Accurate Prediction of NMR Chemical Shifts: Integrating DFT Calculations with Three-Dimensional Graph Neural Networks.

Computer prediction of NMR chemical shifts plays an increasingly important role in molecular structure assignment and elucidation for organic molecule studies. Density functional theory (DFT) and gauge-including atomic orbital (GIAO) have established a framework to predict NMR chemical shifts but often at a significant computational expense with a limited prediction accuracy. Recent advancements in deep learning methods, especially graph neural networks (GNNs), have shown promise in improving the accuracy of predicting experimental chemical shifts, either by using 2D molecular topological features or 3D conformational representation. This study presents a new 3D GNN model to predict 1H and 13C chemical shifts, CSTShift, that combines atomic features with DFT-calculated shielding tensor descriptors, capturing both isotropic and anisotropic shielding effects. Utilizing the NMRShiftDB2 data set and conducting DFT optimization and GIAO calculations at the B3LYP/6-31G(d) level, we prepared the NMRShiftDB2-DFT data set of high-quality 3D structures and shielding tensors with corresponding experimentally measured 1H and 13C chemical shifts. The developed CSTShift models achieve the state-of-the-art prediction performance on both the NMRShiftDB2-DFT test data set and external CHESHIRE data set. Further case studies on identifying correct structures from two groups of constitutional isomers show its capability for structure assignment and elucidation. The source code and data are accessible at https://yzhang.hpc.nyu.edu/IMA.

Developing a High-Umami, Low-Salt Soy Sauce through Accelerated Moromi Fermentation with Corynebacterium and Lactiplantibacillus Strains.

The traditional fermentation process of soy sauce employs a hyperhaline model and has a long fermentation period. A hyperhaline model can improve fermentation speed, but easily leads to the contamination of miscellaneous bacteria and fermentation failure. In this study, after the conventional koji and moromi fermentation, the fermentation broth was pasteurized and diluted, and then inoculated with three selected microorganisms including Corynebacterium glutamicum, Corynebacterium ammoniagenes, and Lactiplantibacillus plantarum for secondary fermentation. During this ten-day fermentation, the pH, free amino acids, organic acids, nucleotide acids, fatty acids, and volatile compounds were analyzed. The fermentation group inoculated with C. glutamicum accumulated the high content of amino acid nitrogen of 0.92 g/100 mL and glutamic acid of 509.4 mg/100 mL. The C. ammoniagenes group and L. plantarum group were rich in nucleotide and organic acid, respectively. The fermentation group inoculated with three microorganisms exhibited the best sensory attributes, showing the potential to develop a suitable fermentation method. The brewing speed of the proposed process in this study was faster than that of the traditional method, and the umami substances could be significantly accumulated in this low-salt fermented model (7% w/v NaCl). This study provides a reference for the low-salt and rapid fermentation of seasoning.

Expression of nuclear receptor co­activator 7 protein is associated with poor prognosis of breast cancer.

Nuclear receptor coactivator 7 (NCOA7) is an estrogen receptor binding protein. Its role in breast cancer progression has so far remained elusive. The present study aimed to determine the expression levels of NCOA7 in breast tumor samples and confirmed its potential utility as a breast cancer prognostic biomarker. The expression of NCOA7 was detected by immunohistochemical staining in 241 breast cancer tumor samples and 163 adjacent normal tissue samples. The association of NCOA7 expression with the clinicopathological characteristics and overall survival were statistically analyzed. Cell proliferation was determined by Cell Counting Kit-8 and colony-formation assays. Cell migration was detected using wound-healing and Transwell assays. NCOA7 was positively expressed in 44% of breast tumor tissues. The expression of NCOA7 was positively associated with tumor size (T-stage; P=0.005) and lymph node metastasis (N-stage; P=0.008). Additional statistical analysis indicated that the expression of NCOA7 was associated with patient age, tumor size and lymph node metastasis in patients with triple-negative breast cancer (TNBC) compared with that in patients with non-TNBC. The overall survival of patients with NCOA7-positive breast cancer was significantly lower than that of patients with NCOA7-negative breast cancer (P=0.006). Among the patients with lymph node metastasis, the overall survival was reversely associated with the expression of NCOA7 (P=0.042). Furthermore, knockdown of NCOA7 expression in breast cancer T47D and MCF7 cells significantly inhibited both cell proliferation and migration, suggesting that this protein may exert a role in driving breast cancer progression. Taken together, these results indicate that the expression of NCOA7 is associated with poor prognosis of breast cancer and suggest that this protein may be a driver for metastasis and a potential therapeutic target for advanced breast cancer.

