Pseudorabies virus upregulates low-density lipoprotein receptors to facilitate viral entry.

Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease in pigs. The low-density lipoprotein receptor (LDLR) is a transcriptional target of the sterol-regulatory element-binding proteins (SREBPs) and participates in the uptake of LDL-derived cholesterol. However, the involvement of LDLR in PRV infection has not been well characterized. We observed an increased expression level of LDLR mRNA in PRV-infected 3D4/21, PK-15, HeLa, RAW264.7, and L929 cells. The LDLR protein level was also upregulated by PRV infection in PK-15 cells and in murine lung and brain. The treatment of cells with the SREBP inhibitor, fatostatin, or with SREBP2-specific small interfering RNA prevented the PRV-induced upregulation of LDLR expression as well as viral protein expression and progeny virus production. This suggested that PRV activated SREBPs to induce LDLR expression. Furthermore, interference in LDLR expression affected PRV proliferation, while LDLR overexpression promoted it. This indicated that LDLR was involved in PRV infection. The study also demonstrated that LDLR participated in PRV invasions. The overexpression of LDLR or inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR and targets it for lysosomal degradation, significantly enhanced PRV attachment and entry. Mechanistically, LDLR interacted with PRV on the plasma membrane, and pretreatment of cells with LDLR antibodies was able to neutralize viral entry. An in vivo study indicated that the treatment of mice with the PCSK9 inhibitor SBC-115076 promoted PRV proliferation. The data from the study indicate that PRV hijacks LDLR for viral entry through the activation of SREBPs.IMPORTANCEPseudorabies virus (PRV) is a herpesvirus that primarily manifests as fever, pruritus, and encephalomyelitis in various domestic and wild animals. Owing to its lifelong latent infection characteristics, PRV outbreaks have led to significant financial setbacks in the global pig industry. There is evidence that PRV variant strains can infect humans, thereby crossing the species barrier. Therefore, gaining deeper insights into PRV pathogenesis and developing updated strategies to contain its spread are critical. This study posits that the low-density lipoprotein receptor (LDLR) could be a co-receptor for PRV infection. Hence, strategies targeting LDLR may provide a promising avenue for the development of effective PRV vaccines and therapeutic interventions.

Pseudorabies virus hijacks the Rab6 protein to promote viral assembly and egress.

Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.

[Research Progress of Pleckstrin Homology Like Domain Family A Member 1 in Tumor].

Pleckstrin homology like domain family A member 1(PHLDA1) is also known as T-cell death-associated gene 51 (TDAG51).Studies have demonstrated that the abnormal expression of PHLDA1 is closely associated with the formation,development,and metastasis of tumors.We summarized the latest research advances in the structure and biological properties of PHLDA1,as well as the roles of PHLDA1 in multiple malignanttumors such as breast cancer,cancer,liver gastric cancer,liver cancer,melanoma,and osteosarcoma,aiming to comprehensively reveal the significance of PHLDA1 in the clinical diagnosis of tumors.

[An evaluation method for physical properties of medicinal film and its application in screening film formulation of Trillium tschonoskii total saponins].

At present, the evaluation methods for pharmaceutical properties of Chinese medicinal films have many problems, such as poor objectivity for the indexes and no quantitative and standardized evaluation methods. This study established a new method using three important physical property parameters, i.e., flow index, weight loss rate, and elongation rate, which were closely related to the pharmaceutical properties of films. On this basis, the above parameters were taken as indicators to optimize the film formulation of Trillium tschonoskii total saponins and verify the feasibility and suitability of the established method and parameters in formulation optimization. A self-made flow distance detection device and a viscometer were used to measure and characterize the fluidity, where the flow index refers to the ratio of the flow distance per unit time to the viscosity. The weight loss rate was measured by the 3 M transpore~(TM) surgical tape. The film-forming property was characterized by the weight loss rate of the sample within a certain period of time. An electronic tension machine was employed to measure the elongation rate after drying, which was used to characterize the ductility of the film. The results showed that the established method for the determination of flow index, weight loss rate, and elongation rate was stable and reliable. The optimal film formulation of T. tschonoskii total saponins could be obtained by optimization with those indicators. As demonstrated, the above evaluation indicators(flow index, weight loss rate, and elongation rate) can guide the optimization and design of formulation, and the new evaluation method constructed based on this shows a good application prospect in formulation optimization and formulation quality evaluation of medicinal films.

