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Introduction: Left bundle branch area pacing (LBBAP) is achieved by advancing the lead tip deep in the septum. Most LBBAP implants are performed using the Medtronic SelectSecure™ MRI SecureScan™ Model 3830 featuring a unique 4 Fr fixed helix lumenless design. Details of lead use conditions and long‐term reliability have not been reported. This study was designed to quantify the mechanical use conditions for the 3830 lead during and after LBBAP implant, and to evaluate reliability using bench testing and simulation. Methods: Fifty bradycardia patients with implantation of the 3830 lead for LBBAP were enrolled. Use conditions of lead deployment at implantation were collected and computed tomography (CT) scans were performed at 3‐month follow‐up. Curvature amplitude along the pacing lead was determined with CT images. Fatigue bending was performed using accelerated testing in a more severe environment than routine clinical use conditions. Conductor fracture rate in a simulated patient population was estimated based on clinical use conditions and fatigue test results. Results: The number of attempts to place the 3830 lead for LBBAP was 2.1 ± 1.3 (range: 1–7) with 13 ± 6 lead rotations at the final attempt. Extreme implant conditions were simulated in bench testing with 5 applications of 20 turns followed by up to 400 million bending cycles. Reliability modeling predicted a 10‐year fracture rate of 0.02%. Conclusions: LBBAP implants require more lead rotations than standard pacing implants and result in unique lead bending. Application of simulated LBBAP use conditions to the 3830 lead in an accelerated in‐vitro model does not produce excess conductor fractures. IMAGE‐LBBP Study ID of ClinicalTrial.GOV: NCT04119323. [ABSTRACT FROM AUTHOR]

Introduction: Left bundle branch area pacing (LBBAP) is a novel physiological pacing modality. The relationship between the pacing lead tip location and paced electrocardiographic (ECG) characteristics remains unclear. The objectives are to determine the lead tip location within the interventricular septum (IVS) and assess the location‐based ECG QRS duration (QRSd) and left ventricular activation time (LVAT). Methods: This multicenter study enrolled 50 consecutive bradycardia patients who met pacemaker therapy guidelines and received LBBAP implantation via the trans‐ventricular septal approach. After at least 3 months postimplant, 12‐lead ECGs and pacing parameters were obtained. Cardiac computed tomography (CT) imaging was performed to assess the LBBAP lead tip distance from the LV blood pool. Results: Among the 50 patients, analyzable CT images were obtained in 42. In 23 of the 42 patients, the lead tips were within 2 mm to the LV blood pool (the LV subendocardial (LVSE) group), 13 between 2 and 4 mm (the Near‐LVSE group), and the remaining 6 beyond 4 mm (the Mid‐LV septal (Mid‐LVS) group). No significant differences in paced QRSd were found among the three groups (LVSE, 107 ± 15 ms; Near‐LVSE, 106 ± 13 ms; Mid‐LVS, 104 ± 15 ms; p =.87). LVAT in the LVSE (64 ± 7 ms) was significantly shorter than in the Mid‐LVS (72 ± 8 ms; p <.05), but not significantly different from that in the Near‐LVSE (69 ± 8 ms; p >.05). Conclusion: In routine LBBAP practice, paced narrow QRSd and fast LVAT, indicative of physiological pacing, were consistently achieved for lead tip location in the LV subendocardial or near LV subendocardial region. [ABSTRACT FROM AUTHOR]

Introduction: Left bundle branch pacing (LBBP) is characterized with a low and stable pacing capture threshold, relatively narrow QRS duration due to fast left ventricular activation, and direct excitation of the diseased left bundle branch. This report aims to describe the methods, procedural skills, and clinical implications of performing LBBP implantation. Methods and Results: LBBP is achieved by transventricular‐septal approach. There are two methods to identify the location for LBBP lead placement: the single‐lead method and the dual‐lead method. During implantation, the unique transition of the paced QRS morphology and pacing parameter changes are important for guiding the lead ‐ advancement to the left side of the interventricular septum. In our experience, LBBP can be safely performed in most patients requiring pacemaker therapy. Conclusion: Clinical development of LBBP is at an early but encouraging phase with increasing clinical use, and a standardized procedure with improved delivery tools and pacing leads is needed, as well as long‐term efficacy and safety. [ABSTRACT FROM AUTHOR]