Efficient removal of tetracycline and Cu2+ by honeycomb derived magnetic carbon: Adsorption mechanism and advanced oxidation regeneration mechanism.

The honeycomb magnetic carbons (xFe@HCNs) were prepared by sacrificial template method novelty using polyacrylamide resin (PAAS) as template and ammonium pyrrolidine dithioate/Fe3+ complex (APDC-Fe) as carbon skeleton and metal source. Tetracycline (TC) and copper (Cu2+) as target pollutants were used to investigate the adsorption properties of xFe@HCNs in single or binary TC and Cu2+ systems. The adsorption capacity sequence for TC among the adsorbents was (mmol·g-1): 2Fe@HCNs (0.088) > 8Fe@HCNs (0.061) > HCNs (0.054) > RC (0.036), and for Cu2+ was (mmol·g-1): 2Fe@HCNs (1.120) > 8Fe@HCNs (1.026) > RC (0.792) > HCNs (0.681). 2Fe@HCNs demonstrated notable affinity for adsorbing both TC and Cu2+. Additionally, the influence of hydrochemical factors (i.e., cation species, anion species, and pH) on the adsorption properties of 2Fe@HCNs. Combined with advanced oxidation technology, the regeneration methods of magnetic adsorbent were explored using oxidizing agents (e.g., H2O2 and peroxymonosulfate) as eluents which could increase the adsorption sites of magnetic carbon adsorbents during the regenerating process, which was the novelty of the study. Furthermore, the regeneration mechanisms of H2O2 as eluent were investigated. This study discussed the application and regeneration methods of magnetic adsorbents in water treatment, offering new insights into environmental remediation using magnetic materials.

Integrated Molecular Modeling and Machine Learning for Drug Design.

Modern therapeutic development often involves several stages that are interconnected, and multiple iterations are usually required to bring a new drug to the market. Computational approaches have increasingly become an indispensable part of helping reduce the time and cost of the research and development of new drugs. In this Perspective, we summarize our recent efforts on integrating molecular modeling and machine learning to develop computational tools for modulator design, including a pocket-guided rational design approach based on AlphaSpace to target protein-protein interactions, delta machine learning scoring functions for protein-ligand docking as well as virtual screening, and state-of-the-art deep learning models to predict calculated and experimental molecular properties based on molecular mechanics optimized geometries. Meanwhile, we discuss remaining challenges and promising directions for further development and use a retrospective example of FDA approved kinase inhibitor Erlotinib to demonstrate the use of these newly developed computational tools.

Small intestinal mucosal abnormalities using video capsule endoscopy in intestinal lymphangiectasia.

