CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis.

Tertiary lymphoid structures (TLSs) are associated with enhanced immunity in tumors. However, their formation and functions in colorectal cancer liver metastasis (CRLM) remain unclear. Here, we reveal that intra- and peri-tumor mature TLSs (TLS+) are associated with improved clinical outcomes than TLS- tumors. Using single-cell-RNA-sequencing and spatial-enhanced-resolution-omics-sequencing (Stereo-seq), we reveal that TLS+ tumors are enriched with IgG+ plasma cells (PCs), while TLS- tumors are characterized with IgA+ PCs. By generating TLS-associated PC-derived monoclonal antibodies in vitro, we show that TLS-PCs secrete tumor-targeting antibodies. As the proof-of-concept, we demonstrate the anti-tumor activities of TLS-PC-mAb6 antibody in humanized mouse model of colorectal cancer. We identify a fibroblast lineage secreting CCL19 that facilitates lymphocyte trafficking to TLSs. CCL19 treatment promotes TLS neogenesis and prevents tumor growth in mice. Our data uncover the central role of CCL19+ fibroblasts in TLS formation, which in turn generates therapeutic antibodies to restrict CRLM.

Existence of Blastocystis infection in bar-headed goose (Anser indicus).

Blastocystis is a common intestinal protist in humans and animals. Currently, Blastocystis infection in bar-headed geese is unknown. To understand the prevalence and distribution of Blastocystis subtypes in bar-headed geese, fecal samples were collected from 358 bar-headed geese in three regions. The total infection rate of Blastocystis in bar-headed in China was 5.9% (21/358), with 5.0% (6/120) in Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, Sichuan province, 11.8% (14/119) in Maqu county, Gansu province, and 0.8% (1/119) in Caohai, Wei ning county, Guizhou province. The differences in prevalence rates by region were statistically significant. Sequences analyses showed that one known subtype (ST7, n = 16) and one potentially novel ST (n = 5) in bar-headed geese were detected in this study. This is the first report on the prevalence and subtype distribution of Blastocystis in bar-headed geese, which will improve our understanding of the epidemiology and public health implications of Blastocystis infection in wild migratory birds.

Complications of ultrasound-guided thermal ablation of thyroid nodules and associated risk factors: an experience from 9667 cases.

OBJECTIVES: To evaluate the safety of ultrasound-guided thermal ablation (UGTA) for thyroid nodules (TNs) by analysing complications and related risks. MATERIALS AND METHODS: This retrospective, single-centre study reviewed patients who underwent UGTA (microwave or radiofrequency ablation) between January 2018 and March 2023. The incidence of complications was recorded and assessed during and immediately after ablation,1-3 h later, and at 1 month, 3 months, and 6 months. Univariate and multivariate analyses were performed to identify risk factors for hoarseness and haemorrhagic complications. RESULTS: We reviewed 9667 cases in this study. Overall, 4494 (46.49%) cases underwent microwave ablation, while 5173 (53.51%) cases underwent radiofrequency ablation. The overall complication rate was 4.43%. The incidence of major complications was 1.94% (haemorrhage, 1.32%; hoarseness, 0.54%; and symptomatic aseptic necrosis, 0.08%). The incidence of minor complications was 2.45%. A large nodule volume, radiofrequency ablation, hyper-enhancing nodules, benign nodules, higher preoperative blood pressure, hyperthyroidism, and higher ablation power were independent risk factors for haemorrhage. Dorsal nodules and a higher ablation power were independent risk factors for hoarseness. All complications were resolved. CONCLUSION: This study suggests that UGTA is a safe treatment for TNs. Several risk factors for haemorrhage and hoarseness should be considered before performing UGTA. Different ablation modalities should be considered for patients with different conditions. CLINICAL RELEVANCE STATEMENT: Thermal ablation may be a safe treatment for eligible patients with TNs. KEY POINTS: We analysed the complications and risk factors associated with UGTA in 9667 cases. The complication rate was 4.43%; 1.94% were major complications. Risk factors of haemorrhage and hoarseness should be considered. UGTA was a safe method for the treatment of TNs.

