PGRP-SC2 promotes gut immune homeostasis to limit commensal dysbiosis and extend lifespan.

Interactions between commensals and the host impact the metabolic and immune status of metazoans. Their deregulation is associated with age-related pathologies like chronic inflammation and cancer, especially in barrier epithelia. Maintaining a healthy commensal population by preserving innate immune homeostasis in such epithelia thus promises to promote health and longevity. Here, we show that, in the aging intestine of Drosophila, chronic activation of the transcription factor Foxo reduces expression of peptidoglycan recognition protein SC2 (PGRP-SC2), a negative regulator of IMD/Relish innate immune signaling, and homolog of the anti-inflammatory molecules PGLYRP1-4. This repression causes deregulation of Rel/NFkB activity, resulting in commensal dysbiosis, stem cell hyperproliferation, and epithelial dysplasia. Restoring PGRP-SC2 expression in enterocytes of the intestinal epithelium, in turn, prevents dysbiosis, promotes tissue homeostasis, and extends lifespan. Our results highlight the importance of commensal control for lifespan of metazoans and identify SC-class PGRPs as longevity-promoting factors.

Variant effect predictors: a systematic review and practical guide.

Large-scale association analyses using whole-genome sequence data have become feasible, but understanding the functional impacts of these associations remains challenging. Although many tools are available to predict the functional impacts of genetic variants, it is unclear which tool should be used in practice. This work provides a practical guide to assist in selecting appropriate tools for variant annotation. We conducted a MEDLINE search up to November 10, 2023, and included tools that are applicable to a broad range of phenotypes, can be used locally, and have been recently updated. Tools were categorized based on the types of variants they accept and the functional impacts they predict. Sequence Ontology terms were used for standardization. We identified 118 databases and software packages, encompassing 36 variant types and 161 functional impacts. Combining only three tools, namely SnpEff, FAVOR, and SparkINFERNO, allows predicting 99 (61%) distinct functional impacts. Thirty-seven tools predict 89 functional impacts that are not supported by any other tool, while 75 tools predict pathogenicity and can be used within the ACMG/AMP guidelines in a clinical context. We launched a website allowing researchers to select tools based on desired variants and impacts. In summary, more than 100 tools are already available to predict approximately 160 functional impacts. About 60% of the functional impacts can be predicted by the combination of three tools. Unexpectedly, recent tools do not predict more impacts than older ones. Future research should allow predicting the functionality of so far unsupported variant types, such as gene fusions.URL: https://cardio-care.shinyapps.io/VEP_Finder/ .Registration: OSF Registries on November 10, 2023, https://osf.io/s2gct .

Development of mitochondrial gene-editing strategies and their potential applications in mitochondrial hereditary diseases: a review.

Mitochondrial DNA (mtDNA) is a critical genome contained within the mitochondria of eukaryotic cells, with many copies present in each mitochondrion. Mutations in mtDNA often are inherited and can lead to severe health problems, including various inherited diseases and premature aging. The lack of efficient repair mechanisms and the susceptibility of mtDNA to damage exacerbate the threat to human health. Heteroplasmy, the presence of different mtDNA genotypes within a single cell, increases the complexity of these diseases and requires an effective editing method for correction. Recently, gene-editing techniques, including programmable nucleases such as restriction endonuclease, zinc finger nuclease, transcription activator-like effector nuclease, clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated 9 and base editors, have provided new tools for editing mtDNA in mammalian cells. Base editors are particularly promising because of their high efficiency and precision in correcting mtDNA mutations. In this review, we discuss the application of these techniques in mitochondrial gene editing and their limitations. We also explore the potential of base editors for mtDNA modification and discuss the opportunities and challenges associated with their application in mitochondrial gene editing. In conclusion, this review highlights the advancements, limitations and opportunities in current mitochondrial gene-editing technologies and approaches. Our insights aim to stimulate the development of new editing strategies that can ultimately alleviate the adverse effects of mitochondrial hereditary diseases.

SeMet alleviates LPS-induced eggshell gland necroptosis mediated inflammation by regulating the Keap1/Nrf2/HO-1 pathway.

