lncRNA BREA2 promotes metastasis by disrupting the WWP2-mediated ubiquitination of Notch1.

Notch has been implicated in human cancers and is a putative therapeutic target. However, the regulation of Notch activation in the nucleus remains largely uncharacterized. Therefore, characterizing the detailed mechanisms governing Notch degradation will identify attractive strategies for treating Notch-activated cancers. Here, we report that the long noncoding RNA (lncRNA) BREA2 drives breast cancer metastasis by stabilizing the Notch1 intracellular domain (NICD1). Moreover, we reveal WW domain containing E3 ubiquitin protein ligase 2 (WWP2) as an E3 ligase for NICD1 at K1821 and a suppressor of breast cancer metastasis. Mechanistically, BREA2 impairs WWP2-NICD1 complex formation and in turn stabilizes NICD1, leading to Notch signaling activation and lung metastasis. BREA2 loss sensitizes breast cancer cells to inhibition of Notch signaling and suppresses the growth of breast cancer patient-derived xenograft tumors, highlighting its therapeutic potential in breast cancer. Taken together, these results reveal the lncRNA BREA2 as a putative regulator of Notch signaling and an oncogenic player driving breast cancer metastasis.

Ruddlesden-Popper Perovskite Nanocrystals as Interface Modification Layer for Efficient Perovskite Solar Cells.

Perovskite nanocrystals are advantageous for interfacial passivation of perovskite solar cells (PSCs), but the insulating long alkyl chain surface ligands impede the charge transfer, while the conventional ligand exchange would possibly introduce surface defects to the nanocrystals. In this work, we reported novel in situ modification of CsPbBr3 nanocrystals using a short chain conjugated molecule 2-methoxyphenylethylammonium iodide (2-MeO-PEAI) for interfacial passivation of PSCs. Transmission electron microscopy studies with atomic resolution unveil the transformation from cubic CsPbBr3 to Ruddlesden-Popper phase (RPP) nanocrystals due to halogen exchange. Synergic passivation by the RPP nanocrystals and 2-MeO-PEA+ has led to suppressed interface defects and enhanced charge carrier transport. Consequently, PSCs with in situ modified RPP nanocrystals achieved a champion power conversion efficiency of 24.39%, along with an improvement in stability. This work brings insights into the microstructural evolution of perovskite nanocrystals, providing a novel and feasible approach for interfacial passivation of PSCs.

Unraveling the pH-Dependent Oxygen Reduction Performance on Single-Atom Catalysts: From Single- to Dual-Sabatier Optima.

Metal-nitrogen-carbon (M-N-C) single-atom catalysts (SACs) have emerged as a potential substitute for the costly platinum-group catalysts in oxygen reduction reaction (ORR). However, several critical aspects of M-N-C SACs in ORR remain poorly understood, including their pH-dependent activity, selectivity for 2- or 4-electron transfer pathways, and the identification of the rate-determining steps. Herein, by analyzing >100 M-N-C structures and >2000 sets of energetics, we unveil a pH-dependent evolution in ORR activity volcanos─from a single peak in alkaline media to a double peak in acids. We found that this pH-dependent behavior in M-N-C catalysts fundamentally stems from their moderate dipole moments and polarizability for O* and HOO* adsorbates, as well as unique scaling relations among ORR adsorbates. To validate our theoretical discovery, we synthesized a series of molecular M-N-C catalysts, each characterized by well-defined atomic coordination environments. Impressively, the experiments matched our theoretical predictions on kinetic current, Tafel slope, and turnover frequency in both acidic and alkaline environments. These new insights also refine the famous Sabatier principle by emphasizing the need to avoid an "acid trap" while designing M-N-C catalysts for ORR or any other pH-dependent electrochemical applications.

Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.

Heterotopic ossification (HO) is a pathological process in which ectopic bone develops in soft tissues within the skeletal system. Endochondral ossification can be divided into the following types of acquired and inherited ossification: traumatic HO (tHO) and fibrodysplasia ossificans progressiva (FOP). Nuclear transcription factor kappa B (NF-κB) signalling is essential during HO. NF-κB signalling can drive initial inflammation through interactions with the NOD-like receptor protein 3 (NLRP3) inflammasome, Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK). In the chondrogenesis stage, NF-κB signalling can promote chondrogenesis through interactions with mechanistic target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/AKT (protein kinase B, PKB) and other molecules, including R-spondin 2 (Rspo2) and SRY-box 9 (Sox9). NF-κB expression can modulate osteoblast differentiation by upregulating secreted protein acidic and rich in cysteine (SPARC) and interacting with mTOR signalling, bone morphogenetic protein (BMP) signalling or integrin-mediated signalling under stretch stimulation in the final osteogenic stage. In FOP, mutated ACVR1-induced NF-κB signalling exacerbates inflammation in macrophages and can promote chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs) through interactions with smad signalling and mTOR signalling. This review summarizes the molecular mechanism of NF-κB signalling during HO and highlights potential therapeutics for treating HO.

