Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

'On Water'-Promoted Three-Component Tandem Michael Addition/D-A Cycloaddition Reaction to Construct Polycyclic N-Heterocycles Derivatives.

'On Water'-promoted the three-component tandem Michael addition/D-A cycloaddition reaction in 80 °C at 3 h has been developed without employing any catalyst and organic solvent. The process allows facile access to polycyclic N-heterocycles derivatives contain indole and maleimide from easily accessible starting materials in moderate to high yields (up to 91 %). Compared with conventional reaction conditions, this reaction not only improves the reaction efficiency and rate but also minimizes the side reaction.

Assembly of polycyclic N-heterocycles via copper-catalyzed cycloamination of indolylquinones and aromatic amines.

The copper-catalyzed cycloamination of indolylquinones and various (hetero)aromatic amines under ligand-free conditions for the synthesis of polycyclic N-heterocycles has been developed. This method allows facile access to polycyclic N-heterocycles with the tolerance of chloride, bromide, amino, thio, etc. groups in moderate to high yields (60-89%).

Long noncoding RNA HAND2-AS1 reduced the viability of hepatocellular carcinoma via targeting microRNA-300/SOCS5 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers with high mortality. Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1 (HAND2-AS1) is down-regulated in several cancers including HCC, yet the precise mechanisms how HAND2-AS1 regulates cell survival in HCC remains poorly understood. METHODS: The expression levels of HAND2-AS1 and miR-300 were measured using quantitative real-time PCR. The protein levels of suppressor of cytokine signaling 5 (SOCS5), Bcl-2, Bax and cleaved caspase-3 were determined by Western blot. Cell viability and cell proliferation were assessed using cell counting kit-8 and clone formation assay, respectively. Cell apoptosis was detected using flow cytometry. The interactions between HAND2-AS1 and miR-300, miR-300 and SOCS5 were validated using luciferase reporter assay. RESULTS: HAND2-AS1 was down-regulated in HCC tissues and cell lines, and the expression level of HAND2-AS1 was positively correlated to patient survival. HAND2-AS1 over-expression reduced viability and proliferation in HCC cells. Elevated HAND2-AS1 level induced apoptosis in HCC cells, accompanied with increased Bax and cleaved caspase-3 levels and decreased Bcl-2 level. We also validated that HAND2-AS1 acted as a sponge of miR-300, and there was a negative correlation between expression levels of HAND2-AS1 and miR-300 in HCC tissues. Furthermore, we found that SOCS5 was a downstream target of miR-300. In addition, miR-300 mimics abolished HAND2-AS1-mediated inhibition of cell viability and proliferation. miR-300 mimics also reversed the HAND2-AS1-induced apoptosis in HCC cells. CONCLUSION: lncRNA HAND2-AS1 inhibits proliferation in HCC through regulating miR-300/SOCS5 axis.

Targeted isolation of prenylated indole alkaloids from the marine-derived fungus Penicillium janthinellum HK1­6 using molecular networking.

Four prenylated indole alkaloids (1-4) were targeted isolated from the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6 by using molecular networking strategies. Among them, the planar structure and relative configuration of notoamide X (1) were elucidated by detailed analysis of the spectroscopic data especially the NOESY spectrum for the first time and its absolute configuration was determined by ECD spectrum. Furthermore, curated molecular networks of MS/MS data were generated with GNPS which allowed highlighting six prenylated indole alkaloids (5, 6, 8, 9, 11, 12) that had not previously been identified in this fungus and two (7, 10) that had never been observed in any fungus. The MS/MS fragmentation pathway of these prenylated indole alkaloids was summarized.

Molecular mechanisms of Baihedihuang decoction as a treatment for breast cancer related anxiety: A network pharmacology and molecular docking study.