Dynamic Behavior Analysis and Stability Control of Tethered Satellite Formation Deployment.

In recent years, Tethered Space Systems (TSSs) have received significant attention in aerospace research as a result of their significant advantages: dexterousness, long life cycles and fuel-less engines. However, configurational conversion processes of tethered satellite formation systems in a complex space environment are essentially unstable. Due to their structural peculiarities and the special environment in outer space, TSS vibrations are easily produced. These types of vibrations are extremely harmful to spacecraft. Hence, the nonlinear dynamic behavior of systems based on a simplified rigid-rod tether model is analyzed in this paper. Two stability control laws for tether release rate and tether tension are proposed in order to control tether length variation. In addition, periodic stability of time-varying control systems after deployment is analyzed by using Floquet theory, and small parameter domains of systems in asymptotically stable states are obtained. Numerical simulations show that proposed tether tension controls can suppress in-plane and out-of-plane librations of rigid tethered satellites, while spacecraft and tether stability control goals can be achieved. Most importantly, this paper provides tether release rate and tether tension control laws for suppressing wide-ranging TSS vibrations that are valuable for improving TSS attitude control accuracy and performance, specifically for TSSs that are operating in low-eccentricity orbits.

Direct Depth SLAM: Sparse Geometric Feature Enhanced Direct Depth SLAM System for Low-Texture Environments.

This paper presents a real-time, robust and low-drift depth-only SLAM (simultaneous localization and mapping) method for depth cameras by utilizing both dense range flow and sparse geometry features from sequential depth images. The proposed method is mainly composed of three optimization layers, namely Direct Depth layer, ICP (iterative closet point) Refined layer and Graph Optimization layer. The Direct Depth layer uses a range flow constraint equation to solve the fast 6-DOF (six degrees of freedom) frame-to-frame pose estimation problem. Then, the ICP Refined layer is used to reduce the local drift by applying local map based motion estimation strategy. After that, we propose a loop closure detection algorithm by extracting and matching sparse geometric features and construct a pose graph for the purpose of global pose optimization. We evaluate the performance of our method using benchmark datasets and real scene data. Experiment results show that our front-end algorithm clearly over performs the classic methods and our back-end algorithm is robust to find loop closures and reduce the global drift.

Photodegradation of methylmercury in Jialing River of Chongqing, China.

Photodegradation (PD) of methylmercury (MMHg) is a key process of mercury (Hg) cycling in water systems, maintaining MMHg at a low level in water systems. However, we possess little knowledge of this important process in the Jialing River of Chongqing, China. In situ incubation experiments were thus performed to measure temporal patterns and influencing factors of MMHg PD in this river. The results showed that MMHg underwent a net demethylation process under solar radiation in the water column, which predominantly occurred in surface waters. For surface water, the highest PD rate constants were observed in spring (12×10(-3)±1.5×10(-3) m2/E), followed by summer (9.0×10(-3)±1.2×10(-3) m2/E), autumn (1.4×10(-3)±0.12×10(-3) m2/E), and winter (0.78×10(-3)±0.11×10(-3) m2/E). UV-A radiation (320-400 nm), UV-B radiation (280-320 nm), and photosynthetically active radiation (PAR, 400-700 nm) accounted for 43%-64%, 14%-31%, and 16%-45% of MMHg PD, respectively. PD rate constants varied substantially with the treatments that filtered the river water and amended it with chemicals (i.e., Cl-, NO3-, dissolved organic matter (DOM), Fe(III)), which reveals that suspended particulate matter and water components are important factors in affecting the PD process. For the entire water column, the PD rate constant determined for each wavelength range decreased rapidly with water depth. UV-A, UV-B, and PAR contributed 27%-46%, 6.2%-12%, and 42%-65% to the PD process, respectively. PD flux was estimated to be 4.7 µg/(m2·year) in the study site. Our results are very important to understand the cycling characteristics of MMHg in the Jialing River of Chongqing, China.