Mediating effect of menopausal symptoms between the lifestyle and depressive symptoms.

PURPOSE: This study aimed to explore relationship between lifestyle and depressive symptoms and evaluated the mediating effect of menopausal symptoms. METHODS: This was a secondary analysis of a survey in Hunan Province, China. We selected 3190 women aged 40 to 55 into final analyses. Menopausal and depressive symptoms were assessed by the Kupperman Menopausal Index and the 9-item Patient Health Questionnaire, respectively. A self-administered questionnaire was used to collect demographic and lifestyle information. RESULTS: The prevalence of depressive symptoms was 19.5%. After adjusting for demographic variables, passive smoking, drinking, and intensity of physical activity were positively associated with depressive symptoms. Frequency of exercise was a protective factor for depressive symptoms (AOR = 0.783, 95%CI: 0.446-0.991). Excess or restricted sleep duration was associated with higher probability of having depressive symptoms (AOR = 1.746, 95% CI: 1.324-2.304). Menopausal symptoms partially mediated the relationship between lifestyle and depressive symptoms. CONCLUSION: Findings highlighted the importance of menopausal symptoms in the relationship between the lifestyle and depressive symptoms, and provided a possibility that active lifestyle might improve depression symptoms among women at perimenopause through changes in sex hormones.

Botrytis cinerea combines four molecular strategies to tolerate membrane-permeating plant compounds and to increase virulence.

Saponins are plant secondary metabolites comprising glycosylated triterpenoids, steroids or steroidal alkaloids with a broad spectrum of toxicity to microbial pathogens and pest organisms that contribute to basal plant defense to biotic attack. Secretion of glycosyl hydrolases that enzymatically convert saponins into less toxic products was thus far the only mechanism reported to enable fungal pathogens to colonize their saponin-containing host plant(s). We studied the mechanisms that the fungus Botrytis cinerea utilizes to be tolerant to well-characterized, structurally related saponins from tomato and Digitalis purpurea. By gene expression studies, comparative genomics, enzyme assays and testing a large panel of fungal (knockout and complemented) mutants, we unraveled four distinct cellular mechanisms that participate in the mitigation of the toxic activity of these saponins and in virulence on saponin-producing host plants. The enzymatic deglycosylation that we identified is novel and unique to this fungus-saponin combination. The other three tolerance mechanisms operate in the fungal membrane and are mediated by protein families that are widely distributed in the fungal kingdom. We present a spatial and temporal model on how these mechanisms jointly confer tolerance to saponins and discuss the repercussions of these findings for other plant pathogenic fungi, as well as human pathogens.

Tandem "One-Shot" Measurement of Residual Chemical Shift Anisotropy and Residual Dipolar Coupling using Biphasic Supramolecular Peptide Liquid Crystals.

Both solitary and tandem applications of residual chemical shift anisotropy (RCSA) and residual dipolar coupling (RDC) show great potential for the structural and configurational determination of organic molecules. A critical component of both RDC and RCSA methodologies is the alignment medium, whose availability is limited, especially for RCSA measurement. Moreover, reported RDC and RCSA acquisitions mainly rely on two experiments conducted under two different conditions, which are relatively time-consuming and easily cause experimental errors. Herein, a biphasic supramolecular lyotropic liquid crystalline (LLC) system was developed through the self-assembly of C21H43-CONH-V4K3-CONH2, which could act as an alignment medium for not only RDC but also RCSA extraction in DMSO-d6. Notably, the RCSA extraction was easily achieved via one-shot measurement from a single one-dimensional 13C NMR experiment, with no need for special instruments, devices, and correction. Relying on the biphasic LLC medium, meanwhile, RDC data were simply extracted from a single F1-coupled HSQC experiment, different from the standard protocol that requires two spectral acquisitions corresponding to the isotropic and anisotropic conditions. Collectively, the biphasic LLC medium is applicable for tandem RCSA and RDC measurements in one single sample, advancing the stereochemical elucidation of molecules of interest.

Enhanced bioaccessibility of interfacial delivered oleanolic acid through self-constructed Pickering emulsion: Effects of oil types.

