Transcriptome and Hormonal Analysis of Agaricus bisporus Basidiome Response to Hypomyces perniciosus Infection.

Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. A. bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield because of malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation caused by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathological, physiological, and transcriptomic analyses. Results showed that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the metabolism level of phytohormones (N6-isopentenyladenosine, cis-zeatin, and N6-[delta 2-isopentenyl]-adenine) of the host's fruiting bodies rather than using toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.

Characterization of nuclear localization signals (NLSs) and function of NLSs and phosphorylation of serine residues in subcellular and subnuclear localization of transformer-2ß (Tra2ß).

The serine/arginine-rich (SR) proteins are one type of major actors in regulation of pre-mRNA splicing. Their functions are closely related to the intracellular spatial organization. The RS domain and phosphorylation status of SR proteins are two critical factors in determining the subcellular distribution. Mammalian Transformer-2ß (Tra2ß) protein, a member of SR proteins, is known to play multiple important roles in development and diseases. In the present study, we characterized the subcellular and subnuclear localization of Tra2ß protein and its related mechanisms. The results demonstrated that in the brain the nuclear and cytoplasmic localization of Tra2ß were correlated with its phosphorylation status. Using deletional mutation analysis, we showed that the nuclear localization of Tra2ß was determined by multiple nuclear localization signals (NLSs) in the RS domains. The point-mutation analysis disclosed that phosphorylation of serine residues in the NLSs inhibited the function of NLS in directing Tra2ß to the nucleus. In addition, we identified at least two nuclear speckle localization signals within the RS1 domain, but not in the RS2 domain. The nuclear speckle localization signals determined the localization of RS1 domain-contained proteins to the nuclear speckle. The function of the signals did not depend on the presence of serine residues. The results provide new insight into the mechanisms by which the subcellular and subnuclear localization of Tra2ß proteins are regulated.

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

BACKGROUND: Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS: In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS: Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS: Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Continuous emission of fundamental solitons from vortices in dissipative media by a radial-azimuthal potential.

We report novel dynamical regimes of dissipative vortices supported by a radial-azimuthal potential (RAP) in the 2D complex Ginzburg-Landau (CGL) equation with the cubic-quintic nonlinearity. First, the stable solutions of vortices with intrinsic vorticity S = 1 and 2 are obtained in the CGL equation without potential. The RAP is a model of an active optical medium with respective expanding anti-waveguiding structures with m (integer) annularly periodic modulation. If the potential is strong enough, m jets fundamental of solitons are continuously emitted from the vortices. The influence of m, diffusivity term (viscosity) ß, and cubic-gain coefficient ε on the dynamic region is studied. For a weak potential, the shape of vortices are stretched into the polygon, such as square for m = 4. But for a stronger potential, the vortices will be broke into m fundamental solitons.

Effects of PGR and ESRα genotypes on the pregnancy rates after embryo transfer in Luxi cattle.

Progesterone receptor (PGR) and estrogen receptor alpha (ESRα), which mediate the biological effects of the steroid hormones progesterone and estrogen, play a central role in the establishment and maintenance of pregnancy. The objectives of this study were to detect bovine PGR and ESRα genes polymorphisms and analyze their relationships with the pregnancy rates after embryo transfer and the hormone concentrations at the day of embryo transfer. One reported SNP of PGR G59752C and a novel SNP of ESRα G75935C were analyzed in 132 recipients of Luxi cattle. For the PGR gene, recipients with g.59752 GG and g.59752 GC genotypes had obviously higher pregnancy rates than g.59752 CC genotype. For the ESRα gene, recipients with g.75935 GC and g.75935 CC genotypes had obviously higher pregnancy rates than g.75935 GG genotype. Furthermore, the same tendency was observed for these two genes that the same genotype groups with high pregnancy rates had high progesterone concentration and low estrogen concentration at the day of embryo transfer. These results showed for the first time that PGR G59752C and ESRα G75935C polymorphisms had obvious effects on the pregnancy rates after embryo transfer, and indicated that PGR G59752C and ESRα G75935C polymorphisms could be potential markers for recipient selection of embryo transfer.

