Effect of compound surface modification of shot peening and DLC coating on surface integrity and fatigue properties of gear steel 16Cr3NiWMoVNbE.

We conducted a study on the surface compound modification of shot peening and pure carbon DLC coating to simultaneously meet the requirements of wear resistance and fatigue resistance of spline structure. The effects of surface compound modification were investigated on the surface morphology, residual stress profile, microstructure, and nano-indentation hardness of 16Cr3NiWMovNbE gear steel, and conducted a comparative study on fatigue performance. The results show that the surface compound modification inherits the surface morphology and compressive residual stress gradient of shot peening, while the surface residual stress is slightly smaller than that of shot peening. In addition, surface compound modification still reflects the characteristics of high hardness and high fracture resistance of DLC coatings. Under the bending load based on spline tooth root, compared to the original specimen, the fatigue life after shot peening, pure carbon DLC coating, and surface compound modification is increased by 3.68, 2.35, and 3.36 respectively. Although the compound modified surface still maintains the shot peening morphology with a increasing surface roughness and stress concentration coefficient, the 100 µm-depth compressive residual stress profile and the subgrain refinement layer introduced, as well as the hard surface layer with good load-bearing capacity, have played the role of fatigue strengthening.

Meta-analysis of FTO expression on the clinicopathologic characteristics and prognosis of gastric cancer.

BACKGROUND: Fat mass and obesity-related gene (FTO) is aberrantly expressed in various cancers including highly expressed in gastric cancer tissues. The aim of this meta-analysis was to explore the effect of FTO expression on clinicopathological and prognostic outcome of gastric cancer. METHODS: China National Knowledge Infrastructure (CNK), Wanfang database, VIP database, Chinese biomedical literature database (CBM), PubMed, Web of Science, the Cochrane library and EMBASE database were searched to screen the literatures according to the inclusion criteria. The search time was the database establishment until May 2023. The two researchers independently searched and screened the literature, extracted pathological data, and conducted The Newcastle-Ottawa scale (NOS) quality evaluation. Analyze the correlation between FTO and pathological indicators of gastric cancer patients and the impact on prognosis, use and Stata 12.0, software for Meta-analysis. RESULTS: A total of 1619 patients were studied in this study. The results of the Meta-analysis showed that higher expression levels of FTO were associated with TMN stage (OR = 1.83, 95% CI: 1.11-3.03, P = .019), liver metastases (OR = 3.73, 95% CI: 1.49-9.31, P = .005), vascular invasion (OR = 2.22, 95% CI: 1.36-3.61, P = .001), poorer overall survival (OS) (HR = 0.46, 95% CI: 0.34-0.58, P < .001) and recurrence-free survival (HR = 0.56, 95% CI: 0.40-0.73, P < .001) in gastric cancer patients. There was no significant relationship with the degree of differentiation (OR = 1.08, 95% CI: 0.49-2.35, P = .852), age (OR = 0.89, 95% CI: 0.71-1.11, P = .306), and gender (OR = 0.92, 95% CI: 0.74-1.14, P = .432). CONCLUSION: High expression of FTO was associated with risk of distant metastases and poor prognosis for patients with gastric cancer. FTO may be a potential prognostic biomarker for gastric cancer, but due to the limited number of literature, the above results need further research.

A New Cyst Nematode, Heterodera luodingensis n. sp. (Nematoda: Heteroderinae) From Rice In China.

