Runs of homozygosity analysis reveals population characteristics of yellow-feathered chickens using re-sequencing data.

1. To evaluate the inbreeding of yellow-feathered chickens (YFCs) and identify genes related to their unique characteristics, whole-genome re-sequencing data were applied to detect runs of homozygosity (ROH) in the genomes of 10 YFC chickens from each of 10 different YFC breeds. The number, length, distribution of ROH, and inbreeding coefficient in different YFC populations were calculated. Genomic regions with high frequency in ROH were annotated.2. In total, 25,547 ROH with an average length of 335 kb were detected, with most being <1 Mb. The domination of short ROH reflected the long breeding history of this chicken. The number, length, frequency, and distribution of ROH varied among chicken populations, and high genetic diversity was maintained.3. Numerous genes related to YFC characteristics were identified in the high-frequency ROH regions. Among these, IFNA, IFNB, IL11 RA, IL22 RA1, IFNLR1, and TRIF genes were involved in disease resistance. The AMY, G6PC, SDHB, GCNT4, and ACO genes were associated with energy material metabolism; and FABPL, AQP7, ACAA2, and RYR2 were related to meat quality and flavour. The KITLG, CREB3, RYR2, and LGR4 genes, related to pigmentation, were detected.4. This ROH-based inbreeding evaluation lays the foundation for breeding and conservation of YFC populations, and the candidate genes identified can be used for marker-assisted selection.

Therapeutic efficacy of dexmedetomidine on chronic obstructive pulmonary disease via downregulating lncRNA PACER.

OBJECTIVE: The aim of the study was to clarify the therapeutic mechanism of Dexmedetomidine (DEX) on the chronic obstructive pulmonary disease (COPD) and its regulatory effect on long non-coding RNA (lncRNA) PACER. PATIENTS AND METHODS: Serum level of PACER in COPD patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic potential of PACER in COPD was assessed by plotting ROC curves. The in vivo COPD model was generated in rats by cigarette smoking exposure. Primary rat alveolar epithelial cells were isolated, purified and cultured. After overexpression of PACER in primary rat alveolar epithelial cells, proliferative and migratory abilities were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Subsequently, we detected changes in PACER expression, viability and migratory potentials in primary rat alveolar epithelial cells harvested from control rats, and those harvested from COPD rats and induced with either DEX or not. Rescue experiments were conducted to uncover the involvement of PP2A in PACER-regulated cell phenotypes. RESULTS: PACER was upregulated in serum of COPD patients, which was a potential biomarker for diagnosing COPD. Overexpression of PACER in primary rat alveolar epithelial cells enhanced proliferative and migratory abilities. Compared with primary rat alveolar epithelial cells harvested from control rats, proliferative and migratory abilities were stronger in those harvested from COPD rats and induced with either DEX or not. Notably, DEX induction decreased PACER expression, and proliferative and migratory abilities in primary rat alveolar epithelial cells harvested from COPD rats. Overexpression of PP2A could partially abolish the promotive effects of PACER on proliferative and migratory abilities in DEX-induced primary rat alveolar epithelial cells harvested from COPD rats. CONCLUSIONS: PACER drives the proliferative and migratory abilities of alveolar epithelial cells through activating PP2A. Dexmedetomidine is conducive to COPD treatment by downregulating PACER.

[QARS1 gene related glutaminyl-tRNA synthetase deficiency syndrome: report of three cases and a review of literature].

