Regulatory role of RGMb in lung injury promoted by the combination of carbon ion irradiation and anti-PD-1 antibody through Erk1/2 and p38 MAPK pathways.

The combination of carbon ion radiotherapy and anti-PD-1 antibody represents a new approach to treating thoracic tumors. However, the lung damage caused by this combination therapy may limit its use, and the potential mechanisms for this are worthy of investigation. The objective of this research was to examine the potential involvement of repulsive guidance molecule b (RGMb) in lung damage promoted by the utilization of carbon ion irradiation combined with an anti-PD-1 antibody. The C57BL/6 mice have been randomly separated into four distinct groups: control, anti-PD-1, whole thorax carbon ion irradiation, and irradiation in combination with anti-PD-1 treatment groups (combination group). Detection of pathological changes in lung tissue using HE staining. Detection of pulmonary fibrosis by Masson staining and the hydroxyproline assay. ELISA to detect TNF-α, TGF-ß, IL-6, and IL-1ß expression levels within lung homogenates. The expression of RGMb, p38 MAPK, and Erk1/2 pathways was detected using a fully automated digital Western blotting system WES (ProteinSimple, USA). Flow cytometry was employed to analyze tissue-resident memory T cells (TRM) within the lung. Subsequently, the siRNA gene was employed to induce the downregulation of RGMb in mice in order to validate the involvement of RGMb in radiation-immune lung injury. The present study observed a significant increase in both inflammatory and fibrotic indicators within the mice group's lung tissue that received the combination treatment. The combination group exhibited elevated levels of TGF-ß, TNF-α, IL-6, and IL-1ß in lung homogenates. Anti-PD-1 antibody and carbon ion irradiation, upregulated RGMb, phospho-p38 MAPK and phospho-Erk1/2. The results obtained from the flow cytometry analysis indicated that the combination group was significantly higher in the number of clonal expansion TRMs, which were predominantly characterized by the expression of CD8+CD103+CD69-TRMs. The downregulate of RGMb via siRNA in mice resulted in a decrease in phospho-p38 MAPK and phospho-Erk1/2. The combination group exhibited a reduction in TNF-α, TGF-ß, IL-6, and IL-1ß in their lung tissues, and the number of CD8+CD103+CD69-TRM was significantly reduced. The combination group exhibited a significant improvement in inflammatory and fibrotic indicators within the lung tissues. Anti-PD-1 antibody and carbon ion irradiation synergistically regulate RGMb, leading to strong clonal expansion of lung TRM through the p38 MAPK and Erk1/2 pathways. The present study offers valuable insights into the treatment of lung injury due to the combined administration of carbon ion radiotherapy and anti-PD-1 antibody therapy.

Tailoring nondiffracting fields with a non-Markovian phase imprint.

We experimentally generate nondiffracting speckles that carry non-Markovian properties by encoding the wavefront of a monochromatic laser beam with ring-shaped non-Markovian phases. The resulting non-Markovian nondiffracting fields present a ring-shaped pattern and central dark notches, which are analyzed with an expression of the orbital angular momentum spectra of the wavefront possessing ring-shaped non-Markovian phases. Furthermore, we demonstrate that the intensity profiles of these non-Markovian nondiffracting fields exhibit stability over multiple Rayleigh ranges, and their statistical properties could be controlled with the non-Markovianity of the input phase masks. This work presents an approach for simultaneously tailoring the diffracting property and non-Markovianity of optical fields and provides a deeper understanding of non-Markovian processes.

How does full-cost insurance for wheat affect pesticide use? From the perspective of the differentiation of farmers' production scale.

Theoretically, agricultural insurance influences farmers' use of pesticides by changing the expected income of agricultural production. Full-cost insurance, with high guarantee and high compensation characteristics, may significantly affect farmers' pesticide use. First, this paper constructs a production function to characterize and compare the marginal incomes of insured and uninsured farmers under risk uncertainty and analyses how insured farmers can increase marginal income by increasing or reducing factor inputs. Considering scale differentiation, it discusses pesticide use strategies different types of farmers may adopt to maximize household utility. Second, using survey data of the pilot counties of full-cost insurance for wheat in Henan Province, China, the simultaneous equation model is used for empirical testing. The results reveal the following: (i) Farmers' insurance participation and pesticide application behaviour are not mutually independent. (ii) For the whole sample, full-cost insurance for wheat has a significant pesticide reduction effect. (iii) However, considering scale differentiation, pesticide application decreases significantly among insured ordinary farmers but does not change significantly among insured large-scale farmers. Third, policy measures are proposed to activate the green development function of agricultural insurance.

