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Abstract Background Long noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy. Methods We analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy. Results We determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis. Conclusions Our results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.

Summary: Background: Atrial cardiomyopathy (ACM) is responsible for atrial fibrillation (AF) and thromboembolic events. Diabetes mellitus (DM) is an important risk factor for ACM. However, the potential mechanism between ACM and DM remains elusive. Methods: Atrial tissue samples were obtained from patients diagnosed with AF or sinus rhythm (SR) to assess alterations in NR4A3 expression, and then two distinct animal models were generated by subjecting Nr4a3−/− mice and WT mice to a high-fat diet (HFD) and Streptozotocin (STZ), while db/db mice were administered AAV9-Nr4a3 or AAV9-ctrl. Subsequently, in vivo and in vitro experiments were conducted to assess the impact of NR4A3 on diabetes-induced atrial remodeling through electrophysiological, biological, and histological analyses. RNA sequencing (RNA-seq) and metabolomics analysis were employed to unravel the downstream mechanisms. Findings: The expression of NR4A3 was significantly decreased in atrial tissues of both AF patients and diabetic mice compared to their respective control groups. NR4A3 deficiency exacerbated atrial hypertrophy and atrial fibrosis, and increased susceptibility to pacing-induced AF. Conversely, overexpression of NR4A3 alleviated atrial structural remodeling and reduced AF induction rate. Mechanistically, we confirmed that NR4A3 improves mitochondrial energy metabolism and reduces oxidative stress injury by preserving the transcriptional expression of Sdha, thereby exerting a protective influence on atrial remodeling induced by diabetes. Interpretation: Our data confirm that NR4A3 plays a protective role in atrial remodeling caused by diabetes, so it may be a new target for treating ACM. Funding: This study was supported by the major research program of National Natural Science Foundation of China (NSFC) No: 82370316 (to Q-S. W.), No. 81974041 (to Y-P. W.), and No. 82270447 (to Y-P. W.) and Fundation of Shanghai Hospital Development Center (No. SHDC2022CRD044 to Q-S. W.).

Abstract Extracellular vesicles (EVs) are emerging as promising carriers for the delivery of therapeutic biologics. Genetic engineering represents a robust strategy for loading proteins of interest into EVs. Identification of EV‐enriched proteins facilitates protein cargo loading efficiency. Many EV‐enriched proteins are sorted into EVs via an endosomal sorting complex required for transport (ESCRT)‐dependent pathway. In parallel, viruses hijack this EV biosynthesis machinery via conserved late domain motifs to promote egress from host cells. Inspired by the similarity of biogenesis between EVs and viruses, we developed a synthetic, Late domain‐based EV scaffold protein that enables the display of a set of single chain variable fragments (scFvs) on the EV surface. We named this scaffold the Late domain‐based exosomal antibody surface display platform (LEAP). We applied the LEAP scaffold to reprogramme HEK293T cell‐derived EVs to elicit T‐cell anti‐tumor immunity by simultaneously displaying αPD‐L1 and αCD3 scFvs on the EV surface (denoted as αPD‐L1×αCD3 bispecific T‐cell engaging exosomes, BiTExos). We demonstrated that αPD‐L1×αCD3 BiTExos actively redirected T cells to bind to PD‐L1+ tumor cells, promoting T‐cell activation, proliferation and tumoricidal cytokine production. Furthermore, the αPD‐L1×αCD3 BiTExos promoted T‐cell infiltration into the tumor microenvironment to mitigate the tumor burden in vivo. Our study suggested that the LEAP scaffold may serve as a platform for EV surface display and could be applied for a broad range of EV‐based biomedical applications.

