The role and mechanism of PDZ binding kinase in hypobaric and hypoxic acute lung injury.

Background: Acute lung injury (ALI) caused by hypobaric hypoxia (HH) is frequently observed in high-altitude areas, and it is one of the leading causes of death in high-altitude-related diseases due to its rapid onset and progression. However, the pathogenesis of HH-related ALI (HHALI) remains unclear, and effective treatment approaches are currently lacking. Methods: A new mouse model of HHALI developed by our laboratory was used as the study subject (Chinese patent No. ZL 2021 1 1517241 X). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the messenger RNA (mRNA) expression levels of PDZ-binding kinase (PBK), sirtuin 1 (SIRT1), and PTEN-induced kinase 1 (PINK1) in mouse lung tissue. Hematoxylin and eosin staining was used to observe the main types of damage and damaged cells in lung tissue, and the lung injury score was used for quantification. The wet-dry (W/D) ratio was used to measure lung water content. Enzyme-linked immunosorbent assay was used to detect changes in inflammatory factors and oxidative stress markers in the lungs. Western blotting verified the expression of various mitochondrial autophagy-related proteins. The 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazoylcarbocyanine iodide (JC-1) method was used determined the health status of mitochondria based on changes in mitochondrial membrane potential. Transmission electron microscopy was used to directly observe the morphology of mitochondria. Multicolor immunofluorescence was used to observe the levels of mitochondrial autophagy markers. Other signaling pathways and molecular mechanisms that may play a role in epithelial cells were analyzed via through RNA sequencing. Results: Low pressure and hypoxia caused pathological changes in mouse lung tissue, mainly ALI, leading to increased levels of inflammatory factors and intensified oxidative stress response in the lungs. Overexpression of PBK was found to alleviate HHALI, and activation of the p53 protein was shown to abrogate this therapeutic effect, while activation of SIRT1 protein reactivated this therapeutic effect. The therapeutic effect of PBK on HHALI is achieved via the activation of mitochondrial autophagy. Finally, RNA sequencing demonstrated that besides mitochondrial autophagy, PBK also exerts other functions in HHALI. Conclusions: Overexpression of PBK inhibits the expression of p53 and activates SIRT1-PINK1 axis mediated mitochondrial autophagy to alleviate HHALI.

Pantoprazole and Vonoprazan Performed Well in Preventing Peptic Ulcer Recurrence in Low-Dose Aspirin Users.

BACKGROUND: Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage. AIMS: This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy. METHODS: This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated. RESULTS: 11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone. CONCLUSIONS: For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage.

Photochemically controlled activation of STING by CAIX-targeting photocaged agonists to suppress tumor cell growth.

Controllable activation of the innate immune adapter protein - stimulator of interferon genes (STING) pathway is a critical challenge for the clinical development of STING agonists due to the potential "on-target off-tumor" toxicity caused by systematic activation of STING. Herein, we designed and synthesized a photo-caged STING agonist 2 with a tumor cell-targeting carbonic anhydrase inhibitor warhead, which could be readily uncaged by blue light to release the active STING agonist leading to remarkable activation of STING signaling. Furthermore, compound 2 was found to preferentially target tumor cells, stimulate the STING signaling in zebrafish embryo upon photo-uncaging and to induce proliferation of macrophages and upregulation of the mRNA expression of STING as well as its downstream NF-kB and cytokines, thus leading to significant suppression of tumor cell growth in a photo-dependent manner with reduced systemic toxicity. This photo-caged agonist not only provides a powerful tool to precisely trigger STING signalling, but also represents a novel controllable STING activation strategy for safer cancer immunotherapy.

Identification and Functional Characterization of WRKY, PHD and MYB Three Salt Stress Responsive Gene Families in Mungbean (Vigna radiata L.).

