Predicting Portal Pressure Gradient in Patients with Decompensated Cirrhosis: A Non-invasive Deep Learning Model.

BACKGROUND: A high portal pressure gradient (PPG) is associated with an increased risk of failure to control esophagogastric variceal hemorrhage and refractory ascites in patients with decompensated cirrhosis. However, direct measurement of PPG is invasive, limiting its routine use in clinical practice. Consequently, there is an urgent need for non-invasive techniques to assess PPG. AIM: To develop and validate a deep learning model that predicts PPG values for patients with decompensated cirrhosis and identifies those with high-risk portal hypertension (HRPH), who may benefit from early transjugular intrahepatic portosystemic shunt (TIPS) intervention. METHODS: Data of 520 decompensated cirrhosis patients who underwent TIPS between June 2014 and December 2022 were retrospectively analyzed. Laboratory and imaging parameters were used to develop an artificial neural network model for predicting PPG, with feature selection via recursive feature elimination for comparison experiments. The best performing model was tested by external validation. RESULTS: After excluding 92 patients, 428 were included in the final analysis. A series of comparison experiments demonstrated that a three-parameter (3P) model, which includes the international normalized ratio, portal vein diameter, and white blood cell count, achieved the highest accuracy of 87.5%. In two distinct external datasets, the model attained accuracy rates of 85.40% and 90.80%, respectively. It also showed notable ability to distinguish HRPH with an AUROC of 0.842 in external validation. CONCLUSION: The developed 3P model could predict PPG values for decompensated cirrhosis patients and could effectively distinguish HRPH.

Corrigendum: Fucoidan ameliorates renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats by targeting FGF23-Klotho signaling axis.

[This corrects the article DOI: 10.3389/fphar.2020.586725.].

Sulfonylation of Pyridyl Phosphonium Salts with Sulfinate Salts in Aqueous Media for the Synthesis of 4-Pyridyl Sulfones via C-P Bond Cleavage.

A Na2S2O8-initiated sulfonylation of pyridyl phosphonium salts with sulfinate salts in aqueous media has been developed for facile access to 4-pyridyl sulfones. The reactions, which employed pyridyl phosphonium salts as efficient pyridylation agents via C-P bond activation, showed both broad substrate generality and good functional group compatibility. In addition, the scale-up synthesis and the late-stage modification of pharmaceutically active complex molecules (e.g., loratadine, bisacodyl) could also be successfully realized.

Electrolyte Composition-Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal-Organic Framework Catalyst.

A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.

Odorant-binding protein CrufOBP1 in Cotesia ruficrus females plays a pivotal role in the detection of Spodoptera frugiperda larvae.

Cotesia ruficrus presents a promising local natural enemy for controlling the invasive fall armyworm Spodoptera frugiperda in China. However, the mechanisms underlying how C. ruficrus locates its target pest remain unclear. In this study, we analyzed the expression patterns of 18 CrufOBPs across different developmental stages of C. ruficrus, and found that CrufOBP1 exhibited consistent and high expression levels in female adults. CrufOBP1 transcript was predominantly localized in sensilla placodea and sensilla trichodea on the antennae. Additionally, we confirmed the binding properties of CrufOBP1 protein to various cuticular compounds of S. frugiperda larvae. Subsequent electroantennogram and behavioral assays revealed that 1-(2-hydroxy-5-methylphenyl)-ethanone attracted female C. ruficrus, consequently increased the parasitism rate. However, upon silencing CrufOBP1, females exhibited reduced attraction towards 1-(2-hydroxy-5-methylphenyl)-ethanone, indicating the crucial role of CrufOBP1 in the chemoreception of C. ruficrus. These findings shed light on the kairomone-based mechanism employed by C. ruficrus to locate S. frugiperda larvae and hold a promise for the development of environmentally friendly pest management strategies.

Involvement of Chemosensory Protein CrufCSP3 in Perception of the Host Location in a Parasitic Wasp Cotesia ruficrus.