Pentacyclic triterpenes have attracted much attention because of their many bioactivities, but their bioaccessibility is low. Oleanolic acid (OA) was used in this study as a typical edible pentacyclic triterpene. In this work, we proposed an OA interfacial delivery model based on W/O Pickering emulsion, and investigated the effects of different oil types on the emulsion properties and OA bioaccessibility of the OA W/O Pickering emulsion interfacial delivery system (EIDS). Medium chain triglyceride (MCT), long chain triglycerides (LCT) and MCT/LCT (1:1, w/w) were selected as carrier oils for the preparation of emulsions, respectively. The results showed that the emulsions formed from LCT had smaller particle sizes, which increased the deformation resistance of the emulsions and exhibited good stability during the simulated in vitro digestion. The extent of free fatty acid (FFA) release during oil digestion was MCT (103.32 ± 3.74 %) > M/L (97.89 ± 2.89 %) > LCT (71.41 ± 6.64 %). Of interest, the bioaccessibility of OA was influenced by the carrier oil: LCT (59.34 ± 2.55 %) > M/L (47.35 ± 6.25 %) > MCT (13.11 ± 1.40 %) ＞ PBS (7.11 ± 1.74 %), and such a difference was mainly attributed to the greater solubilisation of OA in mixed micelles consisting of long-chain fatty acids. In summary, the size of hydrophobic domains in the mixed micelles produced a greater effect than the effect of FFA release on OA bioaccessibility. This study provides a theoretical basis for the interfacial delivery of OA and the enhancement of OA bioaccessibility based on W/O Pickering emulsions with different oil types.

SiO 2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model.

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model. Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.

A functional hydrogel of dopamine-modified gelatin with photothermal properties for enhancing infected wound healing.

Infected skin wound has gradually become a prevalent injury that affects overall health. Currently, biomaterials with good adhesion, efficient antibacterial properties, and angiogenesis are considered as a suitable way to effectively heal infected wound. Herein, a multifunctional hydrogel comprising gelatin, dopamine (DA), and ferric ions (Fe3+) was developed for infected wound healing. The modified gelatin-dopamine (Gel-DA) enhanced adhesive capability. Subsequently introducing ferric ions (Fe3+) to form Gel-DA-Fe3+ hydrogels by Fe3+ and catechol coordination bonds. The designed hydrogels demonstrated multifaceted functionality, encompassing photothermal antibacterial, angiogenesis, and so on. The introduction of DA enhanced the adhesion of Gel-DA-Fe3+ to the skin surface and might serve as a physical barrier to seal wound. Meanwhile, DA and Fe3+ jointly endowed good photothermal effects to composite hydrogels, which could eliminate over 95 % of bacteria. In vitro results revealed that Gel-DA-Fe3+ hydrogels had good biocompatibility and promoted HUVECs migration and tube formation. Furthermore, in vivo studies confirmed that Gel-DA-Fe3+ hydrogels markedly expedited the wound healing of rats through eradicating bacteria, accelerating the deposition of collagen, and promoting angiogenesis. What's more, Gel-DA-Fe3+ hydrogels under near-infrared laser had a more pronounced ability for wound healing. Therefore, Gel-DA-Fe3+ hydrogels had great potential for application in bacteria-infected wound healing.

New lignans from Phyllanthodendron dunnianum.

A new lignan phyllanins A (1) and a lignan phyllanins B (2) for which the absolute configuration was determined for the first time, along with four known lignans (3-6) were isolated from the branch and leaf extracts of Phyllanthodendron dunnianum. Their planar structures were mainly determined by a combination of 1D and 2D NMR, HRESIMS spectral analyses, and the absolute configurations of the compounds 1 and 2 were established by DFT GIAO 13C NMR and electronic circular dichroism (ECD) calculations. In addition, all these six lignans were firstly tested for the antibacterial activities against MRSA, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli. Among these compounds, 2 and 5 showed potential antibacterial activities against MRSA and S. aureus with MIC values of 4 and 8 µg/mL, respectively.

[Research progress in preparations of Panax ginseng].

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.

