Background: Although striking effects of vaccination strategy against pandemic COVID-19, a long-term influence by repeated partial virus mRNA injections are unknown. In addition, the molecular mechanism in accelerated ageing process still remains unclear. Through our clinical research, we observe and reported spontaneous SARS-CoV-2 virion and virion part production after Pfizer-BioNTech mRNA vaccination, observed from 3 weeks after the first injection. A significant destruction in ribosomal RNA structures, enhanced by repeated vaccinations, were also identified. The present study is aimed to define molecular mechanisms for SARSCoV- 2 virion production after injection of mRNA vaccination with a comparison to virion proliferation in non-vaccinated patient with severe COVID-19 pneumonia and fibrosis.

Abstract In the process of caner recovery, Huaier simultaneously promotes significant hair growth and restoration as a typical evidence of its efficacy on induced tissue regeneration and repair function. Hair growth after conventional chemotherapy was a first and significant observation, and that in dose-dependent manner. The molecular basis of hair growth was identified as the activation of Hedgehog signaling pathway and among various perturbed signal transfer network, which initiates systematic tissue repair not only in pathogenic lesions but also to skin problems and inter/intra neural signal transfer. The activation followed by the inhibition at 3-6 months interval resulted in the prevention of subsequent complications, such as recurrence and metastasis by transcriptional control in cancer stem cell production. This regulation was demonstrated to occur irrespectively to SMO (smoothhead) function. The present study thus provides a simple and clear proof of Huaier effects on tissue regeneration, additional to the reported cancer specific-cell death.

Although striking effects of vaccination strategy against COVID-19 world-wide, a long-term influence by sequential viral mRNA injections are unknown. We analysed biological alterations by total RNA sequencing in Pfizer-BioNTech vaccinated normal healthy volunteers and cancer patients, with or without adjuvant Huaier therapy. A significant destruction in ribosomal RNA structures was identified, enhanced by serial shots. Unlike the destruction caused by chemotherapy with platinum (II) complex, progressive destruction in 18S ribosome was identified even at 6 months after vaccination. The influence resulted in massive inhibition of translation and transcription, significantly in intra/inter neural signaling transfer and in lipid metabolism, related to ageing process. Huaier compensated these dysfunctions by miRNA-mediated transcriptional control, by typical activation in PI3K/AKT signaling pathway. Gene Ontology analysis revealed spontaneous virion production in number even after 3 months of the first vaccination. Present study indicated that the adjuvant therapy like Huaier compensates accelerated ageing process by mRNA vaccination.

Background: Clinical significance of anti-cancer effects of Huaier (Trametes robiniophila murr) has been emphasized recently [1-3]. We have already reported the successful Huaier therapy based on the individual genomic potential and miRNA-mediated transcription control [4-7]. In prostate cancer, Huaier also proved to have a significant efficacy on the prevention of cancer progression [6]. Objective: We have been initiating clinical research for thorough understanding of molecular basis of Huaier effects, which contributes to define the responsible molecules and biosystems not only for recovery, but also for prevention of cancer progression and tumorigenesis. Methods: The peripheral blood samples from the volunteer patients were analyzed by total RNA and non-coding small RNA sequencing on BGISEQ-500 Platform [8, 9]. KEGG pathway classification was hired for the analysis of the obtained information in the present study (https://www.genome.jp/kegg/) [10]. Results: In the present study, we focused on the patient and her family correlated with the mutated EGFR [11] and other receptor tyrosine kinases (c-MET [12-14]/erbB-2 [15, 16]). At first, high ratio of SNP variants as A-G transitions (241,896 in total, 37.0%) and A-C transversions (43,213 in total, 6.5 %), with skipped-exon (51%), which influenced significant changes in transcriptional factors and corresponding gene expression in multiple signal transduction pathways. The ratio of alteration ranged from 10% to 30% of total number of transcripts, detected as a drastic down-regulation by Huaier administration. Although the patient was diagnosed as benign meningioma, there were no genomic alteration in RNA polymerase II and its subunits [17], but only quantitative down-regulation in the attached transcriptional factors were observed. Additional to the massive down-regulation in the multiple signaling pathways, we identified additional modifications in neural systems and protein/hormone signal transfer by genetic changes in neural transmitters SLC6A4 solute carrier family 6 member 4 [18], and PRNP (prion protein); CD230 [19]. These alterations were hereditary, familial events. Overall drastic modifications in signal transduction contributed to compensate the defected function by the mutation of EGFR and other receptor tyrosine kinases, related to all the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes regulating a wide variety of cell communications. Huaier seemed to take part in the epigenetic post-transcriptional control for the prevention in carcinogenesis and tumorigenesis for whole family members. Conclusion: The present study provided valuable example for compensation of defecting function by mutated EGFR and receptor tyrosine kinases. We identified hereditary gene expression alterations in EGFR (erbB1), c-MET, HER2/neu (erbB2), together with SLC6A4 solute carrier family 6 member 4 (Htt), and PRNP (prion protein); CD230, in the benign meningioma patient. These mutations were hereditary among family members. Huaier administration contributed the rescue of defected cell communication systems by massive down-regulation in a wide variety of signal transferring pathways. The mutation in transcripts remained even after 2 years of treatment. There are scarce medicine or candidate compounds for mutated EGFR and receptor tyrosine kinases yet, and Huaier is the one successful candidate to prevent carcinogenesis, tumorigenesis, and the other severe health problems correlated with the multiple mutations in those tyrosine kinase regulation systems. The epigenetic post-transcriptional regulation would decide the pathogenicity with hereditary mutations in these transcripts.