BACKGROUND: Intestinal lymphangiectasia (IL) is a rare protein-losing enteropathy caused by disorders of the intestinal lymphatics. There are only a few case reports and case series concerning the VCE (video capsule endoscopy) findings of IL. This work aimed to evaluate the VCE characteristics of small intestinal mucosal abnormalities in patients with IL, and to investigate the relationship between clinical and VCE characteristics. METHODS: Consecutive patients with IL who underwent VCE were enrolled in this retrospective study. The cases were classified into the white villi group and non-white villi group according to mucosal abnormalities detected by VCE. Clinical and endoscopic characteristics were investigated and analyzed. RESULTS: A total of 98 patients with IL with a median onset age of 26.3 ± 19.2 years were included. VCE revealed the following small intestinal lesions: (i) white villi type (57/98, 58.2%), i.e.: white-tipped or granular villi, white nodular villi or plaques; (ii) non-white villi type (41/98, 41.8%), i.e.: diffused low and round villi; (iii) complications (46/98, 46.9%), i.e.: bleeding, ulcers, protruding or vesicular-shaped lesions, stenosis and lymphatic leakage. A total of 58.2% (57) and 41.8% (41) of the cases were classified into the white villi and non-white villi groups respectively. The percentage of chylothorax in the white villi group was significantly lower than that in the non-white villi group (12/57 vs. 19/41, p = 0.008). In VCE, there were no significant differences in the involved segments and total detected rate of complications between the white villi and non-white villi groups (p > 0.05), while the detected rate of lymphatic leakage in the white villi group was significantly higher than that in the non-white villi group (31.6% vs. 12.2%, p = 0.026). CONCLUSIONS: Our study evaluated the entire small intestinal mucosal abnormalities of IL by VCE, especially endoscopic complications. IL has specific VCE abnormalities in addition to classical endoscopic findings.

A clinical study of liposuction followed by lymphovenous anastomosis for treatment of breast cancer-related lymphedema.

Objective: In this work, we studied the clinical effect of liposuction followed by lymphovenous anastomosis (LVAs) for the treatment of breast cancer-related lymphedema (BCRL). Methods: We analyzed 158 patients with unilateral upper limb BCRL who underwent liposuction followed by LVAs 2-4 months later. Arm circumferences before and 7 days after the combined treatments were prospectively recorded. Circumferences of different upper extremities were measured before the procedure, 7 days after LVAs, and during the follow-ups. Volumes were calculated with the frustum method. During the follow-ups, the conditions of patients' treated arms, i.e., the frequency of erysipelas episodes and dependence on compression garments, were recorded. Results: The mean circumference difference between two upper limbs decreased significantly from M (P25, P75) of 5.3 (4.1, 6.9) preoperatively to 0.5 (-0.8, 1.0) (P < 0.05) 7 days after treatments, while at follow-up 0.3 (-0.4, 1.0). The mean volume difference decreased significantly from M (P25, P75) of 838.3 (662.4, 1,129.0) preoperatively to 7.8 (-120.3, 151.4) (P < 0.05) 7 days after treatments, while at follow-up 43.7 (-59.4, 161.1). The incidence of erysipelas also significantly decreased (P < 0.05). 6.3% of patients were already independent of compression garments during the past six months or even more. Conclusion: Liposuction followed by LVAs is an effective method for the treatment of BCRL.

Phospholipase A2 (PLA2) injured lymphatic endothelial cells leading to progression of secondary lymphoedema.

Secondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity.Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production.

Multitask Deep Ensemble Prediction of Molecular Energetics in Solution: From Quantum Mechanics to Experimental Properties.

The past few years have witnessed significant advances in developing machine learning methods for molecular energetics predictions, including calculated electronic energies with high-level quantum mechanical methods and experimental properties, such as solvation free energy and logP. Typically, task-specific machine learning models are developed for distinct prediction tasks. In this work, we present a multitask deep ensemble model, sPhysNet-MT-ens5, which can simultaneously and accurately predict electronic energies of molecules in gas, water, and octanol phases, as well as transfer free energies at both calculated and experimental levels. On the calculated data set Frag20-solv-678k, which is developed in this work and contains 678,916 molecular conformations, up to 20 heavy atoms, and their properties calculated at B3LYP/6-31G* level of theory with continuum solvent models, sPhysNet-MT-ens5 predicts density functional theory (DFT)-level electronic energies directly from force field-optimized geometry within chemical accuracy. On the experimental data sets, sPhysNet-MT-ens5 achieves state-of-the-art performances, which predict both experimental hydration free energy with a RMSE of 0.620 kcal/mol on the FreeSolv data set and experimental logP with a RMSE of 0.393 on the PHYSPROP data set. Furthermore, sPhysNet-MT-ens5 also provides a reasonable estimation of model uncertainty which shows correlations with prediction error. Finally, by analyzing the atomic contributions of its predictions, we find that the developed deep learning model is aware of the chemical environment of each atom by assigning reasonable atomic contributions consistent with our chemical knowledge.