Comparative Efficacy and Safety of Measures for the Treatment of Adults with Isolated Calf Muscular Vein Thrombosis: A Systematic Review and Network Meta-analysis.

BACKGROUND: Isolated calf muscular vein thrombosis (ICMVT) can result in pulmonary embolism, but the treatment of ICMVT remains controversial. Therefore, the purpose of the present study was to investigate the optimal treatment for the ICMVT by comparing the efficacy and safety of different treatments. METHODS: A network meta-analysis was conducted to search for studies published from database inception to April 30, 2022, that compared the outcomes of 2 or more treatments for ICMVT. The primary outcomes were efficacy (resolution rate) and safety (adverse reactions). Data were extracted following predefined hierarchy and the Cochrane Collaboration risk of bias tool was used to evaluate the methodological quality of the included studies. We estimated summary odds ratios with 95% credibility intervals using Bayesian network meta-analysis with random effects. RESULTS: A total of 16 studies were enrolled in the study. In terms of efficacy and safety, urokinase thrombolysis combined with low-molecular-weight heparin (LMWH) was most effective but had the lowest safety, while physical therapy was safest but had the lowest efficacy. More important, direct oral factor Xa inhibitors were most likely to be second most effective and safe compared with other treatments. For the duration of treatment, anticoagulant therapy for at least 3 months could effectively increase the resolution rate of ICMVT. CONCLUSIONS: Considering both efficacy and safety, taking direct oral factor Xa inhibitors for at least 3 months was the optimal treatment compared to LMWH, urokinase thrombolysis combined LMWH, physical therapy and warfarin for patients with ICMVT.

Fusobacterium nucleatum upregulates MMP7 to promote metastasis-related characteristics of colorectal cancer cell via activating MAPK(JNK)-AP1 axis.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignant tumor. Fusobacterium nucleatum (F. nucleatum) is overabundant in CRC and associated with metastasis, but the role of F. nucleatum in CRC cell migration and metastasis has not been fully elucidated. METHODS: Differential gene analysis, protein-protein interaction, robust rank aggregation analysis, functional enrichment analysis, and gene set variation analysis were used to figure out the potential vital genes and biological functions affected by F. nucleatum infection. The 16S rDNA sequencing and q-PCR were used to detect the abundance of F. nucleatum in tissues and stools. Then, we assessed the effect of F. nucleatum on CRC cell migration by wound healing and transwell assays, and confirmed the role of Matrix metalloproteinase 7 (MMP7) induced by F. nucleatum in cell migration. Furthermore, we dissected the mechanisms involved in F. nucleatum induced MMP7 expression. We also investigated the MMP7 expression in clinical samples and its correlation with prognosis in CRC patients. Finally, we screened out potential small molecular drugs that targeted MMP7 using the HERB database and molecular docking. RESULTS: F. nucleatum infection altered the gene expression profile and affected immune response, inflammation, biosynthesis, metabolism, adhesion and motility related biological functions in CRC. F. nucleatum was enriched in CRC and promoted the migration of CRC cell by upregulating MMP7 in vitro. MMP7 expression induced by F. nucleatum infection was mediated by the MAPK(JNK)-AP1 axis. MMP7 was highly expressed in CRC and correlated with CMS4 and poor clinical prognosis. Small molecular drugs such as δ-tocotrienol, 3,4-benzopyrene, tea polyphenols, and gallic catechin served as potential targeted therapeutic drugs for F. nucleatum induced MMP7 in CRC. CONCLUSIONS: Our study showed that F. nucleatum promoted metastasis-related characteristics of CRC cell by upregulating MMP7 via MAPK(JNK)-AP1 axis. F. nucleatum and MMP7 may serve as potential therapeutic targets for repressing CRC advance and metastasis.

