ß-Terrecyclene synthase constructs the quadrane backbone in terrecyclic acid biosynthesis.

Quadrane sesquiterpenes featuring a distinctive tricyclic skeleton exhibit potent antimicrobial and anticancer activities. Although extensive studies have attempted to reveal the multistep carbocation rearrangement involved in the formation of the tricyclic quadrane scaffold, the exact biosynthetic pathway and chemical logic to generate the quadrane structure remains mysterious. Here we identified a novel sesquiterpene synthase that is capable of generating ß-terrecyclene possessing the quadrane scaffold and characterized the biosynthetic pathway of a representative fungal quadrane terrecyclic acid. Further mutagenesis coupled with isotopically sensitive branching studies of this ß-terrecyclene synthase provided insight into the mechanism involved in the formation of the quadrane scaffold.

Factors associated with smoking cessation in Chinese psychiatric professionals: A cross-sectional survey.

INTRODUCTION: Healthcare workers are integral to public smoking cessation; however, their own smoking behavior can create a significant obstacle to intervening in patients' cessation efforts. Conversely, their success in quitting can enhance their ability to support patients. Research on smoking behavior, particularly smoking cessation among Chinese psychiatric professionals is limited. This study addresses this gap by examining the factors associated with smoking cessation in this population, providing insights for targeted tobacco control policies. METHODS: A cross-sectional survey was conducted, targeting psychiatric professionals including psychiatrists and psychiatric nurses, in 41 tertiary psychiatric hospitals in China. From January to March 2021, a WeChat-based questionnaire was distributed to collect demographic, occupational, and health-behaviors (including smoking) data. Statistical analyses, including the chi-squared test and adjusted binary logistic regression analysis, were conducted to identify the factors associated with smoking cessation. RESULTS: Among the 12762 psychiatric professionals who participated in the survey, 11104 (87.0%) were non-smokers, 1196 (9.4%) were current smokers, and 462 (3.6%) were ex-smokers. Several factors were found to be associated with smoking cessation. Women had a higher prevalence of ex-smokers than men (AOR=1.88; 95% CI: 1.332-2.666, p<0.001). Compared to East China, the prevalence of ex-smokers among participants in Central and Northeast China was lower. Older age (≥50 years), higher level of education (Master's degree or higher), and non-drinkers, showed a higher likelihood of being ex-smokers. Notably, compared to current smokers, ex-smokers reported a lower prevalence of burnout (AOR=0.70; 95% CI: 0.552-0.892, p=0.004). CONCLUSIONS: Smoking cessation interventions or health promotion programs should also focus on gender, age, education level, region, alcohol use, and burnout to effectively address smoking cessation within this specific professional group.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

Changes of aqueous humor cytokine profiles of patients with high intraocular pressure after PPV for retinal detachment.

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It's essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV.

Effects of computerized cognitive training on functional brain networks in patients with vascular cognitive impairment and no dementia.

AIMS: Previous neuroimaging studies of vascular cognitive impairment, no dementia (VCIND), have reported functional alterations, but far less is known about the effects of cognitive training on functional connectivity (FC) of intrinsic connectivity networks (ICNs) and how they relate to intervention-related cognitive improvement. This study provides comprehensive research on the changes in intra- and inter-brain functional networks in patients with VCIND who received computerized cognitive training, with a focus on the underlying mechanisms and potential therapeutic strategies. METHODS: We prospectively collected 60 patients with VCIND who were randomly divided into the training group (N = 30) receiving computerized cognitive training and the control group (N = 30) receiving fixed cognitive training. Functional MRI scans and cognitive assessments were performed at baseline, at the 7-week training, and at the 6-month follow-up. Utilizing templates for ICNs, the study employed a linear mixed model to compare intra- and inter-network FC changes between the two groups. Pearson correlation was applied to calculate the relationship between FC and cognitive function. RESULTS: We found significantly decreased intra-network FC within the default mode network (DMN) following computerized cognitive training at Month 6 (p = 0.034), suggesting a potential loss of functional specialization. Computerized training led to increased functional coupling between the DMN and sensorimotor network (SMN) (p = 0.01) and between the language network (LN) and executive control network (ECN) at Month 6 (p < 0.001), indicating compensatory network adaptations in patients with VCIND. Notably, the intra-LN exhibited enhanced functional specialization after computerized cognitive training (p = 0.049), with significant FC increases among LN regions, which correlated with improvements in neuropsychological measures (p < 0.05), emphasizing the targeted impact of computerized cognitive training on language abilities. CONCLUSIONS: This study provides insights into neuroplasticity and adaptive changes resulting from cognitive training in patients with VCIND, with implications for potential therapeutic strategies.