Exposure to lipopolysaccharide (LPS) can lead to inflammation in a variety of tissues and organs. Selenium (Se) plays a crucial role in mitigating inflammatory damage. Compared with inorganic selenium, organic selenium, such as selenomethionine (SeMet), has the advantages of a higher absorption rate and lower toxicity in animals. This study examined the protective effects of SeMet on eggshell gland tissue damage caused by LPS. Hy-Line Brown laying hens were chosen as the experimental animals and were randomly assigned to four groups: control group (C), lipopolysaccharide group (LPS), SeMet group (Se), and SeMet + lipopolysaccharide group (Se + LPS). H&E staining and transmission electron microscope were performed to observe the pathological changes of eggshell glands, oxidative stress related indicators were measured using relevant kits, qRT‒PCR and western blotting were used to evaluate the mRNA and protein levels of the Nrf2 pathway, necroptosis, and inflammation related indicators. The results showed that LPS treatment increased the content of malondialdehyde (MDA), decreased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and decreased the content of glutathione (GSH). LPS increased the levels of Keap1, RIPK1, RIPK3, MLKL, TNF-α, COX-2, and NF-κB, while decreasing the levels of HO-1, NQO1, Nrf2, and Caspase-8. However, SeMet treatment effectively reversed the changes of the above indicators, indicating that SeMet alleviates eggshell gland cell necroptosis-mediated inflammation induced by LPS via regulating the Keap1/Nrf2/HO-1 pathway. This study elucidated the mechanism by which SeMet alleviates LPS-induced eggshell gland tissue damage in Hy-Line Brown laying hens and provided a new direction for expanding the application of SeMet in the feeding and production of laying hens.

IKK1 aggravates ischemia-reperfusion kidney injury by promoting the differentiation of effector T cells.

Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI), and experimental work has revealed detailed insight into the inflammatory response in the kidney. T cells and NFκB pathway play an important role in IRI. Therefore, we examined the regulatory role and mechanisms of IkappaB kinase 1 (IKK1) in CD4+T lymphocytes in an experimental model of IRI. IRI was induced in CD4cre and CD4IKK1Δ mice. Compared to control mice, conditional deficiency of IKK1 in CD4+T lymphocyte significantly decreased serum creatinine, blood urea nitrogen (BUN) level, and renal tubular injury score. Mechanistically, lack in IKK1 in CD4+T lymphocytes reduced the ability of CD4 lymphocytes to differentiate into Th1/Th17 cells. Similar to IKK1 gene ablation, pharmacological inhibition of IKK also protected mice from IRI. Together, lymphocyte IKK1 plays a pivotal role in IRI by promoting T cells differentiation into Th1/Th17 and targeting lymphocyte IKK1 may be a novel therapeutic strategy for IRI.

Effects of exercise intensity on spatial memory performance and hippocampal synaptic function in SAMP8 mice.

Learning and memory impairment is commonly noted in Alzheimer's disease (AD), which is regarded as a progressive synaptic failure disease. Exercise is a nonpharmacological strategy that may help prevent cognitive decline and reduce the risk of AD, which is usually thought to be related to synaptic damage in the hippocampus. However, the effects of exercise intensity on hippocampal memory and synaptic function in AD remain unclear. In this study, senescence-accelerated mouse prone-8 (SAMP8) mice were randomly assigned to the control group (Con), low-intensity exercise group (Low), and moderate-intensity exercise group (Mid). Here, we showed that eight weeks of treadmill exercise beginning in four-month-old mice improved spatial memory and recognition memory in six-month-old SAMP8 mice, while the Con group exhibited impaired spatial memory and recognition memory. Treadmill exercise also improved hippocampal neuron morphology in SAMP8 mice. Furthermore, dendritic spine density and the levels of postsynaptic density protein-95 (PSD95) and Synaptophysin (SYN) increased significantly in the Low and Mid groups as compared with the Con group. We further showed that moderate-intensity exercise (60 % of maximum speed) was more efficacious in increasing dendritic spine density、PSD95 and SYN, than low-intensity exercise (40 % of maximum speed). In conclusion, the positive effect of treadmill exercise is closely related to exercise intensity, with moderate-intensity exercise showing the most optimal effects.