BACKGROUND: The therapeutic effects of a combination of Chinese medicines called Baihedihuang decoction (BD) have been clinically verified, although its molecular targets in breast cancer related anxiety remain unknown. AIM: To explore the molecular mechanisms of BD for breast cancer related anxiety treatment. METHODS: We used the Traditional Chinese Medicine Systems Pharmacology database to screen the active ingredients and potential targets of BD, and constructed the "drug-ingredient-target" network map with the help of Cytoscape 3.8 software. Also, we used the Online Mendelian Inheritance in Man, DrugBank, and Gencards databases to collect the disease targets of breast cancer related anxiety, and used the STRING platform to perform protein interaction analysis and construct the protein-protein interaction network. Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key targets. Molecular docking technology was used to verify the drug component/target disease network. RESULTS: We screened 16 active ingredients of BD for breast cancer related anxiety, with 113 target proteins. There are 931 disease targets of breast cancer related anxiety, and finally, 43 key targets and 305 Kyoto Encyclopedia of Genes and Genomes pathways were generated. The main active ingredients of BD for breast cancer related anxiety are verbascoside, ß-sitosterol, stigmasterol, catalpol, etc. CDK2, TP53, HTR2A, ESR1, etc. are its key targets, and the main involved signaling pathways may include neuroactive ligand-receptor interaction pathway, 5-hydroxytryptaminergic synapse, P53 signaling pathway, cGMP-PKG signaling pathway, the cAMP signaling pathway, etc. Finally, molecular docking was performed with Vina software to validate the key active ingredients in BD with the selected key action targets. The molecular docking results showed that verbascoside, ß-sitosterol, stigmasterol and CDK2 could stably bind and interact through amino acid residues SER249, ARG260, PRO228, ALA282, SER276, LYS273, ASN272, etc. CONCLUSION: The therapeutic effect of BD for breast cancer related anxiety is multi-level, multi-target, and multi-pathway. The findings of this study provide ideas and basis for further research.

Analysis of Outcome Indicators of Cancer-Related Fatigue Treated with Chinese Herbal Compounding.

Objective: In the direction of evaluating the current status of outcome indicators and control group selection in randomized controlled studies of Chinese herbal compounding (such as Sini plus Renshen Decoction, Jianpifuzhengfang, Bufei Jianzhong Decoction, etc) for cancer-caused fatigue and to provide a reference for clinical studies of Chinese herbal compounding for cancer-caused fatigue. Methods: Randomized controlled studies of Chinese herbal medicine for cancer-caused fatigue in the midst of 2012 and 2022 were searched in CNKI, PubMed, and EMBASE databases on the China Knowledge Network, and the literature was screened using NoteExpress. Two researchers independently conducted the literature review, and then the studies that met the criteria were grouped and analyzed adopting qualitative analysis of outcome indicators and control groups. Results: A total of 70 randomized controlled studies that met the requirements were included, and after doing statistical analysis, it can draw to the conclusion that the risk of bias in the included studies was high; at the same time, the TCM evidence score scale, objective indicators, and safety indicators were underutilized; additionally, there were no uniform standards for the fatigue scale, and the selection of control groups lacked balance and consistency. Conclusion: The outcome indicators of TCM compound treatment of cancer-caused fatigue should be on the basis of the principle of "diagnosis and treatment" in TCM, the proportion of objective indicators should be exaggerated, as well as the interventions in the control group should be unified.

Diagnosis and guidance of treatment of breast cancer cutaneous metastases by multiple needle biopsy: A case report.

BACKGROUND: Breast cancer patients have a high skin metastasis rate. However, reports on treatment of cutaneous metastases of breast cancer are scarce. CASE SUMMARY: We report the treatment process for one breast cancer case with bone, lung, and skin metastases. The patient was a 43-year-old woman with advanced breast cancer and skin metastasis. She underwent pathological diagnosis by needle biopsy to guide the treatment. When the disease progressed, a new pathological diagnosis was determined by needle biopsy to guide the treatment. The patient received chemotherapy, endocrine therapy, and photodynamic dynamic therapy, followed by sonodynamic therapy. CONCLUSION: Repeated puncture should be performed for advanced breast cancer with skin metastasis, in order to obtain the pathology and directly determine diagnosis when the disease progresses. The treatment should focus on controlling the systemic metastasis, rather than the local disease.