BackgroundDeviant peer affiliation is considered a potential risk factor for adolescent delinquency. Due to the serious situation of adolescent delinquency in China, it is necessary to investigate the mechanisms by which adolescents associate with deviant peers.ObjectivesThe purpose of this study was to examine the association between adverse childhood experiences (ACEs) and deviant peer affiliation, the mediating effect of relative deprivation, and the moderating effect of age in a sample of Chinese delinquent adolescents.MethodsFive hundred and forty-two Special School students aged 11–18 years were interviewed and completed questionnaires, including demographics, adverse childhood experiences, deviant peer affiliation, and relative deprivation.Results(1) After controlling for gender, adverse childhood experiences and deviant peer affiliation were significantly and positively associated among delinquent adolescents. (2) The effect of ACEs on deviant peer affiliation was mediated by relative deprivation. (3) Age played a moderating role not only in the relationship between ACEs and relative deprivation, but also in the indirect relationship in which ACEs influence deviant peer affiliation through relative deprivation; specifically, the indirect effect of ACEs influencing deviant peer affiliation through relative deprivation was stronger in early adolescence compared with late adolescence.ConclusionOverall, early ACEs play an important role in deviant peer affiliation among delinquent adolescents and relative deprivation is an important mediating variable. The results of the present study emphasize the importance of cognitive interventions for delinquent adolescents who experience ACEs in early adolescence, which may be instructive for the prevention of adolescent delinquency.

While encrypting information with color images, most encryption schemes treat color images as three different grayscale planes and encrypt each plane individually. These algorithms produce more duplicated operations and are less efficient because they do not properly account for the link between the various planes of color images. In addressing the issue, we propose a scheme that thoroughly takes into account the relationship between pixels across different planes in color images. First, we introduce a new 1D chaotic system. The performance analysis shows the system has good chaotic randomness. Next, we employ a shortest-path cross-plane scrambling algorithm that utilizes an enhanced Dijkstra algorithm. This algorithm effectively shuffles pixels randomly within each channel of a color image. To accomplish cross-plane diffusion, our approach is then integrated into the adaptive diffusion algorithm. The security analysis and simulation results demonstrate that the approach can tackle the issue of picture loss in telemedicine by encrypting color images without any loss of quality. Furthermore, the images we utilize are suitable for both standard RGB and medical images. They incorporate more secure and highly sensitive keys, robustly withstanding various typical ciphertext analysis attacks. This ensures a reliable solution for encrypting original images.

Aims The Care Quality Commission report (Smiling matters: oral health care in care homes) showed that too many people living in care homes were not being supported to maintain and improve their oral health. Lime Tree Garden is a purpose-built care home for up to 24 adults with mental health needs supporting people with enduring mental health illness to develop basic life skills so they can live supported in the community. This is a quality improvement project aiming to improve oral health and to reduce the burden of oral diseases in people with mental disorders and ensure timely access to dental treatment in Lime Tree Gardens through meeting the NICE quality standards of care. Methods Auditing current implementing status of oral health procedures in place and comparing with NICE guidelines and quality standards: 1) Adults who move into a care home have their mouth care needs assessed on admission; 2) Adults living in care homes have their mouth care needs recorded in their personal care plan; 3) Adults living in care homes are supported to clean their teeth twice a day and to carry out daily care for their dentures. For each patient, their dental care plan is recorded and compared with NICE guideline. Results There are challenges and space for improvement while implementing Oral health toolkit for adults in care homes at Lime Tree Gardens. A significant amount of patients (>90%) have unmet needs in terms having oral health. Conclusion There is a need to address the dental health challenges in this vulnerable population with recurrent and enduring mental illness. It is important to integrate and highlight dental health, as an important part of physical heath into the overall medical management of patients with severe mental illness in residential rehabilitation psychiatry.

Abstract The chemical transformation of waste polymers into value-added chemicals is of significance for circular economy and sustainable development. Herein, we report upcycling poly(succinates) (PSS) with amines into N-substituted succinimides over succinimide anion-based ionic liquids (ILs, e.g, 1,8-diazabicyclo[5.4.0]undec-7-ene succinimide, [HDBU][Suc]). Assisted with H2O, [HDBU][Suc]) showed the best performance, which could achieve complete transformation of a series of PSS into succinimide derivatives and corresponding diols under mild and metal-free conditions. Mechanism investigation indicates that the cation-anion confined hydrogen-bonding interactions among IL, H2O, ester group, and amino/amide groups, strengthens nucleophilicity of the N atoms in amino/amide groups, and improves electrophilicity of carbonyl C atom in ester group. The attack of the amino/amide N atom on carbonyl C of ester group results in cleavage of carbonyl C-O bond in polyester and formation of amide group. This strategy is also effective for aminolysis of poly(trimethylene glutarate) to glutarimides, and poly(1,4-butylene adipate) to caprolactone diimides.