Characterization of flavor volatiles in raw and cooked pigmented onion (Allium cepa L) bulbs: A comparative HS-GC-IMS fingerprinting study.

Variations in volatile flavor components in pigmented onion bulbs (purple, white, and yellow) before and after cooking were characterized by headspace gas chromatography-ion migration spectrometry (HS-GC-IMS) to investigate their odor traits. Results showed that 39 and 45 volatile flavor compounds were identified from pigmented onion bulbs before and after cooking via the HS-GC-IMS fingerprinting, respectively. Sulfurs (accounting for 50.65%-63.42%), aldehydes (13.36%-22.11%), and alcohols (11.32%-17.94%) ranked the top three prevailing compound categories in all pigmented onions (both raw and cooked). Compared to the raw colored onion bulbs, the relative proportion of sulfurs in cooked onions decreased, whereas the relative proportion of alcohols, esters, pyrazines, and furans increased. Two reliable prediction models were established through orthogonal partial least squares-discriminant analysis (OPLS-DA), and 8 and 22 distinctive odor compounds were sieved out by variable importance in projection (VIP>1.0) as volatile labels, respectively. Both principal component analysis (PCA) and clustering heatmap exhibited favorable distinguishing effects for various pigmented onion bulbs before and after cooking. These results might offer insights into understanding the odor characteristics of different pigmented onions.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

AIM: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP). METHODS: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs). RESULTS: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE. However, oral nifedipine provided less RTATBP and NoD. CONCLUSION: Oral nifedipine was associated with less RTATBP and NoD and otherwise did not differ from intravenous labetalol.

Characterization of volatile organic compounds of different pigmented rice after puffing based on gas chromatography-ion migration spectrometry and chemometrics.

The distinctness in volatile profiles of pigmented rice with various colors (black, green, purple, red, and yellow) after puffing were assayed through gas chromatography-ion migration spectrometry (GC-IMS) to explore their odor characteristics. Fifty-two volatile components were found in those puffed rice, including 27 kinds of aldehydes (accounting for 59.69-64.37 %), 9 ketones (25.55-29.73 %), 5 alcohols (2.45-5.29 %), 4 pyrazines (1.38-2.36 %), 3 ethers (0.81-1.27 %), 2 furans (0.95-1.39 %), 1 pyridine (1.0-1,16 %), and 1 pyrrole (0.59-0.71 %). Aldehydes and ketones were the two chief volatiles in different pigmented puffed rice. These identified volatile flavor components in various pigmented puffed rice obtained by GC-IMS might be well differentiated by principal component and cluster interpretation. Meanwhile, a stable prediction model was fitted via orthogonal partial least squares-discriminant analysis, and 19 differentially volatile components were screened out based on variable importance projection (VIP) above 1. These findings could add certain information for understanding the flavor profiles of pigmented puffed rice and related products.

Characterization and discrimination of flavor volatiles of different colored wheat grains after cooking based on GC-IMS and chemometrics.

Changes in flavor volatiles of three colored wheat grains (black, green, and yellow) after cooking were detected via gas chromatography-ion migration spectrometry (GC-IMS) to explore corresponding volatile flavor traits. A total of 52 volatile chemicals were spotted among these cooked wheat grains, including 30 aldehydes (accounting for 73.86-83.78%), 11 ketones (9.53-16.98%), 3 alcohols (0.88-1.21%), 4 furans (4.82-7.44%), 2 esters (0.28-0.42%), and 2 pyrazines (0.18-0.32%). Aldehydes, ketones, and furans were the main volatile compounds in three different cooked wheat. For black-colored wheat, the relative contents of benzene acetaldehyde, benzaldehyde, 2-methyl butanal, and 3-methyl butanal were much higher (p < 0.05). For green-colored wheat, the relative contents of nonanal, 2-pentyl furan, (E)-hept-2-enal, 2-butanone, and acetone were significantly higher (p < 0.05). For yellow-colored wheat, the relative amounts of heptanal, hexanal, and pentanal were much higher (p < 0.05). The overall volatile substances of the three cooked wheat grains might be classified by GC-IMS data coupled with principal component analysis and heatmap clustering analysis. A reliable forecast set was established through orthogonal partial least squares-discriminant analysis (OPLS-DA), and 22 differential volatile compounds were screened out based on variable importance in projection (VIP) being higher than 1.0, as flavor markers for distinguishing the three cooked wheat grains. These results suggest that GC-IMS could be used for characterizing the flavor volatiles of different colored wheat, and the findings could contribute certain information for understand the aroma traits in different colored cooked wheat and related products in the future.