Huaier (Trametes robiniophila murr) provides significant efficacy not only on cancer, but also various physiological disorders caused by disrupted transcriptional control on multiple signaling pathways. In the process of MEGA-DATA analysis of human transcriptomes, we observed impaired signal transfer in the central and peripheral nervous systems. Here we demonstrate the details of molecular systems to compensate impaired neural transmission, especially by mutated transcripts correlated with neurodegenerative alterations. These significant rescue of signal transfer inter/intra neurons was observed in the patients with the hereditary mutated EGFR, and receptor tyrosine kinases such as c-MET, HER2/neu (erbB2), Htt, Parkin, APP, SOD1, ALS2, and many oncogenes and tumour suppressor genes. The similar compensation has been also reported in the patients with Huaier and conventional chemotherapy using platinum (II) complex. Huaier treatment prevented those patients from pathogenesis, but influenced to cause mild depression. The epigenetic potential seems to influence the pathogenicity in these hereditary mutations, and that typically observed in the defects in DNA mismatch repair systems. With KEGG Arch Clin Biomed Res 2021; 5 (3): 484-518 DOI: 10.26502/acbr.50170181 Archives of Clinical and Biomedical Research Vol. 5 No. 3 – June 2021. [ISSN 2572-9292]. 485 pathway characterization, Huaier showed significant effects on the retrieval of normal function inter/intra neurons. Although we have observed only one case successfully recovered from Parkinson’s disease, the further roles of each representative molecules have not yet defined, and no changes identified in the mechanism of mutations in translation and transcription processes. The present study demonstrated detailed molecules and signaling pathways involved in the onset of neurodegenerative diseases, and the significant effects of Huaier to retain and rescue the impaired neurotransmission and signal transfer. Neurodegenerative damages are inevitably caused by chemical administration, and also by ageing process. However, it is emphasized that, by 2 years’ of Huaier treatment, Huaier could cope with the severity and onset of the diseases.