Chemosensory proteins (CSPs) constitute a class of olfactory proteins localized in insect sensory organs that serve a crucial function in decoding external chemical stimuli. This study aims to elucidate the involvement of CrufCSP3 in olfactory perception within the context of Cotesia ruficrus, an indigenous endoparasitoid targeting the invasive pest Spodoptera frugiperda. Through fluorescence-competitive binding assays and site-directed mutagenesis, we pinpointed four amino acids as pivotal residues involved in the interaction between CrufCSP3 and five host-related compounds. Subsequent RNA interference experiments targeting CrufCSP3 unveiled a reduced sensitivity to specific host-related compounds and a decline in the parasitism rate of the FAW larvae. These findings unequivocally indicate the essential role of CrufCSP3 in the chemoreception process of C. ruficrus. Consequently, our study not only sheds light on the functional importance of CSPs in parasitic wasp behavior but also contributes to the development of eco-friendly and efficacious wasp behavior modifiers for effectively mitigating pest population surges.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Palladium-Catalyzed Esterification of Aryl Fluorosulfates with Aryl Formates.

An efficient palladium-catalyzed carbonylation of aryl fluorosulfates with aryl formates for the facile synthesis of esters was developed. The cross-coupling reactions proceeded effectively in the presence of a palladium catalyst, phosphine ligand, and triethylamine in DMF to produce the corresponding esters in moderate to good yields. Of note, functionalities or substituents, such as nitro, cyano, methoxycarbonyl, trifluoromethyl, methylsulfonyl, trifluoromethoxy, fluoro, chloro, bromo, methyl, methoxy, N,N-dimethyl, and [1,3]dioxolyl, were well-tolerated in the reactions, which could be kept for late-stage modification. The reactions employing readily available and relatively robust aryl fluorosulfates as coupling electrophiles could potentially serve as an attractive alternative to traditional cross-couplings with the use of aryl halides and pseudohalides as substrates.

A CTL - Lys immune function maintains insect metamorphosis by preventing gut bacterial dysbiosis and limiting opportunistic infections.

BACKGROUND: Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. RESULTS: We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. CONCLUSIONS: A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL - Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.

Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature.

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

Characterization of CrufCSP1 and Its Potential Involvement in Host Location by Cotesia ruficrus (Hymenoptera: Braconidae), an Indigenous Parasitoid of Spodoptera frugiperda (Lepidoptera: Noctuidae) in China.

Chemosensory proteins (CSPs) are a class of soluble proteins that facilitate the recognition of chemical signals in insects. While CSP genes have been identified in many insect species, studies investigating their function remain limited. Cotesia ruficrus (Hymenoptera: Braconidae) holds promise as an indigenous biological control agent for managing the invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae) in China. This study aimed to shed light on the gene expression, ligand binding, and molecular docking of CrufCSP1 in C. ruficrus. A RT-qPCR analysis revealed that the expression of CrufCSP1 was higher in the wings, with male adults exhibiting significantly higher relative expression levels than other developmental stages. A fluorescence competitive binding analysis further demonstrated that CrufCSP1 has a high binding ability with several host-related volatiles, with trans-2-hexenal, octanal, and benzaldehyde showing the strongest affinity to CrufCSP1. A molecular docking analysis indicated that specific amino acid residues (Phe24, Asp25, Thr53, and Lys81) of CrufCSP1 can bind to these specific ligands. Together, these findings suggest that CrufCSP1 may play a crucial role in the process of C. ruficrus locating hosts. This knowledge can contribute to the development of more efficient and eco-friendly strategies for protecting crops and managing pests.

Helicobacter pylori intragastric colonization and migration: Endoscopic manifestations and potential mechanisms.

After being ingested and entering the human stomach, Helicobacter pylori (H. pylori) adopts several effective strategies to adhere to and colonize the gastric mucosa and move to different regions of the stomach to obtain more nutrients and escape from the harsher environments of the stomach, leading to acute infection and chronic gastritis, which is the basis of malignant gastric tumors. The endoscopic manifestations and pathological features of H. pylori infection are diverse and vary with the duration of infection. In this review, we describe the endoscopic manifestations of each stage of H. pylori gastritis and then reveal the potential mechanisms of bacterial intragastric colonization and migration from the perspective of endoscopists to provide direction for future research on the effective therapy and management of H. pylori infection.

