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Abstract We present a novel mechanism for realistic electroweak symmetry breaking in Twin Higgs/neutral naturalness models where the Z 2 exchange symmetry can remain exactly unbroken. The exchange symmetry in the Yukawa sector will be implemented as an “N-trigonometric parity” sin N h f ↔ cos N h f $$ \sin N\frac{h}{f}\leftrightarrow \cos N\frac{h}{f} $$ . The Yukawa couplings will be suppressed leading to an N-suppressed Higgs quadratic term, without significantly affecting the quartic. We present a concrete implementation of this idea for general (odd) values of N using maximal symmetry, and a realistic benchmark model for N = 3. We find that the tuning in the resulting Higgs potential is negligible, and also show that two-loop N-suppression violating gauge contributions can be sufficiently small. The Higgs potential and its couplings in top sector are different from other neutral naturalness models, which are the main predictions of our model and can be tested in colliders.

Lymphatic malformation-6 (LMPHM6) is a rarer form of nonimmune hydrops that often manifests as widespread lymphedema involving all segments of the body, namely, subcutaneous edema, intestinal/pulmonary lymphangiectasia, chylothoraces, and pleural/pericardial effusions. Here, we detected one rare and previously unobserved homozygous missense variant in PIEZO1 (c.5162C>G, p.Ser1721Trp) as a novel genetic cause of autosomal recessive LMPHM6, in a family with three adverse pregnancy outcomes due to nonimmune fetal hydrops. Although, the loss-of-function mutations such as those usually including nonsense, frameshift, splice site, and also fewer missense variants in PIEZO1 have been proved to lead to LMPHM6, among these, the biallelic homozygous mutations resulting in the loss of function of PIEZO1 have not been reported before. Here, we first strongly implicated impaired PIEZO1 function–associated LMPHM6 with a homozygous missense mutation in PIEZO1.

BackgroundGiven that the time lag between cytomegalovirus (CMV) screening and diagnosed testing, a better knowledge of the association between pregnant women with CMV screening test positive and stillbirth in an epidemiological perspective was required to assist people being counseled reframe their pregnancy and birth plans based on the magnitude of the risk.MethodsThis study recruited 44048 eligible pregnant women from March 13, 2013 to December 31, 2019. Serological tests including CMV-specific IgM and IgG, and IgG avidity index were used to screen for maternal CMV infection and were measured by automated chemiluminescence immunoassay. The association was assessed using the inverse probability of group-weighted multivariate-adjusted log-binomial models.ResultsA total of 540 infants ended with a stillbirth (12.3 per 1000 pregnancies), and 2472 pregnancies with maternal CMV infection were screened out (56.1 per 1000 pregnancies) among all eligible pregnancies. In the comparison analysis, 326 infants ended with a stillbirth (86.6 per 1000 pregnancies) in the maternal CMV infection group compared with 214 infants (7.8 per 1000 pregnancies) in the group where mothers were not infected with CMV (RR 12.17; 95% CI 9.43–15.71). After excluding the pregnancies of stillbirth with birth defects, a strong association between the two groups was still observed (RR 9.38; 95% CI 6.92–12.70).ConclusionOur findings quantified the risk of a woman having a baby with stillbirth if she had a positive serologic CMV screening test in her first trimester, and supported the value of using CMV serologic tests as part of regular testing in pregnant women.Trial registrationRegistered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

ObjectiveTo estimate the association of selected maternal and fetal characteristics with the risk of perinatal mortality in South China.MethodsA prospective cohort study was conducted from March 2013 to December 2019. The exposures of interest were maternal sociodemographic characteristics, lifestyle and habits during early pregnancy, and complications of pregnancy. Their effects on the development of perinatal death were analyzed in our study.ResultsA total of 44,048 eligible pregnant women were included in the analysis. Of these, 596 fetuses were perinatal deaths (perinatal mortality was 13.5 per 1,000 births). After adjustment, maternal obesity, being employed, history of gestational hypertension, taking antidepressants during early pregnancy, history of gestational diabetes mellitus, gestational diabetes mellitus, infertility drug treatment and assisted reproductive techniques, history of neonatal death, preterm birth, and congenital malformations all significantly increased the risk of perinatal death. Ethnic minority, income > 5,000, multiparous women, and cesarean section associated with reduced risk of perinatal death.ConclusionSome factors of maternal sociodemographic characteristics, abnormal pregnancy history, lifestyle and habits during early pregnancy, and complications of pregnancy were associated with the risk of perinatal death.