A 57‐year‐old male presented with symptomatic systolic heart failure and complete left bundle branch block (LBBB). Left bundle branch pacing corrected LBBB at a low capture threshold (0.5V @0.4ms) with right bundle branch conduction delay and paced QRS morphology changed to near‐normal by adjusting AV delay with diminished RBBD. At 1‐year follow‐up, the patient had a significant improvement in heart failure and LBBB automatically resolved with a rate‐dependent pattern. LBBP may be an alternative to conventional cardiac resynchronization therapy with the likelihood of recovery of LBBB. More research is needed to evaluate the potential use of this pacing strategy in patients with LBBB and heart failure. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the anatomical variations in femoral vasculature and evaluate the clinical value of ultrasound‐guided femoral vein puncture in catheter ablation procedures. Methods: In this retrospective analysis conducted from January 2023 to March 2023, we examined data from patients who underwent catheter ablation with ultrasound‐guided femoral venipuncture. We evaluated the anatomy of the femoral vasculature at both high and low inguinal levels. Based on the relationship between the femoral vein and artery, we classified the anatomy into four types: Type I (vein parallel to artery without overlap), Type II (vein medial to artery with lumen overlap ≤50%), Type III (vein posterior to artery with lumen overlap > 50%), and Type IV (vein lateral to artery). Additionally, we assessed procedure‐related vascular complications that required interventions or prolonged hospital stays. Results: A total of 254 patients were included in this study. At the upper inguinal level, most cases (92.5%) exhibited Type II, followed by Type I (6.5%), while Type III (0.6%) and IV (0.4%) were less common. At the lower inguinal level, Type II accounted for 70.7%, there was a significantly higher proportion of Type III (23.4%) and Type IV (5.9%). The overall complication rate was 0.4%, no pseudoaneurysm or hematoma was observed in our study. Conclusion: Our study revealed significant anatomical variations in the relationship between the femoral vein and femoral artery. Ultrasound‐guided femoral venipuncture significantly reduced vascular complication rate, making it a valuable tool for guiding puncture procedures. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article Clinical use conditions of lead deployment and simulated lead fracture rate in left bundle branch area pacing by Jiangang Zou MD et al., https://doi.org/10.1111/jce.15843. [ABSTRACT FROM AUTHOR]

Abstract: All lepidopteran baculovirus genomes sequenced encode a homolog of the Bombyx mori nucleopolyhedrovirus orf61 gene (Bm61). To determine the role of Bm61 in the baculoviral life cycle, we constructed a Bm61 knockout virus and characterized it in cells. We observed that the Bm61 deletion bacmid led to a defect in production of infectious budded virus (BV). Quantitative PCR analysis of BV in the media culturing the transfected cell indicated that BV was not produced due to Bm61 deletion. Electron microscope analysis showed that in the knockout of Bm61, nucleocapsids were not transported from the nucleus to the cytoplasm. From these results we concluded that BM61 is required in the BV pathway for the egress of nucleocapsids from the nucleus to the cytoplasm. [Copyright &y& Elsevier]

Uridine diphosphate (UDP)‐glycosyltransferases (UGTs) are important metabolizing enzymes functioning by adding a sugar moiety to a small lipophilic substrate molecule and play critical roles in drug/toxin metabolism for all realms of life. In this study, the silkworm Bombyx mori UGT33D1 gene was characterized in detail. UGT33D1 was found localized in the endoplasmic reticulum (ER) compartment just like other animal UGTs and was mainly expressed in the silkworm midgut. We first reported that UGT33D1 was important to BmNPV infection, as silencing UGT33D1 inhibited the BmNPV infection in silkworm BmN cells, while overexpressing the gene promoted viral infection. The molecular pathways regulated by UGT33D1 were analysed via transcriptome sequencing upon UGT33D1 knockdown, highlighting the important role of the gene in maintaining a balanced oxidoreductive state of the organism. In addition, proteins that physically interact with UGT33D1 were identified through immunoprecipitation and mass spectrometry analysis, which includes tubulin, elongation factor, certain ribosomal proteins, histone proteins and zinc finger proteins that had been previously reported for human UGT‐interacting proteins. This study provided preliminary but important functional information on UGT33D1 and is hoped to trigger deeper investigations into silkworm UGTs and their functional mechanisms. [ABSTRACT FROM AUTHOR]

Ribosomal protein L13 (RPL13) is highly conserved in evolution. At present, the properties and functions of RPL13 have not been characterised in insects. In this study, Bombyx mori RPL13 (BmRPL13) was first found to be specifically recruited to the sites of ultraviolet (UV)‐induced DNA damage and contributed to UV damage repair. Escherichia coli expressing BmRPL13 showed better resistance to UV radiation. After knocking down the expression of BmRPL13 in BmN cells, the repair speed of UV‐damaged DNA slowed down. The further results showed that BmRPL13 interacted with B. mori nucleopolyhedrovirus (BmNPV) ORF65 (Bm65) protein to locate at the UV‐induced DNA damage sites of BmNPV and helped repair UV‐damaged viral DNA. [ABSTRACT FROM AUTHOR]