The prevalence and genotypes of Cryptosporidium spp. in bar-headed goose (Anser indicus) in China.

Cryptosporidium spp. is an important foodborne and waterborne pathogen in humans and animals, causing diarrhoea in humans and respiratory and gastrointestinal diseases in birds. However, reports of Cryptosporidium infection in bar-headed goose are limited. To determine the infection rate and species/genotypes of Cryptosporidium in bar-headed goose in China, a total of 358 fecal samples were collected from 3 regions. Nested PCR was used to amplify Cryptosporidium SSU rRNA regions from the fecal extracted-DNA samples. The total infection rate of Cryptosporidium in bar-headed in China was 3.9 % (14/358), with 4.2 % (5/120) in Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, Sichuan province, 7.6 % (9/119) in Maqu county, Gansu province, and 0.0 % (0/119) in Caohai, Wei ning county, Guizhou province. The differences in prevalence rate by region were statistically significant. All positive samples were identified as Cryptosporidium goose genotype I (n = 14). This is the first systematic investigation of the epidemiological status and dominant species/genotypes of Cryptosporidium in bar-headed goose in China, thereby enhancing our understanding of the epidemiology of Cryptosporidium infection in wild migratory birds.

Proanthocyanidins isolated from lotus seed skin mitigate glycolipid metabolism disorder through the p38/Nrf2/NF-κB signaling pathway.

Lotus seed skin extract is rich in flavonoids, making it a promising candidate for developing health products. In a previous study, we found that proanthocyanidins from lotus seed skin, particularly proanthocyanidin B1 (PB1), can indirectly activate the Nrf2 signaling pathway, exerting an antioxidant effect. In this study, we isolate proanthocyanidins from lotus seed skin (PLS) using ethanol extraction and RP-HPLC identification, and investigate its effects on glycolipid metabolism both in vivo and in vitro. Our results demonstrate that PLS reduces body weight in high-fat diet (HFD) mice by decreasing feed efficiency. PLS also normalizes serum glucose, insulin secretion, glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance (IPGTT). Furthermore, PLS significantly improves blood lipid parameters and inhibits the expressions of six proinflammatory factors, including IL-1α, IL-1ß, IL-3, IL-6, IFN-γ and TNF-α in HFD mice. Additionally, analysis of fresh liver tissues reveals that PLS and PB1 induce the expressions of antioxidant proteins such as HO-1 and NQO1 by activating the p38-Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway. In conclusion, proanthocyanidins from lotus seed skin regulate glycolipid metabolism disorders by targeting the p38/Nrf2/NF-κB signaling pathway. Our study offers a new approach for the high-value comprehensive utilization of lotus seed skin by-products and precise dietary intervention for metabolic syndrome.

Integrating trans-omics, cellular experiments and clinical validation to identify ILF2 as a diagnostic serum biomarker and therapeutic target in gastric cancer.

BACKGROUND: Gastric cancer (GC) lacks serum biomarkers with clinical diagnostic value. Multi-omics analysis is an important approach to discovering cancer biomarkers. This study aimed to identify and validate serum biomarkers for GC diagnosis by cross-analysis of proteomics and transcriptomics datasets. METHODS: A cross-omics analysis was performed to identify overlapping differentially expressed genes (DEGs) between our previous aptamer-based GC serum proteomics dataset and the GC tissue RNA-Seq dataset in The Cancer Genome Atlas (TCGA) database, followed by lasso regression and random forest analysis to select key overlapping DEGs as candidate biomarkers for GC. The mRNA levels and diagnostic performance of these candidate biomarkers were analyzed in the original and independent GC datasets to select valuable candidate biomarkers. The valuable candidate biomarkers were subjected to bioinformatics analysis to select those closely associated with the biological behaviors of GC as potential biomarkers. The clinical diagnostic value of the potential biomarkers was validated using serum samples, and their expression levels and functions in GC cells were validated using in vitro cell experiments. RESULTS: Four candidate biomarkers (ILF2, PGM2L1, CHD7, and JCHAIN) were selected. Their mRNA levels differed significantly between tumor and normal tissues and showed different diagnostic performances for GC, with areas under the receiver operating characteristic curve (AUROCs) of 0.629-0.950 in the TCGA dataset and 0.736-0.840 in the Gene Expression Omnibus (GEO) dataset. In the bioinformatics analysis, only ILF2 (interleukin enhancer-binding factor 2) gene levels were associated with immune cell infiltration, some checkpoint gene expression, chemotherapy sensitivity, and immunotherapy response. Serum levels of ILF2 were higher in GC patients than in controls, with an AUROC of 0.944 for the diagnosis of GC, and it was also detected in the supernatants of GC cells. Knockdown of ILF2 by siRNA significantly reduced the proliferation and colony formation of GC cells. Overexpression of ILF2 significantly promotes the proliferation and colony formation of gastric cancer cells. CONCLUSIONS: Trans-omics analysis of proteomics and transcriptomics is an efficient approach for discovering serum biomarkers, and ILF2 is a potential diagnostic biomarker and therapeutic target of gastric cancer.