Circular RNA SESN2 aggravates gestational trophoblast cell damage induced by high glucose by binding to IGF2BP2.

Gestational diabetes mellitus (GDM) is a common disease in pregnant women that threatens maternal and fetal health. Circular RNAs (circRNAs) have been considered potential diagnostic markers for GDM and affect trophoblast cell phenotypes. This study aimed to explore the effect of circSESN2 on high glucose (HG)-treated trophoblast cells. Peripheral blood and placental tissues were taken from patients with GDM, in which circSESN2 and IGF2BP2 levels were detected by quantitative reverse transcription polymerase chain reaction and/or western blot. HTR-8/SVneo cells were treated with 25 mM glucose and transduced with circSESN2 or IGF2BP2 knockdown vectors. HTR-8/SVneo cell viability was evaluated by MTT assay, cell migration by scratch test, and cell invasion by transwell assay, IL-1ß, IL-6, TNF-α, malondialdehyde, and superoxide dismutase levels by ELISA or kits, and reactive oxygen species levels by DCFH-DA probes. The binding between circSESN2 and IGF2BP2 was verified by RNA pulldown and RIP assays. CircSESN2 and IGF2BP2 were overexpressed in GDM patients. Suppressing circSESN2 or IGF2BP2 increased HTR-8/SVneo cell invasion and migration, decreased cell apoptosis, and reduced pro-inflammatory cytokine release and oxidative stress injury. CircSESN2 bound IGF2BP2 and IGF2BP2 overexpression accelerated HG-induced HTR-8/SVneo cell damage despite circSESN2 knockdown. Collectively, circSESN2 exacerbated HG-induced trophoblast cell damage by binding IGF2BP2 and upregulating its protein expression.

House dust mite-induced endoplasmic reticulum stress mediates MUC5AC hypersecretion via TBK1 in airway epithelium.

Purpose: Endoplasmic reticulum (ER) stress regulates mucus hypersecretion, and may activate downstream factors via TBK1 signaling to induce gene expression. However, it remains unclear whether ER stress promotes airway mucus secretion through the TBK1 pathway. We aimed to investigate the role of the TBK1 pathway in the regulation of MUC5AC expression in a mouse model of house dust mite (HDM)-induced allergic asthma. Materials and Methods: Mice with HDM-induced asthma and human bronchial epithelial BEAS-2B cells were treated with amlexanox, an anti-allergy drug (25 µM), or 4-PBA (10 mM). Tissue and cell samples were collected. Tissue samples were stained with hematoxylin and eosin (H&E) or periodic acid Schiff (PAS) to evaluate pathology. Protein expression was analyzed by western blotting and immunofluorescence. Results: Mice exposed to HDM presented ER stress and hypersecretion of mucus Muc5ac from airway epithelial cells (p < 0.001). Similar results were observed in BEAS-2B cells following exposure to HDM. Both in vivo and in vitro studies revealed that HDM-induced ER stress induced MUC5AC overexpression via TBK1 signaling. Amlexanox and 4-PBA markedly reduced mucus production and weakened the TBK1 signal, which mediates MUC5AC hypersecretion. Conclusion: TBK1 plays a pivotal role in HDM-induced ER stress, leading to overproduction of MUC5AC in the asthmatic airway epithelium. The overproduction of MUC5AC can be significantly decreased by inhibiting TBK1 or ER stress using 4-PBA. These findings highlight potential target-specific therapies for patients with chronic allergic asthma.

Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis.