The importance of the solids loading on confirming the dielectric nanosize dependence of BaTiO3 powders by slurry method.

The dielectric nanosize dependence of BaTiO3 powders was investigated by the slurry method, where two series of BaTiO3 slurries with 10 vol% and 30 vol% solids loadings were prepared as model samples. Applying the Bruggeman-Hanai equation, the high-frequency limiting permittivity (ε(h)) of the slurries was extracted from the dielectric spectra. The ε(h) of the 10 vol% slurry showed abnormal size independence in the range from 100 nm to 700 nm, and the ε(h) of the 30 vol% slurry exhibited good agreement with the previous prediction. Through analysing quantitatively the response of ε(h) to the changing permittivity of the powders under different solids loading, it was found that the ε h of the slurry with lower solids loading is more inclined to be interfered by the systematic and random errors. Furthermore, a high permittivity value was found in the BaTiO3 powders with 50 nm particle size.

Current insight on the mechanisms of programmed cell death in sepsis-induced myocardial dysfunction.

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte's programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI.

Monosynaptic restriction of the anterograde herpes simplex virus strain H129 for neural circuit tracing.

Identification of synaptic partners is a fundamental task for systems neuroscience. To date, few reliable techniques exist for whole brain labeling of downstream synaptic partners in a cell-type-dependent and monosynaptic manner. Herein, we describe a novel monosynaptic anterograde tracing system based on the deletion of the gene UL6 from the genome of a cre-dependent version of the anterograde Herpes Simplex Virus 1 strain H129. Given that this knockout blocks viral genome packaging and thus viral spread, we reasoned that co-infection of a HSV H129 ΔUL6 virus with a recombinant adeno-associated virus expressing UL6 in a cre-dependent manner would result in monosynaptic spread from target cre-expressing neuronal populations. Application of this system to five nonreciprocal neural circuits resulted in labeling of neurons in expected projection areas. While some caveats may preclude certain applications, this system provides a reliable method to label postsynaptic partners in a brain-wide fashion.

Troglonectes canlinensis sp. nov. (Teleostei: Nemacheilidae), a New Troglomorphic Loach from Guangxi, China.

A new species of the genus Troglonectes is described based on specimens from a karst cave in Andong Town, Xincheng County, Liuzhou City, Guangxi, China. Troglonectes canlinensis sp. nov. can be distinguished from its congener species by the following combination of characteristics: eye degenerated into a black spot; whole body covered by scales, except for the head, throat, and abdomen; incomplete lateral line; forked caudal fin; 8-10 gill rakers on the first gill arch; 13-14 branched caudal fin rays; 8-9 branched dorsal fin rays; 5-6 anal fin rays; 9-10 pectoral fin rays; upper adipose keel depth mostly 1/2 of the caudal peduncle depth; and caudal fin forked.

Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making.

Understanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract, intratelencephalic and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scales. Cortical activity and optogenetic inactivation during an auditory decision task revealed distinct functional roles. All PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, pyramidal tract neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.

Polymorphisms of the bovine luteinizing hormone/choriogonadotropin receptor (LHCGR) gene and its association with superovulation traits.

The major limitation to the development of embryo transfer technique in cattle is the highly variable between individuals in ovulatory response to FSH-induced superovulation. The objective of this study was to identify a predictor to forecast superovulation response on the basis of associations between superovulation performance and gene polymorphism, variation in the bovine luteinizing hormone/choriogonadotropin receptor (LHCGR) gene was investigated using PCR-single-strand conformational (PCR-SSCP) and DNA sequencing. Four single nucleotide polymorphisms (SNPs) of G51656T, A51703G, A51726G and G51737A were identified at the intron 9 of the LHCGR gene in 171 Chinese Holstein cows treated for superovulation, and evaluated its associations with superovulatory response. Association analysis showed that these four SNPs had significant effects on the total number of ova (TNO) (P < 0.05). Moreover, the A51703G and A51726G polymorphisms significantly associated with the number of transferable embryos (NTE) (P < 0.05). In addition, significant additive effect on TNO was detected in polymorphisms of G51656T (P < 0.05) and A51703G (P < 0.01), and the A51703G polymorphism also had significant additive effects on NTE (P < 0.01). These results indicate that LHCGR gene is a potential marker for superovulation response and can be used to predict the most appropriate dose of FSH for superovulation in Chinese Holstein cows.