Objective: To investigate the clinical characteristics, treatment and prognosis of QARS1 gene related glutaminyl-tRNA synthetase deficiency. Methods: To summarize and analyze the clinical manifestations, imaging, laboratory examination, genetic variant characteristics and treatment of three patients from the Fujian Medical University Affiliated Union Hospital, the 900th Hospital of People's Liberation Army, the First Medical Center of People's Liberation Army General Hsopital carrying compound heterozygous variations in QARS1 gene with a long-term follow-up in China. A literature search was conducted using Wanfang, Weipu, China National Knowledge Infrastructure (CNKI) and Pubmed databases with the keywords "QARS", "QARS1" and "glutaminyl-tRNA Synthetase"(up to December 2019). Results: Case 1, a female 53 days of age, was admitted to the Fujian Medical University Affiliated Union Hospital for treatment because of the complaint of repetitive seizures for one month after birth and fever for one day. The seizure occurred within the first 2 hours of life with multiple forms and often had a status as persisted from hours to days. The seizures were resistant to many anti-epilepsy drugs (AED) and ketogenic diet but later controlled by clonazepam. However, she died at the age of seven years. Case 2 (younger brother of case 1), a one-hour-old boy, was hospitalized because of seizures after birth for 1 hour. Intrauterine growth retardation was discovered during late-pregnancy. The boy presented seizures and microcephaly immediately after birth, and his epilepsy was pharmacoresisitant. Case 3, an 8-month-old girl, was admitted due to recurrent convulsions for nearly two months. The girl had mild developmental retardation and hypotonia after birth. The infantile spasm was observed at her age of 6 months and disappeared under treatment with Vitamin B6, vigabatrin combined with adreno-cortico-tropic-hormone and magnesium sulfate. However, the seizure pattern turned to tonic seizures later. She was seizures free now with clobazam and zonisamide treatment. All of them manifested as a syndrome composed of severe global developmental retardation, progressive microcephaly, hypotonia from the very beginning, mild hypoproteinemia and diffuse brain atrophy. Genetic studies revealed compound heterozygous variations of QARS1 gene which were not reported previously. A review of the literature reported a total of 22 patients from 18 unrelated families all over the world. Except for 5 cases without epilepsy,all the patients shared very similar clinical manifestations as classic pentalogy. The recommended effective treatment for epilepsy has not been reported yet. Conclusions: Glutaminyl-tRNA synthetase deficiency caused by QARS1 gene variations manifested as a clinical syndrome's pentalogy, characterized by microcephaly, cerebral atrophy, intractable early-onset epileptic encephalopathy, global developmental retardation and severe muscle hypotonia.

Study of SU-8 photoresist cross-linking process by atomic force acoustic microscopy.

In this paper, a method is presented to detect the different phases of epoxy cross-linking process and the subsurface structures of SU-8 thin films by atomic force acoustic microscopy (AFAM). The AFAM imaging of SU-8 thin films was investigated under different exposure and bake conditions. Optimized conditions were obtained for the cross-linking of SU-8 thin film at the exposure does of eight laser pulses with the laser fluence 10 mJ cm-2 per pulse and the post exposure bake (PEB) time at 90 s. The subsurface structures of undeveloped SU-8 thin films were visible in the AFAM images. This method provides an effective and low-cost way for the determination of different phases of epoxy cross-linking process in nanostructured compounds, for the non-destructive testing of subsurface defects, and for the evaluation of the quality of patterned structures.

On the fracture mechanisms of nacre: Effects of structural orientation.

The nacre of mollusk shells is distinguished by an exceptional mechanical efficiency which is derived essentially from its lamellar structure and frequently acts as a source of inspiration for the development of biomimetic materials. The structure and mechanical properties of nacre have been intensively investigated with a special focus on its toughening strategies; nevertheless, the fracture mechanisms, more specifically the critical stress/strain conditions for the failure of nacre, and the effects of structural orientation and hydration state remain largely unexplored. Here uniaxial compression tests were performed on nacre of both dry and hydrated states with different off-axis angles, i.e., the inclination of loading axis with respect to the lamellar structure, ranging from 0° to 90°. The mechanical properties and fracture characteristics of nacre and their dependences on the structural orientation and hydration state were elucidated in terms of mechanics behind failure. Quantitative relationships were established between the mechanical properties and off-axis angle based on different failure criteria. The competition between the fracture modes of fragmentation and shearing was quantified by comparing their respective driving force and resistance on the interfacial plane. This study may aid the understanding on the mechanical behavior of nacre and nacre-inspired synthetic materials and promote a better replication of the underlying design principles of nacre in man-made systems.

[Effect and mechanism of mulberry leaf polysaccharide on type 1 diabetic nephropathy in rats].

