conclusions: Our findings demonstrate that the NLRP3 inflammasome is implicated in the pathogenesis of DM/PM. High NLRP3 expression led to elevated levels of IL-1β and IL-18 and could be one of the factors promoting disease progress.