Incidence and association of seizures in stroke patients following endovascular treatment: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Post-stroke seizures (PSSs) are some of the most common complications of stroke and are associated with poor outcomes in patients. Endovascular treatment (EVT) is the standard of care for patients with acute ischaemic stroke related large-vessel occlusion. However, whether EVT increases the risk of PSSs remains controversial; the association between PSSs and EVT is poorly understood. METHODS: PubMed, Embase and the Cochrane Library were searched for relevant studies published from 1995 to 6 December 2021. The overall incidence of PSSs in patients treated with EVT and the separate incidence for all included studies in each subgroup, stratified by the type of treatment or time of onset, were calculated. The pooled odds ratio and confidence interval were calculated to quantify the effects of EVT on PSS occurrence. RESULTS: In all, 946 studies were screened and 16 articles were included, with a total sample size of 12,664 patients; 7836 patients received EVT, of whom 460 had PSS. The pooled incidence of PSS after EVT was 5.8%, which was similar to patients treated with mechanical thrombectomy (5.3%), intra-arterial thrombolysis (6.8%) or bridging therapy (5.4%). The cumulative incidence of post-stroke epilepsy (6.0%) was almost twice that of acute symptomatic seizures (3.6%). The pooled odds ratio for the relationship between EVT and PSS was 1.91 (95% confidence interval 0.98-3.73). CONCLUSIONS: The cumulative incidence of stroke patients treated with EVT who developed seizures was 5.8%, and EVT was non-significantly associated with the occurrence of seizures after stroke.

'Single-shot' pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy.

AIMS: Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath. METHODS AND RESULTS: A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury. CONCLUSION: This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.

Electrophysiological characteristics and long-term outcome of substrate-based catheter ablation for left posterior fascicular ventricular tachycardia targeting fragmented antegrade Purkinje potentials during sinus rhythm.

AIMS: The aim of this study was to investigate the electrophysiological characteristics and long-term outcome of patients undergoing substrate-based ablation of left posterior fascicular ventricular tachycardia (LPF-VT) guided by targeting of fragmented antegrade Purkinje potentials (FAPs) during sinus rhythm. METHODS AND RESULTS: This study retrospectively analysed 50 consecutive patients referred for ablation. Substrate mapping during sinus rhythm was performed to identify the FAP that was targeted by ablation. FAPs were recorded in 48 of 50 (96%) patients during sinus rhythm. The distribution of FAPs was located at the proximal segment of posterior septal left ventricle (LV) in two (4.2%) patients, middle segment in 33 (68.8%) patients, and distal segment in 13 (27.1%) patients. In 32 of 48 (66.7%) patients, the FAP displayed a continuous multicomponent fragmented electrogram, while a fragmented, split, and uncoupled electrogram was recorded in 16 (33.3%) patients. Entrainment attempts at FAP region were performed successfully in seven patients, demonstrating concealed fusion and the critical isthmus of LPF-VT. Catheter ablation targeting at the FAPs successfully terminated the LPF-VT in all 48 patients in whom they were seen. Left posterior fascicular (LPF) block occurred in four (8%) patients after ablation. During a median follow-up period of 61.2 ± 16.8 months, 47 of 50 (94%) patients remained free from recurrent LPF-VT. CONCLUSION: Ablation of LPF-VT targeting FAP during sinus rhythm results in excellent long-term clinical outcome. FAPs were commonly located at the middle segment of posterior septal LV. Region with FAPs during sinus rhythm was predictive of critical site for re-entry.

A prediction nomogram for deep venous thrombosis risk in patients undergoing primary total hip and knee arthroplasty: a retrospective study.

INTRODUCTION: Deep venous thrombosis (DVT) prediction after total hip and knee arthroplasty remains challenging. Early diagnosis and treatment of DVT are crucial. This research aimed to develop a nomogram for early DVT prediction. METHODS: A total of 317 patients undergoing primary total hip and knee arthroplasty in Sun Yat-sen Memorial Hospital were enrolled between May 2020 and September 2022. Data from May 2020 to February 2022 were used as the development datasets to build the nomogram model (n = 238). Using multivariate logistic regression, independent variables and a nomogram for predicting the occurrence of DVT were identified. Datasets used to validate the model for internal validation ranged from March 2022 to September 2022 (n = 79). The nomogram's capacity for prediction was also compared with the Caprini score. RESULTS: For both the development and validation datasets, DVT was found in a total of 38 (15.97%) and 9 patients (11.39%) on post-operative day 7 (pod7), respectively. 59.6% patients were symptomatic DVT (leg swelling). The multivariate analysis revealed that surgical site (Knee vs. Hip), leg swelling and thrombin-antithrombin complex (TAT) were associated with DVT. The previously indicated variables were used to build the nomogram, and for the development and validation datasets, respectively. In development and validation datasets, the area under the receiver operating characteristic curve was 0.836 and 0.957, respectively. In both datasets, the predictive value of the Nomogram is greater than the Caprini score. CONCLUSIONS: A proposed nomogram incorporating surgical site (Knee vs. Hip), leg swelling, and thrombin antithrombin complex (TAT) may facilitate the identification of patients who are more prone to develop DVT on pod7.