The heart rate non-dipping pattern was associated with target organ damage in patients with chronic kidney disease.

PURPOSE: We performed the study to investigate the association between heart rate (HR) non-dipping pattern and target organ damage in patients with chronic kidney disease (CKD) and hypertension. METHODS: In this cross-sectional study, 447 patients with CKD and hypertension were enrolled. 24 h ambulatory blood pressure monitoring was conducted. Linear regression and logistic regression analysis were conducted to investigate the association between HR non-dipping pattern and target organ damage, including estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). RESULTS: Overall, 261 patients (58.4%) followed non-dipping patterns of HR. HR non-dipping pattern remained to be significantly associated with reduced eGFR (ß: -0.384; 95% CI: -0.719 to -0.050; p = 0.025) and the higher prevalence of CKD stages 4-5 (OR: 2.141; 95% CI: 1.153 to 3.977; p = 0.016). Meanwhile, HR non-dipping pattern was independently associated with LVMI (ß: 0.021; 95% CI: 0.000 to 0.041; p = 0.049) and LVH (OR: 1.78; 95% CI: 1.07 to 2.96; p = 0.027) after adjusting for confounding factors. CONCLUSIONS: HR non-dipping pattern was independently associated with impaired renal function and cardiac damage. Non-dipping HR deserves further attention and needs to be detected and treated during the management of CKD patients.

BoaBZR1.1 mediates brassinosteroid-induced carotenoid biosynthesis in Chinese kale.

Brassinazole resistant 1 (BZR1), a brassinosteroid (BR) signaling component, plays a pivotal role in regulating numerous specific developmental processes. Our study demonstrated that exogenous treatment with 2,4-epibrassinolide (EBR) significantly enhanced the accumulation of carotenoids and chlorophylls in Chinese kale (Brassica oleracea var. alboglabra). The underlying mechanism was deciphered through yeast one-hybrid (Y1H) and dual-luciferase (LUC) assays, whereby BoaBZR1.1 directly interacts with the promoters of BoaCRTISO and BoaPSY2, activating their expression. This effect was further validated through overexpression of BoaBZR1.1 in Chinese kale calli and plants, both of which exhibited increased carotenoid accumulation. Additionally, qPCR analysis unveiled upregulation of carotenoid and chlorophyll biosynthetic genes in the T1 generation of BoaBZR1.1-overexpressing plants. These findings underscored the significance of BoaBZR1.1-mediated BR signaling in regulating carotenoid accumulation in Chinese kale and suggested the potential for enhancing the nutritional quality of Chinese kale through genetic engineering of BoaBZR1.1.

Inoculation with Funneliformis mosseae promotes selenium accumulation and transformation in pepper (Capsicum annuum L.).

Selenium (Se) is one of the fifteen essential nutrients required by the human body. Mycorrhizal microorganisms play a crucial role in enhancing selenium availability in plants. However, limited research exists on the impact of arbuscular mycorrhizal fungi (AMF) on selenium accumulation and transport in pepper plants. This study employed a pot experiment to investigate the changes in pepper plant growth, selenium accumulation, and transformation following inoculation with AMF and varying concentrations of exogenous selenium. The results indicate that exogenous selenium application in pepper has dual effects. At low concentrations (≤8 mg L⁻1), it promotes growth and nutrient accumulation, whereas high concentrations (>16 mg L⁻1) inhibit these processes. AMF inoculation positively influences selenium accumulation and transport in peppers, significantly increasing yield per plant by 17.89%, vitamin C content by 67.36%, flavonoid content by 43.26%, capsaicin content by 14.82%, DPPH radical scavenging rate by 18.18%, and ABTS radical scavenging rate by 27.81%. Additionally, it significantly reduces selenocysteine methyltransferase (SMT) enzyme activity, while minimally affecting ATP sulfurylase (ATPS) and adenosyl sulfate reductase (APR) enzyme activities. The combined treatment of AMF and 8 mg L⁻1 exogenous selenium has been proven to be the most effective for selenium enrichment in peppers, offering new insights into utilizing exogenous selenium and AMF inoculation to enhance selenium content in peppers.

Phosphine-catalyzed (3+3) annulation of cinnamaldehyde-derived Morita-Baylis-Hillman carbonates with dinucleophiles.

The phosphine-catalyzed (3+3) annulation reaction of cinnamaldehyde-derived Morita-Baylis-Hillman (MBH) carbonates with 1,3-dicarbonyl compounds as dinucleophiles has been developed, giving hexahydrochromenone derivatives in high yields with moderate to good diastereoselectivities. The reaction worked through double conjugate addition of 1,3-dicarbonyl compounds to the phosphonium intermediates generated from the cinnamaldehyde-derived MBH carbonates.