Research progress on the relationship between TM6SF2 rs58542926 polymorphism and non-alcoholic fatty liver disease.

INTRODUCTION: nonalcoholic fatty liver disease is a common liver disease with a global average prevalence of about 25%. In addition to the incidence of NAFLD being related to obesity, diabetes, hyperlipidemia, etc., genetic factors also have an important impact on the incidence of NAFLD. AREAS COVERED: Current experimental results and clinical studies show that the transmembrane 6 superfamily member 2 (TM6SF2) gene plays an important role in the pathogenesis of NAFLD. The research on genetic polymorphism of TM6SF2 gene mainly focuses on rs58542926 locus (rs58542926 c.449 C > T, p. Glu167Lys, E167K). The Mutations of this site might increase the risk of NAFLD in carriers. EXPERT OPINION: The mutation of this site causes the disorder of triglyceride metabolism in the liver, which leads to the deposition of a large amount of lipids in the liver, and further induces the incidence of NAFLD. With the study of the mechanism of TM6SF2 gene polymorphism in the pathogenesis of NAFLD, it is helpful to understand the molecular mechanism of the pathogenesis of NAFLD, which has a great value for the treatment of NAFLD.

Reactive Hemophagocytic Lymphohistiocytosis Secondary to Ovarian Adenocarcinoma: A Rare Case Report.

Background: Hemophagocytic lymphohistiocytosis (HLH), a syndrome of immune hyperactivation and abnormal regulation that causes life-threatening inflammation, is mainly characterized by fever, hepatosplenomegaly, cytopenia, and other symptoms. Reactive HLH (rHLH) is typically secondary to immune deregulation caused by underlying rheumatologic, infectious, or malignant conditions. Malignancy-associated HLH (M-HLH) continues to be a critical health problem worldwide. Most malignancies associated with HLH are hematologic tumors, and M-HLH in non-hematologic tumors very rarely occurs. Case Report: A 34-year-old Chinese woman had a history of persistent fever, acute dizziness, and bicytopenia. She was found to have developed bilateral ovarian cancer. Additional tests showed splenomegaly, hemophagocytes in the bone marrow, low natural killer activity, and hyperferritinemia, which met the diagnostic criteria put forth in the Histiocyte Society HLH-2004. The patient was treated with correcting anemia, increased platelets, and glucocorticoid therapy but showed no response. She progressively deteriorated and died 55 days later. Conclusion: Hemophagocytic lymphohistiocytosis related to a solid tumor is extremely rare. To the best of the authors' knowledge, the present case was the first to report rHLH secondary to ovarian adenocarcinoma. It is very significant for a better understanding of the disease mechanisms of HLH and should attract the attention of hematologists and other clinicians as the condition progresses and the cost of treating it increases.

HuD regulates the cpg15 expression via the 3'-UTR and AU-rich element.

The candidate plasticity related gene 15 (cpg15) plays important roles in neural development and plasticity. In the present study, we studied the role of the cpg15 3'-untranslated region (UTR) in regulating the expression of the gene. The results showed that the presence of the 3'-UTR significantly decreases, while loss of a putative AU-rich element (ARE) in the 3'-UTR increases the cpg15 expression, indicating that the 3'-UTR and ARE may be essential for regulation of cpg15 expression. In addition, HuD, a neural-specific RNA binding protein, increased the cpg15 expression, which depends on the presence of the 3'-UTR and ARE. RNA-binding protein immunoprecipitation (RIP) assay demonstrated that HuD forms a complex with cpg15 mRNA in the cells of rat hippocampus. Deletion of HuD domains RRM1 plus RRM2 or Hinge region plus RRM3 attenuates the function of HuD in enhancing the cpg15 expression. The results suggest that HuD regulates the cpg15 expression via the 3'-UTR-mediated mechanism, which requires the presence of the ARE.