Uncovering the differences in flavor volatiles of different colored foxtail millets based on gas chromatography-ion migration spectrometry and chemometrics.

The differences of volatile organic compounds in commercially available foxtail millets with different colors (black, green, white and yellow) were assayed through gas chromatography-ion migration spectrometry (GC-IMS) to explore their volatile flavor characteristics. Fifty-five volatile components were found in various colored foxtail millets, including 25 kinds of aldehydes (accounting for 39.19-48.69%), 10 ketones (25.36-32.37%), 15 alcohols (20.19-24.11%), 2 ethers (2.29-2.45%), 2 furans (1.49-2.95%) and 1 ester (0.27-0.39%). Aldehydes, alcohols and ketones were the chief volatiles in different colored foxtail millet, followed by furans, esters and ethers. These identified volatile flavor components in various colored foxtail millets obtained by GC-IMS could be well distinguished by principal components and cluster analysis. Meanwhile, a stable prediction model was fitted via partial least squares-discriminant analysis (PLS-DA), in which 17 kinds of differentially volatile components were screened out based on variable importance in projection (VIP>1). These findings might provide certain information for understanding the flavor traits of colored foxtail millets in future.

Combined effects of microplastics and cadmium on the soil-plant system: Phytotoxicity, Cd accumulation and microbial activity.

Microplastics (MPs), an emerging pollutant of concern, widely cooccurred with heavy metals in soil, however, little is known about the combined effects of the interactions of MPs and cadmium (Cd) on the soil-plant system. In this study, the combined effects of several types of MPs and soil Cd contamination on Brassica juncea growth, Cd uptake, and soil microbial carbon metabolism were investigated in a 50-day pot experiment. Aged polyethylene (PE), aged polypropylene (PP), biodegradable polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA) displayed moderate phytotoxicity, with reductions in leaf chlorophyll content and shoot biomass. Compared with the control treatment without MPs or B. juncea, B. juncea growth significantly increased the soil pH by 0.3 pH units, and the growth of B. juncea in the presence of biodegradable PBAT or PLA MPs increased the soil pH by an additional 0.4 or 0.6 pH units, respectively. The presence of PBAT or PLA MPs greatly reduced soil diethylenetriamine pentaacetic acid (DTPA)-extractable Cd concentrations and plant Cd accumulation. The Cd bioconcentration factor was higher in roots than shoots in all treatments except the treatment containing PBAT MPs. The average well color development (AWCD), an indicator of metabolic activity, was highest in the treatment with B. juncea alone and was reduced by both biodegradable and conventional MPs. The microbial utilization efficiency of esters and alcohols was enhanced in the treatment with PBAT MPs, whereas carboxylic acids were preferentially utilized in the treatment with PLA MPs. These findings indicate that co-exposure to MPs and Cd may alter soil microenvironmental characteristics such as soil pH, leading to changes in Cd bioavailability, plant growth and Cd accumulation, and the microbial community's capacity to metabolize carbon. These effects of MPs in soil warrant further exploration.

Primary malignant melanoma of the cervix: A comprehensive analysis of case reports in the Chinese population.