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GA) is a commonly used first-line treatment regimen for metastatic pancreatic cancer, and many studies will add a novel targeted agent to this regimen for improving patient survival rate. However, the clinical effectiveness of GA is the most controversial issue. AIM: To compare the efficacy and safety of GA regimen with a targeted agent and GA regimen. METHODS: Up to 1 December 2021, the eligible randomized controlled trials (RCTs) relating to GA and GA with a targeted agent were searched on PubMed, EMBASE and Cochrane Library for eligible data. We screened out appropriate studies for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and toxicity, which had been pooled and finally analyzed by using Stata version 15.1. In addition, we use Reference Citation Analysis (https://www.referencecitationanalysis.com/) to collect the latest related literature to improve the latest cutting-edge research results. RESULTS: Seven RCTs involving 1544 patients (848 men and 696 women) were included. There were no significant differences between GA with a targeted agent and GA in PFS [hazard ratio (HR): 1.18 95% confidence interval (CI): 0.91-1.53], OS (HR: 1.12 95%CI: 0.99-1.27), and ORR (HR: 0.96 95%CI: 0.71-1.29). There was no notable difference in the two groups in grade 3/4 toxicity (fatigue, anemia, vomiting and neutropenia), whereas the incidence of grade 3/4 diarrhea considerably increased in GA with a targeted drug. CONCLUSION: Adding a novel targeted agent to the GA regimen did not improve survival rate of patients with metastatic pancreatic cancer.

Metal-free synthesis of C2-quaternary indolinones by (NH4)2S2O8 mediated oxidative dearomatization of indoles.

An efficient metal-free, (NH4)2S2O8 mediated oxidative dearomatization of indoles for the construction of C2-quaternary indolinones was disclosed. A series of C2-quaternary indolinones derivatives with good functional group tolerance were obtained in moderate to excellent yields. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C2 position of indoles. This catalytic approach represents a step-economic and convenient strategy for the oxidative dearomatization of indoles.

Status and causes of soil compaction at apple orchards in the Weibei Dry Highland, Northwest China.

To find out the recessive factors of soil degradation threatening the healthy development of Weibei apple orchards, we examined soil compaction status and its inducing factors. This study could provide a theoretical basis for apple orchard scientific management. We evalua-ted the changes of soil bulk density and compaction with the depth of soil layer in 0-60 cm in four apple orchards with various planting period, including <10 years (4-6 years), 10-20 years (14-16 years) and ＞20 years (24-26 years). The location and degradation degree of soil compaction in orchard were investigated. Through analyzing the number of soil aggregates and the stability, soil clay and organic matter contents, we tried to find the reasons for the internal compacting of soil in Weibei orchards. The results showed that soil bulk density and compactness in the 0-60 cm soil layer significantly increased with increasing planting years and soil depth. With the 20 cm soil layer as a boundary, soil of Weibei orchards in different planting years showed obvious variation characteristics of loose in upper and compact in lower. The above indicators in soil layer above 20 cm basically met the normal requirements of apple trees, whereas soil layer below 20 cm exceeded the threshold for healthy growth of apple trees. The main reasons for soil compaction below the subsurface layer were poor soil aggregation, the lack of soil organic matter, less human disturbance during fruit planting, and the movement of scattered clay particles to the lower layer. With increasing years of fruit planting, soil compaction became more severe.

Clinical and genetic characteristics of two cases with Williams-Beuren syndrome.

Herein, we describe 2 cases of Williams-Beuren syndrome (WBS). In both cases, the patients exhibited mental retardation, characteristic facial features, and indirect inguinal hernia. Case 1, a girl aged 2 years and 5 months old, presented with hypercalcemia, and in case 2, a boy aged 4 years and 11 months old, the disorder manifested as infantile spasms, supravalvular aortic stenosis, and pulmonary stenosis. Brain MRI revealed no abnormalities in either case. The electroencephalogram of case 2 showed hypsarrhythmia. Case 1 was treated with bisphosphonates and somatropin for hypercalcemia and short stature. Case 2 received antiepileptic drug and ketogenic diet therapy. In both cases, a 7q11.23 deletion including fragment deletion of the GTF21 gene was found, which may be associated with mental retardation. Notably, in case 2, a 921.1kb deletion in Yq11.23 was detected, which has not been reported in WBS before. The deletion of Yq11.23 is located in the AZFc region, which is an important factor in male infertility with primary azoospermia and oligozoospermia. The occurrence of hypercalcemia in case 1 may be related to the deletion of BAZ1B, while the supravalvular aortic stenosis and pulmonary stenosis were associated with deletion of the ELN gene. We explored the clinical and genetic characteristics of WBS to better understand disease.

Ambipolar diphenylamino end-capped oligofluorenylthiophenes as excellent electron-transporting emitters.

In addition to hole transport, diphenylamino-end-capped oligofluorenylthiophenes can exhibit efficient electron transport, in which the oligothiophene central core acts as an excellent electron-transporting moiety. The highly efficient undoped multilayer OLEDs using OF(2)TTP-NPh and OF(2)QTP-NPh as an electron-transporting emitter exhibited a maximum luminance of 19,800 and 11,800 cd m(-2) with a luminance efficiency up to 5.3 and 1.0 cd A(-1), respectively.