Anaerobic co-digestion of thermo-alkaline pretreated microalgae and sewage sludge: Methane potential and microbial community.

To improve methane production from sewage sludge (SS), co-digestion of SS and microalgae (MA) was studied and the application of thermo-alkaline pretreatment to MA was evaluated. The results showed that thermo-alkaline pretreatment at 90°C for 120 min on MA was the optimum pretreatment condition. Furthermore, when the volatile solids (VS) ratio of SS and MA was 1:2, the methane yield reached maximum (368.94 mL/g VS). Fourier transform infrared (FT-IR) and thermogravimetric analysis confirmed the synergetic effects of thermo-alkaline pretreated MA on its co-digestion with SS. The analyses of microbial community indicated that Methanobacterium and Methanosarcina were the dominant methanogens during the co-digestion process. However, the relative abundance of Methanosarcina in thermo-alkaline pretreated groups was higher compared to unpretreated groups. The microbial community structure might be affected by thermo-alkaline pretreatment rather than by the MA dosage in the co-digestion.

Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics / 中国中药杂志

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

Survey on health literacy and influencing factor of family caregivers of chronic disease patients in Beijing / 中华全科医师杂志

Objective:To survey the health literacy and related factors of family caregivers of patients with chronic diseases in Beijing.Methods:A survey was conducted from September to November 2018, among 1 350 family caregivers of patients with chronic diseases selected by stratified random sampling from 6 districts of Beijing. A self-filling questionnaire was used for the survey, which consisted of the basic information and health literacy of family caregivers. Health literacy included three parts: daily living habits, basic knowledge (knowledge of prevention and management of behavioral risk factors, knowledge related to chronic diseases and knowledge related to first aid) and chronic disease-related skills.Results:A total of 1 268 valid questionnaires were collected with a recovery rate of questionnaires was 93.9%. The median age of 1 268 family caregivers was 62 years (23-86) and 75.7% (960/1 268) were females. In terms of daily habits, smokers and drinkers accounted for 11.3% (143/1 268) and 21.5% (272/1 268) respectively; 82.7% (1 049/1 268) caregivers exercised regularly accounted, of whom 72.5% (761/1 049) exercised at least 4 times a week; 28.9% (366/1 268) caregivers had habit of light diet. In terms of basic knowledge of health literacy, 12.9% (163/1 268) of family caregivers mastered the basic knowledge (≥80% total score); family caregivers who were able to measure blood pressure, blood sugar, pulse, coping with hypoglycemia, cardiopulmonary resuscitation and dialing the emergency number correctly accounted for 27.4% (347/1 268), 18.1% (230/1 268), 15.1% (191/1 268), 15.7% (199/1 268), 6.0% (76/1 268) and 33.8% (429/1 268), respectively. For the six chronic disease-related skills, 23.7% (301/1 268) were able to call emergency number correctly and only 2.6% (33/1 268) were able to perform CPR. There were significant differences in the knowledge of behavioral risk factors ( χ 2=3.88, P=0.017), chronic disease related knowledge ( χ2=7.40, P=0.025), first-aid related knowledge ( χ2=12.04, P=0.002) and overall basic knowledge ( χ2=13.56, P=0.001) among family caregivers with different educational levels. There were significant differences in the knowledge of chronic diseases among family caregivers in different occupations ( χ2=8.78, P=0.012). Conclusion:The health literacy level of family caregivers of patients with chronic diseases in Beijing needs to be further improved, and there are differences in the health literacy of family caregivers with different educational qualifications and occupations.