BACKGROUND: Bone regeneration is a complex procedure that involves an interaction between osteogenesis and inflammation. Macrophages in the microenvironment are instrumental in bone metabolism. Amount evidence have revealed that exosomes transmitting lncRNA is crucial nanocarriers for cellular interactions in various biotic procedures, especially, osteogenesis. However, the underlying mechanisms of the regulatory relationship between the exosomes and macrophages are awaiting clarification. In the present time study, we aimed to explore the roles of human umbilical vein endothelial cells (HUVECs)-derived exosomes carrying nuclear enrichment enriched transcript 1 (NEAT1) in the osteogenesis mediated by M2 polarized macrophages and elucidate the underlying mechanisms. RESULTS: We demonstrated HUVECs-derived exosomes expressing NEAT1 significantly enhanced M2 polarization and attenuated LPS-induced inflammation in vitro. Besides, the conditioned medium from macrophages induced by the exosomes indirectly facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Mechanically, Exos carrying NEAT1 decreased remarkably both expression of dead-box helicase 3X-linked (DDX3X) and nod-like receptor protein 3 (NLRP3). The level of NLRP3 protein increased significantly after RAW264.7 cells transfected with DDX3X overexpression plasmid. Additionally, the knockdown of NEAT1 in exosomes partially counteracted the aforementioned effect of Exos. The results of air pouch rat model demonstrated that HUVECs-derived exosomes increased anti-inflammatory cytokines (IL-10) and decreased pro-inflammatory cytokines (IL-1ß and IL-6) significantly in vivo, contributing to amelioration of LPS-induced inflammation. Afterwards, we further confirmed that the HUVECs-derived exosomes encapsulated in alginate/gelatin methacrylate (GelMA) interpenetrating polymer network (IPN) hydrogels could promote the bone regeneration, facilitate the angiogenesis, increase the infiltration of M2 polarized macrophages as well as decrease NLRP3 expression in the rat calvarial defect model. CONCLUSIONS: HUVECs-derived exosomes enable transmitting NEAT1 to alleviate inflammation by inducing M2 polarization of macrophages through DDX3X/NLRP3 regulatory axis, which finally contributes to osteogenesis with the aid of alginate/GelMA IPN hydrogels in vivo. Thus, our study provides insights in bone healing with the aid of HUVECs-derived exosomes-encapsulated composite hydrogels, which exhibited potential towards the use of bone tissue engineering in the foreseeable future.

Efficacy Analysis of Neoadjuvant versus Adjuvant Cisplatin-Paclitaxel Regimens for Initial Treatment of FIGO Stages IB3 and IIA2 Cervical Cancer.

BACKGROUND Large cancer lesions are often challenging to treat with surgical intervention alone. Neoadjuvant chemotherapy is frequently used for FIGO stage IB3 and IIA2 cervical cancers to optimize the outcomes of radical surgeries. This study aimed to compare the effectiveness of neoadjuvant chemotherapy, followed by adjuvant chemotherapy and radiotherapy, if necessary, with the traditional approach of adjuvant chemotherapy and radiotherapy after radical hysterectomy in treatment-naïve patients with cervical cancer of specified stages. MATERIAL AND METHODS A total of 245 female patients were administered either 70 to 85 mg/m² cisplatin and 165 to 175 mg/m² paclitaxel every 21 days (2 cycles) prior to radical hysterectomy, followed by adjuvant chemotherapy and radiotherapy if needed (neoadjuvant therapy, NT cohort, n=105), or received adjuvant chemotherapy and radiotherapy after radical hysterectomy adjuvant therapy, AT cohort, n=140). RESULTS In the NT cohort, 76% of patients responded to neoadjuvant chemotherapy, while 24% did not. Adverse operative, intraoperative, and postoperative outcomes were significantly more common among the non-responders (P<0.05). After 5 years, 91% of responders and 72% of non-responders survived without recurrence (P=0.0372), and 3% of responders and 28% of non-responders had died (P=0.0005). CONCLUSIONS The resistance to neoadjuvant chemotherapy is a poor prognostic factor. Neoadjuvant chemotherapy followed by radical hysterectomy and adjuvant chemotherapy/radiotherapy appears to be advantageous for cervical cancer patients who respond well to neoadjuvant chemotherapy.

Identification and validation of a prognostic model for melanoma patients with 9 ferroptosis-related gene signature.