A unique cyst nematode population (Heterodera spp.) was collected from rice roots in Luoding County, Guangdong Province, China. Morphological and molecular analyses revealed it is significantly different from all previously described cyst nematode species. It is described as Heterodera luodingensis n. sp. and classified in the Cyperi group. H. luodingensis n. sp. is characterized by its lemon-shaped cyst with a prominent terminal vulval cone that is ambifenestrate with abundant bullae and a relatively short vulval slit, 31.3 (24.4 -38.7) µm long. The second-stage juveniles (J2) are characterized by dumbbell shaped labials, three lip annules and a lateral field with three incisures. The J2 stylet is 18.7 (16.9 -19.8) µm long with anterior concave or spherical knobs. The tail is elongate conoid, tapering to a rounded terminus or zig tapering to a rounded terminus that is 54.9 (43.9 - 64.3) µm long with a hyaline region comprising 40.3%-52.5% of the tail. Phylogenetic tree analysis based on rDNA 28S D2D3 and ITS fragments showed that the H. luodingensis n. sp. is unique and clearly separated it from other cyst nematodes. It is most closely related to H. oryzicola, H. fengi, H. elachista, H. oryzae, and H. guangdongensis. H. luodingensis n. sp. can be distinguished from H. oryzicola by its shorter vulval slit and underbridge, from H. elachista by abundant bullae, shorter vulval slit and fenestrate width, from H. oryzae by a shorter vulval slit and underbridge, from H. fengi by a shorter vulval slit, from H. guangdongensis by a longer cyst length and abundant bulla. Based on PCR-RFLP of rDNA-ITS, H. luodingensis n. sp. can be clearly distinguished from H. oryzicola, H. mothi, H. elachista, H. guangdongensis and H. cyperi. A parasitism test from a pure culture derived from a single cyst in greenhouse showed that H. luodingensis n. sp. can successfully complete its life cycle on rice and rice is its type host.

Development and validation of a nomogram incorporating multi-parametric MRI and hematological indicators for discriminating benign from malignant central prostatic nodules: a retrospective analysis.

BACKGROUND: Prostate cancer poses a significant risk to men's health. In this study, a model for differentiating benign and malignant nodules in the central region of the prostate was constructed by combining multi-parametric MRI and hematological lab values. METHODS: This retrospective study analyzed the data acquired from Lianyungang First People's Hospital and The Second Affiliated Hospital of Hainan Medical College from January 2018 to December 2021. We included 310 MRI-confirmed prostatic nodule patients. The data were split into a training set (260 cases) and an external validation set (50 cases), with the latter exclusively from The Second Affiliated Hospital of Hainan Medical College to test the model's generalizability. Univariate and multivariate logistic regression identified critical measurements for differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH), which were then integrated into a nomogram model. RESULTS: The key indicators determined by multivariate logistic regression analysis included apparent diffusion coefficient (ADC), standard deviation (StDev), neutrophil to lymphocyte ratio (NLR), and prostate specific antigen (PSA). The nomogram's performance, as indicated by the area under the curve (AUC), was 0.844 (95% CI: 0.811-0.938) in the training set and 0.818 (95% CI: 0.644-0.980) in the external validation set. Calibration and decision curves demonstrated that the nomogram was well-calibrated and could serve as an effective tool in clinical practice. CONCLUSION: The nomogram model based on ADC, StDev, NLR and PSA may be helpful to identify PCa and BPH.

Endoplasmic reticulum stress in diseases.

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases.

Advances in Migratory Plant Endoparasitic Nematode Effectors.

Unlike sedentary plant-parasitic nematodes, migratory plant endoparasitic nematodes (MPENs) are unable to establish permanent feeding sites, and all developmental stages (except eggs) can invade and feed on plant tissues and can be easily overlooked because of the unspecific symptoms. They cause numerous economic losses in agriculture, forestry, and horticulture. In order to understand the pathogenetic mechanism of MPENs, here we describe research on functions and host targets focused on currently identified effectors from six MPENs, namely Radopholus similis, Pratylenchus spp., Ditylenchus destructor, Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Hirschmanniella oryzae. This information will provide valuable insights into understanding MPEN effectors and for future fostering advancements in plant protection.

Magnetic Resonance Imaging Improves Diagnosis of Liver Cancer Compared to Liver Enhanced CT.

