Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

[Therapeutic effect of Shengjiang Powder on experimental autoimmune encephalomyelitis mice through IL-6/JAK2/STAT3 signaling pathway:based on HPLC].

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.

Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Molecular Dynamics Study of the Nanoindentation Behavior of Cu64Zr36/Cu Amorphous/Crystalline Nanolaminate Composites.

Amorphous/crystalline nanolaminate composites have aroused extensive research interest because of their high strength and good plasticity. In this paper, the nanoindentation behavior of Cu64Zr36/Cu amorphous/crystalline nanolaminates (ACNLs) is investigated by molecular dynamics (MD) simulation while giving special attention to the plastic processes occurring at the interface. The load-displacement curves of ACNLs reveal small fluctuations associated with shear transformation zone (STZ) activation in the amorphous layer, whereas larger fluctuations associated with dislocations emission occur in the crystalline layer. During loading, local STZ activation occurs and the number of STZs increases as the indentation depth in the amorphous layer increases. These STZs are mostly located around the indenter, which correlates to the high stresses concentrated around the indenter. When the indenter penetrates the crystalline layer, dislocations emit from the interface of amorphous/crystalline, and their number increases with increasing indentation depth. During unloading, the overall number of STZs and dislocations decreases, while other new STZs and dislocations become activated. These results are discussed in terms of stress distribution, residual stresses, indentation rate and indenter radius.

A bean common mosaic virus-resistance gene in the soybean variant V94-5152 was mapped to the Rsv4 locus conferring resistance to soybean mosaic virus.

KEY MESSAGE: In the soybean variant V94-5152, a BCMV-resistance gene was mapped near to the region of SMV-resistance Rsv4 locus, raising a possibility that V94-5152 may rely on Rsv4 locus to resist against both SMV and BCMV. Both Soybean mosaic virus (SMV) and Bean common mosaic virus (BCMV) can induce soybean mosaic diseases, but few studies have explored soybean resistance against BCMV so far. In this study, V94-5152, a soybean variant resistant to BCMV and SMV, was crossed with a susceptible cultivar, Williams 82 to map the resistance gene. By inoculating 292 F2 individuals with a BCMV isolate HZZB011, a segregation ratio of 3 resistant: 1 susceptible was observed, suggesting that V94-5152 possesses a single-dominant resistance gene against BCMV-HZZB011. Bulk segregation analysis (BSA) then revealed that the resistance gene is closely linked to BARCSOYSSR_02_0617, a simple sequence repeat (SSR) marker on chromosome 2. Genotyping neighboring SSR markers among the 292 F2 individuals enabled us to draw a genetic linkage map, which indicated that the BCMV-resistance gene is located 0.2 cM downstream of BARCSOYSSR_02_0617. Amplification and sequencing ten candidate genes (Glyma02g121300 to Glyma02g122200) around this marker then revealed four genes containing nonsynonymous changes or indels. Also, this location is near to the recently cloned SMV-resistance Rsv4 locus from the cultivar Peking. By obtaining ten more sequences of Rsv4 locus from cultivated and wild soybean materials, we further investigated the variation and evolutionary patterns of this virus-resistance locus. It was evident that positive selections had been acting on this locus, with one critical amino acid change (R55P) shared by all resistance soybeans tested.

New section and species in Talaromyces.

Talaromyces is a monophyletic genus containing seven sections. The number of species in Talaromyces grows rapidly due to reliable and complete sequence data contributed from all over the world. In this study agricultural soil samples from Fujiang, Guangdong, Jiangxi, Shandong, Tibet and Zhejiang provinces of China were collected and analyzed for fungal diversity. Based on a polyphasic approach including phylogenetic analysis of partial ITS, BenA, CaM and RPB2 gene sequences, macro- and micro-morphological analyses, six of them could not be assigned to any described species, and one cannot be assigned to any known sections. Morphological characters as well as their phylogenetic relationship with other Talaromyces species are presented for these putative new species. Penicillium resedanum is combined in Talaromyces section Subinflati as T. resedanus.

Penicillium section Lanata-divaricata from acidic soil.

