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N6-methyladenosine (m6A), an epigenetic modification on RNAs, plays an important role in many physiological and pathological processes. However, the involvement of m6A in goat uterus during early pregnancy remains largely unknown. In this study, we found that the total m6A level was increasing in goat uterus as early pregnancy progressed. Methyltransferase-like 3 (METTL3) is a core catalytic subunit of the m6A methyltransferase. We thus determined the expression and regulation of METTL3 in goat uterus. METTL3 was highly expressed in the luminal and glandular epithelia from day 16 (D16) to D25 of pregnancy, and it could be up-regulated by estrogen and progesterone in goat uterus and primary endometrial epithelial cells (EECs). In EECs, knockdown or overexpression of METTL3 resulted in a significant decrease or increase of cell proliferation, respectively. METTL3 knockdown reduced the m6A level of not only total RNA but also connective tissue growth factor (CTGF) mRNA. Luciferase assay suggested that METTL3 might target the potential m6A sites in the 3'untranslated region (3'UTR) of CTGF mRNA. Moreover, METTL3 positively regulated CTGF expression, and CTGF knockdown significantly counteracted the promoting effect of METTL3 overexpression on EEC proliferation. Collectively, METTL3 is dynamically expressed in goat uterus and can affect EEC proliferation by regulating CTGF in an m6A-dependent manner. Our results will lay a foundation for further studying the crucial mechanism of METTL3-mediated m6A modification in goat uterus during early pregnancy.

Background As neuropeptide Y is associated with endothelial dysfunction, this study explored the relationship between neuropeptide Y and acute myocardial infarction. Methods We included 128 acute myocardial infarction cases and 62 controls. Using the SYNTAX scoring system, the acute myocardial infarction group was sub-grouped into “SYNTAX ≤ 22,” “SYNTAX = 23–32,” and “SYNTAX ≥ 33.” Plasma neuropeptide Y, endothelin, endothelial nitric oxide synthase, and thromboxane A2 levels were measured. Results The acute myocardial infarction group had higher plasma neuropeptide Y, endothelin, and thromboxane A2 levels than controls ([58.76 ± 17.63 vs. 37.48 ± 11.36 ng/ml, P  = 0.000], [36.16 ± 10.04 vs. 27.80 ± 7.18 pg/ml, P  = 0.000], and [27.69 ± 6.91 vs. 24.32 ± 7.28 pg/ml, P  = 0.002], respectively). The acute myocardial infarction group also had lower plasma endothelial nitric oxide synthase levels than controls (3.00 ± 0.94 vs. 4.05 ± 1.44 ng/ml, P  = 0.000). Additionally, the receiver operating characteristic curve analysis showed that a neuropeptide Y value of 49.94 ng/ml could help diagnose acute myocardial infarction (sensitivity: 70.9%; specificity: 91.9%). The SYNTAX scores, smoking, plasma endothelin, thromboxane A2, and neuropeptide Y levels were positively correlated, whereas plasma endothelial nitric oxide synthase and neuropeptide Y levels were negatively correlated. Lastly, plasma neuropeptide Y levels were different among subgroups ( P  < 0.05); patients with higher SYNTAX scores had higher neuropeptide Y levels. Conclusions The levels of plasma NPY may be accociated with the AMI process. Highlights NPY may be involved in the occurrence and progression of AMI. NPY is closely related to endothelial dysfunction. NPY can be used to diagnose AMI and indicate the severity of coronary artery disease.

The quantile regression technique is introduced into the Lotka–Volterra ecosystem analysis framework. The quantile grey Lotka–Volterra model is established to reveal the dynamic trade relationship between China and the United States. An optimisation model is constructed to solve optimum quantile parameters. The empirical results show that the quantile grey Lotka–Volterra model shows higher fitting accuracy and reveals the trade relationships at different quantiles based on quarterly data on China–US trade from 1999 to 2019. The long-term China–US trade relationship presents a prominent predator–prey relationship because exports from China to the US inhibited China’s imports from the United States. Moreover, we divide samples into five stages according to four key events, China’s accession to the WTO, the 2008 global financial crisis, the weak global economic recovery in 2015, and the 2018 China–US trade war, recognising various characteristics at different stages.

Hypomotility is a common symptom of gallstone disease, which is accompanied by a loss of interstitial Cajal-like cells (ICLCs) in the gallbladder. Ursodeoxycholic acid (UDCA) is widely used in treating gallstone disease, and has shown anti-apoptotic and anti-inflammatory effects apart from its ability to dissolve gallstones. In this study, we investigated the anti-apoptotic and anti-inflammatory effects of UDCA on ICLCs in guinea pigs with gallstones. Guinea pigs were fed a high-cholesterol diet for 8 weeks to induce the formation of gallstones. A group of animals was administered UDCA (50 mg·kg −1 ·d −1 , ig) simultaneously. At the end of 8 weeks, the animals were euthanized with anesthesia, cholecystectomy was performed immediately and gallbladder was collected for further analysis. We showed that in the model group the contractility of gallbladder muscle strips in response to both acetylcholine (ACh) and CCK-8 was severely impaired, which was significantly improved by UDCA administration. Furthermore, UDCA administration significantly reduced the apoptotic ratio of ICLCs, based on the observation of co-localization imaging of apoptotic cells and c-kit-positive cells. Western blotting analysis and real-time PCR results revealed that the TNF-α/Caspase8/Caspase3 pathway was suppressed in the UDCA-treated animals, confirming the anti-apoptotic effect of UDCA in the gallbladder. The H&E staining showed that UDCA administration significantly attenuated inflammatory cell infiltration in the gallbladder wall. In conclusion, UDCA can protect ICLCs in the gallbladder from undergoing apoptosis by inhibiting the TNF-α/Caspase8/caspase3 pathway.