BACKGROUND: Melanoma is a highly heterogeneous and aggressive cutaneous malignancy. Ferroptosis, a new pathway of cell death depending on the intracellar iron, has been shown to be significantly associated with apoptosis of a number of tumors, including melanoma. Nevertheless, the relationship between ferroptosis-related genes (FRGs) and the melanoma patients' prognosis needs to be explored. METHODS: Download expression profiles of FRGs and clinical data from The Cancer Genome Atlas (TCGA) database. 70% data were randomly selected from the TCGA database and utilized the univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model to create a prognostic model, and the remaining 30% was used to validate the predictive power of the model. In addition, GSE65904 and GSE22153 date sets as the verification cohort to testify the predictive ability of the signature. RESULTS: We identified nine FRGs relating with melanoma patients' overall survival (OS) and established a prognostic model based on their expression. During the research, patients were divided into group of high-risk and low-risk according to the results of LASSO regression analysis. Survival time was significantly longer in the low-risk group than that of in the high-risk group (P < 0.001). Enrichment analysis of different risk groups demonstrated that the reasons for the difference were related to immune-related pathways, and the degree of immune cell infiltration in the low-risk group was significantly higher than that in the high-risk group. CONCLUSIONS: The FRG prognostic model we established can predict the prognosis of melanoma patients and may further guide subsequent treatment.

High-Pressure Synthesis and Stability Enhancement of Lithium Pentazolate.

The pentazolate anion, cyclo-N5-, has received extensive attention as a new generation of energetic species for explosive or propulsion applications. Binary pentazolate compounds have been obtained under high-pressure conditions and their stability enhancement is crucial for obtaining more competitive high energy density materials (HEDMs). Here, we report the synthesis of a new solid phase of lithium pentazolate (space group P21/c) through the chemical transformation of pure lithium azide under high-pressure and high-temperature conditions. Upon decompression, the structural transition from P21/c-LiN5 to P21/m-LiN5 at ∼15.6 GPa was observed for the first time. Cyclo-N5- can be traced down to ∼5.7 GPa at room temperature and recovered to ambient pressure under a low-temperature condition (80 K). Our results reveal the enhancement of pentazolate anion stability with the increasing content of metal cations and demonstrate that low temperature is an effective route for the recovery of the pentazolate anion.

First prototype checkpoint inhibitor B-cell epitope vaccine (PD1-Vaxx) en route to human Phase 1 clinical trial in Australia and USA: exploiting future novel synergistic vaccine combinations.

We developed a PD-1 B-cell epitope vaccine (PD1-Vaxx) to rival nivolumab therapy which has received ethics approvals for a Phase 1 clinical trial in Australia. The US FDA granted Investigational New Drug approval to Imugene Ltd for clinical testing in NSCLC. We demonstrated synergistic vaccine combinations with an HER-2 targeted vaccine (B-Vaxx).

[Research progress and discussion on traditional Chinese medicine properties of Kaempferia parviflora].

Kaempferiae Parviflorae Rhizoma is the dried rhizome of Kaempferia parviflora in Zingiberaceae. It is originated and widely distributed in Thailand and other tropical and subtropical regions, where it has been used as food and medicine for thousands of years. K. parviflora is also planted in Yunnan and other places of China, but its traditional Chinese medicine properties are not clear, which greatly limits its compatibility with traditional Chinese medicines. In this article, the English and Chinese literatures of K. parviflora were searched from Web of Science, PubMed, Scopus, CNKI, Wanfang, and VIP databases for research and analysis. The medicinal properties of K. parviflora were preliminarily discussed based on the theory of traditional Chinese medicine under the guidance of clinical application and research literatures. The traditional Chinese medicine properties of K. parviflora were inferred as follows: flat, acrid, sweet. The channel tropisms of K. parviflora included kidney, spleen, stomach, and liver. The function of K. parviflora included tonifying kidney to strengthen essence, tonifying Qi and invigorating spleen, soothing liver and relieving depression. K. parviflora was clinically applied for the diseases such as syndrome of kidney essence deficiency, sex apathy, deficiency of spleen Qi, lassitude and asthenia, a weary spirit, obesity, diabetes, liver Qi stagnation, depression, and restless. The equivalent of dry power is 1.5 g·d~(-1) and the equivalent of decoction is 1.5-6 g·d~(-1). The determination of traditional Chinese medicine properties of K. parviflora has indeed laid a theoretical foundation for its application in the field of traditional Chinese medicine and enriched traditional Chinese medicine resources.