Multi-target object scattering imaging with intensity correlation of structured illumination.

Imaging through scattering layers based on the optical memory effect (OME) concept has been widely investigated in recent years. Among many scattering scenarios, it is very important to recover hidden targets with proper spatial distribution in the scene where multiple targets out of the OME range exist. In this Letter, we put forward a method for multi-target object scattering imaging. With the help of intensity correlation between the structured illumination patterns and recorded speckle images, the relative position of all hidden targets can be obtained and the movement of the targets within the OME range can be tracked. We experimentally implement scattering imaging with 16 targets and the motion tracking of them. Our results present a significant advance in a large field of view scattering imaging with multiple targets.

Structure Revisions of Phenolic Bisabolane Sesquiterpenes and a Ferroptosis Inhibitor from the Marine-Derived Fungus Aspergillus versicolor YPH93.

Seven new phenolic bisabolane sesquiterpenoids (1-7), along with 10 biogenetically related analogues (8-17), were obtained from the deep-sea-derived fungus Aspergillus versicolor YPH93. The structures were elucidated based on extensive analyses of the spectroscopic data. Compounds 1-3 are the first examples of phenolic bisabolanes that contain two hydroxy groups attached to the pyran ring. The structures of sydowic acid derivatives (1-6 and 8-10) were carefully studied, leading to the structure revisions of six known analogues, including a revision of the absolute configuration for sydowic acid (10). All metabolites were evaluated for their effects on ferroptosis. Compound 7 exerted inhibition on erastin/RSL3-induced ferroptosis with EC50 values ranging from 2 to 4 µM, while it exhibited no effects on TNFα-induced necroptosis or H2O2-induced cell necrosis.

Criteria to Evaluate Tumor Enlargement During the Active Surveillance of High-Risk Thyroid Nodules: Which is Better, Diameter or Volume?

INTRODUCTION: Tumor enlargement is the most common parameter identifying disease progression during active surveillance, but the value and significance of the changes in tumor diameter and volume in the evaluation of tumor growth have not been compared. METHODS: This cohort study included 468 patients with high-risk thyroid nodule, in whom nodule size change was monitored using ultrasound, to compare the changes in tumor diameter and volume in assessing tumor growth. RESULTS: A total of 569 high-risk thyroid nodules were found in the 468 patients. A total of 14 nodules (2.5%) showed a diameter increase ≥ 3 mm. The number of nodules with a peak volume change exceeding 50% and 100% was 185 (32.5%) and 86 (15.1%), respectively. Among the 555 stable nodules, the number of nodules with volume fluctuations exceeding 50% and 100% was 171 (30.8%) and 72 (13.0%), respectively. Among 212 stable nodules at the baseline and in the first three follow-up, the percentage of peak volume fluctuations exceeding 50% (48.5% vs. 28.5%, p = 0.004) and 100% (26.5% vs. 8.3%, p < 0.001) in the nodules with the sum of three diameters (SOTDs) ≤ 1 cm was significantly higher than that of nodules with SOTDs > 1 cm. A statistically significant difference was also found in the range distribution of SOTDs ≤ 1 cm and SOTDs > 1 cm (p = 0.007). CONCLUSIONS: Volume is not an appropriate method for determining tumor growth. Tumor diameter measurement alone serves as a better surrogate for disease progression in sonographically high-risk thyroid nodules than volume.

Dynamic Changes in the Renal Function of Acute Myocardial Infarction Patients with Reduced eGFR After Emergency Percutaneous Coronary Intervention.