Aim: This study aimed to compare the effectiveness of enhanced CT scanning and MRI as diagnostic tools for the detection of carcinoma of the liver. Methods: The image diagnostic significance of the liver enhanced CT & MRI scans was examined after a retrospective examination of the imaging data of 51 individuals with liver cancer who were identified with postoperative pathology at the First People's Hospital of Lianyungang between May 2020 to May 2022. Results: The number of extrahepatic lesions as well as the rate of extrahepatic positive cases were not significantly different between liver contrast-enhanced CT and liver MRI (P > .05); however, the number of intrahepatic lesions and the rate of intrahepatic positive cases were considerably higher for liver MRI than for liver enhanced CT (P < .05). When identifying tumors with a diameter greater than 3 cm, there was no discernible difference between the detection rates of liver enhanced CT and liver MRI (P > .05); however, in the diagnosis of tumors less than 3 cm in diameter, liver MRI had a greater detection rate than liver contrast-enhanced CT (P < .05). Overall, liver MRI had a higher detection rate than liver contrast-enhanced CT (P < .05). Furthermore, when compared to liver contrast-enhanced CT, liver MRI had greater accuracy, specificity, sensitivity, negative predictive value, and positive predictive value (P < .05). Conclusion: When it comes to detecting liver cancer, liver MRI is more sensitive and specific than liver CT.

Pectate lyase genes from Radopholus similis and their application in pathotype identification.

Radopholus similis is a destructive, migratory, and endophytoparasitic nematode. It has two morphologically indistinguishable pathotypes (or physiological races): banana and citrus pathotypes. At present, the only reliable method to differentiate the two pathotypes is testing the infestation and parasitism of nematodes on Citrus spp. via inoculation. However, differences in inoculation methods and conditions adopted by different researchers complicate obtaining consistent results. In this study, the parasitism and pathogenicity of 10 R. similis populations on rough lemon (Citrus limon) seedlings and the tropism and invasion of rough lemon roots were tested. It revealed that populations SWK, GJ, FZ, GZ, DBSR, and YJ were citrus pathotypes, which showed parasitism and pathogenicity on rough lemon and could invade rough lemon roots, whereas populations XIN, ML, HN6, and HL were banana pathotypes, having no parasitism and pathogenicity on rough lemon and they did not invade the rough lemon roots. Four pectate lyase genes (Rs-pel-2, Rs-pel-3, Rs-pel-4, and Rs-pel-5) belonging to the Class III family from these populations were amplified and analysed. The gene Rs-pel-3 could be amplified from six citrus pathotype populations and was stably expressed in the four developmental stages of the nematode, whereas it could not be amplified from the four banana pathotypes. Rs-pel-3 expression may be related to the parasitism and pathogenicity of R. similis on rough lemon. Hence, it can be used as a molecular marker to distinguish between banana and citrus pathotypes and as a target gene for the molecular identification of these two pathotypes. KEY POINTS: • Four pectate lyase genes (Rs-pels) from Radopholus similis were cloned and analysed. • The expression of Rs-pels is different in two pathotypes of Radopholus similis. • A molecular identification method for two pathotypes of Radopholus similis using pectate lyase gene Rs-pel-3 as the target gene was established.

Quality Evaluation of Shexiang Tongxin Dropping Pill Based on HPLC Fingerprints Combined with HPLC-Q-TOF-MS/MS Method.

Shexiang Tongxin Dropping Pill (STP) is a composite formula of traditional Chinese medicine that is widely used for the treatment of cardiovascular diseases. It consists of seven medicinal extracts thereof or materials, including Bufonis venenum, synthetic Moschus, Panax ginseng, Bovis calculus artifactus, Bear bile powder, Salvia miltiorrhiza Bge and synthetic borneol. However, it is considerably difficult to evaluate the quality of STP due to its complex chemical compositions. This paper was designed to explore a comprehensive and systematic method combining fingerprints and chemical identification for quality assessment of STP samples. Twenty batches of STP samples were analyzed by high-performance liquid chromatography (HPLC) and high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Ten common peaks were detected by HPLC fingerprint similarity evaluation system. Meanwhile, 100 compounds belonging to 4 structural characteristics, including 23 bufadienolides, 36 organic acids, 34 saponins and 7 other types, were systematically identified as the basic components in STP. This study could be used for clarifying the multiple bioactive substances and developing a comprehensive quality evaluation method of STP.