Sum and difference frequency generation in a valley-photonic-crystal-like topological system.

Nonlinear sum frequency generation (SFG) and difference frequency generation (DFG) are fundamental methods to obtain new light sources for various applications. However, most of the on-chip SFG and DFG are based on conventional resonators, lacking robustness against fabrication defects. Here, we demonstrate topologically protected SFG and DFG in a second-order topological photonic system. The mechanism is based on the nonlinear interaction between three high-Q corner modes inside dual topological band gaps. The frequency matching condition for SFG and DFG is precisely satisfied by designing a valley-photonic-crystal-like topological system, which provides more freedoms to tune the corner modes. The topological SFG and DFG are achieved with high conversion efficiency, and the underlying topological physics is revealed. This work opens up avenues toward topologically protected nonlinear frequency conversion, and can find applications in the fields of on-chip single-photon detections and optical quantum memories with robustness against defects.

EEG decoding for effects of visual joint attention training on ASD patients with interpretable and lightweight convolutional neural network.

Visual joint attention, the ability to track gaze and recognize intent, plays a key role in the development of social and language skills in health humans, which is performed abnormally hard in autism spectrum disorder (ASD). The traditional convolutional neural network, EEGnet, is an effective model for decoding technology, but few studies have utilized this model to address attentional training in ASD patients. In this study, EEGNet was used to decode the P300 signal elicited by training and the saliency map method was used to visualize the cognitive properties of ASD patients during visual attention. The results showed that in the spatial distribution, the parietal lobe was the main region of classification contribution, especially for Pz electrode. In the temporal information, the time period from 300 to 500 ms produced the greatest contribution to the electroencephalogram (EEG) classification, especially around 300 ms. After training for ASD patients, the gradient contribution was significantly enhanced at 300 ms, which was effective only in social scenarios. Meanwhile, with the increase of joint attention training, the P300 latency of ASD patients gradually shifted forward in social scenarios, but this phenomenon was not obvious in non-social scenarios. Our results indicated that joint attention training could improve the cognitive ability and responsiveness of social characteristics in ASD patients.

Role of clinical and multidetector computed tomography (MDCT) features in the prediction of patients with intestinal lipoma developing intussusception.

Background: Intestinal lipoma is considered the most common benign tumor that causes intussusception. This retrospective case-control study aimed to present the clinical and multidetector computed tomography (MDCT) features between intestinal lipomas with and without intussusception and examine risk factors that predict intussusception caused by intestinal lipomas. Methods: We retrospectively analyzed 281 adult patients diagnosed with intestinal lipoma by radiologists using whole-abdominal MDCT between January 2015 and August 2022. Patients were divided into adult intussusception (AI) and non-AI groups based on MDCT images. Univariate logistic regression was performed to identify risk factors for intestinal lipoma-induced intussusception. Results: A total of 281 patients with intestinal lipomas were included in the study, with an average age of 68.0±11.3 years, and the male to female ratio was about 1:1.4. Among them, 24 patients developed lipoma-induced intussusception. Patients in the AI group presented with more abdominal pain (70.8% vs. 47.1%, P=0.03), nausea/vomiting (37.5% vs. 14.8%, P=0.009), hematochezia/melena (29.2% vs. 11.3%, P=0.02), and abdominal tenderness (66.7% vs. 24.9%, P<0.001). Lipomas were more common in the small bowel (224/281, 79.7%) than the large bowel (57/281, 20.3%). Lipomas in the AI group showed more heterogeneous hypodensity (41.7% vs. 15.6%, P=0.004), longer length (median, 2.2 vs. 1.2 cm, P<0.001), and larger volume (median, 4.1 vs. 0.6 cm3, P<0.001). In the univariate logistic regression, lipoma density [odds ratio (OR) =3.875, 95% confidence interval (CI): 1.609-9.331, P=0.003] and lipoma length (OR =3.216, 95% CI: 1.977-5.231, P<0.001) were risk factors for intestinal lipoma-induced intussusception. Conclusions: More patients in the AI group have digestive tract symptoms than those in the non-AI group. Lipoma density and length are risk factors for intussusception in patients with intestinal lipoma. In addition, the common site of intestinal lipoma may have changed from the colon to the small intestine.

Quantifying the impact of anthropogenic emissions and aquatic environmental impacts on sedimentary mercury variations in a typical urban river.