Renal dysfunction greatly influences decision-making for emergency percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). This observational study investigated renal function changes and risk factors for renal injury in patients with AMI with reduced estimated glomerular filtration rate (eGFR) who underwent emergency PCI. The study included 85 patients with AMI with decreased eGFR who underwent emergency PCI, categorized into stage 2, 3, and 4 chronic kidney disease groups. Baseline data, laboratory indicators, coronary characteristics, and serum creatinine concentration were monitored at multiple time points. Renal injury was defined using two criteria: an increase in serum creatinine level by 0.3 mg/dL or a 50% increase from baseline. During the 1-year follow-up, renal injury incidence varied from 1.18% to 15.29%. The pattern showed an increasing trend in the 1st week after PCI, peaking at 1 week, followed by a decrease at 3 months, and another increase at one year. Low basal eGFR, high contrast agent dosage, and diabetes were associated with renal injury according to logistic regression analysis. The eGFR cutoff value of 35.475 mL/minute·1.73 m2 had a sensitivity of 83.05% and specificity of 57.69% for predicting renal injury based on receiver operating characteristic curve analysis. In summary, patients with AMI with basal eGFR lower than 35.475 mL/minute·1.73 m2 have a higher risk of renal injury after PCI. These findings emphasize the importance of assessing renal function and considering associated risk factors when deciding on emergency PCI for AMI with reduced eGFR.

circRNA: Regulatory factors and potential therapeutic targets in inflammatory dermatoses.

The skin is the largest organ of the human body and acts as the first line of defence against injury and infection. Skin diseases are among the most common health problems and are associated with a considerable burden that encompasses financial, physical and mental consequences for patients. Exploring the pathogenesis of skin diseases can provide insights into new treatment strategies. Inflammatory dermatoses account for a large proportion of dermatoses and have a great impact on the patients' body and quality of life. Therefore, it is important to study their pathogenesis and explore effective treatment. Circular RNAs (circRNAs) are a special type of RNA molecules that play important regulatory roles in several diseases and are involved in skin pathophysiological processes. This review summarizes the biogenesis, properties and functions of circRNAs as well as their roles in the pathogenesis of inflammatory dermatoses, including psoriasis, lupus erythematosus, atopic dermatitis, lichen planus and severe acne and their potential as therapeutic targets.

Towards fine recognition of orbital angular momentum modes through smoke.

Light beams carrying orbital angular momentum (OAM) have been constantly developing in free-space optical (FSO) communications. However, perturbations in the free space link, such as rain, fog, and atmospheric turbulence, may affect the transmission efficiency of this technique. If the FSO communications procedure takes place in a smoke condition with low visibility, the communication efficiency also will be worse. Here, we use deep learning methods to recognize OAM eigenstates and superposition states in a thick smoke condition. In a smoke transmission link with visibility about 5 m to 6 m, the experimental recognition accuracy reaches 99.73% and 99.21% for OAM eigenstates and superposition states whose Bures distance is 0.05. Two 6 bit/pixel pictures were also successfully transmitted in the extreme smoke conditions. This work offers a robust and generalized proposal for FSO communications based on OAM modes and allows an increase of the communication capacity under the low visibility smoke conditions.

Enabling data-limited chemical bioactivity predictions through deep neural network transfer learning.

The main limitation in developing deep neural network (DNN) models to predict bioactivity properties of chemicals is the lack of sufficient assay data to train the network's classification layers. Focusing on feedforward DNNs that use atom- and bond-based structural fingerprints as input, we examined whether layers of a fully trained DNN based on large amounts of data to predict one property could be used to develop DNNs to predict other related or unrelated properties based on limited amounts of data. Hence, we assessed if and under what conditions the dense layers of a pre-trained DNN could be transferred and used for the development of another DNN associated with limited training data. We carried out a quantitative study employing more than 400 pairs of assay datasets, where we used fully trained layers from a large dataset to augment the training of a small dataset. We found that the higher the correlation r between two assay datasets, the more efficient the transfer learning is in reducing prediction errors associated with the smaller dataset DNN predictions. The reduction in mean squared prediction errors ranged from 10 to 20% for every 0.1 increase in r2 between the datasets, with the bulk of the error reductions associated with transfers of the first dense layer. Transfer of other dense layers did not result in additional benefits, suggesting that deeper, dense layers conveyed more specialized and assay-specific information. Importantly, depending on the dataset correlation, training sample size could be reduced by up to tenfold without any loss of prediction accuracy.