Objective: To observe the effects of mulberry leaf polysaccharide (MLP) on insulin-like growth factor 1 (IGF-1) and insulin-like growth factor blinding protein 3 (IGFBP-3) as well as the expression of IGF-1 and IGFBP-3 mRNA in the kidney of type 1 Diabetic Nephropathy (DN) rats, and to investigate its therapeutic effects and underlying mechanisms. Methods: Type 1 DN rat model was established by intraperitoneally injecting streptozocin (STZ). SD rats were randomly divided into the control, model, insulin and MLP groups, with eight rats in each group. Rats in MLP group were given orally with MLP 200 mg/kg daily for 8 weeks and insulin group rats were given subcutaneously injection of short acting insulin 1 U daily for 8 weeks. The changes in body weight, blood and urine parameters were recorded. Extracellular matrix (ECM) was calculated. The contents of IGF-1 and IGFBP-3 in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of IGF-1 and IGFBP-3 in the kidney were evaluated by fluorescence quantitative PCR. Results: Compared with rats in control group, blood glucose, triglyceride, total cholesterol, low density lipoprotein, very low density lipoprotein, 24 h urine protein, serum creatinine and urea nitrogen in the model group rats were significantly increased (all P<0.01), and these parameters of MLP group were significantly lower than the model group (all P<0.01). The contents of IGF-1 and IGFBP-3 in the blood serum of the model group were significantly higher than those in the control group (both P<0.001), while in the MLP group they were lower than the model group[IGF-1: (0.777±0.018) ng/ml vs (0.864±0.022) ng/ml, P<0.001; IGFBP-3: (0.759±0.016) ng/ml vs (0.846±0.021) ng/ml, P<0.001]. The mRNA expressions of IGF-1 and IGFBP-3 in the kidney of the model group were significantly higher than those in the control group (both P<0.001), while in the MLP group they were lower than in the model group (IGF-1: 1.450±0.032 vs 1.810±0.090, P<0.001; IGFBP-3: 1.684±0.018 vs 1.968±0.044, P<0.001). Compared with the model group rats, there were fewer pathological changes of kidney in MLP group rats. Conclusion: MLP has a certain therapeutic effect on DN, which may be achieved by decreasing the contents of IGF-1 and IGFBP-3 in the blood serum and down-regulating the over-expression of IGF-1 and IGFBP-3 mRNA in the kidney.

Inhibitory effects of 2-methoxyestradiol on cell growth and invasion in human bladder cancer T-24 cells.

Recently, 2-methoxyestradiol (2-ME) has been considered to be a potential anticancer agent but has not been investigated in bladder cancer. This study was conducted to clarify the role of 2-ME in bladder cancer cells. The bladder cancer cell line T-24 was treated with 2 µm 2-ME for 2 d. The T-24 cell viability, colony formation, invasion and apoptosis were observed in 2-ME-treated and control cells. The expression of hypoxia-inducible factor 1 alpha (HIF-1α) was detected using reverse transcription-polymerase chain reaction (RT-PCR). Then western blotting assay was applied to assess expressions of HIF-1α and apoptosis factors caspase-3 and Bcl-x proteins. The mRNA and protein expressions of HIF-1α in 2-ME-treated T-24 cells were remarkably lower than that of the control cells (P < 0.05). Treatment of 2-ME could significantly inhibit T-24 the cell viability, colony formation, invasion, and promote apoptosis (all P < 0.05). In addition, the protein expression of Caspase-3 was higher and that of Bcl-x protein was lower after administration of 2-ME compared to control (both P < 0.05). Collectively, we characterized the efficacy of 2-ME on bladder cancer T-24 cells as being mediated by inhibition of cell viability, colony fomation, invasion and promoting cell apoptosis, which may be achieved by suppressing HIF-1α levels. This study suggests 2-ME as a potential drug for bladder cancer therapy.

Multiple quantum phase transitions and superconductivity in Ce-based heavy fermions.

Heavy fermions have served as prototype examples of strongly-correlated electron systems. The occurrence of unconventional superconductivity in close proximity to the electronic instabilities associated with various degrees of freedom points to an intricate relationship between superconductivity and other electronic states, which is unique but also shares some common features with high temperature superconductivity. The magnetic order in heavy fermion compounds can be continuously suppressed by tuning external parameters to a quantum critical point, and the role of quantum criticality in determining the properties of heavy fermion systems is an important unresolved issue. Here we review the recent progress of studies on Ce based heavy fermion superconductors, with an emphasis on the superconductivity emerging on the edge of magnetic and charge instabilities as well as the quantum phase transitions which occur by tuning different parameters, such as pressure, magnetic field and doping. We discuss systems where multiple quantum critical points occur and whether they can be classified in a unified manner, in particular in terms of the evolution of the Fermi surface topology.

Mechanical behavior of mother-of-pearl and pearl with flat and spherical laminations.

Laminated structure reduces the common inverse relationship of strength and toughness in many biological materials. Here the mechanical behavior of pearl and nacre with spherical and flat laminations was investigated and compared with the geological aragonite counterpart. The biological ceramics demonstrate higher strength, better reliability, and improved damage resistance owing to their laminated arrangement. Kinking and delamination occur in pearl to resist damage in addition to the crack-tip shielding mechanisms as in nacre, such as crack deflection, bridging, and platelet pull-out. The fracture mechanisms were interpreted in terms of the stress state using finite element simulation. This study may help clarify the compressive mechanics of laminated sphere between platens and advance the understanding on the mechanical behavior of biological and bio-inspired laminated materials.