In urban and industrial regions, sedimentary mercury (Hg) serves as the crucial indicator for Hg pollution, posing potential risks to ecology and human health. The physicochemical processes of Hg in aquatic environments are influenced by various factors such as anthropogenic emissions and aquatic environmental impacts, making it challenging to quantify the drivers of total mercury (THg) variations. Here, we analyzed the spatiotemporal variations, quantified driving factors, and assessed accumulation risks of sedimentary THg from the mainstream of a typical urban river (Haihe River). THg in the urban region (37-3237 ng g-1) was significantly higher (t-test, p < 0.01) than in suburban (71-2317 ng g-1) and developing regions (156-916 ng g-1). The sedimentary THg in suburban and developing regions increased from 2003 to 2018, indicating the elevated atmospheric deposition of Hg. Together with the temperature, grain size of sediments, total organic carbon (TOC), the pH and salinity of water, 40 components of parent and substituted polycyclic aromatic hydrocarbons (PAHs) were first introduced to quantify the driver of sedimentary THg based on generalized additive model. Results showed that anthropogenic emissions, including three PAHs components (31%) and TOC (63%), accounted for 94% of sedimentary THg variations. The aquatic environmental impacts accounted for 5% of sedimentary THg variations. The geo-accumulation index of THg indicated moderate to heavy accumulation in the urban region. This study demonstrates that homologous pollutants such as PAHs can be used to trace sources and variations of Hg pollution, supporting their co-regulation as international conventions regulate pollutants.

Palladium-Catalyzed (4 + 1) Annulation of 4-Vinylbenzodioxinones with Sulfur Ylides: Diastereoselective Synthesis of Dihydrobenzofuran Derivatives.

Palladium-catalyzed (4 + 1) annulation of 4-vinylbenzodioxinones with sulfur ylides has been developed to afford various dihydrobenzofuran derivatives in moderate to high yields with excellent diastereoselectivities. The scale-up reaction and further derivations of the product worked well, demonstrating the application potential of the current reaction in organic synthesis.

Redox regulation of Ni hydroxides with controllable phase composition towards biomass-derived polyol electro-refinery.

Electrocatalytic refinery from biomass-derived glycerol (GLY) to formic acid (FA), one of the most promising candidates for green H2 carriers, has driven widespread attention for its sustainability. Herein, we fabricated a series of monolithic Ni hydroxide-based electrocatalysts by a facile and in situ electrochemical method through the manipulation of local pH near the electrode. The as-synthesized Ni(OH)2@NF-1.0 affords a low working potential of 1.36 VRHE to achieve 100% GLY conversion, 98.5% FA yield, 96.1% faradaic efficiency and ∼0.13 A cm-2 of current density. Its high efficiency on a wide range of polyol substrates further underscores the promise of sustainable electro-refinery. Through a combinatory analysis via H2 temperature-programmed reduction, cyclic voltammetry and in situ Raman spectroscopy, the precise regulation of synthetic potential was discovered to be highly essential to controlling the content, phase composition and redox properties of Ni hydroxides, which significantly determine the catalytic performance. Additionally, the 'adsorption-activation' mode of ortho-di-hydroxyl groups during the C-C bond cleavage of polyols was proposed based on a series of probe reactions. This work illuminates an advanced path for designing non-noble-metal-based catalysts to facilitate electrochemical biomass valorization.

Higher N-terminal pro-brain natriuretic peptide level at onset of peritoneal dialysis-related peritonitis is a risk factor for technique failure.

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.

A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis.

OBJECTIVE: To assess the validity of Xpert Tuberculosis Fingerstick score for monitoring treatment response and analyze factors influencing its performance. METHODS: 122 adults with pulmonary tuberculosis were recruited and stratified into three cohorts: Diabetic-drug-susceptible-TB (DM-TB), Non-diabetic-drug-susceptible-TB (NDM-TB) and Non-diabetic Multidrug-resistant TB (MDR-TB). Fingerstick blood specimens were tested at treatment initiation (M0) and the end of the first (M1), second (M2), and sixth month (M6) to generate a TB-score. RESULTS: The TB-score in all participants yielded an AUC of 0.707 (95% CI: 0.579-0.834) at M2 when its performance was evaluated against sputum culture conversion. In all non-diabetes patients, the AUC reached 0.88 (95% CI: 0.756-1.000) with an optimal cut-off value of 1.95 at which sensitivity was 90.0% (95% CI: 59.6-98.2%) and specificity was 81.3% (95% CI: 70.0-88.9%). The mean TB score was higher in patients with low bacterial loads (n = 31) than those with high bacterial loads (n = 91) at M0, M1, M2, and M6, and was higher in non-cavitary patients (n = 71) than those with cavitary lesions (n = 51) at M0, M1, and M2. CONCLUSION: Xpert TB-score shows promising predictive value for culture conversion in non-diabetic TB patients. Sputum bacterial load and lung cavitation status have an influence on the value of TB score.

Hedgehog signaling is required for larval muscle development and larval metamorphosis of the mussel Mytilus coruscus.

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.