Why does dissolving salt in water decrease its dielectric permittivity

The dielectric permittivity of salt water decreases on dissolving more salt. For nearly a century, this phenomenon has been explained by invoking saturation in the dielectric response of the solvent water molecules. Herein, we employ an advanced deep neural network (DNN), built using data from density functional theory, to study the dielectric permittivity of sodium chloride solutions. Notably, the decrease in the dielectric permittivity as a function of concentration, computed using the DNN approach, agrees well with experiments. Detailed analysis of the computations reveals that the dominant effect, caused by the intrusion of ionic hydration shells into the solvent hydrogen-bond network, is the disruption of dipolar correlations among water molecules. Accordingly, the observed decrease in the dielectric permittivity is mostly due to increasing suppression of the collective response of solvent waters.Comment: has accepted by Physical Review Letter

CYP6AE gene cluster knockout in <i>Helicoverpa armigera</i> reveals role in detoxification of phytochemicals and insecticides

Cotton bollworm is an important agricultural pest with widespread resistance to insecticides. Here Wang et al. identifies CYP6AEs from cotton bollworm involved in detoxifying plant toxins and chemical insecticides through the CRISPR-Cas9-based reverse genetics approach in conjunction with in vitro metabolism

DCQA: Document-Level Chart Question Answering towards Complex Reasoning and Common-Sense Understanding

Visually-situated languages such as charts and plots are omnipresent in real-world documents. These graphical depictions are human-readable and are often analyzed in visually-rich documents to address a variety of questions that necessitate complex reasoning and common-sense responses. Despite the growing number of datasets that aim to answer questions over charts, most only address this task in isolation, without considering the broader context of document-level question answering. Moreover, such datasets lack adequate common-sense reasoning information in their questions. In this work, we introduce a novel task named document-level chart question answering (DCQA). The goal of this task is to conduct document-level question answering, extracting charts or plots in the document via document layout analysis (DLA) first and subsequently performing chart question answering (CQA). The newly developed benchmark dataset comprises 50,010 synthetic documents integrating charts in a wide range of styles (6 styles in contrast to 3 for PlotQA and ChartQA) and includes 699,051 questions that demand a high degree of reasoning ability and common-sense understanding. Besides, we present the development of a potent question-answer generation engine that employs table data, a rich color set, and basic question templates to produce a vast array of reasoning question-answer pairs automatically. Based on DCQA, we devise an OCR-free transformer for document-level chart-oriented understanding, capable of DLA and answering complex reasoning and common-sense questions over charts in an OCR-free manner. Our DCQA dataset is expected to foster research on understanding visualizations in documents, especially for scenarios that require complex reasoning for charts in the visually-rich document. We implement and evaluate a set of baselines, and our proposed method achieves comparable results

Advances in immunotyping of colorectal cancer

Immunotherapy has transformed treatment for various types of malignancy. However, the benefit of immunotherapy is limited to a minority of patients with mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) (dMMR-MSI-H) colorectal cancer (CRC). Understanding the complexity and heterogeneity of the tumor immune microenvironment (TIME) and identifying immune-related CRC subtypes will improve antitumor immunotherapy. Here, we review the current status of immunotherapy and typing schemes for CRC. Immune subtypes have been identified based on TIME and prognostic gene signatures that can both partially explain clinical responses to immune checkpoint inhibitors and the prognosis of patients with CRC. Identifying immune subtypes will improve understanding of complex CRC tumor heterogeneity and refine current immunotherapeutic strategies

Can EAT be an INOCA goalkeeper

Ischemia with non-obstructive coronary artery (INOCA) is a blind spot of coronary artery disease (CAD). Such patients are often reassured but offered no specific care, that lead to a heightened risk of adverse cerebrovascular disease (CVD) outcomes. Epicardial adipose tissue (EAT) is proven to correlate independently with CAD and its severity, but it is unknown whether EAT is a specific and sensitive indicator of INOCA. This review focuses on the INOCA epidemiology and related factors, as well as the association between EAT

Advances in reprogramming of energy metabolism in tumor T cells

Cancer is a leading cause of human death worldwide, and the modulation of the metabolic properties of T cells employed in cancer immunotherapy holds great promise for combating cancer. As a crucial factor, energy metabolism influences the activation, proliferation, and function of T cells, and thus metabolic reprogramming of T cells is a unique research perspective in cancer immunology. Special conditions within the tumor microenvironment and high-energy demands lead to alterations in the energy metabolism of T cells. In-depth research on the reprogramming of energy metabolism in T cells can reveal the mechanisms underlying tumor immune tolerance and provide important clues for the development of new tumor immunotherapy strategies as well. Therefore, the study of T cell energy metabolism has important clinical significance and potential applications. In the study, the current achievements in the reprogramming of T cell energy metabolism were reviewed. Then, the influencing factors associated with T cell energy metabolism were introduced. In addition, T cell energy metabolism in cancer immunotherapy was summarized, which highlighted its potential significance in enhancing T cell function and therapeutic outcomes. In summary, energy exhaustion of T cells leads to functional exhaustion, thus resulting in immune evasion by cancer cells. A better understanding of reprogramming of T cell energy metabolism may enable immunotherapy to combat cancer and holds promise for optimizing and enhancing existing therapeutic approaches

Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission.</p> <p>Results</p> <p>Maleic anhydride (ML), succinic anhydride (SU) and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA) for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low <it>in vitro </it>cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells.</p> <p>Conclusion</p> <p>ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.</p