Adult Laryngeal Pleomorphic Rhabdomyosarcoma: A Rare Entity.

Rhabdomyosarcoma (RMS) is a rare and aggressive cancerous tumor that arises from embryonal mesenchymal cells with skeletal muscle differentiation, and it is exceedingly rare that occurs specifically in the larynx. To date, only 22 instances of laryngeal pleomorphic RMSs have been documented in adults. Consequently, there is limited information available to assist healthcare professionals in effectively handling RMS in the larynx of adult patients. Here, we present an uncommon occurrence involving a 45-year-old man who experienced progressive hoarseness and received a diagnosis of pleomorphic RMS affecting the larynx. Pleomorphic RMS had been pathologically diagnosed after a vertical hemilaryngectomy. Following the surgical intervention, the patient underwent chemotherapy and radiation therapy. As of now, there have been no indications of tumor recurrence.

EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A.

OBJECTIVE: Histone modification has a significant effect on gene expression. Enhancer of zeste homolog 2 (EZH2) contributes to the epigenetic silencing of target chromatin through its roles as a histone-lysine N-methyltransferase enzyme. The development of anoikis resistance in tumor cells is considered to be a critical step in the metastatic process of primary malignant tumors. The purpose of this study was to investigate the effect and mechanism of anoikis resistance in ovarian adenocarcinoma peritoneal metastasis. METHODS: In addition to examining EZH2 protein expression in ovarian cancer omental metastatic tissues, we established a model of ovarian cancer cell anoikis and a xenograft tumor model in nude mice. Anoikis resistance and ovarian cancer progression were tested after EZH2 and N6-methyladenosine (m6A) levels were modified. RESULTS: EZH2 expression was significantly higher in ovarian cancer omental metastatic tissues than in normal ovarian tissues. Reducing the level of EZH2 decreased the level of m6A and ovarian cancer cell anoikis resistance in vitro and inhibited ovarian cancer progression in vivo. M6a regulation altered the effect of EZH2 on anoikis resistance. CONCLUSION: Our results indicate that EZH2 contributes to anoikis resistance and promotes ovarian adenocarcinoma abdominal metastasis by m6A modification. Our findings imply the potential of the clinical application of m6A and EZH2 for patients with ovarian cancer.

Primary Treatment for Clinically Early Cervical Cancer with Lymph Node Metastasis: Radical Surgery or Radiation?

OBJECTIVE: To compare survival outcomes between primary radical surgery and primary radiation in early cervical cancer. METHODS: Patient information was extracted from the Surveillance, Epidemiology, and Results database. Patients diagnosed with early cervical cancer of stage T1a, T1b, and T2a (American Joint Committee on Cancer, 7th edition) from 1998 to 2015 were included in this study after propensity score matching. Overall survival (OS) was analyzed using the Kaplan-Meier method. RESULTS: Among the 4964 patients included in the study, 1080 patients were identified as having positive lymph nodes (N1), and 3884 patients were identified as having negative lymph nodes (N0). Patients with primary surgery had significantly longer 5-year OS than those with primary radiotherapy in both the N1 group (P<0.001) and N0 group (P<0.001). In the subgroup analysis, similar results were found in patients with positive lymph nodes of stage T1a (100.0% vs. 61.1%), T1b (84.1% vs. 64.3%), and T2a (74.4% vs. 63.8%). In patients with T1b1 and T2a1, primary surgery resulted in longer OS than primary radiation, but not in patients with T1b2 and T2a2. In multivariate analysis, the primary treatment was identified as an independent prognostic factor in both N1 and N0 patients (HRN1=2.522, 95% CI=1.919-3.054, PN1<0.001; HRN0=1.895, 95% CI=1.689-2.126, PN0<0.001). CONCLUSION: In early cervical cancer stage T1a, T1b1, and T2a1, primary surgery may result in longer OS than primary radiation for patients with and without lymph node metastasis.

Comparative studies of ovipositional preference, larval feeding selectivity, and nutritional indices of Spodoptera frugiperda (Lepidoptera: Noctuidae) on 6 crops.