A positive feedback loop between LINC01605 and NF-κB pathway promotes tumor growth in nasopharyngeal carcinoma.

zong non-coding RNAs (lncRNAs) have been identified as crucial effector in modulating the progression of assorted malignancies. In our study, the main aim was to unveil the role and the underlying regulatory mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in nasopharyngeal carcinoma (NPC). RT-qPCR analysis results suggested that LINC01605 was upregulated in NPC cells. According to the results of function experiments, LINC01605 promoted NPC cell proliferation and impeded cell apoptosis. The oncogenic role of LINC01605 in NPC was further validated by animal experiments. Additionally, we verified that LINC01605 regulated Ikbkb expression to promote the nuclear translocation of p65 and thereby activated the NF-κB pathway in NPC cells. Mechanism experiments further suggested that LINC01605 could regulate Ikbkb expression via sponging miR-942-5p. Moreover, LINC01605 recruited IGF2BP2 to stabilize ubiquitin-specific protease 3 (USP3) mRNA and thereby enhanced the stability of IkB subunit beta (IKKß) protein. In addition, p65 acted as a transcription activator to upregulate LINC01605 in NPC cells. In conclusion, this study demonstrated a positive feedback loop between LINC01605 and the NF-κB signalling pathway that promoted NPC cell growth, thus providing new insights to better understand NPC. [Figure: see text].

lncRNA DLG1-AS1 promotes cervical cancer cell gemcitabine resistance by regulating miR-16-5p/HDGF.

AIM: To investigate the long non-coding RNA DLG1 Antisense RNA 1 (lncRNA DLG1-AS1) mechanism in cervical cancer cells with gemcitabine (GEM) resistance. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect DLG1-AS1, miR-16-5p, and hepatoma-derived growth factor (HDGF) expression in cervical cancer cells. The effects of DLG1-AS1 knockdown on cell viability, proliferation, and apoptosis were investigated in GEM-resistant cervical cancer cells. The binding of DLG1-AS1 with miR-16-5p and of miR-16-5p with HDGF was confirmed through dual-luciferase reporter assays. HDGF expression was detected through Western blotting. A xenograft model was established using stably transfected GEM-resistant cervical cancer cells to detect the role of DLG1-AS1 in tumorigenesis in vivo. RESULTS: DLG1-AS1 expression was significantly elevated in HeLa/GEM and SiHa/GEM cells. DLG1-AS1 silencing significantly reduced the viability and proliferation of GEM-resistant cervical cancer cells. DLG1-AS1 also promoted GEM sensitivity in cervical cancer cells by inhibiting miR-16-5p. Moreover, the tumor volume in nude mice in the DLG1-AS1 knockdown group decreased after GEM treatment. In addition, DLG1-AS1 targeted miR-16-5p, and miR-16-5p targeted HDGF. The miR-16-5p inhibitor reversed the DLG1-AS1 knockdown effect in GEM-resistant cervical cancer cells. CONCLUSION: Knockdown of DLG1-AS1 promoted GEM sensitivity in cervical cancer cells by regulating miR-16-5p/HDGF.

Relationship Between NT-proBNP Levels and Left Ventricular Ejection Fraction in Patients with Unstable Angina and Diabetes Mellitus and Preserved LVEF.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is suggested to be altered in patients with systolic heart failure or acute coronary syndrome. We explored the relationship between left ventricular ejection fraction (LVEF) and levels of NT-proBNP in patients with unstable angina and type 2 diabetes mellitus and preserved LVEF.Patients with unstable angina were divided into normal glucose tolerance (controls) and type 2 diabetes mellitus groups. The plasma NT-proBNP concentration was measured in these patients within 30 minute of admission for a comparative study. The severity of coronary arterial lesions was evaluated using Syntax scores. Results: NT-proBNP levels were not significantly different in patients with unstable angina and type 2 diabetes mellitus (median [quartiles]: 167.0 [66.1, 623.3] pg/mL) from those of controls (116.0 [69.8, 233.0], P = 0.278). Subsequent analyses indicated that ln (NT-proBNP) was positively associated with the following parameters: left ventricular end-diastolic diameter (r = 0.495, P = 0.019), left ventricular end-systolic diameter (r = 0.648, P = 0.001), and Syntax score (r = 0.567, P = 0.006); ln (NT-proBNP) was negatively associated with LVEF (r = -0.652, P = 0.001) in patients with unstable angina and type 2 diabetes mellitus. In multiple linear regression analysis, ln (NT-proBNP) levels were significantly independently correlated with the LVEF and Syntax score. However, no correlation was observed between ln (NT-proBNP) and each parameter in patients with unstable angina and normal glucose tolerance (controls).The NT-proBNP level is independently correlated with the LVEF in patients with unstable angina and type 2 diabetes mellitus and preserved LVEF.