Penicillium species in section Lanata-divaricata are common soil-inhabiting fungi, but their presence in acidic soil has rarely been investigated. In an ongoing survey of Penicillium species occurring in China, 465 strains were isolated from soil, and of which 60 belonged to section Lanata-divaricata. The majority of these strains were isolated from acidic soil. The phylogenetic relationship between these 60 isolates and accepted species of section Lanata-divaricata was studied using ITS, BenA, CaM and RPB2 sequences, which revealed the presence of seven accepted species and 13 novel lineages. Combining phylogenetic data with data generated during macro- and microscopic observations resulted in the description of 13 new species. The growth rate of the new species obtained in this study was determined under acidic, neutral and alkaline conditions (pH 4, 7, 10). With the exception of P. hainanense, which was not able to grow at pH 10, all strains were able to grow at the three examined pH levels. Eleven species (i.e. P. austrosinense, P. flaviroseum, P. globosum, P. griseoflavum, P. hainanense, P. jianfenglingense, P. laevigatum, P. rubriannulatum, P. soliforme, P. spinuliferum, P. yunnanense) grew faster at low pH (pH 4) than at pH 7 or 10, and these species are therefore referred to as acid-preferential. Penicillium viridissimum grew fastest on neutral medium and P. guangxiense grew best at pH 10, and is therefore considered to be acid-tolerant. By isolating strains from a unique environment, combined with targeted isolation using a well-designed protocol, we are able to describe new fungal diversity with specific physiological characteristics.

A bean common mosaic virus (BCMV)-resistance gene is fine-mapped to the same region as Rsv1-h in the soybean cultivar Suweon 97.

KEY MESSAGE: In the soybean cultivar Suweon 97, BCMV-resistance gene was fine-mapped to a 58.1-kb region co-localizing with the Soybean mosaic virus (SMV)-resistance gene, Rsv1-h raising a possibility that the same gene is utilized against both viral pathogens. Certain soybean cultivars exhibit resistance against soybean mosaic virus (SMV) or bean common mosaic virus (BCMV). Although several SMV-resistance loci have been reported, the understanding of the mechanism underlying BCMV resistance in soybean is limited. Here, by crossing a resistant cultivar Suweon 97 with a susceptible cultivar Williams 82 and inoculating 220 F2 individuals with a BCMV strain (HZZB011), we observed a 3:1 (resistant/susceptible) segregation ratio, suggesting that Suweon 97 possesses a single dominant resistance gene against BCMV. By performing bulked segregant analysis with 186 polymorphic simple sequence repeat (SSR) markers across the genome, the resistance gene was determined to be linked with marker BARSOYSSR_13_1109. Examining the genotypes of nearby SSR markers on all 220 F2 individuals then narrowed down the gene between markers BARSOYSSR_13_1109 and BARSOYSSR_13_1122. Furthermore, 14 previously established F2:3 lines showing crossovers between the two markers were assayed for their phenotypes upon BCMV inoculation. By developing six more SNP (single nucleotide polymorphism) markers, the resistance gene was finally delimited to a 58.1-kb interval flanked by BARSOYSSR_13_1114 and SNP-49. Five genes were annotated in this interval of the Williams 82 genome, including a characteristic coiled-coil nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR, CNL)-type of resistance gene, Glyma13g184800. Coincidentally, the SMV-resistance allele Rsv1-h was previously mapped to almost the same region, thereby suggesting that soybean Suweon 97 likely relies on the same CNL-type R gene to resist both viral pathogens.

Facet- and structure-dependent catalytic activity of cuprous oxide/polypyrrole particles towards the efficient reduction of carbon dioxide to methanol.

The preparation of cost-effective, stable catalysts for the selective reduction of carbon dioxide (CO2) to C1 products such as methanol is extremely important because methanol can be used directly as a fuel or it can be converted into other value-added products. However, the catalysts currently used for the reduction of CO2 to methanol exhibit poor selectivity, poor stability and very low faradaic efficiency. Herein, we used low-cost, stable cuprous oxide/polypyrrole (Cu2O/Ppy) particles having structures of octahedra and icosahedra (microflowers) that were prepared on linen texture (LT) papers for the selective reduction of CO2 to form a value-added single C1 product, methanol. The Cu2O/Ppy particles possessing both octahedral and microflower shapes with exposed low-index (111) facets and high-index (311) and (211) facets are denoted as Cu2O(OL-MH)/Ppy particles. The as-prepared Cu2O(OL-MH)/Ppy particles exhibited high catalytic activity and selectivity towards the electrochemical reduction of CO2 at -0.85 V vs. RHE to form methanol, with a faradaic efficiency of 93 ± 1.2% and an average methanol formation rate of 1.61 ± 0.02 µmol m-2 s-1. The X-ray photoelectron spectroscopy (XPS) analysis revealed that the pyrrolic nitrogen atoms present in the Ppy shell played a dominant role as active sites for CO2 molecules. The Raman bands of Ppy and Cu2O did not shift even after being subjected to electrolysis for several hours, suggesting superior stability of the Cu2O(OL-MH)/Ppy particles. The high resolution microscopic, spectroscopic, diffraction and electrochemical analysis results clearly revealed that the Ppy shell protected the Cu2O particles and avoided corrosion, dissolution, and structural and crystal facet changes, leading to greater stability. The low-cost, durable, flexible, and catalytically active Cu2O(OL-MH)/Ppy LT paper holds great potential for catalytic, photocatalytic and energy storage applications.