Comparison of Transcriptome between Tolerant and Susceptible Rice Cultivar Reveals Positive and Negative Regulators of Response to Rhizoctonia solani in Rice.

Rice (Oryza sativa L.) is one of the world's most crucial food crops, as it currently supports more than half of the world's population. However, the presence of sheath blight (SB) caused by Rhizoctonia solani has become a significant issue for rice agriculture. This disease is responsible for causing severe yield losses each year and is a threat to global food security. The breeding of SB-resistant rice varieties requires a thorough understanding of the molecular mechanisms involved and the exploration of immune genes in rice. To this end, we conducted a screening of rice cultivars for resistance to SB and compared the transcriptome based on RNA-seq between the most tolerant and susceptible cultivars. Our study revealed significant transcriptomic differences between the tolerant cultivar ZhengDao 22 (ZD) and the most susceptible cultivar XinZhi No.1 (XZ) in response to R. solani invasion. Specifically, the tolerant cultivar showed 7066 differentially expressed genes (DEGs), while the susceptible cultivar showed only 60 DEGs. In further analysis, we observed clear differences in gene category between up- and down-regulated expression of genes (uDEGs and dDEGs) based on Gene Ontology (GO) classes in response to infection in the tolerant cultivar ZD, and then identified uDEGs related to cell surface pattern recognition receptors, the Ca2+ ion signaling pathway, and the Mitogen-Activated Protein Kinase (MAPK) cascade that play a positive role against R. solani. In addition, DEGs of the jasmonic acid and ethylene signaling pathways were mainly positively regulated, whereas DEGs of the auxin signaling pathway were mainly negatively regulated. Transcription factors were involved in the immune response as either positive or negative regulators of the response to this pathogen. Furthermore, our results showed that chloroplasts play a crucial role and that reduced photosynthetic capacity is a critical feature of this response. The results of this research have important implications for better characterization of the molecular mechanism of SB resistance and for the development of resistant cultivars through molecular breeding methods.

Single-cell RNA sequencing reveals the cell types heterogenicity of human discoid lateral meniscus cells.

Discoid lateral meniscus (DLM) is more prone to injury than a normally shaped meniscus. No study has compared the gene expression and cell heterogeneity between discoid and normal menisci. We aimed to identify specific cell clusters and their marker genes in discoid meniscus, thereby providing a theoretical basis for the treatment and etiology of DLM. ScRNA-seq was used in DLM and osteoarthritis lateral meniscus (OAM) cells to identify cell subsets and their gene signatures. Pseudo-time analysis and immunohistochemical staining were used to investigate the temporal and spatial distribution of DLM-specific clusters. ScRNA-seq identified nine clusters originating from DLM and OAM, composed of seven empirically defined populations and two novel populations specific to DLM, namely, the prehypertrophic chondrocyte 2 (PreHTC-2) and regulatory chondrocyte (RegC-2) populations. Single-cell trajectory showed that RegC-2 and PreHTC-2 were mainly distributed in a specific cell fate, with the PreHTC-2 marker gene HAPLN1 highly expressed at the end of this fate. Immunohistochemical staining showed that HAPLN1 + cells were mainly distributed in the white zone of DLM. Matrix metalloproteinase (MMP) variants were expressed in DLM and OAM, with MMP2 highly expressed in OAM-dominant cell clusters, while MMP3 was highly expressed in DLM-dominant cell clusters. We concluded that two novel cell clusters including PreHTC-2 were identified using single-cell sequencing, which were mainly distributed in the white areas of DLM. Differentiated MMP expression in the trajectory may be a possible mechanism of DLM formation.

Prevalence of congenital heart disease among school children in Qinghai Province.