Experimentally measuring the mode indices of Laguerre-Gaussian beams by weak measurement.

As a special experimental technique, weak measurements extract very little information from the measured system and does not cause the measured state to collapse. When coupling the Laguerre-Gaussian (LG) state with a well-defined pre- and post-selected system of a weak measurement process, there will be an indirect interconnection between the expected value of coordinate operators of the final state and the mode indices of the measured LG state. The mode of the light is impacted very slightly after the weak measurement. Based on this we propose an experiment scheme and have managed to experimentally measure the mode indices of LG beams spanning from l = -6 to l = +6, p = 0 to p = +8 accurately with the final intensity distributions approximatly at their origin.

Silencing of the lncRNA H19 enhances sensitivity to X-ray and carbon-ions through the miR-130a-3p /WNK3 signaling axis in NSCLC cells.

BACKGROUND: The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. METHODS: The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). RESULTS: Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19-miR-130a-3p-WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. CONCLUSION: Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

Generation of Non-Rayleigh Nondiffracting Speckles.

Optical speckle fields with both non-Rayleigh statistics and nondiffracting characteristics in propagation are an important light source for many applications. However, tailoring either non-Rayleigh statistical speckles or nondiffracting speckles are only investigated independently in previous studies. Here, we report the first observation of optical speckles that remain diffraction-free over a long axial distance while keeping non-Rayleigh statistics simultaneously. We further show the enhancement of Anderson localization of light with the non-Rayleigh nondiffracting speckles. The work presented here provides a versatile framework for customizing optical fields with desired speckle patterns for applications in the fields of solid-state physics, cold atoms, and optical imaging.

Locoregional recurrence of parathyroid carcinoma: how to identify this rare but fatal condition using ultrasonography.

Parathyroid carcinoma (PC) is a rare condition with propensity to relapse. The purpose of this study was to evaluate the sonographic findings of locoregional recurrences of parathyroid carcinoma, in order to facilitate diagnosis of this condition using ultrasound (US). This was a retrospective observational study including 21 patients confirmed with pathologically confirmed locoregional recurrence of parathyroid carcinoma. All patients had undergone preoperative US examination at a tertiary center. The imaging, clinical and laboratory data of each case were collected. Sonographic appearance of the largest lesion at each recurrence was evaluated by two experienced radiologists according to a pre-agreed protocol. Overall, 29 relapses occurred in 21 patients. The median age of the patients was 45 years (range 24-71 years). The median size of the largest recurrent lesion at each relapse was 1.8 cm (range 0.8-3.8 cm). Ultrasound images showed hypoechoic solid nodules in 28 relapses (96.6%), inhomogeneous echo-texture in 28 relapses (96.6%), intralesional echogenic septa-like structures in 21 relapses (72.4%), intralesional cystic change in two relapses (6.9%), infiltrative or blurred boundary in 20 relapses (69.0%), irregular shape in 22 relapses (75.9%), marked vascularization on color Doppler imaging in 19 relapses (65.5%), multiple lesions in 26 relapses (89.7%), contralateral recurrence in 3 relapses (10.3%), and subcutaneous recurrence in 10 relapses (34.5%). None of the recurrent lesions exhibited calcification. The total size of all the recurrent lesions at each relapse fairly correlated with the serum intact parathyroid hormone levels (r = 0.450; p = 0.014).

Chromone Derivatives with α-Glucosidase Inhibitory Activity from the Marine Fungus Penicillium thomii Maire.