PURPOSE: Malignant melanoma is a tumor generated from the basal melanocytes of human epidermis. Primary malignant melanoma of the cervix (PMMC) is derived from cervical melanocytes. It is an uncommon disease, mostly occurring in perimenopausal women. PMMC has a bad prognosis and lacks a defined protocol or treatment standards. The aim of this study was to analyze the impact of different surgical procedures and different adjuvant treatment modalities on their prognosis and to find risk factors for their prognosis by integrating published case report data based on the Chinese population. METHODS AND RESULTS: This study included 165 patients with PMMC in the Chinese population. We used the Kaplan-Meier method to build the survival curve, and the log-rank test to examine the variations among the subgroups. Prognostic factors were examined utilizing the Cox proportional hazards regression model. We found that patients who underwent radical hysterectomy-based surgery, those who underwent lymphadenectomy, and those who underwent other treatments in addition to surgery had significantly better survival rates. The overall analysis, showed that age, and FIGO Stage II, III, and IV, increased the risk of death. Moreover, radical hysterectomy (RH), total hysterectomy (TAH), lymphadenectomy, and adjuvant therapy were correlated with a decreased mortality risk. CONCLUSION: After summarizing the current data, we recommend radical hysterectomy, and lymphadenectomy treatment for patients with PMMC. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis; therefore patient-specific treatment options need to be further discussed.

A case report of delayed treatment of acute exertional osteofascial compartment syndrome in the anterior compartment of the calf.

RATIONALE: Acute exertional osteofascial compartment syndrome (OCS) is a rare cause of lower-leg pain and is often associated with delayed diagnosis, which can lead to irreversible muscle and nerve damage. PATIENT CONCERNS: A 23-year-old man presented with acute-onset anterior calf pain and ankle dorsiflexion after hiking. DIAGNOSIS: The patient's pain was initially diagnosed as muscle strain at a county hospital, but was eventually diagnosed as OCS at our hospital 8 days after the injury. This case presents several challenges in the diagnosis and treatment phases. INTERVENTIONS: Three surgeries were performed in total. On the day after admission (9 days after injury), fasciotomy was performed, followed by vacuum sealing drainage (VSD). Six days after the first surgery, necrotic muscle debridement was performed and VSD was reperformed. Ten days after the second surgery, the covering foam material was removed and the incision was sutured. OUTCOMES: Satisfactory postoperative results were achieved. The erythrocyte sedimentation rate, C-reactive protein level, and white blood cell count were within normal ranges. The skin healed well, and nerve damage and muscle strength improved significantly 3 months after surgery. LESSONS: OCS in the absence of trauma or fracture is rare, but treatment delays can have devastating consequences. Acute nontraumatic OCS requires prompt diagnosis and surgical intervention to prevent adverse outcomes. VSD is an effective surgical treatment for this disease.

Retraction Notice to: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1ß and IL-6.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.022.].

A lipophilic chitosan-modified self-nanoemulsifying system influencing cellular membrane metabolism enhances antibacterial and anti-biofilm efficacy for multi-drug resistant Pseudomonas aeruginosa wound infection.

Wound infections, especially infections with multidrug-resistant bacteria, are a serious public health issue worldwide. In addition, the accumulation microbial biofilm of multidrug-resistant Pseudomonas aeruginosa increases the risk and physically obstruct its healing activity at the wound site. Therefore, the development of an eminent agent to control wound infection is urgently needed. Here, we report a novel chitosan (a natural biological macromolecule)-modified self-nanoemulsifying system (CSN) with lipophilic chlorhexidine acetate (CAA, a poorly water-soluble agent) that was designed and prepared using low-energy emulsification methods. We found that CSN displays better antibacterial efficacy, which occurs more quickly than its aqueous solution, in destroying the structure of the bacterial cell membrane and promoting the leakage of nucleic acids, proteins, K+, and Mg2+ from Pseudomonas aeruginosa cells. Importantly, CSN also accelerates skin wound healing after Pseudomonas aeruginosa infection by inhibiting biofilm formation and eradicating mature biofilms. Moreover, the proteomic results suggested that CSN altered membrane permeability and cellular membrane metabolism, allowing more drug molecules to enter the cytosol. Based on these results, this lipophilic self-nanoemulsifying system may be applied in the treatment of skin wounds caused by multidrug-resistant bacteria, especially Pseudomonas aeruginosa.

Ionic liquid-based liposome for selective SERS detection.

An ionic liquid (IL)-based liposome was utilized as a substrate to construct a SERS platform. The isotropy of the IL outer surface together with its ion-exchange property led to the array-like growth of Au nanoparticles (NPs), generating hot-spots and resulting in anionic probes being present on the hot-spot regions. The simultaneous strategy of enrichment and localization endowed the platform with ability to detect trace amounts of anionic probes.