OBJECTIVES: This study aimed to investigate the prevalence of congenital heart disease (CHD) among school children in Qinghai province, a high-altitude region in China. METHODS: A cross-sectional study was conducted among school-aged children in 2019. All subjects completed a survey with a structure questionnaire and underwent CHD screening. CHD was screened by standard physical examination and further confirmed by echocardiography. Multivariate logistic regression were used to estimate the association of CHD prevalence with gender, nationality, and altitude. RESULTS: A total of 43,562 children aged 3-19 years participated in the study. The mean (SD) age was 11.2 (3.3) years. 49.7% were boys, and 80.0% were of Tibetan. CHD was identified in 293 children, with an overall prevalence of 6.73 ‰. Among them, 239 were unrecognized CHD, yielding a prevalence of 5.49 ‰. Atrial septal defect accounted for 51.9% of the CHD, followed by patent ductus arteriosus (31.1%), ventricular septal defect (9.9%). The CHD prevalence was significantly higher in female (8 ‰), Han race (18 ‰), children lived in Qumalai county (13 ‰), and children lived in a higher altitude (13 ‰). Female had greater prevalence of total CHD, atrial septal defect, and patent ductus arteriosus, but insignificant difference was observed in ventricular septal defect prvalence than male. In multivariable logistic regression analyses, female (OR, 1.48; 95% CI, 1.17-1.87, P = 0.001), Han population (OR, 3.28; 95% CI, 1.67-6.42, P = 0.001), and higher altitudes (OR, 2.28; 95% CI, 1.74-3.00, P < 0.001) were shown to be independently association with CHD prevalence. CONCLUSIONS: The prevalence of CHD in Qinghai province was 6.73 ‰. Altitude elevation, female, and Han population were independently association with CHD prevalence.

Thrombin antithrombin complex concentration as an early predictor of deep vein thrombosis after total hip arthroplasty and total knee arthroplasty.

AIM: Early predictive markers of venous thromboembolism (VTE) after total hip arthroplasty (THA)/total knee arthroplasty (TKA) remain unclear. Our study identified early predictive markers for VTE after THA/TKA. METHODS: A single-institution retrospective review study was conducted between May 2020 and April 2022 (n = 256). All patients underwent Doppler ultrasounds exam in preoperation and seventh day after surgery. Deep vein thrombosis (DVT) was defined by Doppler ultrasound of the lower extremities, which revealed thrombosis. Thrombin-antithrombin complex (TAT), thrombomodulin (TM), and plasmin-antiplasmin complex (PIC) concentration were tested from each patient's preoperative and postoperative days 1, 4, 7, 14. These values were then accessed via receiver operating characteristic (ROC) curve analysis and further quantified the level of this risk by concentration. RESULTS: On postoperative day 1 (pod-1), all patients' TAT and PIC concentrations were significantly higher than those preoperatively (p < 0.05). The levels of TAT and PIC in patients in the DVT group on pod-1 were significantly higher than those in the non-DVT group (p < 0.05). At pod-1, the TAT concentration for DVT patients was 49.47 ng/mL compared to 20.70 ng/mL for non-DVT patients, PIC was 3.72µg/mL compared to 1.65µg/mL. ROC curve analysis demonstrated that a TAT concentration of 24.3 ng/mL had a sensitivity of 87.9% and a specificity of 69.1%. CONCLUSION: TAT levels on pod-1 may predict DVT early after THA/TKA, which makes it possible for early intervention to decrease the incidence of DVT.

Applicability of Zipf's Law in Traditional Chinese Medicine Prescriptions.

Objective Traditional Chinese medicine (TCM) prescriptions have been used to cure diseases in China for thousands of years, in which many TCM herbs have no definite common quantity. Some key TCM herbs are commonly used and thus deserve in-depth investigations based on a more acceptable classification method. This study analyzes whether TCM prescriptions follow Zipf's law and attempts to obtain the thresholds of key TCM herbs based on the application of Zipf's law. Methods A total of 84,418 TCM prescriptions were collected and standardized. We tested whether Zipf's law and Zipf's distribution fit the Chinese herb distributions. A linear fitting experiment was performed to verify the relationship between the frequency distribution and frequency of TCM herbs. Results The distribution of TCM herbs in TCM prescriptions conformed to Zipf's law. Accordingly, the thresholds were obtained for the key TCM herbs. Conclusion The distribution of TCM herbs in TCM prescriptions follows Zipf's law.

[Effect of Nrf2/HO-1 signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis in mice].