Inhibitory effect of sodium ferulate on inflammatory response in migraine rats based on c-Jun N-terminal kinase / p38 mitogen-activated protein kinase signaling pathway / 解剖学报

[Abstract] Objective To explore the inhibitory effect of sodium ferulate (SF) on the inflammatory response in migraine rats by regulating the c-Jun N-terminal kinase (JNK) / p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Methods The migraine rat model was prepared by intraperitoneal injection of nitroglycerin. After successful modeling, the rats were randomly grouped into model group, SF low dose (SF-L) group (50 mg/ kg), SF high dose (SF-H) group (100 mg/ kg), SF+JNK inhibitor (SF + SP600125) group (SF 100 mg/ kg +SP600125 10 mg/ kg), and SF+JNK activator [SF + anisomycin(AN)] group (SF 100 mg/ kg +AN 5 mg/ kg), 12 in each group, another 12 SD rats without treatment were taken as blank group. The behavioral changes of the rats in each group were observed 24 hours after the administration, the levels of 5-hydroxytryptamine (5-HT), nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum were detected by ELISA, the neuronal apoptosis in brain tissue was observed by TUNEL staining, immunohistochemistry was used to evaluate the expressions of TNF-α, IL-6 and calcitonin gene-related peptide (CGRP) in brain tissue, Western blotting was used to detect the expressions of JNK/ p38 MAPK pathway-related proteins in brain tissue. Results Compared with the blank group, the number of times of scratching the head and climbing the cage of the rats in the model group increased significantly, and the apoptosis rate of neurons increased significantly; the content of 5-HT in serum decreased significantly, and the levels of NO, TNF-α and IL-6 increased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of phosphorylated JNK (p-JNK) / JNK and phosphorylated p38 MAPK(p-p38 MAPK) / p38 MAPK in brain tissue obviously increased (all P<0. 05). Compared with the model group, the number of times of scratching the head and the times of climbing the cage of the rats in the SF-L group and the SF-H group reduced significantly, and the neuron apoptosis rate reduced significantly; the content of 5-HT in serum increased significantly, and the levels of NO, TNF-α and IL-6 decreased significantly; the expressions of TNF-α, IL-6 and CGRP, and the ratios of p-JNK/ JNK and p-p38 MAPK/ p38 MAPK in brain tissue obviously decreased (all P<0. 05). Compared with SF-H group, the protective effect of SF on migraine rats in SF+SP600125 group enhanced significantly; the protective effect of SF on migraine rats in the SF+AN group reversed significantly. Conclusion SF may inhibit the expression of JNK/ p38 MAPK signaling pathway, effectively inhibit neurogenic inflammatory response in migraine rats, reduce neuronal apoptosis, and achieve a protective effect on migraine rats.

Practice and analysis of clinical pharmacist participating in the treatment of a case of acanthoma caused by navulizumab / 中国药房

This paper reports the clinical pharmacist participated in the diagnosis and treatment of a patient with acanthoma caused by nivolumab. This patient developed acanthoma 2 weeks after medication， involving scalp， neck， trunk， back of hand， sole of foot and other parts， with moderate pruritus. The clinical pharmacist determined it as “yes” according to the causality evaluation method of adverse reactions. After reviewing the literature， clinical pharmacists found that acanthoma caused by immune checkpoint inhibitors was more commonly seen in male elderly patients with malignant melanoma， and mainly involved the trunk， extremities and hands. Under the general principle of considering the effectiveness， safety， economy and accessibility of therapeutic drugs， the clinical pharmacist finally decided to give the patient a comprehensive treatment scheme of Halometasone cream for external use + oral administration of Retinoic acid capsules + oral administration of Ebastine tablets after discussion with the doctor， with maximum respect for the patient’s wishes，and continued to use navulizumab for immunotherapy. At the same time， pharmaceutical care and psychological counseling were conducted by clinical pharmacist. Finally， the patient successfully completed the treatment， and the acanthoma gradually subsided after the end of navulizumab treatment. The diagnosis and treatment process of this patient indicated that the participation of clinical pharmacists is helpful to improve the continuity and safety of immunotherapy.