Silk gland size in silkworms (Bombyx mori) affects silk output. However, the molecular mechanisms by which genes regulate silk gland size remain unclear. In this study, silk glands from three pure silkworm strains (A798, A306 and XH) with different silk gland weight phenotypes were compared using transcriptomics and proteomics to identify differentially expressed genes (DEGs) and proteins (DEPs). When comparing A798 to A306 and A798 to XH, 830 and 469 DEGs were up‐regulated, respectively. These genes were related to the gene ontology terms, metabolic process, transport activity and biosynthesis process. In addition, 372 and 302 up‐regulated differentially expressed proteins were detected in A798 to A306 and A798 to XH, respectively, related to the gene ontology terms, ribosome and protein export, ribosome and polypeptide biosynthesis processes. Moreover, combined transcriptomics, proteomics and weighted correlation network analyses showed that five genes (BGIBMGA002524, BGIBMGA002629, BGIBMGA005659, BGIBMGA005711 and BGIBMGA010889) were significantly associated with the silk gland weight. Reverse Transcription‐quantitative real‐time Polymerase Chain Reaction (RT‐qPCR) and Enzyme linked immunosorbent assay (ELISA) were used to verify the mRNA and protein expression of five genes in the silk glands and tissues of 18 silkworm strains. The results showed that four genes have higher expression levels in heavier silk glands. These genes are associated with glycogen metabolism, fatty acid synthesis and branched chain amino acid metabolism, thus potentially promoting growth and silk protein synthesis. These findings provide valuable insights into the molecular mechanisms underlying the relationship between silk gland weight and silk yield in silkworms. [ABSTRACT FROM AUTHOR]

Eukaryotic initiation factor 6 (eIF6) is necessary for ribosome biogenesis and translation, but eIF6 has been poorly elucidated in insects. Phylogenetic analysis demonstrated that eIF6 originated from one ancestral gene among animals and exhibited specific duplication in Tribolium, yielding three homologues in Tribolium castaneum, eIF6, eIF6‐like 1 (eIF6l1), and eIF6‐like 2 (eIF6l2). It was found that eIF6 was highly expressed in the embryonic and early adult stages, eIF6l1 had peak expression at the adult stage, and eIF6l2 showed peak expression in late adults of T. castaneum. Tissue‐specific analyses in late‐stage larvae demonstrated that eIF6 was abundantly expressed in all tissues, while eIF6l1 and eIF6l2 had the highest expression in the gut and the lowest expression in the head of T. castaneum. Knockdown of eIF6 caused precocious pupation and eclosion, impaired ovary and testis development and completely repressed egg production. The expression levels of vitellogenin 1 (Vg1), Vg2 and Vg receptor (VgR) significantly decreased in ds‐eIF6 females 5 days post‐adult emergence. Silencing eIF6 activated ecdysteroid biosynthesis and juvenile hormone degradation but reduced the activity of insulin signalling in T. castaneum, which might mediate its roles in metamorphosis, reproduction and gene expression regulation. However, silence of eIF6l1 or eIF6l2 had no effects on metamorphosis and reproduction in T. castaneum. This study provides comprehensive information for eIF6 evolution and function in the insect. [ABSTRACT FROM AUTHOR]

We previously observed an over‐dominant silkworm heterosis of increased yield in a cross of Bombyx mori nuclear polyhydrosis virus‐resistant strain NB with a susceptible strain 306. In the present study, we found that heterosis also exists in crosses of NB with other susceptible strains, indicating it is a more general phenomenon. We performed comparative transcriptome and proteome and identified 1624 differentially expressed genes (DEGs) and 298 differentially expressed proteins (DEPs) in silk glands between parents and F1 hybrids, of which 24 DEGs/DEPs showed consistent expression at mRNA and protein levels revealed by Venn joint analysis. Their expressions are completely non‐additive, mainly transgressive and under low‐parent, suggesting recombination of parental genomes may be the major genetic mechanism for the heterosis. GO and KEGG analyses revealed that they may function in generally similar but distinctive aspects of metabolisms and processes with signal transduction and translation being most affected. Notably, they may not only up‐regulate biosynthesis and transport of silk proteins but also down‐regulate other unrelated processes, synergistically and globally remodelling the silk gland to increase yield and cause the heterosis. Our findings contribute insights into the understanding of silkworm heterosis and silk gland development and provide targets for transgenic manipulation to further increase the silk yield. [ABSTRACT FROM AUTHOR]