The completed mitochondrial genomes of Globodera vulgaris reveals new insights into the genus Globodera phylogeny.

Due to the highly conserved structure, animal mitochondrial genome (mtDNA) is widely used in classification, evolution, phylogeny, population genetic structure and other fields. We reported on the five circle multipartite mtDNAs of a newly described species of Globodera, Globodera vulgaris (Gv) from potatoes in China. The results showed that the mtDNA of Gv was obtained through second- and third-generation sequencing, with a total length of 42,995 bp. It contained 12 protein-coding genes, two rRNA genes and 17 tRNA genes, which were distributed in different subgenomic circles. Comparison of the differences in mtDNA among Gv, G. rostochiensis, G. pallida and G. ellingtonae showed that the size and arrangement of the genes in the mtDNA of the genus Globodera were variable and not conserved. The codon usage bias of the mitochondrial protein-coding gene of Gv showed that Gv might have originated from locally and more primitive group of existing Globodera. Based on the cytochrome c oxidase subunits I genes (COX1) and the nicotinamide adenine dinucleotide dehydrogenase subunits I genes (ND1), and the results showed that Gv was clustered with Globodera spp. according to the COX1 and ND1 in scmtDNA-V, while Gv was clustered with Meloidogyne spp. according to ND1 in scmtDNA-III. The results of this study provided a new basis for understanding the multipartite structure of mtDNA as a phylogenetic and taxonomic feature of the genus Globodera. The number of subgenomic circles is a diagnostic feature of species and the arrangement order and size of mitochondrial protein-coding genes also have important application value in species identification within the genus.

The effect of working memory training on test anxiety symptoms and attentional control in adolescents.

OBJECTIVE: The percentage of adolescents with test anxiety is increasing rapidly. Working memory (WM) training has been demonstrated to reduce anxiety levels and enhance attentional control in individuals. Therefore, we investigated whether adaptive dual n-back WM training could lower test anxiety level and improve attentional control in adolescents. METHODS: Forty adolescents were allocated to either adaptive dual n-back WM training (n = 21) or non-adaptive dual 1-back WM training (n = 19) for 10 days. The Test Anxiety Scale was applied to measure individuals' test anxiety symptoms. The Attentional Control Scale (ACS), the flanker task, and the Go/Nogo task were used to measure attentional control. RESULTS: Compared with the control group, the training group reported significantly relief of test anxiety symptoms; however, there were no significant differences between the two groups in pre-to-post changes in ACS scores or performance on the flanker task and Go/Nogo task. CONCLUSION: In sum, adaptive dual n-back WM training effectively reduced adolescents' level of test anxiety but did not improve their attentional control.

Acute acquired concomitant esotropia with congenital paralytic strabismus: A case report.

BACKGROUND: An unusual case of acute acquired concomitant esotropia (AACE) with congenital paralytic strabismus in the right eye is reported. CASE SUMMARY: A 23-year-old woman presented with complaints of binocular diplopia and esotropia of the right eye lasting 4 years and head tilt to the left since 1 year after birth. The Bielschowsky head tilt test showed right hypertropia on a right head tilt. She did not report any other intracranial pathology. A diagnosis of AACE and right congenital paralytic strabismus was made. Then, she underwent medial rectus muscle recession and lateral rectus muscle resection combined with inferior oblique muscle myectomy in the right eye. One day after surgery, the patient reported that she had no diplopia at either distance or near fixation and was found to be orthophoric in the primary position; furthermore, her head posture immediately and markedly improved. CONCLUSION: In future clinical work, in cases of AACE combined with other types of strabismus, we can perform conventional single surgery for both at the same time, and the two types of strabismus can be solved simultaneously.

TGF-ß1/SMAD3 Regulates Programmed Cell Death 5 That Suppresses Cardiac Fibrosis Post-Myocardial Infarction by Inhibiting HDAC3.

