Geography and similarity of regional cuisines in China

Food occupies a central position in every culture and it is therefore of great interest to understand the evolution of food culture. The advent of the World Wide Web and online recipe repositories has begun to provide unprecedented opportunities for data-driven, quantitative study of food culture. Here we harness an online database documenting recipes from various Chinese regional cuisines and investigate the similarity of regional cuisines in terms of geography and climate. We found that the geographical proximity, rather than climate proximity is a crucial factor that determines the similarity of regional cuisines. We develop a model of regional cuisine evolution that provides helpful clues to understand the evolution of cuisines and cultures.Comment: 13 pages, 11 figures and 2 table

Effect of Lycii fructus polysaccharides on ovulation failure in rats

Purpose: To investigate the effect of Lycii Fructus polysaccharides (LFPS) on ovulation failure.Methods: A rat model of ovulation failure was established by intragastric administration of hydroxyurea (300 mg/kg). Rats with ovulation failure then received LFPS via oral administration at doses of 100, 200, or 400 mg/kg. The body, uterus and ovary of each rat were weighed using electronic scales. The hypothalamic-pituitary-ovarian (HPO) axis hormones, including estradiol (E2) level, follicle-stimulating hormone (FSH) activity, and luteinizing hormone (LH) activity in the serum of each rat were determined by enzyme-linked immunosorbent assay (ELISA). The levels of pro-apoptotic proteins (Fas, FasL, FADD, c-caspase-8, c-caspase-10, c-caspase-3, c-caspase-6, and c-caspase-7) in the ovarian tissue of each rat were detected by western blot.Results: Hydroxyurea reduced significantly (p < 0.01) uterus and ovary indices (uterus or ovary weight/body weight) (0.119 and 0.026 %), E2 level (3.42 pmol/L), and FSH and LH activities (2.28 and 2.76 U/L), compared with those in the normal group (0.169 and 0.039 %; 6.72 pmol/L; 2.76 and 3.75 U/L). Hydroxyurea increased significantly (p < 0.01) the levels of the above-mentioned pro-apoptotic proteins relative to those in the normal group. LFPS (100, 200, or 400 mg/kg) reversed significantly (p < 0.05 or 0.01) the effect of hydroxyurea on all of the above indices.Conclusion: LFPS exhibits a protective effect on hydroxyurea-induced ovulation failure by regulating the HPO axis hormones and death receptor-mediated apoptotic pathway.Keywords: Lycii Fructus polysaccharides, Ovulation failure, Hypothalamic-pituitary-ovarian axis, Death receptor-mediated apoptotic pathwa

Synthesizing Speech Test Cases with Text-to-Speech? An Empirical Study on the False Alarms in Automated Speech Recognition Testing

Recent studies have proposed the use of Text-To-Speech (TTS) systems to automatically synthesise speech test cases on a scale and uncover a large number of failures in ASR systems. However, the failures uncovered by synthetic test cases may not reflect the actual performance of an ASR system when it transcribes human audio, which we refer to as false alarms. Given a failed test case synthesised from TTS systems, which consists of TTS-generated audio and the corresponding ground truth text, we feed the human audio stating the same text to an ASR system. If human audio can be correctly transcribed, an instance of a false alarm is detected. In this study, we investigate false alarm occurrences in five popular ASR systems using synthetic audio generated from four TTS systems and human audio obtained from two commonly used datasets. Our results show that the least number of false alarms is identified when testing Deepspeech, and the number of false alarms is the highest when testing Wav2vec2. On average, false alarm rates range from 21% to 34% in all five ASR systems. Among the TTS systems used, Google TTS produces the least number of false alarms (17%), and Espeak TTS produces the highest number of false alarms (32%) among the four TTS systems. Additionally, we build a false alarm estimator that flags potential false alarms, which achieves promising results: a precision of 98.3%, a recall of 96.4%, an accuracy of 98.5%, and an F1 score of 97.3%. Our study provides insight into the appropriate selection of TTS systems to generate high-quality speech to test ASR systems. Additionally, a false alarm estimator can be a way to minimise the impact of false alarms and help developers choose suitable test inputs when evaluating ASR systems. The source code used in this paper is publicly available on GitHub at https://github.com/julianyonghao/FAinASRtest.Comment: 12 pages, Accepted at ISSTA202

Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives

20(S)-Sulfonylamidine CPT-derivatives were prepared and tested for cytotoxicity.Several analogs showed superior cytotoxic activity compared to irinotecan.Key structural features related to cytotoxicity were identified by SAR analysis.Compounds 9 and 15c interacted with Topo I-DNA by a different binding mode from CPT.These compounds are new generation CPT-derived antitumor agents.In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure–activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π–π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.CPT (green), 9 (magenta), and 15c (blue) in the binding site of DNA-Topo-I

Elevated Expression of miR-19b Enhances CD8+ T Cell Function by Targeting PTEN in HIV Infected Long Term Non-progressors With Sustained Viral Suppression