Abstract MiR-21, a non-coding miRNA with 22 nucleotides, plays an important part in the proliferation, invasion, and metastasis of tumor cells. The present study demonstrates that isomers of chiral ruthenium(II) complexes with alkynes (Λ-1 and Δ-1) were synthesized by Songogashira coupling reaction by using microwave-assisted synthetic technology. The isomers can recognize and stabilize miR-21, with the Λ-isomer showing a stronger binding capacity than the Δ-isomer. Further studies showed that both isomers can be uptaken by MDA-MB-231 cells and enriched in the nucleus. Treatment with the Λ-/Δ-isomer downregulated the expression of miR-21. In a word, the development of chiral ruthenium(II) complexes act as potential inhibitors against tumor cells by recognizing, stabilizing, and regulating the expression of miR-21.

The nature of dark matter remains obscure in spite of decades of experimental efforts. The mass of dark matter candidates can span a wide range, and its coupling with the Standard Model sector remains uncertain. All these unknowns make the detection of dark matter extremely challenging. Ultralight dark matter, with m∼10^{−22} eV, is proposed to reconcile the disagreements between observations and predictions from simulations of small-scale structures in the cold dark matter paradigm while remaining consistent with other observations. Because of its large de Broglie wavelength and large local occupation number within galaxies, ultralight dark matter behaves like a coherently oscillating background field with an oscillating frequency dependent on its mass. If the dark matter particle is a spin-1 dark photon, such as the U(1)_{B} or U(1)_{B−L} gauge boson, it can induce an external oscillating force and lead to displacements of test masses. Such an effect would be observable in the form of periodic variations in the arrival times of radio pulses from highly stable millisecond pulsars. In this study, we search for evidence of ultralight dark photon dark matter (DPDM) using 14-year high-precision observations of 26 pulsars collected with the Parkes Pulsar Timing Array. While no statistically significant signal is found, we place constraints on coupling constants for the U(1)_{B} and U(1)_{B−L} DPDM. Compared with other experiments, the limits on the dimensionless coupling constant ε achieved in our study are improved by up to two orders of magnitude when the dark photon mass is smaller than 3×10^{−22} eV (10^{−22} eV) for the U(1)_{B} (U(1)_{B−L}) scenario.

ObjectivesThis study aimed at assessing the association between maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring.MethodsFrom November 2017 to March 2019, a case-control study comprising 360 mothers of VSD cases and 504 mothers of healthy infants was conducted in Han Chinese populations. The main exposures of interest were maternal dietary habits in early pregnancy and MTHFD1 gene polymorphisms. Logistic regression models were used to estimate the main effects and interaction effects.ResultsIt was observed that maternal excessive intake of pickled vegetables (aOR = 1.85, 95%CI: 1.45–2.37), smoked foods (aOR = 1.93, 95%CI: 1.48–2.51), barbecued foods (aOR = 1.74, 95%CI: 1.28–2.36), and fried foods (aOR = 1.68, 95%CI: 1.30–2.17) were associated with a higher risk of VSD in offspring, whereas maternal excessive intake of fresh meat (aOR = 0.61, 95%CI: 0.47–0.79), fish and shrimp (aOR = 0.29, 95%CI: 0.23–0.38), fresh eggs (aOR = 0.54, 95%CI: 0.42–0.70), fresh fruits or vegetables (aOR = 0.44, 95%CI: 0.33–0.60), soy foods (aOR = 0.65, 95%CI: 0.53–0.80), and milk products (aOR = 0.49, 95%CI: 0.40–0.59) could contribute significantly to a lower risk of VSD in offspring. Furthermore, the genetic polymorphisms of maternal MTHFD1 gene at rs1950902 (GA vs. GG: aOR = 0.67, 95%CI: 0.50–0.90) and rs2236222 (GG vs. AA: aOR = 2.75, 95%CI: 1.57–4.83) were significantly associated with the risk of VSD in offspring. In addition, there was a significant interaction effect between maternal dietary habits and MTHFD1 gene polymorphisms on the risk of VSD.ConclusionsMaternal dietary factors, MTHFD1 genetic polymorphisms, and their interactions were all associated with the risk of VSD in offspring. However, further research in diverse ethnic populations and with a larger sample size is warranted to corroborate our findings.Trial RegistrationRegistered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

With the increasing demand for quality control in the traditional Chinese medicine industry, there is a need for the development of quality markers and a quick, non-destructive technique for the discrimination of related species. In our previous study, ultra-performance liquid chromatography (UPLC) was used for the simultaneous determination of five compounds, including three alkaloids (nitidine chloride, chelerythrine, and magnoflorine), one flavonoid (aurantiamarin), and one lignan (sesamin). In this study, the simultaneous quantification of the above-mentioned compounds could be used to discriminate the powders of roots from those of stems. To further test the reliability of the five compounds, seventy-two batches of wild and seventy-five batches of cultivated Zanthoxylum nitidum samples collected from Guangdong, Guangxi, and Fujian provinces in China were analyzed by UPLC and near-infrared spectroscopy (NIRS). In general, the quantitative results of UPLC were consistent with those of NIRS, and cultivated Z. nitidum has similar major bioactive compounds as the wild one, as supported by principal component analysis. Consequently, these five major bioactive compounds are suggested as potential quality markers. In addition, the NIRS method with discriminant analysis successfully differentiated Z. nitidum from three related species (Z. avicennae, Z. scandens and Toddalia asiatica) of the Rutaceae family. In summary, this study provides a method for the rapid identification of Z. nitidum and discrimination of root and stem powders, and suggests five compounds as quality markers for the evaluation of Z. nitidum.