WRKY-, PHD-, and MYB-like proteins are three important types of transcription factors in mungbeans, and play an important role in development and stress resistance. The genes' structures and characteristics were clearly reported and were shown to contain the conservative WRKYGQK heptapeptide sequence, Cys4-His-cys3 zinc binding motif, and HTH (helix) tryptophan cluster W structure, respectively. Knowledge on the response of these genes to salt stress is largely unknown. To address this issue, 83 VrWRKYs, 47 VrPHDs, and 149 VrMYBs were identified by using comparative genomics, transcriptomics, and molecular biology methods in mungbeans. An intraspecific synteny analysis revealed that the three gene families had strong co-linearity and an interspecies synteny analysis showed that mungbean and Arabidopsis were relatively close in genetic relationship. Moreover, 20, 10, and 20 genes showed significantly different expression levels after 15 days of salt treatment (p < 0.05; Log2 FC > 0.5), respectively. Additionally, in the qRT-PCR analysis, VrPHD14 had varying degrees of response to NaCl and PEG treatments after 12 h. VrWRKY49 was upregulated by ABA treatment, especially in the beginning (within 24 h). VrMYB96 was significantly upregulated in the early stages of ABA, NaCl, and PEG stress treatments (during the first 4 h). VrWRKY38 was significantly upregulated by ABA and NaCl treatments, but downregulated by PEG treatment. We also constructed a gene network centered on the seven DEGs under NaCl treatment; the results showed that VrWRKY38 was in the center of the PPI network and most of the homologous Arabidopsis genes of the interacted genes were reported to have response to biological stress. Candidate genes identified in this study provide abundant gene resources for the study of salt tolerance in mungbeans.

Pulmonary perfusion imaging and delayed imaging to measure pulmonary capillary permeability in pulmonary contusion.

PURPOSE: Explore the application value of pulmonary perfusion imaging and delayed imaging for evaluating pulmonary capillary permeability. MATERIALS AND METHODS: After establishing a rat model of pulmonary contusion, changes in the metabolic index of technetium-99m macroaggregated albumin (99mTC-MAA) in the lungs of model rats were evaluated for two consecutive days. 99mTC-MAA metabolic indices of rat lungs with pulmonary contusion of varying severity (mild, moderate, and severe) were correlated with lung wet/dry weight ratio (W/D) and Evans blue extravasation. Finally, the method was validated in patients with pulmonary contusion and one healthy volunteer. RESULTS: The 99mTC-MAA metabolic index was 23.56% ± 2.44% in healthy control (HC) rat lung, 8.56% ± 3.42% immediately after lung contusion (d0), 8.35% ± 3.20% after 1 day (d1), and 17.45% ± 6.44% after 2 days (d2); indices at d0 and d1 were significantly higher than those at HC (P < 0.05). The metabolic index of 99mTC-MAA in lung had significant negative correlations with W/D (r = -0.8025; P = 0.0092) and Evans blue extravasation (r = -0.9356; P = 0.0002). Metabolic and oxygenation indices of 99mTC-MAA exhibited a significant positive linear correlation in patients with pulmonary contusion (r = 0.8925; P = 0.0416). CONCLUSION: Pulmonary perfusion and delayed imaging of 99mTC-MAA have potential value for evaluating pulmonary capillary permeability.

Safety and efficacy of minimally invasive McKeown esophagectomy in 1023 consecutive esophageal cancer patients: a single-center experience.

OBJECTIVE: By analyzing the perioperative, postoperative complications and long-term overall survival time, we summarized the 8-year experience of minimally invasive McKeown esophagectomy for esophageal cancer in a single medical center. METHODS: This retrospective follow-up study included 1023 consecutive patients with esophageal cancer who underwent MIE-McKeown between Mar 2013 and Oct 2020. Relevant variables were collected and evaluated. Overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier method. RESULTS: For 1023 esophageal cancer undergoing MIE-McKeown, the main intraoperative complications were bleeding (3.0%, 31/1023) and tracheal injury (1.7%, 17/1023). There was no death occurred during operation. The conversion rate of thoracoscopy to thoracotomy was 2.2% (22/1023), and laparoscopy to laparotomy was 0.3% (3/1023). The postoperative morbidity of complications was 36.2% (370/1023), of which anastomotic leakage 7.7% (79/1023), pulmonary complication 13.4% (137/1023), chylothorax 2.3% (24/1023), and recurrent laryngeal nerve injury 8.8% (90/1023). The radical resection rate (R0) was 96.0% (982/1023), 30-day mortality was 0.3% (3/1023). For 1000 cases with squamous cell carcinoma, the estimated 3-year and 5-year overall survival was 37.2% and 17.8% respectively. In addition, neoadjuvant chemotherapy offered 3-year disease-free survival rate advantage in advanced stage patients (for stage IV: 7.2% vs. 1.8%). CONCLUSIONS: This retrospective single center study demonstrates that MIE-McKeown procedure is feasible and safe with low perioperative and postoperative complications' morbidity, and acceptable long-term oncologic results.

Viral infection in thymoma and thymic tumors with autoimmune diseases.