Polymer/reduced graphene oxide functionalized sponges as superabsorbents for oil removal and recovery.

Polyurethane dish-washing (PU-DW) sponges are functionalized sequentially with polyethylenimine (PEI) and graphene oxide (GO) to form PEI/reduced graphene oxide (RGO) PU-DW sponges. The PEI/RGO PU-DW sponge consists of PEI/RGO sheets having numerous pores, with diameters ranging from 236 to 254nm. To further enhance hydrophobicity and absorption capacity of oil, PEI/RGO PU-DW sponge is further coated with 20% phenyltrimethoxysilane (PTMOS). The PTMOS/PEI/RGO PU-DW sponge absorbs various oils within 20s, with maximum absorption capacity values of 880% and 840% for bicycle chain oil and motorcycle engine oil, respectively. The absorbed oils were released completely by squeezing or immersed in hexane. The PTMOS/PEI/RGO PU-DW sponge efficiently separates oil/water mixtures through a flowing system. Having the advantages of faster absorption rate, reusability, and low cost, the PTMOS/PEI/RGO PU-DW sponge holds great potential as a superabsorbent for efficient removal and recovery of oil spills as well as for the separation of oil/water mixtures.

Fine mapping of the Rsv1-h gene in the soybean cultivar Suweon 97 that confers resistance to two Chinese strains of the soybean mosaic virus.

KEY MESSAGE: The Rsv1 - h gene in cultivar Suweon 97, which confers resistance to SMVs, was mapped to a 97.5-kb location (29,815,195-29,912,667 bp on chromosome 13) in the Rsv1 locus, thereby providing additional insights into the molecular nature underlying variations in resistance alleles in this particular locus. Soybean mosaic virus (SMV) is a well-known devastating pathogen of soybean (Glycine max (L.) Merrill.) causing significant yield losses and seed quality deterioration. A single dominant allele, Rsv1-h, which confers resistance to multiple SMV strains, was previously reported in the cultivar Suweon 97, but its exact location is unknown. In the present study, Suweon 97 was crossed with a SMV-sensitive cultivar, Williams 82. Inoculating 267 F 2 individuals with two Chinese SMV strains (SC6-N and SC7-N) demonstrated that one single dominant gene confers SMV resistance. Another 1,150 F 2 individuals were then screened for two simple sequence repeat (SSR) markers (BARCSOYSSR_13_1103 and BARCSOYSSR_13_1187) that flank the Rsv1 locus. Seventy-four recombinants were identified and 20 additional polymorphic SSR markers within the Rsv1 region were then employed in genotyping these recombinants. F 2:3 and F 3:4 recombinant lines were also inoculated with SC6-N and SC7-N to determine their phenotypes. The final data revealed that in Suweon 97, the Rsv1-h gene that confers resistance to SC6-N and SC7-N was flanked by BARCSOYSSR_13_1114 and BARCSOYSSR_13_1115, two markers that delimit a 97.5-kb region in the reference Williams 82 genome. In such region, eight genes were present, of which two, Glyma13g184800 and Glyma13g184900, encode the characteristic CC-NBS-LRR type of resistance gene and were considered potential candidates for Rsv1-h.

Nanoindentation Investigation of Temperature Effects on the Mechanical Properties of Nafion® 117.

Operating temperature can be a limiting factor in reliable applications of Proton Exchange Membrane (PEM) fuel cells. Nanoindentation tests were performed on perfluorosulfonic acid (PFSA) membranes (Nafion® 117) in order to study the influence of the temperature condition on their mechanical properties. The hardness and reduced modulus of Nafion® 117 were measured within a certain temperature range, from 10 to 70 °C. The results indicate that both hardness and elastic modulus show non-monotonic transition with the increase of the test temperature, with reaching peak values of 0.143 and 0.833 GPa at 45 °C. It also found that the membranes have a shape memory effect and a temperature dependent shape recovery ratio.