The progress in cancer research has been processed by the discovery of molecules, genes, and mechanisms to cause carcinogenesis. Even with the advent of a novel technologies, the consequent drug discovery is still not enough to meet the demands, with the limited numbers of choice for anti-cancer strategy are not satisfactory. It is considered partly because mono-targeted agents should have certain limitations against diseases originated from multiple factors and environmental stresses throughout a lifelong time. These defects in the current anti-cancer strategy of cancer therapy chiefly are caused by the lack of information required for cancer recovery. It is extremely required to obtain minimum-essential information to define the molecular basis for cancer Arch Clin Biomed Res 2021; 5 (3): 457-483 DOI: 10.26502/acbr.50170180 Archives of Clinical and Biomedical Research Vol. 5 No. 3 – June 2021. [ISSN 2572-9292]. 458 recovery, with a comparison to that in the process of carcinogenesis. For this purpose, we should have successful agents possibly and reliably to cure the disease. We have identified anti-cancer effects of Huaier, and its unique characteristics of 1) no side effects or toxicity, 2) in dose dependent manner, 3) causing specific cancer cell death with simultaneous tissue regeneration, 4) miRNA-mediated transcriptional control on the rescue of multiple signal transduction, by dependent on individual genomic potential. Here we summarize the results of our genome scope project on clinical research of Huaier therapy on cancer patients. MEGA-DATA analysis in the process of cancer recovery by total RNA and small non-coding RNA sequencing. The results revealed significant differences in the behavior and coordination of RNA editing events, biomolecules, and multiple signaling pathways which beyond any speculations from the findings in the process of carcinogenesis. The time has come to change a point of view of “cancer therapy”, from the mere killing of cancer cells to regenerate the disrupted biophysiological functions through ageing and stress-accumulation in a long-range of life. Huaier provides a timely trigger to induce the spontaneous genomic ability and flexibility to rescue damaged, and impaired functions toward the reconstruction of homeostasis. We will add the Huaier effects on the population with hereditary mutations for prevention of carcinogenesis, and on the compensation of impaired signal transfer inter/intra neurons.

Background: The severe advanced stage cancer has scarce choice of treatment except pain control. Conventional chemotherapy is commonly not applicable for these patients from severe adverse events and toxicity.

Clinical significance of anti-cancer effects of Huaier has been emphasized recently. We have proved that a broad spectrum of Huaier effects was based on the rescue of the disrupted Hippo signalling pathway, especially through the rescue of transcriptional dysregulation. We initiated clinical research for thorough understanding of mode of action by total RNA- and small non-coding RNA-sequencing. Here we provide the surprising genomic plasticity by Huaier observed in the time course of recovery from cancer. The extensive changes in RNA editing events were first observed, such as average 92,427 SNP variances per individual (22,688 in normal control). The subsequent changes in the process of translation and transcription resulted in the drastic changes in number of up/down-regulated transcripts. The ratio of the changes at maximum was 85% (23,210/27,447). With the advent of many novel sequences found in small nuclear RNAs and the consequent gene-silencing derived from miRNA-mediated post-transcriptional control, quantitative and qualitative changes of expression in transcriptional factors (mean 1,115/person) contributed to rescue dysregulated functions occurred in almost all required physiological functions for cancer recovery. The transcription control was demonstrated as functional lineage map between the core transcriptional factor and functionally linked transcripts, and the recovery could be clearly shown as the silencing of those massive changes in the end. The genetic alterations, especially related to the inhibition of NFκB and TGF-β signalling pathways showed significant effects on the improvement of prognosis. Thus, Huaier therapy contributes to cancer cell death with damaged tissue regeneration by extensive and systematic genomic modulations.

Background: Clinical significance of anti-cancer effects of Huaier has been emphasized recently. We have proved that a broad spectrum of Huaier effects was based on the rescue of the disrupted Hippo signalling pathway in Drosophila mutants, especially through the rescue of transcriptional dysregulation. Objective: We initiated clinical research for thorough understanding of molecular basis of Huaier effects. Methods: The obtained peripheral blood samples were analyzed by total RNA and non-coding small RNA sequencing on BGISEQ-500 Platform. Results: In the present study, we sequenced 92 samples sequencing from 31 patients, average generating over 7.4 Giga bases per sample. The results showed significant changes in transcriptional factors and corresponding genes, which resulted in quantitative and qualitative alterations of signaling networks responsible for rescuing all the molecular biological function, cellular component and biological processes. Those changes were identified through genome wide range, and that from RNA editing events, to the resulting transcriptomes with discovery of 24,344 novel transcripts. Drastic variance of up/down regulated genes were associated with siRNA- and miRNA-mediated post-transcription control. Transcriptional factor changes, mean 1,115 per person, integrated those altered transcripts and their functional networks for the rescue of damaged or disrupted control. We provided functional lineage map of these results to show the process of cancer recovery by the time course of Huaier administration. Conclusion: The present study identified that the cancer recovery by Huaier therapy was based on the rescue of transcription control not only in cancer lesion, but also in almost all biological systems. These changes depended on individual capability and flexibility of genomic potential to undergo extensive modulations in the genome, and not specified in limited numbers and variety of genes. These alterations were thus individual spontaneous reaction, so there are no toxicity and side effects.

