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IntroductionMushroom-forming fungi comprise diverse species that develop complex multicellular structures. In cultivated species, both ecological adaptation and artificial selection have driven genome evolution. However, little is known about the connections among genotype, phenotype and adaptation in mushroom-forming fungi.ObjectivesThis study aimed to (1) uncover the population structure and demographic history of Lentinula edodes, (2) dissect the genetic basis of adaptive evolution in L. edodes, and (3) determine if genes related to fruiting body development are involved in adaptive evolution.MethodsWe analyzed genomes and fruiting body-related traits (FBRTs) in 133 L. edodes strains and conducted RNA-seq analysis of fruiting body development in the YS69 strain. Combined methods of genomic scan for divergence, genome-wide association studies (GWAS), and RNA-seq were used to dissect the genetic basis of adaptive evolution.ResultsWe detected three distinct subgroups of L. edodes via single nucleotide polymorphisms, which showed robust phenotypic and temperature response differentiation and correlation with geographical distribution. Demographic history inference suggests that the subgroups diverged 36,871 generations ago. Moreover, L. edodes cultivars in China may have originated from the vicinity of Northeast China. A total of 942 genes were found to be related to genetic divergence by genomic scan, and 719 genes were identified to be candidates underlying FBRTs by GWAS. Integrating results of genomic scan and GWAS, 80 genes were detected to be related to phenotypic differentiation. A total of 364 genes related to fruiting body development were involved in genetic divergence and phenotypic differentiation.ConclusionAdaptation to the local environment, especially temperature, triggered genetic divergence and phenotypic differentiation of L. edodes. A general model for genetic divergence and phenotypic differentiation during adaptive evolution in L. edodes, which involves in signal perception and transduction, transcriptional regulation, and fruiting body morphogenesis, was also integrated here.

Objective To investigate the clinical characteristics of fumarate hydratase-deficient renal cell carcinoma (FH-RCC) in kidney transplant patients so as to improve the diagnosis and treatment of the disease clinically. Methods We retrospectively analyzed and summarized the clinical data of one kidney transplanted patient with FH-RCC who was treated in the urological department of our medical center in March 2022, including clinical characteristics, treatment and prognosis. A literature review was also performed to analyze and summarize its characteristics. Results A 52-year-old female patient who received a kidney transplant 20 years ago was diagnosed with right kidney cancer with multiple metastases. Cytoreductive nephrectomy was performed and pathological type was FH-RCC based on Revised Version of WHO 2022 Classification of Renal Tumors. She then received targeted therapy until discontinuation due to elevated serum creatinine and the disease progressed rapidly. Conclusion FH-RCC is characterized by rapid progress and poor prognosis. Its diagnosis relies on immunohistochemistry and genetic test. There are no currently standard-of-care treatment options for kidney transplant patients with renal cell carcinoma. Individualized treatment regimens should be suggested for these patients.

With the development of liquefied natural gas(LNG) port, as one of the crucial LNG port sitting process, the LNG terminal site’s condition assessment method has always received attention from experts, scholars concern more and more about the method’s practicality and reliability. In the traditional condition assessment method, due to the characteristics of the complex and extensive factors in the comprehensive assessment of the LNG terminal site, the assessment system is not comprehensive enough, or the assessment is too complex, the indexes are not easy to quantify, such problems are emerging. In view of the above reasons, the principal component analysis(PCA) method is used to transform the multi-indicators that affect the comparison of terminal sites into a few comprehensive indicators. A comprehensive evaluation model of the LNG terminal site based on cloud matter element theory and subjective and objective comprehensive weighting method was constructed. By the subjective and objective comprehensive weighting method, the comprehensive weight of each index is determined and the LNG terminal site comprehensive assessment standard cloud element model is constructed with the combination of cloud model and matter-element theory. The cloud matter-element correlation function is established to determine the degree of association between the matter element to be evaluated and the standard cloud matter element model. In order to eliminate random errors and improve the credibility of the results, the algorithm is used for multiple calculations and analysis to achieve the purpose of simultaneously giving the evaluation results and coefficients of credible degree. Finally, the reliability and rationality of the method are verified by an example.