ETS1 is a prognostic biomarker of triple-negative breast cancer and promotes the triple-negative breast cancer progression through the YAP signaling.

E26 transcription factor-1 (ETS1) is involved in extracellular matrix remodeling, migratory infiltration and angiogenesis in tumors and known to play an important role in tumor progression. However, the mechanism by which ETS1 promotes tumor progression remains elusive. In this report, we show that ETS1 is highly expressed in breast tumor tissues and specifically associated with the tumor metastasis and poor survival in triple negative breast cancer (TNBC) tumors, upon analysis by immunohistochemical (IHC) staining of tumor samples from 240 breast cancer cases. Depletion of ETS1 in TNBC cells by shETS1 significantly inhibited the cell proliferation and migration. Mechanistically, knockdown of ETS1 in TNBC cells dramatically reduced expression of YAP and the YAP target genes, and overexpression of YAP in the ETS1 knockdown cells restored the cell proliferation and migration. These data indicate that YAP is a downstream effector mediating the ETS1-promoted TNBC cell proliferation and migration. Taken together, our results suggest that ETS1 promotes TNBC progression through the YAP signaling.

Large-angle broadband transmission of electromagnetic waves through dielectric plates by embedding meta-atoms.

In many practical applications, dielectric electromagnetic (EM) windows are usually under large-angle incidence of EM waves rather than normal incidence. To guarantee normal operation of devices inside, high transmission must be maintained under large incident angles, especially for TE-polarized waves. In this work, we propose a method of achieving broadband transmission of TE-polarized waves under large incident angles by embedding meta-atoms within dielectric plates. To this end, long metallic wires and S-shaped structures are embedded in the original dielectric plate, the former of which will dilute the effective permittivity due to plasma oscillation and the latter will increase the effective permeability due to induced strong current loops under large incident angles. In this way, two consecutive transmission peaks can be generated, forming a broad transmission band under large incident angles. A proof-of-principle Ku-band prototype was designed, fabricated, and measured to verify this strategy. Both simulated and measured results show that the prototype can operate in the whole Ku-band under incident angle [60°, 85°] for TE-polarized waves, with significantly enhanced transmission. This work provides an effective method of enhancing large-angle transmission of EM waves and may find applications in radar, communications and others.

Bioinformatics analysis of inflammation and oncology in pulmonary lymphangioleiomyomatosis.

This study investigates the molecular markers and biological pathways of pulmonary lymphangioleiomyomatosis. We analyzed 2 gene expression profiles in the gene expression omnibus Gene Expression Omnibus database for normal lung tissue and lymphangioleiomyomatosis and identified differential expressed genes in pulmonary lymphangioleiomyomatosis. Ninety-one differentially expressed genes were identified, including 36 upregulated genes and 55 downregulated genes. Hub genes and pathogenic pathways associated with disease development were subsequently identified by enrichment analysis and protein-protein interaction network. Analysis showed that differential expressed genes are mainly involved in the biological behavior of tumor cell proliferation and invasion as well as the inflammatory response. We have identified 10 hub genes in the protein-protein interaction network. Hub genes play an important role in the proliferation and inflammatory response involved in tumor cell proliferation. This study deepens the understanding of lymphangioleiomyomatosis disease and provides a biological basis for further clinical diagnosis and treatment.

Effect of Moderate-to-Severe Iodine Deficiency in Early Pregnancy on Subclinical Hypothyroidism: A Longitudinal Study in an Iodine-Sufficient Region in China.