Background: Among historical nature remedies in Eastern Asia, Huaier (Trametes robiniophila murr) has long been reported for its significant efficacy on longevity and health maintenance, and more importantly, on cancer. The target cancers of Huaier show the almost complete overlap with those strongly influenced by the Hippo pathway function, which is also well known as a tumor suppressor mechanism. Objective: We have initiated the present study in order to prove the hypothesis that the Hippo signaling pathway is a main molecular mechanism of Huaier effects on cancer and on multiple physiological disorders. Methods: We performed in vivo study using Drosophila flies genetically disrupted transcriptional control in the Hippo pathway with overexpressing non-phosphorylatable Yorkie (Yki:V5S168A) as a cancer model. In addition, metabolome analysis was performed using those cancer-model mutants with a comparison to healthy controls. Results: The administration of Huaier clearly resulted in the recovery of rough eye formation of the mutants, indicating the rescue of tumor suppressor mechanism disrupted by the genetically inoculated overabundant transcriptional activators. These improvements occurred in a dose-dependent manner, just as shown in clinical observations. Simultaneously, the GC/MS-based metabolome analysis revealed that Huaier uptake lead the metabolic profile of the mutant flies strongly shifted to that of the early developmental stage. Conclusion: The present study emphasizes that a broad spectrum of Huaier effects was based on the rescue of the disrupted Hippo signaling pathway control, especially on the recovery in transcriptional dysregulation. The metabolome profile shift would explain the molecular basis of the tissue recovery after a long course of Huaier treatment, by the potential to modulate the cell fate through the embryogenesis and subsequent normal specification of the cells in the damaged tissues.

Treatment of β-fluoroalkylated-α,β-unsaturated ketones with 1.2 equiv. of various arylboronic acids in the presence of 5 mol% of [Rh(COD)(2)]BF(4) and 6 mol% of (S)-BINAP in toluene/H(2)O (v/v = 4/1) at the reflux temperature for 3 h gave the corresponding Michael adducts in high yields with over 90% enantioselectivity. Though other electron-deficient alkenes, such as vinylsulfone and vinylphosphonate, were found to be much less reactive in the rhodium-catalyzed conjugate addition with arylboronic acids, the reaction of various arylstannanes toward such electron-deficient alkenes took place very smoothly to afford the corresponding adducts in high yields.

To investigate the off-center rattling motion and its charge-carrier dependence in type-I clathrate compounds, we carried out ultrasonic measurements on type-I Ba${}_{8}$Ga${}_{16}$Sn${}_{30}$ and a reference compound, K${}_{8}$Ga${}_{8}$Sn${}_{38}$. We found elastic softening of ${C}_{44}$ originating from a lattice instability due to the off-center rattling motion of Ba atom in Ba${}_{8}$Ga${}_{16}$Sn${}_{30}$. Elastic softening below 1 K suggests that the lattice instability remains at very low temperatures. We also found ultrasonic dispersion which has no mode selectivity. No-mode-selective ultrasonic dispersion in Ba${}_{8}$Ga${}_{16}$Sn${}_{30}$ would be caused by a strong electron-phonon coupling. No charge-carrier dependence is observed between $n$-type and $p$-type Ba${}_{8}$Ga${}_{16}$Sn${}_{30}$. The significant softening on the bulk modulus in Ba${}_{8}$Ga${}_{16}$Sn${}_{30}$ contrasts to the continuous hardening in K${}_{8}$Ga${}_{8}$Sn${}_{38}$, indicating the central role of the rattling motion in the softening.