[Effects of Biochar Pyrolyzed at Varying Temperatures on Soil Organic Carbon and Its Components: Influence on the Composition and Properties of Humic Substances].

Application of biochar (BC) is an important way to increase soil organic carbon sequestration. At the same time, the effect of BC on fractions and properties of soil humic substances is concerned. A laboratory experiment was conducted to study the influences of BC pyrolyzed at different temperatures on the composition and properties of humic substances. The modified method for the extraction and fractionation of humic substances was adopted in this work. The carbon (C) contents of Humin (Hu), Humic acids (HA), Fulvic acids (FA) were analyzed by the thermal oxidation of K2Cr2O7 and TOC analyzer, and the optical properties of HA and FA were measured by using spectrophotometer. The results showed that the increasing temperature (from 300 to 600℃) decreased like-humic substances (LHS) from 10.93 g·kg-1 to 0.26 g·kg-1, while the structure of theLHS tended to be complicated. Compared with control treatment (CK), the addition of BC produced under 400℃ increased the contents of HA and FA (after 240 d incubation a lower FA content was found in treatments) and increased as BC application rate increased, after 360 d of incubation, BC300 and BC400 significantly increased by 69.93% and 48.75% for HA (P<0.05), while decreased by 1.35% and 5.19% for FA. Higher contents of HA and FA were found in soil samples amended with BC prepared at above 400℃ only during the initial period of 3-10 d of incubation and increased as BC application rate increased, at the end of the incubation, the contents of HA and FA significantly decreased by 34.38%, 44.48% in BC500 treatments and 42.84%, 49.27% in the BC600 treatments (P<0.05). During the incubation, the addition of BC significantly increased the contents of Hu (P<0.05), and the treatments amended with BC500 were the highest. The addition of BC decreased the relative contents of HA and FA, while increased the relative content of Hu, indicating that the proportion of relatively stable organic carbon in the soil was increased. The ratio of HA/FA (H/F) varied between 0.88 and 2.52 and increased with decreasing pyrolysis temperature and increasing BC application. A significantly lower color tonal coefficient (ΔlgK) and E4/E6 values in treatments amended with BC produced at temperatures above 400℃, indicating that higher temperatures derived BC complicated the structure of soil humic substance, while an opposite rend was observed in treatments amended with BC produced at temperatures under 400℃. Considering the improvement of the stability of organic carbon, when the BC products were applied to the Loutu soil, 500℃ was the optimal temperature for preparing apple-derived BC not only because it could significantly increase the content of inert soil organic carbon, but also improve the quality of the soil as a result of enhancing the degree of soil humification.

[Effects of Biochar Pyrolyzed at Varying Temperatures on Soil Organic Carbon and Its Components:Influence on the Soil Active Organic Carbon].

Soil active organic carbon is the most important carbon pool and a good indicator in ecosystem management due to its great significance in soil carbon cycling and soil quality.In order to investigate the effect of biochar (BC) addition on soil organic matter fractions,apple tree twigs were used to produce BC at 300,400,500 and 600℃,respectively.Elemental analysis and Fourier transform infrared (FTIR) spectroscopy were used to determine the characteristics of BC.Four kinds of BC were added into soils at five application rates (0,0.5%,1%,2% and 3%) and incubated at 25℃ in lab for over 360 days.Soil organic carbon (SOC),microbial biomass carbon (MBC),water soluble organic carbon (WSOC) and readily oxidized organic carbon (ROC) were measured during the incubation.The mass fraction of carbon (C) in the generated BC ranged from 62.20%-80.01%,while hydrogen (H) ranged from 2.72%-5.18% and Oxygen (O) ranged from 15.98%-30.92%.The increasing temperature increased the mass fraction of C,while decreased the O and H mass content,as well as the ratio of H/C and O/C.The addition of BC significantly increased SOC,and the treatments amended with BC500 had the highest increments.Compared with the control treatment (CK),the addition of BC produced at temperatures below 400℃ increased the contents of MBC,WSOC and ROC during the incubation,at the end of the incubation,BC300 treatments significantly increased the contents by 38.25%,82.09% and 63.53%(P<0.05),respectively;BC400 treatments significantly increased the contents by 26.07%,65.61% and 48.09%(P<0.05),respectively;while lower contents of MBC,WSOC and ROC were found in the treatments amended with BC produced at temperatures above 400℃ after 40-60 d incubation.After 360 d of incubation,the contents of MBC,WSOC and ROC were significantly decreased by 0.27%,13.48% and 14.67% in BC500 treatments and 7.80%,14.66% and 15.79% in BC600 treatments (except for the MBC in BC500 treatment)(P<0.05).The relative contents of ROC ranged from 3.39% to 15.65%,BC application decreased the relative content of ROC,suggesting that the increase was in proportion to the stability of organic carbon in the soil.Considering the content and quality of SOC,when the BC products were applied to the Loutu soil,500℃ was the optimal temperature for preparing apple-derived BC due to its significant increase of the soil organic carbon and a slight decrease of the relative content of soil active organic carbon.