Hepatic steatosis is one of the most important features of the pathogenesis for non-alcoholic fatty liver disease. Fat deposition in liver cells can influence hepatic lipogenesis along with other metabolic pathways and further lead to the irreversible liver cirrhosis and injury. However, the underlying mechanism of steatosis remains largely unexplored. Our previous study revealed that AQP7 played an important role in liver steatosis. In this study, we determined that the transcriptional level of AQP7 was up-regulated by estrogen receptor alpha (ERα) upon 17β-estradiol (E2) and oleic acids treated HepG2 cells. Furthermore, we identified long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) as a potential hallmark which was down-regulated in ERα silencing HepG2 cells by RNA-Seq. Finally, we validated that the 3’ terminal nucleotides of NEAT1 were contributed for the interaction with ERα to facilitate AQP7 transcription to suppress liver steatosis. Overall, our study gave evidence that NEAT1 played an important role in the activation of ERα to regulate AQP7-mediated hepatic steatosis.

Soft robots can create complicated structures and functions for rehabilitation. The posture perception of soft actuators is critical for performing closed-loop control for a precise location. It is essential to have a sensor with both soft and flexible characteristics that does not affect the movement of a soft actuator. This paper presents a novel end-to-end posture perception method that employs flexible sensors with kirigami-inspired structures and long short-term memory (LSTM) neural networks. The sensors were developed with conductive sponge materials. With one-step calibration from the sensor output, the posture of the soft actuator could be calculated by the LSTM network. The method was validated by attaching the developed sensors to a soft fiber-reinforced bending actuator. The results showed the accuracy of posture prediction of sponge sensors with three kirigami-inspired structures ranged from 0.91 to 0.97 in terms of R2. The sponge sensors only generated a resistive torque value of 0.96 mNm at the maximum bending position when attached to a soft actuator, which would minimize the effect on actuator movement. The kirigami-inspired flexible sponge sensor could in future enhance soft robotic development.

Abstract Six top signatures provide a novel probe of new physics. We discuss production of six top quarks as the decay products of a pair of top partners in the setting of a composite Higgs model, and argue that the six top signal may generically provide one of the first final states to show a discrepancy. We construct an analysis based on quantities such as H T and the numbers of jets which are tagged as boosted tops, W s, or containing b-tags, and show that the LHC with 3 ab −1 can discover top partners with masses up to around 2.5 TeV in the six top signature.

Abstract We present the most general sum rules reflecting the cancellation of ultraviolet divergences in the Higgs potential, which provide necessary conditions for any weakly-coupled extension of the Standard Model to be natural. There is a separate sum rule for the cancellation of the quadratic and logarithmic divergences, and their forms depend on whether the divergences are canceled by same-spin or opposite-spin partners. These sum rules can be applied to mass eigenstates and conveniently used for direct collider tests of naturalness. We study in detail the feasibility of testing these sum rules in the top sector at a future 100 TeV proton collider within two benchmark models, the Little Higgs (LH) and the Maximally Symmetric Composite Higgs (MSCH). We show how the two ingredients of the sum rules, the top partner masses and their Yukawa couplings to the Higgs, can be measured with sufficient accuracy to provide a highly non-trivial quantitative test of the sum rules. In particular, we study observables sensitive to the sign of the top partner Yukawa, which is crucial for verifying the sum rules but is notoriously difficult to measure. We demonstrate that in the benchmark models under study, a statistically significant discrimination between the two possible signs of each Yukawa will be feasible with a 30 ab−1 data set at 100 TeV.

Abstract Background Abdominal ectopic pregnancies are rare category of ectopic pregnancies.We describe a ectopic pregnancy implanted on the surface of diaphragm and highlight the difficult clinical course of an abdominal ectopic pregnancy managed with strategic procedural intervention. Case presentation A 33-year-old Chinese woman with abdominal pain was diagnosed with ectopic pregnancy implanted in the liver according to CT and advised to transfer the patient to tertiary referral center. The patient had a significant increasing abdominal pain and intense reflex sensitivity in the right shoulder when she presented to our hospital. Laparoscopic surgery was decided immediately with the impression of ruptured abdominal pregnancy and hemorrhagic shock. It was found that ectopic pregnancy was implanted on the diaphragmatic surface.The pregnant tissue was completely resected from the diaphragm and bipolar electrocoagulation was used to control bleeding. The patient was stable and discharged 3 days after surgery in a good condition. Conclusion CT or MRI should be considered as an alternative to TVS in the management of ectopic pregnancy patients with unusual presentations. A thorough observation of the entire pelvis and upper abdomen during laparoscopic exploration is crucial for diagnosis.