BACKGROUND: Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying mechanisms of PDCD5 in the pathogenesis of cardiac fibrosis. METHODS AND RESULTS: PDCD5 levels were found to be elevated in the serum obtained from patients with cardiac fibrosis, in fibrotic mice heart tissues after myocardial infarction, and in cardiac fibroblasts stimulated by Ang II (angiotensin II)- or TGF-ß1 (transforming growth factor-ß1). Overexpression of PDCD5 in cardiac fibroblasts or treatment with PDCD5 protein reduced the expression of profibrogenic proteins in response to TGF-ß1 stimulation, while knockdown of PDCD5 increased fibrotic responses. It has been demonstrated that SMAD3, a protein that is also known as mothers against decapentaplegic homolog 3, directly upregulated PDCD5 during cardiac fibrosis. Subsequently, the increased PDCD5 promoted HDAC3 (histone deacetylase 3) ubiquitination, thus, inhibiting HDAC3 to reduce fibrotic responses. Fibroblast-specific knock-in of PDCD5 in mice ameliorated cardiac fibrosis after myocardial infarction and enhanced cardiac function, and these protective effects were eliminated by AAV9-mediated HDAC3 overexpression. CONCLUSIONS: The findings of this study demonstrated that PDCD5 is upregulated by SMAD3 during cardiac fibrosis, which subsequently ameliorated progressive fibrosis and cardiac dysfunction through HDAC3 inhibition. Thus, this study suggests that PDCD5 functions as a negative feedback factor on fibrotic signaling pathways and might serve as a potential therapeutic target to suppress the progression of fibrotic responses.

Redescription and Molecular Characterization of Trichotylenchus dispersus (Nematoda: Dolichodoridae) in China.

A species of Trichotylenchus nematode was isolated from the rhizosphere of banana root in Leizhou City, Guangdong Province, China. The species assumes the following characteristics: open C-shaped body; head offset from body; lateral field with three incisures, pharyngeal and tail regions irregularly areolated; stylet 18.6-20.7 µm long; pharyngeal gland not extending over intestine; fibrous tissue present in the intestine; post-anal intestinal sac present; elongate-subcylindroid tail, bluntly conoid terminus, lack of striations, and containing 34-44 annuli. In addition, scanning electron microscopy was used to elucidate some morphological details, but only some juveniles were observed. Partial 18S rRNA, ITS, and 28S D2-D3 expansion sequences were amplified with universal primers and deposited in GenBank under accession numbers ON622716, ON622717, and ON622714, respectively. Here, this species was identified as T. dispersus [(Siddiqi & Sharma, 1995) Geraert, 2011].

Morphological and Molecular Characterization, Including Parasitic and Pathogenic Studies of a New Spherical Cyst Nematode Species, Globodera vulgaris n. sp. (Nematoda: Heteroderidae), Associated with Potatoes in China.

In this study, a new spherical cyst nematode belonging to the genus Globodera, herein described as Globodera vulgaris n. sp., was extracted from the roots and rhizosphere soil of potato and circumjacent weeds belonging to different families in three provinces in southwest China. The new species was characterized by 8 to 24 ridges between the anus and fenestra and an average Granek's ratio of 2.8 to 3.8 in cysts, a head with three to four annules, a dorsal knob anteriorly projected, ventral knobs round or anteriorly projected in second stage juveniles, a head with three to five annules, a short spicule with an average length of less than 30.0 µm, and a developed velum in males. Pathogenicity tests showed that G. vulgaris n. sp. infected potato but did not damage or affect the potato yield compared with the control, and it parasitized tomato with a low reproduction rate (RF < 1) while it did not parasitize tobacco (RF = 0). The new species was closely related to G. rostochiensis, based on molecular diagnostic marker sequences and constructed phylogenetic analysis, based on internal transcribed spacers of ribosomal DNA, large-subunit rDNA, and small-subunit rDNA. However, the new species exhibited differences from G. rostochiensis in terms of morphological characteristics, a wide host preference, lack of damage to hosts, and an egg-hatching rate induced by hatching factors.

A key virulence effector from cyst nematodes targets host autophagy to promote nematode parasitism.