Tunable Surface Charge of Layered Double Hydroxide Membranes Enabling Osmotic Energy Harvesting from Anion Transport.

Membrane-based osmotic energy harvesting is a promising technology with zero carbon footprint. High-performance ion-selective membranes (ISMs) are the core components in such applications. Recent advancement in 2D nanomaterials opens new avenues for building highly efficient ISMs. However, the majority of the explored 2D nanomaterials have a negative surface charge, which selectively enhances cation transport, resulting in the underutilization of half of the available ions. In this study, ISMs based on layered double hydroxide (LDH) with tunable positive surface charge are studied. The membranes preferentially facilitate anion transport with high selectivity. Osmotic energy harvesting device based on these membranes reached a power density of 2.31 W m-2 under simulated river/sea water, about eight times versus that of a commercial membrane tested under the same conditions, and up to 7.05 W m-2 under elevated temperature and simulated brine/sea water, and long-term stability with consistent performance over a 40-day period. A prototype reverse electrodialysis energy harvesting device, comprising a pair of LDH membranes and commercial cation-selective membranes, is able to simultaneously harvest energy from both cations and anions achieving a power density of 6.38 W m-2 in simulated river/sea water, demonstrating its potential as building blocks for future energy harvesting systems.

PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets.

BACKGROUND: Atherosclerosis is a chronic and complex disease caused by lipid disorder, inflammation, and other factors. It is closely related to cardiovascular diseases, the chief cause of death globally. Peroxisome proliferator-activated receptors (PPARs) are valuable anti-atherosclerosis targets that showcase multiple roles at different pathological stages of atherosclerosis and for cell types at different tissue sites. AIM OF REVIEW: Considering the spatial and temporal characteristics of the pathological evolution of atherosclerosis, the roles and pharmacological and clinical studies of PPARs were summarized systematically and updated under different pathological stages and in different vascular cells of atherosclerosis. Moreover, selective PPAR modulators and PPAR-pan agonists can exert their synergistic effects meanwhile reducing the side effects, thereby providing novel insight into future drug development for precise spatial-temporal therapeutic strategy of anti-atherosclerosis targeting PPARs. KEY SCIENTIFIC: Concepts of Review: Based on the spatial and temporal characteristics of atherosclerosis, we have proposed the importance of stage- and cell type-dependent precision therapy. Initially, PPARs improve endothelial cells' dysfunction by inhibiting inflammation and oxidative stress and then regulate macrophages' lipid metabolism and polarization to improve fatty streak. Finally, PPARs reduce fibrous cap formation by suppressing the proliferation and migration of vascular smooth muscle cells (VSMCs). Therefore, research on the cell type-specific mechanisms of PPARs can provide the foundation for space-time drug treatment. Moreover, pharmacological studies have demonstrated that several drugs or compounds can exert their effects by the activation of PPARs. Selective PPAR modulators (that specifically activate gene subsets of PPARs) can exert tissue and cell-specific effects. Furthermore, the dual- or pan-PPAR agonist could perform a better role in balancing efficacy and side effects. Therefore, research on cells/tissue-specific activation of PPARs and PPAR-pan agonists can provide the basis for precision therapy and drug development of PPARs.