Abstract Background The development and assessment of clinical judgment ability are essential in nursing education. The Lasater Clinical Judgment Rubric (LCJR) was shown to be valid in evaluating nursing students’ learning outcomes and skills in western cultures but has not been validated in mainland China. This study aimed to compare a simulation-teaching model with a traditional teaching method in enhancing the clinical judgment ability of nursing undergraduate students and to validate the Chinese version of the Lasater Clinical Judgment Rubric (C-LCJR). Methods Four classes of nursing students (n = 157) at Hubei University of Chinese Medicine, China, were randomly assigned to two control and two experimental classes. The experimental classes were taught using simulation teaching with standardized patients, while the control classes were taught using traditional teaching methods. At the end of the experiment, students in both kinds of classes evaluated their clinical judgment using the C-LCJR. Teachers also rated the students but without knowing who had received the simulation teaching. Confirmatory factor analysis and a Multiple Indicators Multiple Causes (MIMIC) model with Bayesian estimation was fit to the rating data to investigate measurement properties and experimental effects. Results Compared to the control classes, students in the experimental classes performed better in all subdomains of C-LCJR (noticing, interpreting, responding, and reflecting). The measurement properties of the C-LCJR were found to be satisfactory with high factor loadings and reliabilities and no bias from age, gender, and raters. Conclusions The simulation teaching model is more effective than the traditional (non-simulation-based) teaching method in improving clinical judgment of Chinese nursing students. The C-LCJR is a valid and reliable instrument for measuring clinical judgment in nursing students in China.

We develop formalisms for a network of vector sensors, sensitive to certain spatial components of the signals, to identify the properties of a light axion or a dark photon background. These bosonic fields contribute to vectorlike signals in the detectors, including effective magnetic fields triggering the spin precession, effective electric currents in a shielded room, and forces on the matter. The interplay between a pair of vector sensors and a baseline that separates them can potentially uncover rich information of the bosons, including angular distribution, polarization modes, source localization, and macroscopic circular polarization. Using such a network, one can identify the microscopic nature of a potential signal, such as distinguishing between the axion-fermion coupling and the dipole couplings with the dark photon.

Cucumbers are rich in vitamins and minerals. The cucumber has recently become one of China’s main vegetable crops. More specifically, the adjustment of the Chinese agricultural industry’s structure and rapid economic development have resulted in increases in the planting area allocated to Chinese cucumber varieties and in the number of Chinese cucumber varieties. After complete sequencing of the “Chinese long” genome, the transcriptome, proteome, and metabolome were obtained. Cucumber has a small genome and short growing cycle, and these traits are conducive to the application of molecular breeding techniques for improving fruit quality. Here, we review the developments and applications of molecular markers and genetic maps for cucumber breeding and introduce the functions of gene families from the perspective of genomics, including fruit development and quality, hormone response, resistance to abiotic stress, epitomizing the development of other omics, and relationships among functions.

The development of rootstocks with a high-quality dwarf-type root system is a popular research topic in the apple industry. However, the precise breeding of rootstocks is still challenging, mainly because the root system is buried deep underground, roots have a complex life cycle, and research on root architecture has progressed slowly. This paper describes ideas for the precise breeding and domestication of wild apple resources and the application of key genes. The primary goal of this research is to combine the existing rootstock resources with molecular breeding and summarize the methods of precision breeding. Here, we reviewed the existing rootstock germplasm, high-quality genome, and genetic resources available to explain how wild resources might be used in modern breeding. In particular, we proposed the ‘from genotype to phenotype’ theory and summarized the difficulties in future breeding processes. Lastly, the genetics governing root diversity and associated regulatory mechanisms were elaborated on to optimize the precise breeding of rootstocks.

We generalize the recently proposed PT-symmetric axion haloscope to a larger array with more PT-symmetric structures. By broadening the response bandwidth of the signal without increasing the readout noise, the optimized scan rate of the axion haloscope is significantly enhanced, as well as is the signal power. Furthermore, we show that the robustness of the detector towards the variations of the array coupling is the strongest when a binary tree structure is introduced which contains a largely enhanced PT symmetry. The multiple allowed probing sensors can further increase the scan rate by a factor of the sensors' number due to the correlation of the signals. This type of array can strongly boost the search for an axion compared to single-mode resonant detection. The enhancement to the scan rate becomes the most manifest when applied to the proposed detection using a superconducting radio-frequency cavity with an ac magnetic field where most of the parameter space of the QCD axion above kHz can be probed.