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration‐resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient‐derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

In this study, we report here a rare case of polycythemia and cRCC in the same patient, which may be helpful in understanding clinical features and molecular mechanisms underlying VHL–mutation-associated cRCC and polycythemia induced by germline mutation of HIF2A. Firstly, we identified a rare but well studied germline mutation resulting in polycythemia in HIF2A (c.1609G>A, p.Gly537Trp) in the blood of the patient and his daughter. Meanwhile, we identified an inactivating VHL mutation (c.391A>T, p.N131Y), as well as TP53 mutation(c.977A>T, p.E326V) and mTOR mutation(c.7498A>T, p.I2500F) in renal cancer tissue. Moreover, protein levels of VHL, HIF1A, HIF2A, EPO, and VEGF estimated by immunohistochemical staining substantiated hyperactivation of the oxygen-sensing pathway. In addition, we identified 158 somatic SNP/indel mutations, including 90 missense/nonsense/splice/stop-loss mutations by whole-exome sequencing (WES) of the tumor specimen and matched normal DNA. [ABSTRACT FROM PUBLISHER]

Rechargeable zinc-air batteries (ZABs) are regarded as a remarkably promising alternative to current lithium-ion batteries, addressing the requirements for large-scale high-energy storage. Nevertheless, the sluggish kinetics involving oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) hamper the widespread application of ZABs, necessitating the development of high-efficiency and durable bifunctional electrocatalysts. Here, we report oxygen atom-bridged Fe, Co dual-metal dimers (FeOCo-SAD), in which the active site Fe-O-Co-N 6 moiety boosts exceptional reversible activity toward ORR and OER in alkaline electrolytes. Specifically, FeOCo-SAD achieves a half-wave potential ( E 1/2 ) of 0.87 V for ORR and an overpotential of 310 mV at a current density of 10 mA cm -2 for OER, with a potential gap (Δ E ) of only 0.67 V. Meanwhile, FeOCo-SAD manifests high performance with a peak power density of 241.24 mW cm -2 in realistic rechargeable ZABs. Theoretical calculations demonstrate that the introduction of an oxygen bridge in the Fe, Co dimer induced charge spatial redistribution around Fe and Co atoms. This enhances the activation of oxygen and optimizes the adsorption/desorption dynamics of reaction intermediates. Consequently, energy barriers are effectively reduced, leading to a strong promotion of intrinsic activity toward ORR and OER. This work suggests that oxygen-bridging dual-metal dimers offer promising prospects for significantly enhancing the performance of reversible oxygen electrocatalysis and for creating innovative catalysts that exhibit synergistic effects and electronic states., Competing Interests: Competing interests statement:The authors declare no competing interest.

Therapeutic resistance has been and remains to be the major challenge in developing successful treatments for different cancers and therefore, understanding the underlying mechanisms in the development of therapeutic resistance is crucial in combating cancers. Multiple mechanisms underlie the development of therapeutic resistance, and the signaling pathways involved in cancer stem cell repopulation, enhanced epithelial-mesenchymal transition (EMT), inflammatory infiltration, and immunosuppression play pivotal roles in this process. Accumulating evidence indicates that the COX2/PGE2/EP axis plays crucial roles not only in tumor development including initiation and progression but also in the development of therapeutic resistance. In this review, we will first dissect the relationship between the COX2/PGE2/EP axis and therapeutic resistance by focusing on the roles of the COX2/PGE2/EP axis in cancer stem cell repopulation, EMT, and anti-cancer immunity. Then, we will summarize the currently available compounds/drugs targeting each component of this axis as well as some of the underlying mechanisms. We hope that better understanding the underlying mechanisms of the functional compounds will be helpful in seeking additive and/or synergistic effects against therapeutic resistance without or with minimal adverse consequence.