[Discussion on traditional Chinese medicine properties of Myrtus communis leaves based on literature analysis and Chinese medicine theory].

Myrtus communis is a traditional medicinal aromatic plant in the Mediterranean. At present, the plant has been introduced and cultivated in the southern part of China, and it is mostly used for ornamental or cosmetic purposes. Based on literature analysis and the theory of Chinese medicine, we discussed the medicinal parts and properties of M. communis in this paper to provide a theoretical basis for exploring the medicinal value of M. communis and its compatibility with traditional Chinese medicines. Literatures were searched from Web of Science(core collection), PubMed, CNKI, VIP and Wanfang by using the set conditions as key words. Then the obtained literatures were screened and classified. Finally, a total of 376 articles were included, consisting of 44 reviews, 54 germplasm resources, 78 chemical researches, 48 studies on application, extraction, or quality, 18 human trials, 132 pharmacological studies, and 2 safety studies. Based on literature analysis and theories of Chinese medicine, the leaves of M. communis were finally selected as the medicinal part of Chinese medicine, and the traditional Chinese medicine properties of M. communis leaves were deduced as pungent, bitter, and cool. The channel tropisms of M. communis leaves included lung, liver, and large intestine, with functions of detoxifying, resolving a mass, and insecticide. It was used for mouth sores, vaginal itching, hemorrhoids and warts, etc.; appropriate amount shall be applied for external use, and the decoction form shall be used for washing the affected parts; 3-12 g equivalent product shall be used in decoction, and this herb shall be put into the decoction in a later stage. The clarification of the medicinal parts of M. communis, and the determination of the Chinese medicine properties of M. communis leaves would lay a theoretical foundation for its compatibility and application with Chinese medicines, and can do more contribution to the medical and healthcare industry in our country.

T-lymphocyte-specific knockout of IKK-2 or NEMO induces Th17 cells in an experimental nephrotoxic nephritis mouse model.

Experimental nephrotoxic serum nephritis (NTN) is a model for T-cell-mediated human rapid progressive glomerulonephritis. T-cell receptor stimulation involves intracellular signaling events that ultimately lead to the activation of transcription factors, such as NF-κB. We explored the involvement of the NF-κB components IKK-2 and NEMO in NTN, by using cell-specific knockouts of IKK-2 and NEMO in CD4+ T lymphocytes. Our results demonstrate that although the course of disease was not grossly altered in CD4xIKK2Δ and CD4xNEMOΔ animals, renal regulatory T cells were significantly reduced and T helper (Th)1 and Th17 cells significantly increased in both knockout mouse groups. The expression of the renal cytokines and chemokines IL-1ß, CCL-2, and CCL-20 was also significantly altered in both knockout mice. Lymphocyte transcriptome analysis confirmed the increased expression of Th17-related cytokines in spleen CD4+ T cells. Moreover, our array data demonstrate an interrupted canonical NF-κB pathway and an increased expression of noncanonical NF-κB pathway-related genes in nephritic CD4xNEMOΔ mice, highlighting different downstream effects of deletion of IKK-2 or NEMO in T lymphocytes. We propose that better understanding of the role of IKK-2 and NEMO in nephritis is essential for the clinical application of kinase inhibitors in patients with glomerulonephritis.-Guo, L., Huang, J., Chen, M., Piotrowski, E., Song, N., Zahner, G., Paust, H.-J., Alawi, M., Geffers, R., Thaiss, F. T-lymphocyte-specific knockout of IKK-2 or NEMO induces Th17 cells in an experimental nephrotoxic nephritis mouse model.

Environmental behavior and influencing factors of glyphosate in peach orchard ecosystem.