Here, a series of half-sandwich arene Ru(II) complexes with difluorinated ligands [Ru(η6-arene)(L)Cl] (L1 = 2-(2,3-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; L2 = 2-(2,4-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; arene = benzene, toluene, and p-cymene) were synthesized and characterized. Molecular docking analysis showed that these complexes bind to c-myc G-quadruplex DNA through either groove binding or π–π stacking, and the relative difluorinated site in the main ligand plays a role in regulating the binding mode. The binding behavior of these complexes with c-myc G-quadruplex DNA was evaluated using ultraviolet–visible spectroscopy, fluorescence intercalator displacement assay, fluorescence resonance energy transfer melting assay, and polymerase chain reaction. The comprehensive analysis indicated that complex 1 exhibited a better affinity and stability in relation to c-myc G-quadruplex DNA with a DC50 of 6.6 μM and ΔTm values of 13.09 °C, than other molecules. Further activity evaluation results displayed that this class of complexes can also inhibit the growth of various tumor cells, especially complexes 3 and 6, which exhibited a better inhibitory effect against human U87 glioblastoma cells (51.61 and 23.75 μM) than other complexes, even superior to cisplatin (32.59 μM). Owing to a befitting lipophilicity associated with the high intake of drugs by tumor cells, complexes 3 and 6 had favorable lipid-water partition coefficients of −0.6615 and −0.8077, respectively. Moreover, it was found that complex 6 suppressed the proliferation of U87 cells mainly through an induced obvious S phase arrest and slight apoptosis, which may have resulted from the stabilization of c-myc G-quadruplex DNA to block the transcription and expression of c-myc. In brief, these types of arene Ru(II) complexes with difluorinated ligands can be developed as potential inducers of S-phase arrest and apoptosis through the binding and stabilization of c-myc G-quadruplex DNA, and could be used in clinical applications in the future.

Objective Observational studies have shown that circulating vitamin D (VitD) deficiency is associated with atherogenic lipid patterns among polycystic ovary syndrome (PCOS) patients. However, interventional studies have shown inconsistent results. The aim of this meta-analysis was to investigate how VitD supplementation influences lipid indices in PCOS patients. Methods The authors searched four electronic databases through August 2019 to identify randomized controlled trials (RCTs) that assessed the effect of VitD intervention on serum lipids among PCOS patients. Mean differences were generated for statistical evaluation. Results We included eight studies and performed nine comparisons across 467 participants. VitD supplementation reduced serum triglyceride levels (−11.88 mg/dL; 95% confidence interval [CI]: −17.03 to −6.73), total cholesterol (−9.09 mg/dL; 95% CI: −14.90 to −3.29), low-density lipoprotein cholesterol (−5.22 mg/dL; 95% CI: −10.32 to −0.13), and very-low-density lipoprotein cholesterol (−2.43 mg/dL; 95% CI: −3.69 to −1.17) compared with no VitD supplementation. However, high-density lipoprotein cholesterol levels showed no differences with or without VitD supplementation (−0.39 mg/dL; 95% CI: −1.39 to 0.61). Conclusions VitD supplementation improved serum lipid levels among PCOS patients, but serum high-density lipoprotein cholesterol levels were not changed. VitD intervention might benefit PCOS patients who are at high risk of an atherogenic lipid profile.

Objective This study aimed to determine the role of uterine artery blood flow (UABF) in recurrent spontaneous abortion (RSA) and to determine a viable option to promote the outcome of pregnancy. Methods A total of 421 women were prospectively recruited for this research. UABF indices, including the systolic/diastolic ratio, pulsatility index and resistance index, during the midluteal phase were compared between patients with RSA and women without RSA (controls). After low-molecular-weight heparin (LMWH) was administered to patients with RSA, indices at 7, 10, and 12 weeks of gestation were compared between the two groups. Results UABF indices during the midluteal phase were significantly higher in the RSA group than in the control group. After LMWH was administered to the RSA group, UABF indices in the first trimester were similar to those in the control group. The rate of spontaneous miscarriage was also similar between the groups after LMWH treatment. Conclusions Our study shows that sufficient uterine perfusion is crucial for a successful pregnancy. LMWH reduces the rate of spontaneous miscarriage in patients with RSA to a similar rate in women without RSA. LMWH might play a role in decreasing UABF resistance and increasing uterine perfusion.