The zona pellucida domain protein Dusky (Dy) plays a vital role in wing morphogenesis in insects, but little information on its function has been reported. In this study, we found that dy regulated wing cell size, larval and pupal duration, and the metabolism of amino acid and 20‐hydroxyecdysone in Tribolium castaneum. Using RNA‐seq, 413 differentially expressed genes were identified between physiological buffer‐injected and dy‐double‐stranded RNA‐treated larvae, including 88 downregulated genes and 325 upregulated genes. Among these genes, dy knockdown increased CYP18A1 expression to elevate the 26‐hydroxylation of 20‐hydroxyecdysone, which ultimately led to growth defects in wing cells. Silencing of dy upregulated the transcription of genes encoding tyrosine aminotransferase, 4‐hydroxyphenylpyruvate dioxygenase, homogentisate 1, 2‐dioxygenase, and Pale to promote the catabolism of tyrosine and phenylalanine, which eventually reduced amino acid content. Furthermore, dy knockdown upregulated 4E‐BP expression, and 4E‐BP silencing partially phenocopied dy RNA interference‐mediated wing morphogenesis. These results suggest that Dy controls 20‐hydroxyecdysone and amino acid metabolism to regulate wing morphogenesis in the insect. [ABSTRACT FROM AUTHOR]

Abstract: The silkworm Bombyx mori L., representing an important economic insect and one of the best models for studying insect immunity, possesses an efficient and sophisticated innate immune system against invasive microorganisms. The innate immune system basically includes humoural immunity and cellular immunity. The humoural immunity, which functions via molecules including humoural factors, lysozymes, phenoloxidase, hemolin, lectins and, in particular, antimicrobial peptides, plays a central role in eliminating the invading pathogens. The cellular immunity is primarily carried out and mediated by plasmatocytes and granular cells of haemocytes in the haemolymph, usually followed by melanization. Additionally, apoptosis, a primary viral defence for insects lacking adaptive immunity, comprises an important part of the silkworm immune system. Currently, there is still the lack of a comprehensive and systematic understanding of the molecular mechanisms of silkworm immunity. We review the latest research progress on silkworm immune mechanisms, including phenoloxidase‐dependent melanization and apoptosis, which is conducive to improving our understanding of the silkworm immune mechanism, clarifying the relationship of various immune mechanisms, and also providing a theoretical basis and reference for the future research of insect immunity. [ABSTRACT FROM AUTHOR]

Moderate exercise helps improve competition results, providing a balanced muscle tone and biochemical activity, whereas excessive training disrupts the balance between training and recovery, causes harm to the organism, and leads to overtraining syndrome (OTS). To explore the mechanisms of different protein expressions during training and acquisition of immunity, we used proteomic analyses to investigate the differences of liver-protein expressions between 2 swimming modes. Sprague-Dawley rats were randomly divided into control (CT), fatigue training (FT), and exhaustive training (ET) groups, and liver tissues from each group were subjected to 2-dimensional electrophoresis (2DE). A total of 4518 protein spots were detected in 9 replicates, and 45 protein spots exhibited a >2-fold difference in expression (P < .05), 31 of which was successfully identified by mass spectrometry. SERPINA3K expression decreased markedly during 2 stages from CT → FT and FT → ET, while DDT, RHOT1, and RBP4 decreased significantly only from CT → ET but not from the former 2 stages. By contrast, KRT8, PCBD1, KRT18, PRDX1, and ACY1A showed significant >2-fold increase in expression in either the CT → FT or FT → ET stages. Bioinformatic analyses showed that among the identified proteins, 30.2%, 54.18%, and 15.62% were involved in biological processes, molecular functions, and cell composition, respectively. Notably, PCBD1, PRDX1, and PPP1CB were involved in redox processes, while PPP1CB was only expressed in the FT group. RGN, PSMB9, and AGT, commonly recognized as oxidative stress biomarkers, may involve in regulating homeostasis in the locomotor mode and may provide diagnostic criteria for the occurrence and prevention of exercise-induced fatigue and OTS. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of micro RNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2 BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2 BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2 BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2 BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2 BP2 during skin wound healing. [ABSTRACT FROM AUTHOR]