Abstract Objective Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end‐products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)‐AGEage (SAF‐AGEs × age/100) with ELC. Methods This cross‐sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF‐AGEs). SAF‐AGEage was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes. Results The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC‐positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF‐AGEage and ELC (odds ratio [OR] 1.526, 95% CI 1.324–1.759; OR 2.072, CI 1.791–2.396; and OR 2.983, CI 2.551–3.489) for the multivariate‐adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF‐AGEage and ELC. Conclusion ELC is associated with coronary heart disease, and the SAF‐AGE has a potential role in ELC development in elder people.

Abstract Objective To analyze the abundance of infiltrating tumor immune cells in patients with oral squamous cell carcinoma (OSCC) and to search for potential targets that can predict patient prognosis. Methods A total of 400 samples from 210 patients with OSCC were collected using The Cancer Genome Atlas (TCGA) database. CIBERSORTx was used to evaluate the infiltration abundance of tumor immune cells. Potential target genes were searched to predict patient prognosis through case grouping, differential analysis, and enrichment analysis. Surgical excisional tissue sections of patients with oral squamous cell carcinoma admitted to the Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Shantou University Medical College, from 2015 to 2018 were collected and followed up. Results The CIBERSORTx deconvolution algorithm was used to analyze the infiltration abundance of immune cells in the samples. Cases with a high infiltration abundance of naive and memory B lymphocytes improved the prognosis of OSCC patients. The prognosis of patients with low CD79A expression was significantly better than that of patients with high CD79A expression. Conclusion CD79A can predict the infiltration abundance of B lymphocytes in the tumor microenvironment of patients with OSCC. CD79A is a potential target for predicting the prognosis of patients with OSCC. This study provides novel ideas for the treatment of OSCC and for predicting patient prognosis.

Abstract Background We established a MSBOS for flap reconstruction in oral and maxillofacial cancer patients. Method We enrolled 2080 cases of oral and maxillofacial flap reconstruction from January 1, 2010 to December 31, 2021. Patient data were collected, including age, sex, BMI, preoperative Hb levels, ASA grade, T stage, flap type, tumor location, and bone flap. Scoring criteria were established based on a multivariate model of independent risk variables and their odds ratios. Two flap-type groups were divided into low-risk, intermediate-risk and high-risk groups by the scoring criteria, and analyzed using univariate and multivariate logistic regression. Perioperative transfusion analysis identified independent risk factors at various Hb levels. The cumulative percentage of patients requiring perioperative blood transfusion for each surgical procedure was calculated to establish the MSBOS. Results (1) Regression analysis showed that BMI, tumor T staging, ASA grade, preoperative Hb level (male: Hb

Abstract Background To assess the contributing risk factors for the progression of, and the postoperative poor prognosis associated with, osteoradionecrosis of jaw (ORNJ) following non-nasopharyngeal cancer treatment in head and neck. Methods A retrospective study of 124 non-nasopharyngeal carcinoma patients in head and neck treated at one institution between 2001 and 2020 was conducted. A cumulative meta-analysis was conducted according to PRISMA protocol and the electronic search was performed on the following search engines: PubMed, Embase, and Web of Science. After assessing surgery with jaw lesions as a risk factor for the occurrence of ORNJ, 124 cases were categorized into two groups according to the “BS” classification, after which jaw lesions, chemotherapy, flap reconstruction and onset time of ORNJ were analyzed through the chi-square test and t-test to demonstrate the potential association between them and the progression of ORNJ. Postoperative outcomes of wound healing, occlusal disorders, and nerve injury were statistically analyzed. Results With the statistically significant results of the meta-analysis (odds ratio = 3.07, 95% CI: 1.84–5.13, p