Giant panda׳s tooth enamel: Structure, mechanical behavior and toughening mechanisms under indentation.

The giant panda׳s teeth possess remarkable load-bearing capacity and damage resistance for masticating bamboos. In this study, the hierarchical structure and mechanical behavior of the giant panda׳s tooth enamel were investigated under indentation. The effects of loading orientation and location on mechanical properties of the enamel were clarified and the evolution of damage in the enamel under increasing load evaluated. The nature of the damage, both at and beneath the indentation surfaces, and the underlying toughening mechanisms were explored. Indentation cracks invariably were seen to propagate along the internal interfaces, specifically the sheaths between enamel rods, and multiple extrinsic toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament bridging, were active to shield the tips of cracks from the applied stress. The giant panda׳s tooth enamel is analogous to human enamel in its mechanical properties, yet it has superior hardness and Young׳s modulus but inferior toughness as compared to the bamboo that pandas primarily feed on, highlighting the critical roles of the integration of underlying tissues in the entire tooth and the highly hydrated state of bamboo foods. Our objective is that this study can aid the understanding of the structure-mechanical property relations in the tooth enamel of mammals and further provide some insight on the food habits of the giant pandas.

Two-Gap Superconductivity in LaNiGa_{2} with Nonunitary Triplet Pairing and Even Parity Gap Symmetry.

The nature of the pairing states of superconducting LaNiC_{2} and LaNiGa_{2} has to date remained a puzzling question. Broken time reversal symmetry has been observed in both compounds and a group theoretical analysis implies a nonunitary triplet pairing state. However, all the allowed nonunitary triplet states have nodal gap functions but most thermodynamic and NMR measurements indicate fully gapped superconductivity in LaNiC_{2}. Here we probe the gap symmetry of LaNiGa_{2} by measuring the London penetration depth, specific heat, and upper critical field. These measurements demonstrate two-gap nodeless superconductivity in LaNiGa_{2}, suggesting that this is a common feature of both compounds. These results allow us to propose a novel triplet superconducting state, where the pairing occurs between electrons of the same spin, but on different orbitals. In this case the superconducting wave function has a triplet spin component but isotropic even parity gap symmetry, yet the overall wave function remains antisymmetric under particle exchange. This model leads to a nodeless two-gap superconducting state which breaks time reversal symmetry, and therefore accounts well for the seemingly contradictory experimental results.

Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion.

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

Water-assisted self-healing and property recovery in a natural dermal armor of pangolin scales.

Self-healing capacity, of which the inspiration comes from biological systems, is significant for restoring the mechanical properties of materials by autonomically repairing damages. Clarifying the naturally occurring self-healing behaviors and mechanisms may provide valuable inspiration for designing synthetic self-healing materials. In this study, water-assisted self-healing behavior was revealed in a natural dermal armor of pangolin scales. The indentation damages which imitate the injury caused by predatory attack can be continuously mitigated through hydration. The healing kinetics was characterized according to the variations of indentation crater dimension and quantitatively described in terms of the viscoelastic behavior of biopolymer. The mechanical properties of original, damaged, and recovered scales in both dry and wet states were systematically evaluated by three-point bending and compared through statistical analysis. The hydration effects and mechanisms were explored by examining the dynamic mechanical properties and thermal behaviors. The promoted self-healing process can be attributed to the improved flexibility of macromolecules in the biopolymer. This study may stimulate useful self-healing strategies in bio-inspired design and aid in developing high-performance synthetic self-healing materials.

Structure and mechanical behaviors of protective armored pangolin scales and effects of hydration and orientation.

As natural flexible dermal armor, pangolin scales provide effective protection against predatory threats and possess other notable properties such as anti-adhesion and wear-resistance. In this study, the structure, mechanical properties, deformation and damage behaviors of pangolin scales were systematically investigated with the effects of hydration and orientation evaluated. The scales are divided into three macro-layers constituted by overlapping keratin tiles with distinct lamellar arrangements which are further composed of lower-ordered lamellae. Both hardness and strength are significantly decreased by hydration; while the plasticity is markedly improved concomitantly, and as such, the mechanical damages are mitigated. The tensile strength invariably approximates to one third of hardness in value. The tensile deformation is dominated by lamellae stretching and pulling out under wet condition, which is distinct from the trans-lamellar fracture in dry samples. The compressive behaviors are featured by pronounced plasticity in both dry and wet scales; and notable strain-hardening capacity is introduced by hydration, especially along the thickness direction wherein kinking occurs. Inter-lamellar cracking is effectively alleviated in wet samples compared with the dry ones and both of them deform by macroscopic buckling. This study may help stimulate possible inspiration for the design of high-performance synthetic armor materials by mimicking pangolin scales.