Sclerotinia sclerotiorum causes a devastating disease in oilseed rape ( Brassica napus) resulting in a tremendous yield loss worldwide. Studies on various host-pathogen interactions have shown that plant WRKY transcription factors are essential for defence. For the B. napus- S. sclerotiorum interaction, little direct evidence has been found with regard to the biological roles of specific WRKY genes in host resistance. In this study, we isolated a B. napus WRKY gene, BnWRKY33, and found that the gene is highly responsive to S. sclerotiorum infection. Transgenic B. napus plants overexpressing BnWRKY33 showed markedly enhanced resistance to S. sclerotiorum, constitutive activation of the expression of BnPR1 and BnPDF1.2, and inhibition of H2O2 accumulation in response to pathogen infection. Further, we isolated a mitogen-activated protein ( MAP) kinase substrate gene, BnMKS1, and found that not only can BnWRKY33 interact with BnMKS1, which can also interact with BnMPK4, using the yeast two-hybrid assay, consistent with their collective nuclear localization, but also BnWRKY33, BnMKS1 and BnMPK4 are substantially and synergistically expressed in response to S. sclerotiorum infection. In contrast, the three genes showed differential expression in response to phytohormone treatments. Together, these results suggest that BnWRKY33 plays an important role in B. napus defence to S. sclerotiorum, which is most probably associated with the activation of the salicylic acid ( SA)- and jasmonic acid ( JA)-mediated defence response and inhibition of H2O2 accumulation, and we propose a potential mechanism in which BnMPK4- BnMKS1- BnWRKY33 exist in a nuclear localized complex to regulate resistance to S. sclerotiorum in oilseed rape. [ABSTRACT FROM AUTHOR]

Preventive Effectiveness of Implantable Cardioverter. Introduction: This prospective and multicenter trial of the implantable cardioverter-defibrillator (ICD) aimed to evaluate the mortality rate (including sudden cardiac death [SCD]) and the efficacy of ICD in Chinese patients with high risk of sudden death. Methods and Results : This trial was conducted in 31 centers in China. We enrolled 497 patients who fulfilled Class I indication for ICD (2002 ACC/AHA/NASPE guideline). All patients were followed-up at 3, 6, and 12 months. Clinical characteristics and echocardiographic parameters were collected at baseline and follow-up; Kaplan-Meier survival analysis was performed. Among 497 enrolled patients with Class I indication of ICD therapy, 112 (22.5%) agreed to and received ICD implantation (ICD group). The remaining 385 patients who were not available for ICD therapy were designated as the non-ICD group. During a mean follow-up of 11 ± 3 months, there were a total of 38 deaths, 2 in the ICD group with a mortality of 1.8% and 36 in the non-ICD group, with a mortality of 9.4% and 26 due to SCD. The overall survival rate was 93% at 3 months of follow-up, 91% at 6 months, and 89% at 12 months, with an incidence of SCD of 5%, 7%, and 8% at 3, 6, and 12 months, respectively. Conclusions : In patients with Class I indication of ICD implantation, the total mortality and incidence of SCD were high. ICD therapy can effectively reduce the mortality in such patients. (J Cardiovasc Electrophysiol, Vol. 23, pp. S5-S9, November 2012) [ABSTRACT FROM AUTHOR]

Background: Intracardiac non-contact mapping provides a rapid and accurate isopotential mapping that facilitates catheter ablation of the ventricular tachyarrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods: Thirty-two consecutive patients (26 men and 6 women, mean 37.2 ± 13.8 years) were treated with ablation. Fourteen patients had a history of syncope/pre-syncope. Two patients had an implantable cardiac defibrillator (ICD) previously implanted. Results: There were 67 ventricular tachycardias (VTs) induced in the 32 patients. The average VT rate was 210 ± 32.2 (130–310) bpm. There were 42 episodes of VT that had a heart rate ≥200 bpm and 24 of the 32 patients (75%) had ≥2 morphologies of VT. Regional ablation was applied by targeting the earliest VT activation sites under the guidance of non-contact mapping. Acute success was achieved in 84.4% (27/32) patients, and significant improvement was seen in 15.6% (5/32) patients as evidenced by a slower rate of VT. None of the patients experienced syncope/pre-syncope or sudden death during the 28.6 ± 16 (9–72) month follow-up. There were no complications of the procedure. At the end of follow-up, 81.3% of the patients were free of VT without medication while the rest of the patients achieved a modified success. Conclusions: The rapid ventricular tachyarrhythmias in ARVC patients can be abolished or improved significantly by regional RF catheter ablation under the guidance of non-contact mapping. There was no sudden cardiac arrest or death in those patients without ICD implantation. Delayed efficacy may occur in some patients after ablation. [ABSTRACT FROM AUTHOR]