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), is a significant invasive pest identified as a serious threat to global agricultural production and food security. However, its ovipositional preference, larval feeding selectivity, and nutritional indices are less studied. Here, we investigated these traits of FAW when fed on maize, wheat, soybean, tomato, cotton, and Chinese cabbage, and analyzed the correlation between its nutritional indices and the nutritional contents of crops. The results showed that the highest number of eggs were laid on maize and the lowest number were laid on tomato. The highest feeding choice rate of third instar larvae was on maize, and the lowest was on Chinese cabbage. The fifth instar larvae showed the highest feeding choice rate on maize, but no significant differences were found among other crop species. The food consumption (FC), the relative growth rate (RGR), and the approximate digestibility (AD) were significantly higher on maize and wheat, while the efficiency of conversion of ingested food (ECI) and the efficiency of conversion of digested food (ECD) were significantly higher when fed on cotton and Chinese cabbage. The FC, the relative consumption rate (RCR), RGR, and AD were significantly and positively correlated with soluble sugar and protein contents of host plants, while the ECI and ECD were significantly and negatively correlated with the soluble sugar content. The present study indicates that FAW may cause potential economic losses to these crops besides maize, and these findings are valuable in managing and controlling this pest.

Silencing of the calcium-dependent protein kinase TaCDPK27 improves wheat resistance to powdery mildew.

BACKGROUND: Calcium ions (Ca2+), secondary messengers, are crucial for the signal transduction process of the interaction between plants and pathogens. Ca2+ signaling also regulates autophagy. As plant calcium signal-decoding proteins, calcium-dependent protein kinases (CDPKs) have been found to be involved in biotic and abiotic stress responses. However, information on their functions in response to powdery mildew attack in wheat crops is limited. RESULT: In the present study, the expression levels of TaCDPK27, four essential autophagy-related genes (ATGs) (TaATG5, TaATG7, TaATG8, and TaATG10), and two major metacaspase genes, namely, TaMCA1 and TaMCA9, were increased by powdery mildew (Blumeria graminis f. sp. tritici, Bgt) infection in wheat seedling leaves. Silencing TaCDPK27 improves wheat seedling resistance to powdery mildew, with fewer Bgt hyphae occurring on TaCDPK27-silenced wheat seedling leaves than on normal seedlings. In wheat seedling leaves under powdery mildew infection, silencing TaCDPK27 induced excess contents of reactive oxygen species (ROS); decreased the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT); and led to an increase in programmed cell death (PCD). Silencing TaCDPK27 also inhibited autophagy in wheat seedling leaves, and silencing TaATG7 also enhanced wheat seedling resistance to powdery mildew infection. TaCDPK27-mCherry and GFP-TaATG8h colocalized in wheat protoplasts. Overexpressed TaCDPK27-mCherry fusions required enhanced autophagy activity in wheat protoplast under carbon starvation. CONCLUSION: These results suggested that TaCDPK27 negatively regulates wheat resistance to PW infection, and functionally links with autophagy in wheat.

Pangenome obtained by long-read sequencing of 11 genomes reveal hidden functional structural variants in pigs.

Long-read sequencing (LRS) facilitates both the genome assembly and the discovery of structural variants (SVs). Here, we built a graph-based pig pangenome by incorporating 11 LRS genomes with an average of 94.01% BUSCO completeness score, revealing 206-Mb novel sequences. We discovered 183,352 nonredundant SVs (63% novel), representing 12.12% of the reference genome. By genotyping SVs in an additional 196 short-read sequencing samples, we identified thousands of population stratified SVs. Particularly, we detected 7,568 Tibetan specific SVs, some of which demonstrate significant population differentiation between Tibetan and low-altitude pigs, which might be associated with the high-altitude hypoxia adaptation in Tibetan pigs. Further integrating functional genomic data, the most promising candidate genes within the SVs that might contribute to the high-altitude hypoxia adaptation were discovered. Overall, our study generates a benchmark pangenome resource for illustrating the important roles of SVs in adaptive evolution, domestication, and genetic improvement of agronomic traits in pigs.