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Systemic lupus erythematosus (SLE) is a common autoimmune illness. However, it is not clear that systemic lupus erythematosus is compatible with which host immunological pathway. THalpha/beta host immunological pathway is the host immunity against viruses and prions. It is a newly identified host immune response against DNA, RNA, and protein pathogens. Systemic lupus erythematosus patients often generate anti-double strand antibody and anti-nuclear antibody. Thus, it is highly possible that SLE belongs to THalpha/beta host immune reaction. During the disease process of SLE, type 1 interferons, type 3 interferons, and interleukin-10 are elevated in SLE patients. IgG1 and IgA1 are also commonly noted in SLE patients. These cytokines and antibody isotypes are characteristic of THalpha/beta host immunological pathway. Thus, if SLE is associated with dysregulated THalpha/beta immune response, we can use therapeutic strategies such as anti-interleukin-10 or anti-interferons alpha/beta to control this detrimental disorder.

The framework of host protective immunological pathways is provided in this article. Clonal anergy is mediated by IgD B cells and rδ T cells. rδ1 T cells are for clonal anergy for food in intestine, rδ2 T cells are for clonal anergy for self-antigens, and rδ3 T cells are for clonal anergy for food metabolites in liver.Host immune responses can be categorized into eradicable immune reactions and tolerable immune reactions. Eradicable immune responses are triggered by follicular helper T cells and include TH1, TH2a, TH2b, TH22, and THalpha/beta. Tolerable immune responses are triggered by regulatory T cells and include TH1-like, TH9, TH17, and TH3. TH1/TH1-like immune reactions are host protective immunities against intracellular micro-organisms (bacteria, fungi, and protozoa). TH2a/TH2b/TH9 immune reactions are host protective immunities against parasites. TH2a is the immunity against endoparasites (helminths). TH2b is the immunity against ectoparasites (insects). TH22/TH17 immune reactions are host protective immunities against extracellular micro-organisms (bacteria, fungi, and protozoa). THalpha/beta/TH3 immune reactions are host protective immunities against infectious particles (viruses and prions). Based on this framework of host immunological pathways, we can find out that pro-tumor immune response is mainly TH1-like immune response and anti-tumor immune response is mainly THalpha/beta immune response. If know that cancer is associated with an immune dysfunctional disorder, we can develop therapeutic strategies to diagnose or treat solid tumors.

This manuscript focuses on the derivation of spinity wave and the gravitoelectromagnetic Maxwell-like equations. This paper provides an important insight to the above issue.

更正敝人統一場論公式變成：BxExAxS=gamma*pi*H*c^2這是此公式在運動下校正gamma是洛侖茲因子作泰勒展開 變成：BxExAxS=pi*H*c^2+1/2*pi*H*v^2這是把原我書中重新推導用盎魯霍金效應T=ah'/2piKc=ch'/2piKR代入拉莫公式與史帝分公式恆等式把加速度a與距離R消去最後右邊分母剩下的角度用洛侖茲因子校正另外本來提出電荷造成時間收縮此觀點也要修改 電荷不敵質量因為KQq/2r

BxExAxS=gamma*pi*H*c^2這是此公式在運動下校正gamma是洛侖茲因子作泰勒展開 變成：BxExAxS=pi*H*c^2+1/2*pi*H*v^2這是把原我書中重新推導用盎魯霍金效應T=ah'/2piKc=ch'/2piKR代入拉莫公式與史帝分公式恆等式把加速度a與距離R消去最後右邊分母剩下的角度用洛侖茲因子校正另外本來提出電荷造成時間收縮此觀點也要修改 電荷不敵質量因為KQq/2r

The coronavirus disease 2019 (COVID-19) pandemic continues to burden healthcare systems worldwide. COVID-19 symptoms are highly heterogeneous, and the patient may be asymptomatic or may present with mild to severe or fatal symptoms. Factors, such as age, sex, and comorbidities, are key determinants of illness severity and progression. Aging is accompanied by multiple deficiencies in interferon production by dendritic cells or macrophages in response to viral infections, resulting in dysregulation of inflammatory immune responses and excess oxidative stress. Age-related dysregulation of immune function may cause a more obvious pathophysiological response to SARS-CoV-2 infection in elderly patients and may accelerate the risk of biological aging, even after recovery. For more favorable treatment outcomes, inhibiting viral replication and dampening inflammatory and oxidative responses before induction of an overt cytokine storm is crucial. Resveratrol is a potent antioxidant with antiviral activity. Herein, we describe the reasons for impaired interferon production, owing to aging, and the impact of aging on innate and adaptive immune responses to infection, which leads to inflammation distress and immunosuppression, thereby causing fulminant disease. Additionally, the molecular mechanism by which resveratrol could reverse a state of excessive basal inflammatory and oxidative stress and low antiviral immunity is discussed.

Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.

Birth and end of our universe is provided in this deduction. In addition, grand unified field theories are discussed.

Transcription factors, especially STATs proteins, play vital roles in the host immunological pathways. These STATs proteins compete each other and drive different immunological pathways in reaction to different pathogens. Here, I summarize the JAK-STAT signaling for each immunological pathway. In addition, specific important transcription factors for specific immune response are also given. Tfh is related to STAT5 and BCL6. Treg is related to STAT5a, STAT5b, and FOXP3. TH1 immunity is related to STAT1a, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1a, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is related to STAT3 and AHR. THab immunity is related to STAT1a, STAT1b, STAT2, STAT3b, and ISGF. TH1-like immunity is related to STAT1a, STAT4, STAT5a, and STAT5b. TH9 immunity is related to STAT6, STAT5a, STAT5b, and PU.1. TH17 immunity is related to STAT3a, STAT5a, STAT5b and RORG. TH3 immunity is related to STAT1a, STAT1b, STAT2, STAT3b, STAT5a, STAT5b, and ISGF.

The mass acquiring mechanism of meson or gluon is discussed in this article. Higgs-meson interaction and Higgs-gluon interaction are the key mechanism. Finally, we can get the mass origin of neutron or proton. The detail deduction is provided in the manuscript. We can get same mass of charged pions, neutral pion, charged gluons, and neutral gluons. This article solves the mass gap problem of Yang-Mills theory.

We can derive spinity wave by the deduction steps. Spinity wave equation can be derived by gravitospinity Maxwell-like equations. The curl of curl of spinity field can give the formula of spinity wave. The spinity wave is actually Einstein’s gravitational wave.

Human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages, interferon gamma (IFNg) CD4 T cells, innate lymphoid cells 1 (ILC1), CD8 T cells, invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils, interleukin (IL)-22/IL-17 CD4 T cells, innate lymphoid cells 3 (ILC3), iNKT17 cells, and IgG2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), IL-5/IL-4 CD4 T cells, IL-25 inducing inflammatory innate lymphoid cells 2 (iILC2), mast cells-tryptase (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, mast cells-tryptase/chymase (MCtc), IL-3/IL-4 CD4 T cells, IL-33 inducing nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, IL-9 mast cells (MMC9), thymic stromal lymphopoietin inducing innate lymphoid cells 2, IL-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. This categorization provides a complete framework of immunological pathways against four types of parasitic infections.

In my previous study, I summarized a framework for all host immunological pathways, including eradicable immune responses and tolerable immune responses. C-X-C motif chemokine receptor (CXCR) 5 is a marker of follicular helper T cells, and other chemokine receptors can also be categorized into a framework based on host immunological pathways. Here, a literature review of the relationship between chemokines and immunological pathways was performed, and the following relationships were observed: T-helper (Th) 1 responses are related to C-C motif chemokine receptor (CCR) 5, Th1-like responses are related to CCR1, Th2 and Th9 responses are related to CCR4 (basophils) and CCR3(eosinophils), Th22 responses are related to CCR10, Th17 responses are related to CCR6, Thalpha/beta(Tr1) responses are related to CXCR3, regulatory T cells (Treg) are related to CCR2, and Th3 responses are related to CCR8. Moreover, CCR7 is related to lymph node homing, and CCR9 is related to thymus homing. CXCR1 and CXCR2 are important for the chemotaxis of neutrophils and are important in innate immunity. CX3CR1 is linked to NK cells, and XCR1 is linked to CD8 T cells. Additionally, CXCR4 is involved in immune cell homing to the bone marrow, and CXCR6 is involved in immune cell homing to the spleen. These findings can help to identify biomarkers of immune cells and provide new insights into host immunological pathways.

This article deducts that electromagnetic field, strong interaction, and weak interaction are actually torsion tensors. Since we know gravity field is actually a curvature tensor, we can use geometry to unite gravity, electromagnetism, strong, and weak interaction. Perfect fluid combines with Faraday tensor with geometrized unit can give a 4x4 rank2 spacetime matrix to include the above force field. In addition, strong interaction mediating gluons can acquire mass based on Higgs mechanism. This article also provides evidence of Yang-Mills theory existence and solves the mass gap problem in strong interaction.