Plasma exchange parameter selection and safety observation of children with severe ricinism.

The aim of this study was to investigate the selection of plasma exchange (PE) parameters and the safety of children with severe ricinism. The PE parameters and heparin dosage in 7 children with severe ricinism were recorded, and changes in the patients' vital signs and coagulation function were monitored before and after PE. All patients successfully completed PE. The speed of blood flow was 50-80 mL/min, speed of exchange flow was 600-800 mL/h, and isolating rate of blood plasma was 12.5-19.05%. Transmembrane pressure was stable at approximately 100 mmHg, and venous pressure was stable at approximately 95 mmHg. The first dose of heparin was 0.39 ± 0.04 mg/kg, and the maintaining heparin dose was 0.40 ± 0.05 to 0.22 ± 0.03 mg·kg(-1)·h(-1). During the PE process, mean arterial pressure, heart rate, respiratory rate, and pulse oxygen saturation were steady. After PE, the activated partial thromboplastin time and thrombin time prolonged to 2-3 times greater than that before PE. However, no bleeding tendency was seen. For children with severe ricinism, the choice of PE to eliminate the toxin from blood, tissues, and organs was safe and effective.

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome.

The aim of this study is to investigate the role of the purinergic receptor P2X3 in the peripheral and central nervous systems during acupuncture treatment for the visceral pain of irritable bowel syndrome (IBS). A total of 24 8-day-old Sprague-Dawley (SD) neonatal male rats (SPF grade) were stimulated using colorectal distention (CRD) when the rats were awake. The modeling lasted for 2 weeks with one stimulation per day. After 6 weeks, the rats were randomly divided into three groups of eight each: (1) the normal group (NG, n = 8); (2) the model group (MG, n = 8); and (3) the model + electroacupuncture group (EA, n = 8) that received electroacupuncture at a needling depth of 5 mm at the Shangjuxu (ST37, bilateral) and Tianshu (ST25, bilateral) acupoints. The parameters of the Han's acupoint nerve stimulator (HANS) were as follows: sparse-dense wave with a frequency of 2/100 Hz, current of 2 mA, 20 min/stimulation, and one stimulation per day; the treatment was provided for seven consecutive days. At the sixth week after the treatment, the abdominal withdrawal reflex (AWR) score was determined; immunofluorescence and immunohistochemistry were used to measure the expression of the P2X3 receptor in myenteric plexus neurons, prefrontal cortex, and anterior cingulate cortex; and, a real-time PCR assay was performed to measure the expression of P2X3 messenger RNA (mRNA) in the dorsal root ganglion (DRG) and spinal cord. After stimulation with CRD, the expression levels of the P2X3 receptor in the inter-colonic myenteric plexus, DRG, spinal cord, prefrontal cortex, and anterior cingulate cortex were upregulated, and the sensitivity of the rats to IBS visceral pain was increased. Electroacupuncture (EA) could downregulate the expression of the P2X3 receptor and ease the sensitivity to visceral pain. The P2X3 receptor plays an important role in IBS visceral pain. The different levels of P2X3 in the peripheral enteric nervous system and central nervous system mediate the effects of the EA treatment of the visceral hyperalgesia of IBS.

Superconductivity and structural distortion in BaPt2As2.

We report the synthesis of BaPt2As2 single crystals and the discovery of superconductivity and a structural phase transition in this compound by measuring the electrical resistivity, magnetic susceptibility and specific heat as well as the x-ray diffraction at low temperatures. BaPt2As2 crystallizes in the CaBe2Ge2-type tetragonal structure (P4/nmm) at room temperature and undergoes a first-order structural transition at TS ≃ 275 K, which is likely to be associated with a charge-density-wave (CDW) instability. BCS-like superconductivity with two subsequent transitions Tc1 ≃ 1.67 K and Tc2 ≃ 1.33 K is observed. Our results demonstrate that BaPt2As2 may serve as a new system for studying the interplay of superconductivity and the CDW order.