The absorbent resin for Cu2+ removal was prepared under microwave irradiation through grafting acrylamide (AM) and acrylic acid (AA) to cellulose. The initiator is a kind of redox system composed of potassium persulfate/sodium thiosulfate. The crosslinking agent is N,N′-methylene bisacrylamide. The optimal reaction conditions are as follows: the ratio of AA to cellulose is 10 : 1, initiator to AA is 0.65 wt%, crosslinking agent to AA is 1.0 wt%, neutralization degree of AA is 75%, microwave power level is 320 W, and time is 300 s. The maximum absorption capability of the resin is 65 mg·g−1. Different from previous studies, the reaction was carried out without the protection of nitrogen and troublesome posttreatment. The product was obtained directly by one-step synthesis without purification and drying of the crude product. The pollution and cost caused by organic solvent are avoided, and the whole preparation period is shortened deeply. Moreover, the time of absorption equilibrium is shorter. In a word, the preparation in this paper has the obvious advantages, such as simple process, short time, no pollution, low-energy, and low-cost.

In this paper we investigate the phenomenology of the electron flavored Dirac dark matter with two types of portal interactions. We analyze constraints from the electron magnetic moment anomaly, LHC searches of singly charged scalar, dark matter relic abundance as well as direct and indirect detections. Our study shows that the available parameter space is quite constrained, but there are parameter space that is compatible with the current data. We further show that the DAMPE cosmic ray electron excess, which indicates cosmic ray excess at around 1.5 TeV, can be interpreted as the annihilation of dark matter into electron positron pairs in this model. Keywords: Dark matter theory, BSM particle physics

Summary: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs) from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2). The results showed that the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure defects by decreasing the stability of 16S rRNA, which led to reduced levels of mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential were also reduced, thereby elevating the intracellular Ca2+ concentration, which was associated with numerous HCM-specific electrophysiological abnormalities. Our findings therefore provide an innovative insight into the pathogenesis of maternally inherited HCM. : In this article, Yan Q, Liu Z, Huang W, and colleagues show that patient-specific iPSCs as well as their derived cardiomyocytes carrying the m.2336T>C mutation in MT-RNR2 were generated to understand the pathogenic mechanism of maternally inherited HCM. MT-RNR2 mutation resulted in mitochondrial dysfunctions and ultrastructure defects, which induced abnormal Ca2+ homeostasis, then HCM-specific cellular and electrophysiological characteristics in iPSC-CMs. Keywords: mitochondrion, hypertrophic cardiomyopathy, induced pluripotent stem cells, MT-RNR2, maternal inheritance

Plant peptide hormones play important roles in plant growth and development. Among these hormones, the C-TERMINALLYENCODED PEPTIDE (CEP) belongs to a newly found peptide family that regulates root development in Arabidopsis as well as in other species. However, nothing is known about the CEP genes in apple (Malus×domestica, MdCEP). In this study, a total of 27 apple CEP genes were identified through a genome-wide analysis and were phylogenetically divided into three classes (I, II and III). The predicted MdCEP genes were distributed across 10 of 17 chromosomes with different densities. Next, the gene structures and motif compositions of the MdCEP genes were analyzed. Subsequently, the expression analysis suggested that the MdCEP genes were highly activated in roots and that MdCEP23 may play an important role in regulating the growth and development of roots. Moreover, all of the MdCEP genes were responsive to multiple abiotic stresses, indicating that MdCEP genes may be involved with various aspects of physiological processes in apple. Nearly one-third of MdCEP genes had a significant response to low nitrogen treatment. Most of the MdCEP genes were up-regulated under stress, including mannitol, polyethylene glycol (PEG) and abscisic acid (ABA), suggesting that MdCEP genes may be involved in the drought stress response. This study provides insight into the putative functions of the MdCEP genes using a genome-wide analysis of the CEP gene family.

Abstract Background Hepatic iron overload has been implicated in many liver diseases; however, whether it is involved in clonorchiasis remains unknown. The purpose of this study is to investigate whether Clonorchis sinensis (C. sinensis) infection causes hepatic iron overload, analyze the relationship between the iron overload and associated cell apoptosis, so as to determine the role of excess iron plays in C. sinensis-induced liver injury. Methods The Perls’ Prussian staining and atomic absorption spectrometry methods were used to investigate the iron overload in hepatic sections of wistar rats and patients infected with C. sinensis. The hepatic apoptosis was detected by transferase uridyl nick end labeling (TUNEL) methods. Spearman analysis was used for determining the correlation of the histological hepatic iron index and the apoptotic index. Results Blue iron particles were deposited mainly in the hepatocytes, Kupffer cells and endothelial cells, around the liver portal and central vein area of both patients and rats. The total iron score was found to be higher in the infected groups than the respective control from 8 weeks. The hepatic iron concentration was also significantly higher in treatment groups than in control rats from 8 weeks. The hepatocyte apoptosis was found to be significantly higher in the portal area of the liver tissue and around the central vein. However, spearman’s rank correlation coefficient revealed that there was a mildly negative correlation between the iron index and hepatocyte apoptosis. Conclusions This present study confirmed that hepatic iron overload was found during C. sinensis infection. This suggests that iron overload may be associated with hepatocyte apoptosis and involved in liver injury during C. sinensis infection. Further studies are needed to investigate the molecular mechanism involved here.