Autophagy, an intracellular degradation system conserved in eukaryotes, has been increasingly recognized as a key battlefield in plant-pathogen interactions. However, the role of plant autophagy in nematode parasitism is mostly unknown. We report here the identification of a novel and conserved effector, Nematode Manipulator of Autophagy System 1 (NMAS1), from plant-parasitic cyst nematodes (Heterodera and Globodera spp.). We used molecular and genetic analyses to demonstrate that NMAS1 is required for nematode parasitism. The NMAS1 effectors are potent suppressors of reactive oxygen species (ROS) induced by flg22 and cell death mediated by immune receptors in Nicotiana benthamiana, suggesting a key role of NMAS1 effectors in nematode virulence. Arabidopsis atg mutants defective in autophagy showed reduced susceptibility to nematode infection. The NMAS1 effectors contain predicted AuTophaGy-related protein 8 (ATG8)-interacting motif (AIM) sequences. In planta protein-protein interaction assays further demonstrated that NMAS1 effectors specifically interact with host plant ATG8 proteins. Interestingly, mutation in AIM2 of GrNMAS1 from the potato cyst nematode Globodera rostochiensis abolishes its interaction with potato StATG8 proteins and its activity in ROS suppression. Collectively, our results reveal for the first time that cyst nematodes employ a conserved AIM-containing virulence effector capable of targeting a key component of host autophagy to promote disease.

Aphelenchoides besseyi Ab-FAR-1 Interacts with Arabidopsis thaliana AtADF3 to Interfere with Actin Cytoskeleton, and Promotes Nematode Parasitism and Pathogenicity.

Fatty acid and retinol binding proteins (FAR) are unique proteins found in nematodes and are considered potential targets for controlling these parasites. However, their functions in nematode parasitism and pathogenicity and interaction with hosts are still unclear. In this study, we investigated the specific roles of rice white tip nematodes (RWTNs), Aphelenchoides besseyi, and a protein, Ab-FAR-1, to elucidate the parasitic and pathogenic processes of nematodes. The results showed that the expression level of Ab-far-1 was significantly up-regulated after A. besseyi infection of the plant. The immunofluorescence and subcellular localisation showed that Ab-FAR-1 was secreted into plant tissues mainly through the body wall of nematodes and might act in the nucleus and cytoplasm of plant cells. The pathogenicity of RWTNs was enhanced in Arabidopsis thaliana overexpressing Ab-FAR-1 and inhibited in Ab-far-1 RNAi A. thaliana. Yeast two-hybrid, Co-IP, BiFC, and nematode inoculation experiments showed that Ab-FAR-1 could interact with the A. thaliana actin-depolymerizing factor protein AtADF3, and the A. thaliana adf3 mutant was more susceptible to nematodes. An in vitro actin filament depolymerisation assay demonstrated that Ab-FAR-1 could inhibit AtADF3-mediated depolymerisation of actin filaments, and the turnover process of cellular actin filaments was also affected in A. thaliana overexpressing Ab-FAR-1. In addition, flg22-mediated host defence responses were suppressed in A. thaliana overexpressing Ab-FAR-1 and adf3 mutants. Therefore, this study confirmed that RWTNs can affect the turnover of actin filament remodelling mediated by AtADF3 through Ab-FAR-1 secretion and thus inhibit plant PAMP-triggered immunity (PTI), promoting the parasitism and pathogenicity of nematodes.

Biology of Peptide Transporter 2 in Mammals: New Insights into Its Function, Structure and Regulation.

Peptide transporter 2 (PepT2) in mammals plays essential roles in the reabsorption and conservation of peptide-bound amino acids in the kidney and in maintaining neuropeptide homeostasis in the brain. It is also of significant medical and pharmacological significance in the absorption and disposing of peptide-like drugs, including angiotensin-converting enzyme inhibitors, ß-lactam antibiotics and antiviral prodrugs. Understanding the structure, function and regulation of PepT2 is of emerging interest in nutrition, medical and pharmacological research. In this review, we provide a comprehensive overview of the structure, substrate preferences and localization of PepT2 in mammals. As PepT2 is expressed in various organs, its function in the liver, kidney, brain, heart, lung and mammary gland has also been addressed. Finally, the regulatory factors that affect the expression and function of PepT2, such as transcriptional activation and posttranslational modification, are also discussed.