Objective: To investigate iodine status among pregnant women in an iodine-sufficient region in China after the implementation of revised universal salt iodization (USI) standards in 2012 and assess the association between urinary iodine concentrations (UIC) in early pregnancy and the incidence of subclinical hypothyroidism (SCH) in euthyroid women negative for antithyroid Ab during different trimesters. Methods: We measured the iodine status of 1,264 pregnant women, and performed follow-up assessment of thyroid function at 20 and 30 weeks of gestation among a cohort of 250 euthyroid women. We assessed the association of UIC in the 1st trimester with the incidence of SCH in subsequent trimesters. UIC and serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured. Results: The median UIC was 135.95 µg/L among 1,264 women. Serum FT4 level was significantly higher in the group of UIC 150 to 249 µg/L compared with other UIC groups (P < 0.001). TSH was significantly higher in the UIC more than or equal to 250 µg/L group than the UIC 150 to 249 g/L group (P = 0.043). Of the 250 euthyroid women negative for antithyroid Ab (TSH value of 2.5-3.55 mU/L) in the 1st trimester, pregnant women with UIC lower than 100 µg/L in the 1st trimester exhibited a significantly increased risk of SCH (odds ratio [OR] = 2.47; 95% confidence interval [CI] = 1.22-5.71; P = 0.012, according to the Chinese Medical Association criteria; OR = 5.22, 95% CI = 1.73-6.09, P = 0.004, according to ATA criteria) during the latter half of pregnancy compared with the UIC 150 to 249 µg/L group. Conclusion: Moderate-to-severe iodine deficiency (UIC lower than 100 µg/L) in the 1st trimester was associated with a significantly higher risk of SCH during the 2nd or 3rd trimesters among euthyroid pregnant women who had negative for antithyroid Ab. Women with SCH during pregnancy require regular UIC tests to maintain appropriate iodine status.

Estrogen Receptor Bio-Activities Determine Clinical Endocrine Treatment Options in Estrogen Receptor-Positive Breast Cancer.

In estrogen receptor positive (ER+) breast cancer therapy, estrogen receptors (ERs) are the major targeting molecules. ER-targeted therapy has provided clinical benefits for approximately 70% of all breast cancer patients through targeting the ERα subtype. In recent years, mechanisms underlying breast cancer occurrence and progression have been extensively studied and largely clarified. The PI3K/AKT/mTOR pathway, microRNA regulation, and other ER downstream signaling pathways are found to be the effective therapeutic targets in ER+ BC therapy. A number of the ER+ (ER+) breast cancer biomarkers have been established for diagnosis and prognosis. The ESR1 gene mutations that lead to endocrine therapy resistance in ER+ breast cancer had been identified. Mutations in the ligand-binding domain of ERα which encoded by ESR1 gene occur in most cases. The targeted drugs combined with endocrine therapy have been developed to improve the therapeutic efficacy of ER+ breast cancer, particularly the endocrine therapy resistance ER+ breast cancer. The combination therapy has been demonstrated to be superior to monotherapy in overall clinical evaluation. In this review, we focus on recent progress in studies on ERs and related clinical applications for targeted therapy and provide a perspective view for therapy of ER+ breast cancer.

Accurate Prediction of Aqueous Free Solvation Energies Using 3D Atomic Feature-Based Graph Neural Network with Transfer Learning.

Graph neural network (GNN)-based deep learning (DL) models have been widely implemented to predict the experimental aqueous solvation free energy, while its prediction accuracy has reached a plateau partly due to the scarcity of available experimental data. In order to tackle this challenge, we first build a large and diverse calculated data set Frag20-Aqsol-100K of aqueous solvation free energy with reasonable computational cost and accuracy via electronic structure calculations with continuum solvent models. Then, we develop a novel 3D atomic feature-based GNN model with the principal neighborhood aggregation (PNAConv) and demonstrate that 3D atomic features obtained from molecular mechanics-optimized geometries can significantly improve the learning power of GNN models in predicting calculated solvation free energies. Finally, we employ a transfer learning strategy by pre-training our DL model on Frag20-Aqsol-100K and fine-tuning it on the small experimental data set, and the fine-tuned model A3D-PNAConv-FT achieves the state-of-the-art prediction on the FreeSolv data set with a root-mean-squared error of 0.719 kcal/mol and a mean-absolute error of 0.417 kcal/mol using random data splits. These results indicate that integrating molecular modeling and DL would be a promising strategy to develop robust prediction models in molecular science. The source code and data are accessible at: https://yzhang.hpc.nyu.edu/IMA.