Abstract GSDMD is the key effector of pyroptosis, but its non-pyroptosis-related functions have seldom been reported. Here, we report that GSDMD is overexpressed in different types of tumours, including head and neck squamous-cell carcinoma, and it promotes the sensitivity of tumour cells to cisplatin. Unexpectedly, the enhanced cisplatin sensitivity is mediated by apoptosis but not pyroptosis, the well-known function of GSDMD. Furthermore, we found that GSDMD can activate the unfolded protein response by promoting the phosphorylation of eIF2α. Mechanistically, we demonstrated that GSDMD can directly bind to eIF2α and enhance the interaction between eIF2α and its upstream kinase PERK, leading to eIF2α phosphorylation. Consequently, the protein levels of ATF-4 were upregulated, downstream apoptosis-related proteins such as CHOP were activated, and apoptosis was induced. Remarkably, activation of endoplasmic-reticulum (ER) stress induced by GSDMD promotes cell apoptosis during cisplatin chemotherapy, thereby increasing the treatment sensitivity of tumours. Therefore, for the first time, our work reveals an unreported nonpyroptotic function of the classic pyroptosis protein GSDMD: it promotes cell apoptosis during cisplatin chemotherapy by inducing eIF2α phosphorylation and ER stress, which are related to the drug sensitivity of tumours. Our study also indicated that GSDMD might serve as a biomarker for cisplatin sensitivity.

BackgroundCastleman Disease (CD) is a group of diseases with characteristic lymph node histopathology, characterized by marked enlargement of deep or superficial lymph nodes. Adrenal CD is rarely reported, and an accurate preoperative diagnosis of adrenal CD is difficult.MethodWe report four cases of CD in the adrenal gland confirmed by pathology and review the characteristics of this rare disease, highlighting the necessity of diagnostic evaluation and follow-up of the patients.ResultsAll of the patients sought medical advice because of adrenal incidentalomas. No significant abnormalities were presented in the biochemistry or endocrine systems. The imaging suggested a moderate-to-large mass with uneven moderate contrast enhancement of the adrenal region, similar to a pheochromocytoma. All cases were misdiagnosed as pheochromocytomas before operation and finally confirmed by histopathology. Three cases were pathologically diagnosed as hyaline vascular CD, and one case was diagnosed as plasma cell CD. All the patients are alive without recurrence after a median follow-up of 8 years.ConclusionThe adrenal CD should be considered after excluding pheochromocytoma and malignancy in the adrenal region. The long-term prognosis of patients with complete resection of the mass is excellent.

Abstract Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the head and neck, and the prognosis of patients is poor due to chemotherapeutic resistance. Interestingly, patients with HNSCC induced by human papillomavirus (HPV) infection are more sensitive to chemotherapy and display a better prognosis than HPV‐negative patients. The biological relevance of HPV infection and the mechanism underlying chemosensitivity to cisplatin remain unknown. Herein, SERPINB3 is identified as an important target for regulation of cisplatin sensitivity by HPV‐E6/E7 in HNSCC. Downregulation of SERPINB3 inhibits cisplatin‐induced DNA damage repair and enhances the cytotoxicity of cisplatin. In detail, decreasing SERPINB3 expression reduces the USP1‐mediated deubiquitination of FANCD2–FANCI in the Fanconi anemia pathway, thereby interfering with cisplatin‐induced DNA interstrand crosslinks repair and further contributing to HNSCC cell apoptosis. To translate this finding, pH‐responsive nanoparticles are used to deliver SERPINB3 small interfering RNA in combination with cisplatin, and this treatment successfully reverses cisplatin chemotherapeutic resistance in a patient‐derived xenograft model from HPV‐negative HNSCC. Taken together, these findings suggest that targeting SERPINB3 based on HPV‐positive HNSCC is a potential strategy to overcome cisplatin resistance in HPV‐negative HNSCC and improves the prognosis of this disease.

Doxorubicin (DOX) is limited in clinical application because of its cardiotoxicity. Oxidative stress and apoptosis are crucial in DOX-induced cardiac injury. Dimethyl fumarate (DMF) is an FDA-approved oral drug with powerful effects to reduce oxidative stress and apoptosis through the Nrf2 pathway. This study was aimed to determine whether DMF can protect against DOX-induced cardiac injury. We used both neonatal rat cardiomyocytes (NRCMs) in vitro and DOX-induced cardiac toxicity in vivo to explore the effects of DMF. The results showed that DMF significantly improved cell viability and morphology in NRCMs. In addition, DMF alleviated DOX-induced cardiac injury in rats, as evidenced by decreased CK-MB, LDH levels, improved survival rates, cardiac function, and pathological changes. Moreover, DMF significantly inhibited cardiac oxidative stress by reducing MDA levels and increasing GSH, SOD, and GSH-px levels. And DMF also inhibited DOX-induced cardiac apoptosis by modulating Bax, Bcl-2 and cleaved caspase-3 expression. Moreover, DMF exerted its protective effects against DOX by promoting Nrf2 nuclear translocation, which activated its downstream antioxidant gene Hmox1. Silencing of Nrf2 attenuated the protective effects of DMF in NRCMs as manifested by increased intracellular oxidative stress, elevated apoptosis levels, and decreased cell viability. In addition, DMF showed no protective effects on the viability of DOX-treated tumor cells, which suggested that DMF does not interfere with the antitumor effect of DOX in vitro. In conclusion, our data confirmed that DMF alleviated DOX-induced cardiotoxicity by regulating oxidative stress and apoptosis through the Nrf2 pathway. DMF may serve as a new candidate to alleviate DOX-related cardiotoxicity in the future.