Human immunodeficiency virus (HIV)-infected long-term non-progressors (LTNPs) are of particular importance because of their unique disease progression characteristics. Defined by the maintenance of normal CD4+T cells after more than 8 years of infection, these LTNPs are heterogeneous. Some LTNPs exhibit ongoing viral production, while others do not and are able to control viral production. The underlying basis for this heterogeneity has not been clearly elucidated. In this study, the miRNA expression profiles of LTNPs were assessed. The levels of microRNA-19b (miR-19b) were found to be significantly increased in peripheral blood mononuclear cells of LTNPs with lower rather than higher viral load. We made clear that miR-19b may regulate CD8+T cell functions in HIV infection, which has not been addressed before. Overexpression of miR-19b promoted CD8+T cell proliferation, as well as interferon-γ and granzyme B expression, while inhibiting CD8+T cells apoptosis induced by anti-CD3/CD28 stimulation. The target of miR-19b was found to be the “phosphatase and tensin homolog”, which regulates CD8+T cells function during HIV infections. Furthermore, we found that miR-19b can directly inhibit viral production in in-vitro HIV infected T cells. These results highlight the importance of miR-19b to control viral levels, which facilitate an understanding of human immunodeficiency virus pathogenesis and provide potential targets for improved immune intervention

Can Measuring the ‘Dual Anchors of Aorta’ Enhance the Success Rate of TAVR?—A Single-Center Experience

Introduction: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study’s primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients. Methods: The study enrolled retrospectively and prospectively patients diagnosed with severe AR who eventually underwent TAVR procedure from January 2019 to September 2022 at Fuwai cardiovascular Hospital, Beijing. Baseline information, MDCT measurements, anatomical classification, perioperative, and 1-year follow-up outcomes were collected and analyzed. Based on a novel anatomical categorization and dual anchoring theory, patients were divided into four categories according to the level of anchoring area. Type 1, 2, and 3 patients (with at least two anchoring regions) will receive TAVR with a transcatheter heart valve (THV), but Type 4 patients (with zero or one anchoring location) will be deemed unsuitable for TAVR and will instead receive medical care (retrospectively enrolled patients who already underwent TAVR are an exception). Results: The mean age of the 37 patients with severe chronic AR was 73.1 ± 8.7 years, and 23 patients (62.2%) were male. The American Association of Thoracic Surgeons’ score was 8.6 ± 2.1%. The MDCT anatomical classification included 17 cases of type 1 (45.9%), 3 cases of type 2 (8.1%), 13 cases of type 3 (35.1%), and 4 cases of Type 4 (10.8%). The VitaFlow valve (MicroPort, Shanghai, China) was implanted in 19 patients (51.3%), while the Venus A valve (Venus MedTech, Hangzhou, China) was implanted in 18 patients (48.6%). Immediate TAVR procedural and device success rates were 86.5% and 67.6%, respectively, while eight cases (21.6%) required THV-in-THV implantation, and nine cases (24.3%) required permanent pacemaker implantation. Univariate regression analysis revealed that the major factors affecting TAVR device failure were sinotubular junction diameter, THV type, and MDCT anatomical classification (p &lt; 0.05). Compared with the baseline, the left ventricular ejection fraction gradually increased, while the left ventricular end-diastolic diameter remained small, and the N-terminal-pro hormone B-type natriuretic peptide level significantly decreased within one year. Conclusion: According to the results of our study, TAVR with a self-expanding THV is safe and feasible for patients with chronic severe AR, particularly for those who meet the criteria for the appropriate MDCT anatomical classification with intact dual aortic anchors, and it has a significant clinical effect for at least a year.</p

Effectiveness of non-invasive chromosomal screening for normal karyotype and chromosomal rearrangements