Long non-coding RNA CDKN2B-AS1 contributes to atherosclerotic plaque formation by forming RNA-DNA triplex in the CDKN2B promoter.

BACKGROUND: Atherosclerosis involves a slow process of plaque formation on the walls of arteries, and comprises a leading cause of cardiovascular disease. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of atherosclerosis. In this study, we aim to explore the possible involvement of lncRNA 'cyclin-dependent kinase inhibitor 2B antisense noncoding RNA' (CDKN2B-AS1) and CDKN2B in the progression of atherosclerosis. METHODS: Initially, we quantified the expression of CDKN2B-AS1 in atherosclerotic plaque tissues and, in THP-1 macrophage-derived, and human primary macrophage (HPM)-derived foam cells. Next, we established a mouse model of atherosclerosis using apolipoprotein E knockout (ApoE-/-) mice, where lipid uptake, lipid accumulation, and macrophage reverse cholesterol transport (mRCT) were assessed, in order to explore the contributory role of CDKN2B-AS1 to the progression of atherosclerosis. RIP and ChIP assays were used to identify interactions between CDKN2B-AS1, CCCTC-binding factor (CTCF), enhancer of zeste homologue 2 (EZH2), and CDKN2B. Triplex formation was determined by RNA-DNA pull-down and capture assay as well as EMSA experiment. FINDINGS: CDKN2B-AS1 showed high expression levels in atherosclerosis, whereas CDKN2B showed low expression levels. CDKN2B-AS1 accelerated lipid uptake and intracellular lipid accumulation whilst attenuating mRCT in THP-1 macrophage-derived foam cells, HPM-derived foam cells, and in the mouse model. EZH2 and CTCF were found to bind to the CDKN2B promoter region. An RNA-DNA triplex formed by CDKN2B-AS1 and CDKN2B promoter was found to recruit EZH2 and CTCF in the CDKN2B promoter region and consequently inhibit CDKN2B transcription by accelerating histone methylation. INTERPRETATION: The results demonstrated that CDKN2B-AS1 promotes atherosclerotic plaque formation and inhibits mRCT in atherosclerosis by regulating CDKN2B promoter, and thereby could be a potential therapeutic target for atherosclerosis.

Emerging roles of let­7d in attenuating pulmonary arterial hypertension via suppression of pulmonary artery endothelial cell autophagy and endothelin synthesis through ATG16L1 downregulation.

Pulmonary arterial hypertension (PAH) is a severe disease characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance, resulting in right ventricular failure and death. Compelling evidence has suggested the roles of microRNAs (miRNAs/miRs) in PAH. The present study investigated the possible effects of miR­let­7d on PAH through autophagy­related 16­like 1 (ATG16L1). Initially, the serum levels of let­7d in PAH patients were detected. Rats were then treated with monocrotaline to induce a rat model of PAH, after which the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were determined. Next, the putative binding sites between let­7d and ATG16L1 were detected. The expression of let­7d and ATG16L1 in PAH rat models and cells was upregulated or downregulated to assess the effects of these molecules on autophagy in pulmonary artery vascular endothelial cells (PAECs) and on endothelin synthesis. In addition, the levels of p62, LC3­I, LC3­II, LC3B and endothelin­1 (ET­1) were assessed. The results obtained revealed that let­7d was downregulated in the serum of PAH patients and rats with PAH. Importantly, ATG16L1 was found to be a target gene of let­7d and let­7d could suppress the expression of ATG16L1. Overexpression of let­7d was found to reduce RVSP and RVHI values. Additionally, upregulation of let­7d or depletion of ATG16L1 led to suppression of PAEC autophagy and endothelin synthesis, corresponding to decreased ratios of LC3­II to LC3­I and reduced levels of LC3B but elevated levels of p62 in PAECs and ET­1 in plasma and lung tissues. In summary, let­7d upregulation alleviates PAH by inhibiting autophagy in PAECs and suppressing endothelin synthesis through negative regulation of ATG16L1.