Clinical Characteristics and Short-Term Prognosis of Autoimmune Encephalitis: A Single-Center Cohort Study in Changsha, China

Background and Purpose: The incidence and prevalence of autoimmune encephalitis is gradually increasing. This retrospective observational study primarily aimed to analyze the clinical characteristics of autoimmune encephalitis patients in the Second Xiangya Hospital and report patient prognoses after immunotherapy.Methods: The clinical data of 86 patients who were diagnosed with autoimmune encephalitis from October 2014 to September 2018 were collected, and their corresponding clinical characteristics, laboratory examination, treatment, and outcome data analyzed.Results: In our study, 72 patients (83.7%) were positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibody; 5 patients (6%) for anti-GABABR (γ-aminobutyric acid receptor-A); 4 patients (4.7%) for anti-LGI1 (leucine-rich, glioma inactivated 1); 3 patients (3.5%) for anti-Caspr2 (contactin-associated protein-like 2) (1 patient was positive for both anti-LGI1 and anti-Caspr2 antibodies); and 3 patients (3.5%) for onconeural antibodies. Among the 86 patients diagnosed as having autoimmune encephalitis, 50% showed acute disease onset (≤2 weeks). The most common inducing factor was fever or cold (17/86, 19.8%). The main clinical symptoms included, among others, psychiatric disturbances (82.5%), epilepsy (60.5%), autonomic dysfunction (58.1%), sleep disorders (45.3%), consciousness disorders (45.3%), and speech disorders (46.5%). No significant correlation between ICU admission rates and CSF or serum antibody scores was observed. However, CSF antibody scores of (+ + +) and (++) were associated with longer lengths of hospitalization (p &lt; 0.05) and a higher CSF WBC count when compared with CSF antibody scores of (+) in patients with anti-NMDAR encephalitis (p &lt; 0.05). Additionally, there was no significant correlation between mRS score difference on admission and discharge (after immunotherapy) and age, sex, and choice of immune treatment, while immune therapy taken within 15 days from onset was more inclined to be associated with an mRS score difference ≥2 after immunotherapy in patients with anti-NMDAR encephalitis (p = 0.006).Conclusions: Autoimmune encephalitis has an acute or sub-acute onset and presents with psychotic symptoms, epilepsy, and autonomic dysfunction. The sex ratio in anti-NMDAR encephalitis was nearly balanced. Infection was a major factor inducing anti-NMDAR encephalitis, and the CSF antibody scores could be helpful in determining its prognosis since these scores showed associations with hospitalization duration and CSF WBC counts

Potential Blood Pressure Goals in IgA Nephropathy: Prevalence, Awareness, and Treatment Rates in Chronic Kidney Disease Among Patients with Hypertension in China (PATRIOTIC) Study

Background/Aims: IgA nephropathy is the most prevalent form of primary glomerulonephritis worldwide. Among patients with kidney disease, hypertension is one of the most important risk factors of disease progression. Considering the limited evidence regarding the appropriate blood pressure (BP) goal for patients with IgA nephropathy, our aim was to critically appraise the potential BP goal in IgA nephropathy. Methods: We performed a retrospective analysis of the BP data from 1055 patients with IgA nephropathy, extracted from the database of a nationwide, multi-center, cross-sectional study, including 61 tertiary hospitals in China. Hypertension was defined by a BP ≥140/90 mmHg. Three BP cutoff levels were evaluated as control values: &#x3c; 140/90 mmHg, &#x3c; 130/80 mmHg and &#x3c; 125/75 mmHg. The primary outcome of our study was the prevalence of BP control among patients with a 24-h proteinuria &#x3c; 1 g/d or ≥ 1 g/d. Multivariate logistic regression analysis was used to identify demographic and clinical factors associated with a decrease in renal function for the different target levels of BP. Results: The overall prevalence of hypertension was 63.3%. BP was controlled under 140/90 mmHg in 49.1% of patients, with 34.3% of patients with proteinuria &#x3c; 1 g/d reaching the target BP &#x3c; 130/80 mmHg and only 12.9% of patients with proteinuria &#x3e; 1 g/d achieving a BP &#x3c; 125/75 mmHg. Among patients with proteinuria &#x3c; 1 g/d, the adjusted odds ratios (OR) and 95% confidence interval (95% CI) of a decrease in renal function, for the 3 target BP levels, were as follows (P &#x3e; 0.05): &#x3c; 140/90 mmHg, 0.9 (0.5 - 1.6); &#x3c; 130/80 mmHg, 1.0 (0.5 - 1.8); and &#x3c; 125/75 mmHg, 1.0 (0.5 - 2.0). With proteinuria ≥1 g/d, the adjusted ORs (95%CI) of attaining the BP targets of &#x3c; 140/90 mmHg, &#x3c; 130/80 mmHg and &#x3c; 125/75 mmHg were 0.4 (0.2 - 0.6), 0.2 (0.1 - 0.4) and 0.3 (0.1 - 0.5), respectively (P &#x3c; 0.05). Conclusion: Hypertension was common in IgA nephropathy and hypertensive control was suboptimal. Our result supports a benefit of intensive control of BP &#x3c; 130/80 mmHg for patients with proteinuria ≥1 g/d. However, in patients with proteinuria &#x3c; 1 g/d, a renoprotective effect of this BP goal was not identified

Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways

Objective(s): Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin’s function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-β1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients’ serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-β1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-β/Smad pathway