Purpose: To study the accuracy of non-invasive chromosomal screening (NICS) results, in normal chromosomes and chromosomal rearrangement groups and to investigate whether using trophoblast cell biopsy along with NICS, to choose embryos for transfer can improve the clinical outcomes of assisted pregnancy.Methods: We retrospectively analyzed 101 couples who underwent preimplantation genetic testing at our center from January 2019 to June 2021 and collected 492 blastocysts for trophocyte (TE) biopsy. D3-5 blastocyst culture fluid and blastocyst cavity fluid were collected for the NICS. Amongst them, 278 blastocysts (58 couples) and 214 blastocysts (43 couples) were included in the normal chromosomes and chromosomal rearrangement groups, respectively. Couples undergoing embryo transfer were divided into group A, in which both the NICS and TE biopsy results were euploid (52 embryos), and group B, in which the TE biopsy results were euploid and the NICS results were aneuploid (33 embryos).Results: In the normal karyotype group, concordance for embryo ploidy was 78.1%, sensitivity was 94.9%, specificity was 51.4%, the positive predictive value (PPV) was 75.7%, and the negative predictive value (NPV) was 86.4%. In the chromosomal rearrangement group, concordance for embryo ploidy was 73.1%, sensitivity was 93.3%, specificity was 53.3%, the PPV was 66.3%, and the NPV was 89%. In euploid TE/euploid NICS group, 52 embryos were transferred; the clinical pregnancy rate was 71.2%, miscarriage rate was 5.4%, and ongoing pregnancy rate was 67.3%. In euploid TE/aneuploid NICS group, 33 embryos were transferred; the clinic pregnancy rate was 54.5%, miscarriage rate was 5.6%, and ongoingpregnancy rate was 51.5%. The clinical pregnancy and ongoing pregnancy rates were higher in the TE and NICS euploid group.Conclusion: NICS was similarly effective in assessing both normal and abnormal populations. Identification of euploidy and aneuploidy alone may lead to the wastage of embryos due to high false positives. More suitable reporting methods for NICS and countermeasures for a high number of false positives in NICS are needed. In summary, our results suggest that combining biopsy and NICS results could improve the outcomes of assisted pregnancy

Superconductivity emerged from density-wave order in a kagome bad metal

Unconventional superconductivity (USC) in a highly correlated kagome system has been theoretically proposed for years, yet the experimental realization is hard to achieve. The recently discovered vanadium-based kagome materials, which exhibit both superconductivity and charge density wave (CDW) orders, are nonmagnetic and weakly correlated, thus unlikely host USC as theories proposed. Here we report the discovery of a chromium-based kagome bad metal, CsCr$_3$Sb$_5$, which is contrastingly characterised by significant electron correlations and frustrated magnetism. Successive phase transitions at $\sim$54 K with stripe-like $4a_0$ structural modulations are observed, probably associated with CDW and antiferromagnetic spin-density-wave (SDW) orderings. Under moderately high pressures of 4-8 GPa, these density-wave orders are suppressed and, remarkably, superconductivity emerges with a maximum $T_\mathrm{c}$ of 6.4 K. A quantum critical point at $P_\mathrm{c}\approx$ 4 GPa is revealed, by which non-Fermi-liquid behaviours show up, reminiscent of USC in iron-based superconductors. The electronic structure calculations indicate that the electron filling is close to the characteristic flat bands of the kagome lattice. Our work offers an unprecedented platform for investigating the mechanism of USC in a correlated kagome system.Comment: 26 pages, 10 figure

Impeding the interaction between ​Nur77 and p38 reduces LPS-induced inflammation

该成果阐明了一条孤儿核受体Nur77通过p38-NF-κB信号通路参与炎症反应调控的新途径，为新的抗炎药物的筛选提供了新的靶标和理论基础。 吴乔课题组长期以来一直致力于孤儿核受体Nur77作用机理和生物学功能研究。该成果是吴乔课题组近年来在NatureChemicalBiology发表的第四篇系列研究论文，也是与不同学科领域相关课题组（包括结构生物学、化学生物学、天然产物药物研究等）合作的原创性成果。这些研究成果充分体现了学科交叉的优势，代表了相关研究的发展趋势。他们从分子机制、信号调控网络、共晶结构、小分子探针、药物靶点和疾病治疗等角度全面系统地阐明了Nur77作为临床重要的靶标，调控不同疾病的重要生物学功能，丰富和发展了孤儿核受体的理论知识，并且找到了能够降低血糖、抑制黑色素瘤生长和抗炎反应的小分子化合物，为治疗相关疾病提供了重要的先导化合物。该系列研究先后得到了多个国家自然科学基金重点项目和科技部“973”项目的长期支持。Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor ​Nur77 (also known as ​TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-κB activity and suppressing aberrant cytokine production. ​Nur77 directly associates with ​p65 to block its binding to the κB element. However, this function of ​Nur77 is countered by the LPS-activated ​p38α phosphorylation of ​Nur77. Dampening the interaction between ​Nur77 and ​p38α would favor ​Nur77 suppression of the hyperinflammatory response. A compound, ​n-pentyl 2-[3,5-dihydroxy-2-(1-nonanoyl) phenyl]acetate, screened from a ​Nur77-biased library, blocked the ​Nur77-​p38α interaction by targeting the ligand-binding domain of ​Nur77 and restored the suppression of the hyperinflammatory response through ​Nur77 inhibition of NF-κB. This study associates the nuclear receptor with immune homeostasis and implicates a new therapeutic strategy to treat hyperinflammatory responses by targeting a ​p38α substrate to modulate ​p38α-regulated functions.This work was supported by grants from the National Natural Science Fund of China, the '973' Project of the Ministry of Science and Technology (91413113, 2014CB910602, 31370724, 31221065) and the Program of Introducing Talents of Discipline to Universities (B12001). The crystallographic data collection at Beamline BL17U1 at Shanghai Synchrotron Radiation Facility is gratefully acknowledged