The author Wan-Chung Hu(born1973) is a MD (National Taiwan University) and PhD (Johns Hopkins University). This book contains theories in physics, chemistry, biology, geosciences, and mathematics. Spinity is a force to drag spacetime to rotate around central mass. Rest mass produces gravity, spinning mass produces spinity; rest charge produces electricity, spinning charge produces magnetism. Gravitospinity Maxwell equations can be obtained. Light is also the gravity wave, and light decides time. Space-time has smallest unit as new Planck volume and Planck time. Flight principle is given. Lightity is dark energy. Photon emitted from galaxy expands the universe acceleratedly via light pressure. General relativity suggests mass induces spacetime curvature; charge relativity suggests charge induces spacetime torsion. There is no dark matter, and spiral galaxies are formed due to charge relativity which replaces quantum electrodynamics. Integrating general relativity, charge relativity, and light pressure, we get 4x4 universe field tensor. The birth and end of universe can be deducted. Unified field theory can also be obtained by integrating electric field, magnetic field, gravity field, spinity field, and temperature field. Combining gravitospinity, electromagnetism, and matter standing wave, I deduct a determinative atom model replacing quantum mechanics. In addition, I propose a new chemical bond theory according to the new atom model. Homochirality is due to co-catalysis of L-amino acids and D-sugars. Extinction is due to Milankovitch cycle. Earthquake is caused by abrupt light release from inner earth which explains electromagnetism/ ionosphere anomaly and intra-tectonic earthquakes replacing plate tectonic earthquake theory. Tornado genesis is related to charge relativity. In mathematics, I propose MilankovitchThis book is very important to earthquake prediction. Many nuclear plants of Taiwan are located near fault areas. If huge earthquake happens, it will cause detrimental effect. I used several nights and weekends to finish this book without affecting my normal work. I am still most interested in biomedicine including vaccine science. Both biomedicine and earthquake research can save millions of lives.

This manuscript discussed about the fate of our universe and the formula of grand unified theories.

Objective To find out host gene expression profiles after malarial infection. Methods Further time-course microarray analysis of peripheral blood mononuclear cells focusing on malaria pathogenesis was performed. Results Up-regulation of coagulation-related genes, heat shock proteins, glycolytic enzymes, glucose transporters, and vacuolar H + -ATPases was found in acute febrile malaria. In early malaria, prior to detectable parasitemia, CD36 and ICAM1 were up-regulated. During acute malaria, there is correlation between IL-1β and heat shock proteins. CD163, a hemoglobin scavenger receptor, was up-regulated in acute malaria to potentially facilitate free hemoglobin up-take by leukocytes. In acute malaria, high MafB gene expression was negatively correlated with hemoglobin and platelet counts. Consistent with hemoglobin down-regulation, peripheral red blood cell counts tended to increase during acute malaria. Up-regulations of red blood cell and leukocyte binding mediators like CD36, ICAM1, thrombospondin, and thrombomodulin may contribute to the pathogenesis of cerebral malaria. Similarly, up-regulation of correlated glycolytic enzymes, glucose transporter and H + -ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in serious malaria patients. Overall gender effects on gene expression profiles between male and female were not apparent, except for some hemoglobins were significantly down-regulated in male versus female, which suggesting males are prone to malaria-related anemia. Conclusions Leukocyte gene expression profiles can explain the pathogenesis of malarial complication such as fever, metabolic acidosis, hypoglycemia, anemia, and coagulopathy.

Traditional Chinese medicine (TCM) formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess theYang-Xuconstitution using a body constitution questionnaire (BCQ) and clinical blood variables. A BCQ was employed to assess the clinical manifestation ofYang-Xu. The logistic regression model was conducted to explore the relationship between BC scores and biomarkers. Leave-one-out cross-validation (LOOCV) and K-fold cross-validation were performed to evaluate the accuracy of a predictive model in practice. Decision trees (DTs) were conducted to determine the possible relationships between blood biomarkers and BC scores. According to the BCQ analysis, 49% participants without any BC were classified as healthy subjects. Among them, 130 samples were selected for further analysis and divided into two groups. One group comprised healthy subjects without any BC (68%), while subjects of the other group, named as the sub-healthy group, had three BCs (32%). Six biomarkers, CRE, TSH, HB, MONO, RBC, and LH, were found to have the greatest impact on BCQ outcomes inYang-Xusubjects. This study indicated significant biochemical differences inYang-Xusubjects, which may provide a connection between blood variables and theYang-XuBC.