Subtypes of Blastocystis in Tibetan Antelope (Pantholops hodgsonii).

Blastocystis is a protist that is distributed in the gut tract of humans and animals. However, the reports about Blastocystis infection in Tibetan antelope are scarce. We collected 173 Tibetan antelope feces samples from Xinjiang, Qinghai and Xizang, and amplified the SSU rRNA gene of 600 bp region of Blastocystis in our research. Fifty-one samples in total were positive for Blastocystis, with all subtypes being ST31. The lowest prevalence of Blastocystis was observed in Xizang (2/20, 9.1%), followed by Qinghai (18/92, 16.4%), Xinjiang (31/61, 33.7%). The highest prevalence of Blastocystis in Tibetan antelope was detected during the summer was (19/30, 38.8%). This is the first research work regarding the Blastocystis subtypes ST31 in Tibetan antelope. Our research provides information for future researches on the distribution of this Blastocystis subtype and the control of Blastocystis infection.

Protein phosphatase 4 mediates palmitic acid-induced endothelial dysfunction by decreasing eNOS phosphorylation at serine 633 in HUVECs.

Plasma saturated free fatty acid (FFA)-induced endothelial dysfunction (ED) contributes to the pathogenesis of atherosclerosis and cardiovascular diseases. However, the mechanism underlying saturated FFA-induced ED remains unclear. This study demonstrated that palmitic acid (PA) induced ED by activating the NADPH oxidase (NOX)/ROS signaling pathway to activate protein phosphatase 4 (PP4) and protein phosphatase 2A (PP2A), thereby reducing endothelial nitric oxide synthase (eNOS) phosphorylation at Ser633 and Ser1177, respectively. Okadaic acid (OA) and fostriecin (FST), which are inhibitors of PP2A, inhibited the PA-induced decreases in eNOS phosphorylation at Ser633 and Ser1177. The antioxidants N-acetylcysteine (NAC) and apocynin (APO) or knockdown of gp91phox or p67phox (NOX subunits) restored PA-mediated downregulation of PP4R2 protein expression and eNOS Ser633 phosphorylation. Knockdown of the PP4 catalytic subunit (PP4c) specifically increased eNOS Ser633 phosphorylation, while silencing the PP2A catalytic subunit (PP2Ac) restored only eNOS Ser1177 phosphorylation. Furthermore, PA dramatically decreased the protein expression of the PP4 regulatory subunit R2 (PP4R2) but not the other regulatory subunits. PP4R2 overexpression increased eNOS Ser633 phosphorylation, nitric oxide (NO) production, cell migration and tube formation but did not change eNOS Ser1177 phosphorylation levels. Coimmunoprecipitation (Co-IP) suggested that PP4R2 and PP4c interacted with the PP4R3α and eNOS proteins. In summary, PA decreases PP4R2 protein expression through the Nox/ROS pathway to activate PP4, which contributes to ED by dephosphorylating eNOS at Ser633. The results of this study suggest that PP4 is a novel therapeutic target for ED and ED-associated vascular diseases.

Global prevalence and risk factors associated with Toxoplasma gondii infection in wild birds: A systematic review and meta-analysis.

A systematic review and meta-analysis were performed to identify the global prevalence and factors associated with Toxoplasma gondii infection in wild birds. Six bibliographic databases (Chinese National Knowledge Infrastructure, VIP Chinese Journal Database, Wanfang Data, PubMed, Web of science and ScienceDirect) were searched from inception to February 2023. The search yielded 1220 records of which 659 articles underwent full-text evaluation, which identified 49 eligible articles and 16,030 wild bird samples that were included in the meta-analysis. The estimated pooled global prevalence of T. gondii infection in wild birds was 16.6%. Out of the variables tested, publication year after 2020 and climate type were significantly associated with T. gondii infection (P<0.01). Our data indicate that the prevalence of T. gondii in wild birds can be influenced by epidemiological variables. Further research is needed to identify the biological, environmental, anthropogenic, and geographical risk factors which impact the ecology and prevalence of T. gondii in wild birds.