Auxin has been identified to play critical roles in regulating plant growth and development. The polar transport of auxin is regulated by auxin transporters. In the present study, an auxin efflux carrier gene MdPIN1 was cloned from Malus×domestic, Royal Gala, and introduced into wild-type Arabidopsis thaliana (Col-0). The transgenic plants exhibited the phenotype of inhibition of primary root (PR) elongation and increased lateral root (LR) number in compared with Col-0. Overexpression of MdPIN1 affected auxin transport, and enhanced phototropic responses and geotropism reaction, whereas had no significant difference in the auxin biosynthesis. These findings suggest that the MdPIN1 gene plays a vital role in auxin transport and root development.

After the LHC is turning on and accumulating more data low scale seesaw mechanisms for small neutrino masses with signature manifesting at TeV scale are gaining more and more attention once they provide neutrino masses at sub-eV scale and can be probed at the LHC. In this regard inverse seesaw mechanism arises as an interesting candidate for performing such proposal. This mechanism is a kind of counterpart of canonical mechanism which requires lepton number be violated explicitly at high energy scale while the inverse one requires the contrary, that lepton number be violated explicitly at low energy scale. There are three ways of performing canonical seesaw mechanism. For each one of it there is its inverse counterpart. Here we restrict our investigation to the study of the inverse type II seesaw mechanism. Our main goal is to implement the mechanism into the 3-3-1 model with right-handed neutrinos, but first we revisit the main ideas and consequences of the inverse type I and II seesaw mechanisms when incorporated into the standard model. In regard to the 3-3-1 model, as interesting result, we show that the mechanism may provide small masses to both the standard neutrinos as well as to the right-handed ones. As phenomenological aspect, its best signature are the doubly charged scalars which are sextet by the 3-3-1 symmetry. We investigate their production at the LHC through the process σ(pp→Z⁎,γ⁎,Z′→Δ++Δ−−) and their signal through four leptons final state decay channel.

In this work, we introduce an extra singlet pseudoscalar into the Type-III two Higgs doublet model (2HDM) which is supposed to solve a series of problems in the modern particle-cosmology. With existence of a light pseudoscalar, the h→μτ excess measured at CMS and as well as the (g−2)μ anomaly could be simultaneously explained within certain parameter spaces that can also tolerate the data on the flavor-violating processes τ→μγ and Higgs decay gained at LHC. Within the same parameter spaces, the DM relic abundance is well accounted. Moreover, the recently observed Galactic Center gamma ray excess (GCE) is proposed to realize through dark matter (DM) pair annihilations, and in this work, the scenario of the annihilation being mediated by the pseudoscalar is also addressed.

Membrane receptors at the surface of target cells are key host factors for virion entry; however, it is unknown whether trafficking and secretion of progeny virus requires host intracellular receptors. In this study, we demonstrate that dengue virus (DENV) interacts with KDEL receptors (KDELR), which cycle between the ER and Golgi apparatus, for vesicular transport from ER to Golgi. Depletion of KDELR by siRNA reduced egress of both DENV progeny and recombinant subviral particles (RSPs). Coimmunoprecipitation of KDELR with dengue structural protein prM required three positively charged residues at the N terminus, whose mutation disrupted protein interaction and inhibited RSP transport from the ER to the Golgi. Finally, siRNA depletion of class II Arfs, which results in KDELR accumulation in the Golgi, phenocopied results obtained with mutagenized prME and KDELR knockdown. Our results have uncovered a function for KDELR as an internal receptor involved in DENV trafficking.

BACKGROUND: Clonorchiasis is an important zoonotic parasitic disease worldwide. Past estimates showed the prevalence increased based on studies undertaken ten years or more ago. However, control strategies, changing ecology and migration may have resulted to changes in the prevalence of clonorchiasis. The purpose of the present study was to analysis the prevalence and epidemiological characterisation of clonorchiasis in Heilongjiang Province, Northeast China. METHODOLOGY/PRINCIPAL FINDINGS: A total of 4951 clinically suspected outpatients were examined from January 2009 to December 2012. Overall prevalence of clonorchiasis was 25.93% (1284/4951) by the combination strategy of the Kato-Katz technique (KK) and enzyme-linked immunosorbent assay (ELISA), with a significant increase from 22.53% in 2009 to 34.25% in 2012. Apart from Daxinganling city, clonorchiasis was reported throughout Heilongjiang Province and mainly along the Songhua River and Nen River basin, with an increased annual prevalence. The annual prevalence in men increased significantly in 2012 and was higher than that in women over 4 years. A similar pattern was seen for the annual infection rate in rural and urban areas. Farm labourers accounted for the majority of cases (65.93%), with a higher prevalence than in other occupations. Consumption of freshwater fish was considered the strongest risk factor of clonorchiasis. The infection rates in the 40-49 and 50-59 years age groups showed a significant increasing trend in 2012. Cases of re-infection were common. CONCLUSIONS/SIGNIFICANCE: The present study revealed that clonorchiasis remained widespread and prevalent in Heilongjiang Province. An integrated control programme is urgently needed to reduce the public health impact of clonorchiasis in this endemic area.