Witebsky’s criteria for autoimmune diseases were used for decades since 1957. His postulates are: 1. Direct demonstration of free circulating antibodies active at body temperature 2. Recognition of the specific antigen 3. Production of antibodies against same antigen in experimental animals 4. Experimental animal demonstrates same tissue changes in human. More updated and applicable criteria for autoimmune disorders are required due to recent advance in molecular immunology. Here, I propose new criteria. Possible criteria is HLA association. Probable criteria is HLA association plus TH subtype restriction without pathogen. Definite criteria is experimentally reproducible by autoantibody or self reactive T cell transfer. Optional criteria is Clinical or pathology clues. This new criteria is more practical. It should help to explore the actual disease pathophysiology and lead to better diagnosis and treatment strategies.

Using genome-wide expression profiles from persons either experimentally challenged with malaria-infected mosquitoes or naturally infected withPlasmodium falciparummalaria, we present details of the transcriptional changes that occur with infection and that either are commonly shared between subjects with presymptomatic and clinically apparent malaria or distinguish these two groups. Toll-like receptor signaling through NF-κB pathways was significantly upregulated in both groups, as were downstream genes that function in phagocytosis and inflammation, including the cytokines tumor necrosis factor alpha, gamma interferon (IFN-γ), and interleukin-1β (IL-1β). The molecular program derived from these signatures illuminates the closely orchestrated interactions that regulate gene expression by transcription factors such asIRF-1in the IFN-γ signal transduction pathway. Modulation of transcripts in heat shock and glycolytic enzyme genes paralleled the intensity of infection. Major histocompatibility complex class I molecules and genes involved in class II antigen presentation are significantly induced in 90% of malaria-infected persons regardless of group. Differences between early presymptomatic infection and natural infection involved genes that regulate the induction of apoptosis through mitogen-activated protein (MAP) kinases and signaling pathways through the endogenous pyrogen IL-1β, a major inducer of fever. The induction of apoptosis in peripheral blood mononuclear cells from patients with naturally acquired infection impacted the mitochondrial control of apoptosis and the activation of MAP kinase pathways centered around MAPK14 (p38α and p38β). Our findings confirm and extend findings regarding aspects of the earliest responses to malaria infection at the molecular level, which may be informative in elucidating how innate and adaptive immune responses may be modulated in different stages of infection.

Background Using microarray analysis, this study showed up-regulation of toll-like receptors 1, 2, 4, 7, 8, NF-κB, TNF, p38-MAPK, and MHC molecules in human peripheral blood mononuclear cells following infection with Plasmodium falciparum. Methods This analysis reports herein further studies based on time-course microarray analysis with focus on malaria-induced host immune response. Results The results show that in early malaria, selected immune response-related genes were up-regulated including α β and γ interferon-related genes, as well as genes of IL-15, CD36, chemokines (CXCL10, CCL2, S100A8/9, CXCL9, and CXCL11), TRAIL and IgG Fc receptors. During acute febrile malaria, up-regulated genes included α β and γ interferon-related genes, IL-8, IL-1b IL-10 downstream genes, TGFB1, oncostatin-M, chemokines, IgG Fc receptors, ADCC signalling, complement-related genes, granzymes, NK cell killer/inhibitory receptors and Fas antigen. During recovery, genes for NK receptorsand granzymes/perforin were up-regulated. When viewed in terms of immune response type, malaria infection appeared to induce a mixed TH1 response, in which α and β interferon-driven responses appear to predominate over the more classic IL-12 driven pathway. In addition, TH17 pathway also appears to play a significant role in the immune response to P. falciparum. Gene markers of TH17 (neutrophil-related genes, TGFB1 and IL-6 family (oncostatin-M)) and THαβ (IFN-γ and NK cytotoxicity and ADCC gene) immune response were up-regulated. Initiation of THαβ immune response was associated with an IFN-αβ response, which ultimately resulted in moderate-mild IFN-γ achieved via a pathway different from the more classic IL-12 TH1 pattern. Conclusions Based on these observations, this study speculates that in P. falciparum infection, THαβ/TH17 immune response may predominate over ideal TH1 response.

Background: Severe Acute Respiratory Syndrome (SARS) is characterized by acute respiratory distress (ARDS) and pulmonary fibrosis, and the monocyte/macrophage is the key player in the pathogenesis of SARS. Methods: In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV) infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection and the gene expression was profiled by oligonucleotide-based microarray. Results: Analysis of immune-related gene expression profiles showed that 24 h after SARS-CoV infection, (i) IFN-alpha/beta-inducible and cathepsin/proteosome genes were down-regulated; (ii) the hypoxia/hyperoxia-related genes were up-regulated; and (iii) the TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, the lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. Conclusion: These results elucidate that monocyte/macrophage dysfunction and dysregulation of fibrosis-related genes are two important pathogenic events of SARS.