Cardiac fibrosis is an important pathological process in many diseases. Wdr5 catalyzes the trimethylation of lysine K4 on histone H3. The effects of Wdr5 on the cardiac fibrosis phenotype and the activation or transformation of cardiac fibroblasts were investigated by Ang-II-infused mice by osmotic mini-pump and isolated primary neonatal rat cardiac fibroblasts. We found that the Wdr5 expression and histone H3K4me3 modification were significantly increased in Ang-II-infused mice. By stimulating primary neonatal rat cardiac fibroblasts with Ang II, we detected that the expression of Wdr5 and H3K4me3 modification were also significantly increased. Two Wdr5-specific inhibitors, and the lentivirus that transfected Sh-Wdr5, were used to treat primary mouse cardiac fibroblasts, which not only inhibited the histone methylation by Wdr5 but also significantly reduced the activation and migration ability of Ang-II-treated fibroblasts. To explore its mechanism, we found that the inhibition of Wdr5 increased the expression of P53, P21. Cut&Tag-qPCR showed that the inhibition of Wdr5 significantly reduced the enrichment of H3K4me3 in the Mdm2 promoter region. For in vivo experiments, we finally proved that the Wdr5 inhibitor OICR9429 significantly reduced Ang-II-induced cardiac fibrosis and increased the expression of P21 in cardiac fibroblasts. Inhibition of Wdr5 may mediate cardiac fibroblast cycle arrest through the Mdm2/P53/P21 pathway and alleviate cardiac fibrosis.

The complexity of hydraulic fractures (HF) significantly affects the success of reservoir reconstruction. The existence of a bedding plane (BP) in shale impacts the extension of a fracture. For shale reservoirs, in order to investigate the interaction mechanisms of HF and BPs under the action of coupled stress-flow, we simulate the processes of hydraulic fracturing under different conditions, such as the stress difference, permeability coefficients, BP angles, BP spacing, and BP mechanical properties using the rock failure process analysis code (RFPA2D-Flow). Simulation results showed that HF spread outward around the borehole, while the permeability coefficient is uniformly distributed at the model without a BP or stress difference. The HF of the formation without a BP presented a pinnate distribution pattern, and the main direction of the extension is affected by both the ground stress and the permeability coefficient. When there is no stress difference in the model, the fracture extends along the direction of the larger permeability coefficient. In this study, the in situ stress has a greater influence on the extension direction of the main fracture when using the model with stress differences of 6 MPa. As the BP angle increases, the propagation of fractures gradually deviates from the BP direction. The initiation pressure and total breakdown pressure of the models at low permeability coefficients are higher than those under high permeability coefficients. In addition, the initiation pressure and total breakdown pressure of the models are also different. The larger the BP spacing, the higher the compressive strength of the BP, and a larger reduction ratio (the ratio of the strength parameters of the BP to the strength parameters of the matrix) leads to a smaller impact of the BP on fracture initiation and propagation. The elastic modulus has no effect on the failure mode of the model. When HF make contact with the BP, they tend to extend along the BP. Under the same in situ stress condition, the presence of a BP makes the morphology of HF more complex during the process of propagation, which makes it easier to achieve the purpose of stimulated reservoir volume (SRV) fracturing and increased production.