The human Sept4/Bradeion GTPase (56Kda) is specifically expressed in colorectal cancer, malignant melanoma, prostate cancer and other urologic cancers such as renal cell carcinoma and bladder cancer.Significance of Bradeion is that, 1) 'all or none' expression, 2) no genetic alterations among patients, and 3) strong tissue-and cell typespecificity.This character satisfies the desired criteria as a target to monitor and control cancer.With the advent of current technology development in nano-scale, we have succeeded to develop the effective serum test for early diagnosis of cancer.Fluorescence correlation spectroscopy (FCS) can directly and quickly analyse protein-protein binding in a sample solution by reflecting the molecular weight of the labeled molecules.We present a novel and successful diagnostic methods by the quantitative detection of Sept4/Bradeion in the patients' serum using monoclonal antibodies.The resulting diagnostic efficacy was as follows; 100% (colorectal cancer), 89.0 % (prostate cancer), 92.3 % (renal cell carcinoma), and 89.0 % (bladder cancer).More importantly, the increased Bradeion titers decreased to the normal level after one week (polypectomy with colonoscope) to 3 weeks after surgical detection of the cancer.

We report on thermoelectric and Raman scattering studies of single crystalline samples of a type I clathrate Ba8Ga16Sn30. The n- and p-type samples have a thermopower of −300 μV/K and +270 μV/K, and electrical resistivity of 20 mΩ cm and 40 mΩ cm at room temperature, respectively. Regardless of the charge carrier type, the lattice thermal conductivity κ L shows typical glass-like behavior. The low-energy vibration of Ba(2) in the tetrakaidecahedron is manifested in the Raman scattering spectrum as a peak at 15 cm−1. This energy agrees with the characteristic vibrational temperature of 20 K derived from the analysis of the specific heat data with a soft-potential model. The fact that both the vibrational energy and the magnitude of κ L for Ba8Ga16Sn30 are lowest among the type I clathrates is evidence that off-center vibrations are responsible for the strong reduction of κ L. Analysis of κ L(T) revealed that the positional disorder associated with the off-center vibrations acts as the Rayleigh scattering center, and the coupling between guest vibrational modes and acoustic phonons is stronger than that in Sr8Ga16Ge30 and Eu8Ga16Ge30.

The septins are a family of conserved proteins involved in cytokinesis and cortical organization. An increasing amount of data implicates different septins in diverse pathological conditions including neurodegenerative disorders, neoplasia and infections. Human SEPT4 is a member of this family and its tissue-specific ectopic expression profile in colorectal and urologic cancer makes it a useful diagnostic biomarker. Thermal unfolding of the GTPase domain of SEPT4 (SEPT4-G) revealed an unfolding intermediate which rapidly aggregates into amyloid-like fibers under physiological conditions. In this study, we examined the effects of protein concentration, pH and metals ions on the aggregation process of recombinant SEPT4-G using a series of biophysical techniques, which were also employed to study chemical unfolding and stability. Divalent metal ions caused significant acceleration to the rate of SEPT4-G aggregation. Urea induced unfolding was shown to proceed via the formation of a partially unfolded intermediate state which unfolds further at higher urea concentrations. The intermediate is a compact dimer which is unable to bind GTP. At 1 M urea concentration, the intermediate state was plagued by irreversible aggregation at temperatures above 30 degrees C. However, higher urea concentration resulted in a marked decay of the aggregation, indicating that the partially folded structures may be necessary for the formation of these aggregates. The results presented here are consistent with the recently determined crystal structure of human septins and shed light on the aggregation properties of SEPT4 pertinent to its involvement in neurodegenerative disease.

Recent activities on optimizing the base design of the large helical device (LHD)-type helical reactor FFHR (force free helical reactor) are presented. Three candidates to secure the blanket space are proposed with the aim of reactor size optimization without deteriorating α-heating efficiency and by taking cost analyses into account. In this way the key engineering aspects are investigated; from 3D blanket designs, it is demonstrated that the peaking factor of the neutron wall loading is 1.2–1.3 and a blanket covering ratio of over 90% is possible by proposing discrete pumping with a semi-closed shield (DPSS) concept. Helical blanket shaping along the divertor field lines is the next big issue. For large superconducting magnet systems under the maximum nuclear heating of 200W/m3, cable-in-conduit conductor (CICC) and alternative conductor designs are proposed with a robust design of cryogenic support posts. For access to ignited plasmas, new methods are proposed, in which a long rise-up time over 300s reduces the heating power to 30MW and a new proportional-integration-derivative (PID) control of the fueling can handle the thermally unstable plasma at high-density operation. This paper focuses on FFHR2m1, which is a modified version of FFHR.