The fungal strain YPGA3 was isolated from the sediments of the Yap Trench and identified as Penicillium thomii. Eight new chromone derivatives, named penithochromones M-T (1-8), along with two known analogues, 9 and 10, were isolated from the strain. The structures were established by detailed analyses of the spectroscopic data. The absolute configuration of the only chiral center in compound 1 was tentatively determined by comparing the experimental and the calculated specific rotations. Compounds 7 and 8 represent the first examples of chromone derivatives featuring a 5,7-dioxygenated chromone moiety with a 9-carbon side chain. Bioassay study revealed that compounds 6-10 exhibited remarkable inhibition against α-glucosidase with IC50 values ranging from 268 to 1017 µM, which are more active than the positive control acarbose (1.3 mmol).

Peripheral blood soluble elastin and elastase as auxiliary diagnostic indicators for coronary artery ectasia

Background/aim: Damage to elastin fibres in coronary media might lead to coronary artery ectasia (CAE). This study evaluated whether CAE can be distinguished by detecting circulating soluble elastin (s-elastin), which is a degradation product of elastin fibres, and elastase, which is the main enzyme of elastin fibres. Materials and methods: Fifty-eight patients with CAE, 58 with coronary heart disease (CHD) and 61 with relatively normal coronary arteries, were included. Circulating s-elastin and elastase were measured, and receiver operating characteristic curves were used to demonstrate their respective optimal cut-off values for predicting CAE. Results: The concentrations of s-elastin and elastase were higher in the CAE group than in the CHD and relatively-normal-coronary groups. Their cut-off values for screening of CAE were 13.148 ng/mL and 25.549 ng/mL, respectively; for sensitivity of CAE were 0.690 and 0.773, respectively; and for specificity of CAE were 0.862 and 0.571, respectively. A combination of s-elastin and elastase in series (one of the two higher than its cut-off value) had a better sensitivity for screening for CAE, whereas their combination in parallel (both higher than their cut-off values) had a better specificity. Conclusion: Circulating s-elastin and elastase are promising biomarkers for assisting in CAE diagnosis.

Multi-omics study in monozygotic twins confirm the contribution of de novo mutation to psoriasis.

BACKGROUND: Genome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.0 in Chinese population. Although rare variations still account for a small proportion of phenotypic variances in complex diseases, their effect on phenotypes is large. Recently, more and more studies focus on the low-frequency functional variants and have achieved a certain amount of success. METHOD: Whole genome sequencing and sanger sequencing was performed on 8 MZ twin pairs discordant for psoriasis to scan and verified the de novo mutations (DNMs). Additionally, 665 individuals with about 20 years' medical history versus 2054 healthy controls and two published large population studies which had about 8 years' medical history (including 10,727 cases versus 10,582 controls) were applied to validate the enrichment of rare damaging mutations in two DNMs genes. Besides, to verify the pathogenicity of candidate DNM in C3, RNA-sequencing for CD4+, CD8+ T cells of twins and lesion, non-lesion skin of psoriasis patients were carried out. Meanwhile, the enzyme-linked immunosorbent assay kit was used to detect the level of C3, C3b in the supernatant of peripheral blood. RESULT: A total of 27 DNMs between co-twins were identified. We found six of eight twins carry HLA-C∗0602 allele which have large effects on psoriasis. And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele. In the replication stage, we found 2 loss-of-function (LOF) variants of C3 only in 665 cases with about 20 years' medical history and gene-wise analysis in 665 cases and 2054 controls showed that the rare missense mutations in C3 were enriched in cases (OR = 1.91, P = 0.0028). We further scanned the LOF mutations of C3 in two published studies (about 8 years' medical history), and found one LOF mutation in the case without carrying HLA-C*0602. In the individual with DNM in C3, RNA sequencing showed the expression level of C3 in skin was significant higher than healthy samples in public database (TPM fold change = 1.40, P = 0.000181) and ELISA showed protein C3 in peripheral blood was higher (~2.2-fold difference) than the other samples of twins without DNM in C3. CONCLUSION: To the best of our knowledge, this is the first report that DNM in C3 is the likely pathological mutations, and it provided a better understanding of the genetic etiology of psoriasis and additional treatments for this disease.