In this paper, several experiments were carried out to study the environmental behavior and influencing factors of glyphosate (PMG) in peach orchard ecosystem. The results of field experiments showed that PMG and its metabolite aminomethylphosphonic acid (AMPA) were detected in peach tree leaves and peach tree fruits, although PMG was only sprayed on the soil. The residues of PMG and AMPA in peach tree leaves were ~0.1 mg/kg and ~0.5 mg/kg and in peach tree fruits were ~0.01 mg/kg and 0.07-0.11 mg/kg, respectively. By conducting a series of laboratory simulation experiments, the environmental factors affecting the degradation of PMG were screened and evaluated. The results showed that PMG metabolized much faster in loess soil than red soil and black soil (with the DT50 of 11.6 days, 62.4 days, and 34.1 days, respectively). By analyzing the basic properties of the soil, we investigated the effects of pH, moisture content, organic matter (exogenous biochar) and ambient temperature using orthogonal experiments, and the results were further confirmed by microbial experiment. The results showed that alkaline conditions (pH = 7.8/9), high water content (25%) and microorganisms could promote the degradation of PMG. Sterile soil environment had a negative impact on the metabolic behavior of PMG to AMPA.

Characteristics of Pulmonary Vascular Remodeling in a Porcine Model of Shunt-Associated Pulmonary Arterial Hypertension.

Lung biopsy is the gold standard for evaluating pathological changes in the pulmonary vascular bed. Knowing the distribution characteristics of pulmonary vascular lesions can improve the accuracy of lung biopsy. To investigate the distribution characteristics of pulmonary vascular remodeling, a reliable porcine model of shunt-associated pulmonary arterial hypertension (PAH) was established. Twenty piglets were randomly divided into the experimental group (n = 10) and the control group (n = 10). A modified Blalock-Taussig shunt (MBTS, left innominate artery to main pulmonary artery) was created surgically in the experimental group. Three months later, an invasive catheter was used to obtain hemodynamic parameters, and lung biopsy was performed to assess the remodeling of pulmonary vascular bed. MBTS was successfully implemented in six piglets. There's no significant difference in hemodynamic parameters of the two groups before the shunt. However, these parameters and right ventricular hypertrophy index of the experimental group were significantly increased after three months shunting. Pathological changes in the experimental group, including thickening of pulmonary artery media, intimal fibrosis, and right ventricular hypertrophy, were observed. Furthermore, the percentage of media thickness and medial area of the experimental group were significantly higher than control group. Histopathology showed that vascular remodeling of the lung was inhomogeneous and that the lateral lesion was more severe than other segments. These results indicated that MBTS could be used to establish a reliable porcine model of shunt-associated PAH and that multisite detection with different segments should be applied to assess the severity of pulmonary vascular remodeling.

Genome-Wide Analysis of the Shi-Related Sequence Family and Functional Identification of GmSRS18 Involving in Drought and Salt Stresses in Soybean.

The plant-special SHI-RELATED SEQUENCE (SRS) family plays vital roles in various biological processes. However, the genome-wide analysis and abiotic stress-related functions of this family were less reported in soybean. In this work, 21 members of soybean SRS family were identified, which were divided into three groups (Group I, II, and III). The chromosome location and gene structure were analyzed, which indicated that the members in the same group may have similar functions. The analysis of stress-related cis-elements showed that the SRS family may be involved in abiotic stress signaling pathway. The analysis of expression patterns in various tissues demonstrated that SRS family may play crucial roles in special tissue-dependent regulatory networks. The data based on soybean RNA sequencing (RNA-seq) and quantitative Real-Time PCR (qRT-PCR) proved that SRS genes were induced by drought, NaCl, and exogenous abscisic acid (ABA). GmSRS18 significantly induced by drought and NaCl was selected for further functional verification. GmSRS18, encoding a cell nuclear protein, could negatively regulate drought and salt resistance in transgenic Arabidopsis. It can affect stress-related physiological index, including chlorophyll, proline, and relative electrolyte leakage. Additionally, it inhibited the expression levels of stress-related marker genes. Taken together, these results provide valuable information for understanding the classification of soybean SRS transcription factors and indicates that SRS plays important roles in abiotic stress responses.