A thymoma is a type of thymic tumor which is rarely malignant that is frequently reported in adult patients. A number of thymoma-related immune disorders are observed including autoimmune diseases, which suggests a strong connection between thymoma development and immunological mechanisms. Characterized by association with humoral and cellular immunodeficiency, thymoma patients are susceptible to opportunistic infections by environmental factors. Recent reports have suggested that viral infection may play a role in the etiological mechanisms of thymoma development associated with dysregulated immunity. In this review, we summarize the case reports and studies related to viral infection, such as CMV, EBV and HSV, that probably play a part in the pathogenesis of thymoma and related diseases. Furthermore, we demonstrate the underlying mechanisms by which viruses may induce the occurrence of thymoma with autoimmune diseases. Lastly, we discuss the potential application of antiviral therapy in the treatment of thymic diseases.

Two-step preparation of Keggin-PW12@UIO-66 composite showing high-activity and long-life conversion of soybean oil into biodiesel.

A polyoxometalate acid can be encapsulated into a metal-organic framework to construct a novel kind of solid-acid catalyst. In this work, the two-step method -high-temperature preparation of Zr6O4(OH)4(CH3COO)12 and low-temperature self-assembly-has been adopted to synthesize the PW12@UIO-66 composite (PW12 = H3PW12O40; UIO-66 = Zr6O4(OH)4(OOC-C6H4-COO)12). The as-synthesized PW12@UIO-66 composite exhibits highly crystalline, good octahedron morphology, large specific surface area (1960 m2 g-1) and high thermal stability (>500 °C), which clearly demonstrates the potential as a solid-acid catalyst. Additionally, the PW12@UIO-66 composite may be accomplished with 85% utilization of H3PW12O40 and 95% yield through this synthetic procedure. The performances of the PW12@UIO-66 composite are investigated by catalyzing the simultaneous transesterification and esterification of soybean oil into biodiesel. Under the optimal conditions, the conversion of the soybean oil into biodiesel would exceed 90% over the as-synthesized PW12@UIO-66 composite. As the crucial indexes for industrial prospects, the recycling and life experiments were surveyed. After 10 times recycling and 4 weeks, the structure and performance of the PW12@UIO-66 composite remained unchanged and in the meantime the PW12@UIO-66 composite still maintained a high activity to convert soybean oil into biodiesel.

Outbreak of Haff Disease along the Yangtze River, Anhui Province, China, 2016.

We investigated a large outbreak of Haff disease that occurred along the Yangtze River in Anhui Province, China, in 2016. Of the 672 cases identified during the outbreak, 83.3% (560/672) occurred in Wuhu and Ma'anshan. Patients experienced myalgia (100%) and muscle weakness (54.7%). The mean value of myoglobin was 330 + 121.2 ng/mL and of serum creatine kinase 5,439.2 + 4,765.1 U/L. Eating crayfish was the only common exposure among all cases; 96.8% (240/248) of implicated crayfish were caught on the shores of the Yangtze River or its connected ditches. Mean incubation period was 6.2 + 3.8 hours. This case-control study demonstrated that eating the liver of crayfish and eating a large quantity of crayfish were associated with an increased risk for Haff disease. The seasonal increases in crayfish population along the Yangtze River might explain the seasonal outbreaks of Haff disease.

Exploring transcription factors reveals crucial members and regulatory networks involved in different abiotic stresses in Brassica napus L.

BACKGROUND: Brassica napus (B. napus) encompasses diverse transcription factors (TFs), but thorough identification and characterization of TF families, as well as their transcriptional responsiveness to multifarious stresses are still not clear. RESULTS: Totally 2167 TFs belonging to five families were genome-widely identified in B. napus, including 518 BnAP2/EREBPs, 252 BnbZIPs, 721 BnMYBs, 398 BnNACs and 278 BnWRKYs, which contained some novel members in comparison with existing results. Sub-genome distributions of BnAP2/EREBPs and BnMYBs indicated that the two families might have suffered from duplication and divergence during evolution. Synteny analysis revealed strong co-linearity between B. napus and its two ancestors, although chromosomal rearrangements have occurred and 85 TFs were lost. About 7.6% and 9.4% TFs of the five families in B. napus were novel genes and conserved genes, which both showed preference on the C sub-genome. RNA-Seq revealed that more than 80% TFs were abiotic stress inducible and 315 crucial differentially expressed genes (DEGs) were screened out. Network analysis revealed that the 315 DEGs are highly co-expressed. The homologous gene network in A. thaliana revealed that a considerable amount of TFs could trigger the differential expression of targeted genes, resulting in a complex clustered network with clusters of genes responsible for targeted stress responsiveness. CONCLUSIONS: We identified and characterized five TF families in B. napus. Some crucial members and regulatory networks involved in different abiotic stresses have been explored. The investigations deepen our understanding of TFs for stress tolerance in B. napus.