An MspI polymorphism in the inhibin alpha gene and its associations with superovulation traits in Chinese Holstein cows.

To identify a predictor to forecast superovulation response on the basis of associations between superovulation performance and gene polymorphism, the PCR-RFLP method was applied to detect an A>G transition determining an MspI polymorphism at position 192 in the exon I of the bovine inhibin alpha (INHA) gene and evaluate its associations with superovulatory response in 118 Chinese Holstein cows treated for superovulation. Association analysis showed that cows with the GG genotype resulted in a significant increase in the number of ova (TNO) than AG and AA genotypes in the first (P=0.023), second (P=0.004) and third (P=0.002) superovulation treatments and produced more transferable embryos (NTE) than that of AG and AA genotypes in the third (P=0.045) superovulation treatment. Moreover, individuals with GG genotype produced more transferable embryos than AA (P<0.05) genotype in the second superovulation treatment and all cows without superovulation response were mutations with genotypes of AA and AG. These results indicate that INHA gene can be used as a predictor for superovulation in Chinese Holstein cows, and imply that cows with AA genotype should be excluded for superovulation practices.

Oxytocin Regulates Synaptic Transmission in the Sensory Cortices in a Developmentally Dynamic Manner.

The development and stabilization of neuronal circuits are critical to proper brain function. Synapses are the building blocks of neural circuits. Here we examine the effects of the neuropeptide oxytocin on synaptic transmission in L2/3 pyramidal neurons of the barrel field of the primary somatosensory cortex (S1BF). We find that perfusion of oxytocin onto acute brain slices significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSC) of S1BF L2/3 pyramidal neurons at P10 and P14, but reduces it at the later ages of P22 and P28; the transition occurs at around P18. Since oxytocin expression is itself regulated by sensory experience, we also examine whether the effects of oxytocin on excitatory synaptic transmission correlate with that of sensory experience. We find that, indeed, the effects of sensory experience and oxytocin on excitatory synaptic transmission of L2/3 pyramidal neurons both peak at around P14 and plateau around P18, suggesting that they regulate a specific form of synaptic plasticity in L2/3 pyramidal neurons, with a sensitive/critical period ending around P18. Consistently, oxytocin receptor (Oxtr) expression in glutamatergic neurons of the upper layers of the cerebral cortex peaks around P14. By P28, however, Oxtr expression becomes more prominent in GABAergic neurons, especially somatostatin (SST) neurons. At P28, oxytocin perfusion increases inhibitory synaptic transmission and reduces excitatory synaptic transmission, effects that result in a net reduction of neuronal excitation, in contrast to increased excitation at P14. Using oxytocin knockout mice and Oxtr conditional knockout mice, we show that loss-of-function of oxytocin affects baseline excitatory synaptic transmission, while Oxtr is required for oxytocin-induced changes in excitatory synaptic transmission, at both P14 and P28. Together, these results demonstrate that oxytocin has complex and dynamic functions in regulating synaptic transmission in cortical L2/3 pyramidal neurons. These findings add to existing knowledge of the function of oxytocin in regulating neural circuit development and plasticity.

Ionic Carbazole-Based Water-Soluble Two-Photon Photoinitiator and the Fabrication of Biocompatible 3D Hydrogel Scaffold.