BACKGROUND: Peritoneal fluid (PF) from patients with endometriosis can inhibit early embryo development via probable functional changes of embryo mitochondria in the early stage of embryo development. The purpose of this study was to determine the effect of PF from patients with endometriosis on mitochondrial function and development of early mouse embryos. METHODOLOGY/PRINCIPAL FINDINGS: PF was collected from patients with infertility and endometriosis, infertility due to tubal factors, and normal control subjects, and the level of NO was measured. Early murine embryos were then cultured with PF from normal control subjects, those with endometriosis, and with human tubal fluid (HTF), respectively. Cleavage and blastulation rates, mitochondrial DNA (mtDNA) copy numbers, adenosine triphosphate (ATP) level, and mitochondrial membrane potential (ΔΨm) of the different groups were compared. The NO level in the PF of patients with endometriosis was significantly greater than in those without endometriosis and control patients. The embryos cultures with PF from patients with endometriosis had a lower cleavage rate and blastulation rate, and higher ATP and ΔΨm level at the 2- and 4-cell stages. No significant difference was found in mtDNA copies among the 3 groups. CONCLUSIONS/SIGNIFICANCE: PF from patients with endometriosis can inhibit early embryo development via probable functional changes of embryo mitochondria in the early stage of embryo development. Understanding the effects of PF on embryo development may assist in developing new methods of treatment for infertility.

BACKGROUND: Cryptosporidium and Giardia are the two important zoonotic pathogens causing diarrhea of humans and animals worldwide. Considering the human cryptosporidiosis outbreak and sporadic cases caused by C. cuniculus, the important public health significance of G. duodenalis and little obtained information regarding rabbit infected with Cryptosporidium and Giardia in China, the aim of this study is to determine the prevalence and molecularly characterize Cryptosporidium and Giardia in rabbits in Heilongjiang Province, China. METHODOLOGY/PRINCIPAL FINDINGS: 378 fecal samples were obtained from rabbits in Heilongjiang Province. Cryptosporidium oocysts and Giardia cysts were detected using Sheather's sugar flotation technique and Lugol's iodine stain method, respectively. The infection rates of Cryptosporidium and Giardia were 2.38% (9/378) and 7.41% (28/378), respectively. Genotyping of Cryptosporidium spp. was done by DNA sequencing of the small subunit rRNA (SSU rRNA) gene and all the nine isolates were identified as Cryptosporidium cuniculus. The nine isolates were further subtyped using the 60-kDa glycoprotein (gp60) gene and two subtypes were detected, including VbA32 (n = 3) and a new subtype VbA21 (n = 6). G. duodenalis genotypes and subtypes were identified by sequence analysis of the triosephosphate isomerase (TPI) gene. The assemblage B (belonging to eight different subtypes B-I to B-VIII) was found in 28 G. duodenalis-positive samples. CONCLUSIONS/SIGNIFICANCE: The rabbits have been infected with Cryptosporidium and Giardia in Heilongjiang Province. The results show that the rabbits pose a threat to human health in the studied areas. Genotypes and subgenotypes of C. cuniculus and G. duodenalis in this study might present the endemic genetic characterization of population structure of the two parasites.

BACKGROUND: Examination of feces by light microscopy is widely used for specific parasitological diagnosis of clonorchiasis. However, the true incidence of infection is underestimated owing to the high missing diagnosis rate of this method. The enzyme-linked immunosorbent assay (ELISA) is widely used for the detection and control of clonorchiasis but the practicality of this method is unclear. The purpose of this study was to evaluate the effect of ELISA as a supplementary method for the diagnosis of clonorchiasis. METHODOLOGY/PRINCIPAL FINDINGS: The present study recruited 2,359 clinically suspected patients from Heilongjiang Province, China. In all, 954 cases were identified as antibody-positive by immunoglobulin (IgG)-ELISA and 495 individuals were diagnosed as egg-positive by the Kato-Katz (KK) method. The seropositive and egg-negative individuals were re-examined by repeated egg counts and/or the number of KK slides and 18 (18.18%) cases were confirmed as clonorchiasis. The 40.44%, antibody-positive rate determined by IgG-ELISA was significantly higher (P