Synthesis and functional properties of end-dendronized oligo(9,9-diphenyl)fluorenes.

[structure: see text] A facile approach for the synthesis of a family of dendrimers OFn-EG with hole-transporting ability moieties by copper-catalyzed Buchwald's double-amination as a key reaction has been developed. These novel dendrimers exhibit good energy transfer efficiencies and very high thermal and electrochemical stabilities and have potential applications as hole transfer and emitting layers in the field of organic emitting diodes (OLEDs) or as host materials for electrophosphorescent applications.

Synthesis and light-emitting properties of bipolar oligofluorenes containing triarylamine and 1,2,4-triazole moieties.

A facile approach for synthesis of bipolar oligofluorenes, TAZ-OF(n)-NPh, n = 2 or 3 end-capped with hole-transporting diphenylamino and electron-transporting triazole moieties by Suzuki cross-coupling as the key reaction has been developed. This novel bipolar oligofluorenes exhibited blue-emission, high thermal and morphological stabilities. The single-layer OLED based on TAZ-OF(2)-NPh exhibited superior device performance with a maximum luminance of 1128 cd m(-2) and luminance efficiency of up to 0.83 cd A(-1).

Simultaneous encapsulation of an infinite T4(0)A(0)6(0) water tape and discrete water hexamers in a hydrogen-bonded Ag(I) supramolecular framework.

Self-assembly of Ag2O, 1,4-bis(pyrid-4-yl)benzene (dpb) and 1,3-benzenedicarboxylic acid (H2bdc) resulted in a one-dimensional mixed-ligand Ag(I) coordination polymer [Ag2(dpb)2(bdc)·9H2O]n (1), in which infinite 1D T4(0)A(0)6(0) water tapes and discrete water hexamers were simultaneously encapsulated. Chair-like water hexamers and D2h water tetramers with two dangling water molecules were alternately hydrogen-bonded into the unprecedented 1D T4(0)A(0)6(0) water tape. Additionally, results on the thermal stability, UV-Vis absorption and photoluminescence spectra of 1 were discussed.

Non-coplanar 9,9-diphenyl-substituted oligofluorenes with large two-photon absorption enhancement.

The non-coplanar substituted phenyl rings at the 9-position of a fluorenyl unit can be involved in pi-electron delocalization in which the resulting oligofluorenes exhibit a very large enhancement of two-photon absorption cross sections up to 2559 GM at 710 nm.

Diphenylamino end-capped oligofluorenes with enhanced functional properties for blue light emission: synthesis and structure-property relationships.

A novel series of monodisperse asymmetrically and symmetrically substituted diphenylamino end-capped oligofluorenes, OF(2)-NPhR, R = H or An (An = 9-anthryl) and OF(n)-NPh, n = 2-4, has been synthesized by a convergent approach using palladium-catalyzed Suzuki cross-coupling. End-capping of oligofluorenes with diphenylamino group(s) has been shown to offer advantages in terms of lowering their first ionization potentials, enhancing thermal stability, and inducing good amorphous morphological stability. By tuning the number of diphenylamino end-caps and the chain length, the optimal conjugated length for optical and luminescence properties has been determined. Of all the hitherto reported oligofluorenes capable of serving as non-doped blue emitters, OF(3)-NPh, with an optimal conjugated length, exhibits some of the best hole-transport and blue-emitting properties. A maximum luminance of 7500 cd m(-2) and a luminance efficiency up to 1.8 cd A(-1) have been achieved.