The present study aimed to explore the effect of nuclear factor erythroid 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway in intestinal protection by Sishen Pills against ulcerative colitis(UC). After the UC model was induced by 3% dextran sodium sulfate(DSS), experimental animals were randomly divided into control group, model group, salazosulfapyridine(SASP) group, and low-and high-dose Sishen Pills groups. Drug intervention(ig) was performed for seven consecutive days during modeling. On the 7 th day, the mice were euthanized. The body weight and colon length were recorded, and the histopathological changes of the colon were observed by HE staining. Serum interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and reactive oxygen species(ROS) were detected by ELISA. The protein and mRNA expression of Nrf2, HO-1, and NADPH quinine oxidoreductase-1(NQO-1) was determined by Western blot and reverse transcription-polymerase chain reaction(RT-PCR). Compared with the normal group, the model group exhibited reduced body weight, colon length, and T-AOC, increased IL-6, TNF-α, MDA, and ROS, and diminished protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. Compared with the model group, the SASP group and high-dose Sishen Pills group showed elevated body weight, colon length, and T-AOC, lowered IL-6, TNF-α, MDA, and ROS levels, and increased protein and mRNA expression of Nrf2, HO-1, and NQO-1 in the colon tissues. As assessed by HE staining, Sishen Pills could improve the pathological changes of the colon. The findings suggested that Sishen Pills could protect the colon against UC induced by 3% DSS. The specific mechanism of action may be related to the anti-inflammatory and anti-oxidative stress effects by the activation of the Nrf2/HO-1 signaling pathway.

High hydrostatic pressure induces atrial electrical remodeling through angiotensin upregulation mediating FAK/Src pathway activation.

Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of ICa,L, Ito, and IKur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in ICa,L, upregulation of Ito and IKur, and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes.

Decapentaplegic function in wing vein development and wing morph transformation in brown planthopper, Nilaparvata lugens.

The decapentaplegic (dpp) gene plays a variety of roles in diverse cellular and molecular processes of the growth and development. In insects, dpp is mainly required for dorsal-ventral patterning and appendage formation. The brown planthopper (BPH) Nilaparvata lugens, a major pest of rice, possesses two distinct wing morphs described as long-winged (LW) and short-winged (SW) morphs. With our lab-maintained stable strains of LW and SW BPH, RNA interference (RNAi) was used to research the functions of N. lugens dpp (Nldpp) on wing development. Silencing of Nldpp in the SW strain led to the significant lengthening of the forewing, while Nldpp-knockdown in the LW strain resulted in distorted wings. Moreover, knockdown of Nldpp caused the complete absence of wing veins. During the development of wing-pads, the Nldpp abundance in the terga of the SW strain was significantly higher than that of the LW strain. Through controlling the direction of wing morph transformation, we found that the expression level of Nldpp increased in the NlInR1-knockdown BPH (tending to SW) and abundance of Nldpp declined after dsNlInR2 injection (tending to LW). Our results showed that Nldpp is mainly responsible for the formation and development of veins in BPH. Also, Nldpp can be regulated by NlInR1/2 and participate in the wing morph transformation.

Inability to capture with increasing current strength: Is this near-field or far-field?

We present a case of wide-complex tachycardia in which the clinical electrophysiological diagnosis was considered to be bundle branch re-entry ventricular tachycardia. A series of ventricular entrainment attempts were performed from the left and right ventricular septum to confirm the diagnosis. Entrainment pacing with a general current output (10 mA) was performed from the right ventricular septum with manifest fusion and a post-pacing interval similar to tachycardia cycle length. Thereafter, another entrainment attempt with a greater current output (20 mA) was performed from the same site. Paradoxically, concealed fusion was demonstrated by selective RB capture only, though there was no clear "RB" potential seen. In this case, we attempt to explain and illustrate the mechanism of paradoxical near-field inability to capture with increasing current strength.

High optical nonlinearity in low-dimensional halide perovskite polycrystalline films.

The nonlinear optical properties of low-dimensional polycrystalline halide perovskite films consisting of ethylammonium (EA) and butylammonium (BA) cations are investigated using Z-scan technique. Across the band-edge, two-dimensional (BA)2PbI4 exhibits a transition from saturable absorption (SA) to reverse-SA and its nonlinear absorption and nonlinear refractive index are much smaller than those of bulk counterparts. Meanwhile, EAPbI3 with one-dimensionality of the inorganic structure shows the SA behavior both above and below band-edge and the estimated nonlinear optical parameters of polycrystalline EAPbI3 are comparable to those of single-crystalline ones, attributed to high dielectric contrast between the inorganic and organic elements in one-dimensional structures.