Background Activin receptor‐like kinase 4 (ALK4) is highly expressed in mammal heart. Atrial fibrillation (AF) is closely related to ventricular pressure overload. Because pressure overload increases atrial pressure and leads to atrial remodeling, it would be informative to know whether ALK4 exerts potential effects on atrial remodeling and AF vulnerability in a pressure‐overload model. Methods and Results Wild‐type littermates and ALK4+/− mice were subjected to abdominal aortic constriction or a sham operation. After 4 or 8 weeks, echocardiographic and hemodynamic measurements were performed, and inducibility of AF was tested. The hearts were divided into atria and ventricles and then were fixed in formalin for staining, or they were weighted and snap‐frozen for quantitative real‐time polymerase chain reaction and Western blot analysis. Compared with wild‐type littermates, ALK4+/− mice demonstrated a similar extent of atrial hypertrophy but significantly suppressed atrial fibrosis at 8 weeks post–abdominal aortic constriction. ALK4 haplodeficiency partially blocked abdominal aortic constriction–induced upregulation of monocyte chemotactic protein 1 and interleukin‐6, and the increased chemotaxin of macrophages. ALK4 haplodeficiency also blunted a reduction of connexin 40 and redistribution of connexin 43 from the intercalated disk to the lateral membranes, thereby improving localized conduction abnormalities. Meanwhile, ALK4 haplodeficiency inhibited abdominal aortic constriction–induced decreased INa, ICa‐L and IK1 densities as well as the accompanying action potential duration shortening. Mechanistically, ALK4 haploinsufficiency resulted in the suppression of Smad2/3 activity in this model. Conclusions Our results demonstrate that ALK4 haplodeficiency ameliorates atrial remodeling and vulnerability to AF in a pressure‐overload model through inactivation of the Smad2/3 pathway, suggesting that ALK4 might be a potential therapeutic target in combating pressure overload–induced AF.

The role of genetic abnormality of δ-sarcoglycan (δ-SG) gene in dilated (DCM) and hypertrophied (HCM) cardiomyopathy patients is still unfolding. In this study we first defined the promoter region and then searched for polymorphisms/mutations among the promoter, 5'-untranslated region, and the encoding exons in δ-SG gene in 104 Chinese patients with DCM, 145 with HCM, and 790 normal controls. Two novel polymorphisms were found, an 11 base-pair (bp) deletion (c.-100~-110; -) in the promoter region and a missense polymorphism of A848G resulting in p.Q283R in the highly conserved C-terminus. The prevalence of homozygous genotype -/- of c.-100~-110 was slightly higher in DCM (14.42%) and HCM patients (14.48%), as compared with normal controls (11.01%). The prevalence of genotype of 848A/G was significantly higher in DCM (6.73%; OR = 9.43; p = 0.0002), but not in HCM patients (1.38%; OR = 1.37; p = 0.62), as compared with controls (0.76%). Haplotype -_G consisting c.-100~-110 and A848G was associated with increased risk of DCM (OR = 17.27; 95%CI = 3.19-93.56; p = 0.001) but not associated with HCM (OR = 1.90; 95%CI = 0.38-9.55; p = 0.44). Co-occurrence of the genotypes -/- of c.-100~-110 and 848A/G was found in 5 patients with DCM (4.81%; OR = 39.85; p = 0.0001), none of HCM patients, and only 1 of the controls (0.13%). Both polymorphisms were also found in the Japanese population, but not in the Africans and Caucasians. C.-100~-110 resulted in a decrease of δ-SG promoter activity to 64±3% of the control level (p

The accumulation of single-stranded DNA-binding (SSB) proteins is essential for organisms and has various applications. However, no study has simultaneously and systematically compared the characteristics of SSB proteins. In addition, SSB proteins may bind RNA and play an unknown biological role in RNA metabolism. Here, we expressed a novel species of SSB protein derived from Thermococcus kodakarensis KOD1 (KOD), as well as SSB proteins from Thermus thermophilus (TTH), Escherichia coli, and Sulfolobus Solfataricus P2 (SSOB), abbreviated kod, tth, bl21, and ssob, respectively. These SSB proteins could bind ssDNA and viral RNA. bl21 resisted heat treatment for more than 9 h, Ssob and kod could withstand 95°C for 10 h and retain its ssDNA- and RNA-binding ability. Four SSB proteins promoted the specificity of the DNA polymerase in PCR-based 5- and 9-kb genome fragment amplification. kod also increased the amplification of a 13-kb PCR product, and SSB protein-bound RNA resisted Benzonase digestion. The SSB proteins could also enter the host cell bound to RNA, which resulted in modulation of viral RNA metabolism, particularly ssob and bl21.