Two-photon polymerization of a three-dimensional (3D) hydrogel structure has been widely applied in biological tissue engineering. For improving the biocompatibility of hydrogel structures, a new kind of ionic carbazole water-soluble photoinitiator was prepared to realize the fabrication of a 3D hydrogel structure in aqueous phase. 3,6-Bis[2-(1-methyl-pyridinium)vinyl]-9-methyl-carbazole diiodide (BMVMC) and cucurbit[7]uril (CB7) have been employed to generate a complex with better water solubility by host-guest interactions. The binding ratio of the complex was demonstrated to be 1:1 through the characterization of isothermal titration calorimetry (ITC). The two-photon absorption (TPA) cross section of the complex increases to 2500 GM compared with the 750 GM of the BMVMC molecule. Then, an aqueous-phase photoresist was obtained using the CB7/BMVMC complex as the photoinitiator and poly(ethylene glycol) diacrylate (PEGda) as the hydrogel monomer. Two-photon fabrication capability in aqueous phase has been studied using the as-prepared photoresist. A low laser threshold of 3.7 mW as well as a high resolution of 180 nm are achieved. Benefiting from the fluorescence properties of the photoinitiator, we can achieve the confocal fluorescence images without any assistance of fluorescent probes. Subsequently, a 3D engineered hydrogel scaffold microstructure was fabricated by the two-photon polymerization technology, whose biocompatibility was demonstrated by culturing the structure with living cells of L929. The BMVMC-CB7 complex and the as-prepared photoresist are demonstrated to have good biocompatibility, which is prospective for further application in tissue engineering.

Red wine-inspired tannic acid-KH561 copolymer: its adhesive properties and its application in wound healing.

Damaged tissue with an open wound is one of the daily injuries and can have different levels of severity. Inspired by the textile dyeing, coloration and skin care effect of pyrogallol-rich red wine, tannic acid-KH561 (TA561) copolymer was fabricated by phenol-silanol reaction and polycondensation of silane in an aqueous medium under mild conditions. This copolymer could undergo sol-gel transition via continuous heating or when simply placed at room temperature, during which liquid TA561 oligomers connected with each other to form solid TA561 as a bulk resin or thin film. Combining the advantages of the polyphenols and polysiloxane, TA561 can be used as an adhesive for multiple surfaces, including wood, polytetrafluoroethylene, poly(vinyl chloride), aluminum chips and silicon rubber. Furthermore, TA561 also possessed reducing activity towards Ag+ or Au3+ ions to form the corresponding nanoparticles. An in vivo antimicrobial ability test indicated that TA561 could promote wound healing and showed resistance to methicillin-resistant Staphylococcus aureus (MRSA) infection in comparison with KH561. Indeed, TA561 has the potential to be utilized as a low-cost, green bioadhesive material for skin preparations.

[Relationship of ubiquitin-ligases APC/C and SCF complex to cancer].

Ubiquitin ligases are an important component in ubiquitination system, which can recognize substrate proteins specially to promote their degradation. Closely related to the generation and development of many tumors, ubiquitin ligases can regulate the growth, differentiation and apoptosis of cells by influencing protein stability, which makes them a potential new target for tumor molecular therapy. There are many kinds of ubiquitin ligases, mainly including APC/C and SCF complex. This article will introduce the structures and functions of these two kinds of ubiquitin ligases and their roles in the tumor generation and development.

Retinoid X Receptor α Regulates DHA-Dependent Spinogenesis and Functional Synapse Formation In Vivo.

Coordinated intracellular and extracellular signaling is critical to synapse development and functional neural circuit wiring. Here, we report that unesterified docosahexaenoic acid (DHA) regulates functional synapse formation in vivo via retinoid X receptor α (Rxra) signaling. Using Rxra conditional knockout (cKO) mice and virus-mediated transient gene expression, we show that endogenous Rxra plays important roles in regulating spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. We further show that the effects of RXRA are mediated through its DNA-binding domain in a cell-autonomous and reversible manner. Moreover, unesterified DHA increases spine formation and excitatory synaptic transmission in vivo in an Rxra-dependent fashion. Rxra cKO mice generally behave normally but show deficits in behavior tasks associated with social memory. Together, these results demonstrate that unesterified DHA signals through RXRA to regulate spinogenesis and functional synapse formation, providing insight into the mechanism through which DHA promotes brain development and cognitive function.