Radiomics signature for predicting postoperative disease-free survival of patients with gastric cancer: development and validation of a predictive nomogram.

PURPOSE Radiomics can be used to determine the prognosis of gastric cancer (GC). The objective of this study was to predict the disease-free survival (DFS) after GC surgery based on computed tomography-enhanced images combined with clinical features. METHODS Clinical, imaging, and pathological data of patients who underwent gastric adenocarcinoma resection from June 2015 to May 2019 were retrospectively analyzed. The primary outcome was DFS. Radiomics features were selected using Least Absolute Shrinkage and Selection Operator algorithm and converted into the Rad-score. A nomogram was constructed based on the Radscore and other clinical factors. The Rad-score and nomogram were validated in the training and validation groups. RESULTS Totally, 179 patients were randomly divided into the training (n=124) and validation (n=55) groups. In the training group, validation group, and overall population, the Rad-score could be divided into categories indicating low, moderate, and high risk of recurrence, metastasis, or death; all risk categories showed a significant difference between the training, validation, and overall population groups (all P < .001). Positive lymph nodes (hazard ratio (HR)=3.07, 95% CI: 1.52-6.23, P=.002), cancer antigen-125 (HR=3.24, 95% CI: 1.54-6.80, P=.002), and the Radscore (HR=0.73, 95% CI: 0.61-0.87, P < .001) were independently associated with DFS. These 3 variables were used to construct a nomogram. In the training group, the areas under the curve at 3 years were 0.758 and 0.776 for the Rad-score and the nomogram, respectively, while they were both 1.000 in the validation group. The net benefit rate was analyzed using a decision curve in the training and validation groups, and the nomogram was superior to the single Rad-score. CONCLUSION Rad-score is an independent factor for DFS after gastrectomy for GC. The nomogram established in this study could be an effective tool for the clinical prediction of DFS after gastrectomy.

FUNDC1-mediated mitophagy and HIF1α activation drives pulmonary hypertension during hypoxia.

Hypoxic pulmonary hypertension (PH) is a progressive disease characterized by hyper-proliferation of pulmonary vascular cells including pulmonary artery smooth muscle cells (PASMCs) and can lead to right heart failure and early death. Selective degradation of mitochondria by mitophagy during hypoxia regulates mitochondrial functions in many cells, however, it is not clear if mitophagy is involved in the pathogenesis of hypoxic PH. By employing the hypoxic mitophagy receptor Fundc1 knockout (KO) and transgenic (TG) mouse models, combined hypoxic PH models, the current study found that mitophagy is actively involved in hypoxic PH through regulating PASMC proliferation. In the pulmonary artery medium from hypoxic PH mice, mitophagy was upregulated, accompanied with the increased active form of FUNDC1 protein and the enhanced binding affinity of FUNDC1 with LC3B. In PASMCs, overexpression of FUNDC1 increased mitophagy and cell proliferation while knockdown of FUNDC1 inhibited hypoxia-induced mitophagy and PASMC proliferation. Stimulation of mitophagy by FUNDC1 in PASMCs elevated ROS production and inhibited ubiquitination of hypoxia inducible factor 1α (HIF1α), and inhibition of mitophagy by FUNDC1 knockdown or knockout abolished hypoxia-induced ROS-HIF1α upregulation. Moreover, Fundc1 TG mice developed severe hemodynamics changes and pulmonary vascular remodeling, and Fundc1 KO mice were much resistant to hypoxic PH. In addition, intraperitoneal injection of a specific FUNDC1 peptide inhibitor to block mitophagy ameliorated hypoxic PH. Our results reveal that during hypoxic PH, FUNDC1-mediated mitophagy is upregulated which activates ROS-HIF1α pathway and promotes PASMC proliferation, ultimately leads to pulmonary vascular remodeling and PH.