Maritime transportation is a crucial component of international cargo transport, offering several advantages, such as route flexibility, large capacity, and cost-effectiveness. The competition and collaboration among the node enterprises in the sea-cargo supply chain system (SCSCS) directly impact the overall structure and efficiency of the supply chain system, introducing complexity in analysis. This research focuses on a two-level SCSCS comprising one shipping company and two competing freight forwarders, considering their altruistic preferences manifested through contributing to the shipping company’s brand building. Employing a Stackelberg game model, this study examines the effects of the shipping company’s brand investment willingness and the freight forwarders’ altruistic preferences on the decision making and profits of all stakeholders. The findings reveal that a higher willingness of the shipping company to invest in its brand building leads to increased profits for all parties involved. However, while the altruistic behaviors of the freight forwarders can enhance the shipping company’s profits, their own profits may not necessarily see the same impact. Furthermore, moderate competition between the freight forwarders can enhance the profits for all members. This research identifies the circumstances in which the freight forwarders’ altruistic preferences can lead to increased profits for themselves, achieving both altruistic and self-interested outcomes.

The effect of metabolic factors on cardiovascular risk in obstructive sleep apnea (OSA) is unclear. This study aimed to investigate the effect of metabolic factors on the left ventricular diastolic function in patients with OSA. This cross-sectional study included a total of 478 patients with OSA from September 2018 to September 2023. After propensity score matching, wherein 193 patients with OSA with metabolic syndrome (MS) were 1:1 matched to patients with OSA without MS by sex and age, data from 386 patients were ultimately analyzed. Furthermore, all patients were divided into mild, moderate, and severe OSA groups according to their sleep apnea-hypopnea index (AHI). Measurements included nocturnal polysomnography, biochemical testing, and transthoracic echocardiography data. The AHI in the MS group was higher (30.24±21.69 vs 23.19±17.65, p<0.001) and the lowest oxygen saturation at night was lower (77.67±9.23 vs 80.59±9.26, p<0.001) than those in the non-MS group. Additionally, the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), end-diastolic ventricular septal thickness (IVST), left ventricular end-diastolic posterior wall thickness (LVPWT), left atrial internal diameter (LAD), and E peak to A peak velocity ratio (E/A) in the MS group were higher than those in the non-MS group (P<0.05). The E peak to e' peak velocity ratio (E/e') in the MS group was higher than that in the non-MS group (12.02±3.68 vs 11.13±3.12, P=0.011) and was positively correlated with the diagnosis of MS and metabolic factors ( =0.115, p=0.024; =0.131, p=0.010, respectively). Patients with five metabolic factors had a significantly higher risk of E/e' elevation than patients in the non-MS group (odds ratio=4.238, p=0.007). MS may be related to OSA severity and left ventricular diastolic dysfunction. An increase in metabolic factors may increase the risk of diastolic dysfunction. Among metabolic factors, blood pressure may be the most important.

Due to the increasing use of immunosuppressant therapy, Pneumocystis jirovecii pneumonia (PJP) has become an emerging concern in human immunodeficiency virus (HIV)-negative patients. In this study, we conducted a retrospective study of 96 hospitalized patients with PJP from January 2015 to June 2019 at three tertiary comprehensive hospitals in Southern China. Information was collected regarding patient demographics, clinical manifestations, risk factors, laboratory analyses, radiological images, and treatment outcomes. PJP infection was most commonly found in middle-aged men. Kidney diseases (35.5%) and connective tissue diseases (38.7%) were the predominant risk factors for PJP. About half of the patients (48.4%) received glucocorticoid, immunosuppressant, and/or chemotherapy in a low dose or in a short-term (< 3 months). None of the patients had previously received trimethoprim–sulfamethoxazole (TMP-SMX) for PJP prophylaxis. All patients had two or more clinical manifestations (cough, dyspnea, fever, and chest pain). Biochemical investigations of CRP, ESR, PaO 2 , LDH, and KL-6 showed that over 90% of the patients exceeded the reference range of indicators. Our analyses revealed the dominant risk factors (HIV, kidney diseases, and connective tissue diseases) and the most consistent biochemical indicators (LDH, BG, and KL-6) for PJP. Moreover, early prophylaxis, diagnosis, and treatment should contribute to improve the survival of these PJP patients.

Polygonum capitatum has unique curative effects on the urinary system. In fact, many Polygonum capitatum-based preparations are currently used in the clinic. In China, the combination of levofloxacin (LVFX) with a Chinese herbal preparation derived from Polygonum capitatum has been used for the clinical treatment of urinary system diseases, which can improve the curative effects and reduce the side effects of LVFX. However, the herb-drug interaction (HDI) between these drugs has not been reported and the effect of Polygonum capitatum on the in vivo process of LVFX is unclear. In this article, a sensitive ultraperformance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed to evaluate the effects of the combined application of LVFX and the Polygonum capitatum extract on tissue distribution and excretion. Thereafter, the method was validated for selectivity, accuracy, precision, linearity, lower limit of quantification (LLOQ), dilution integrity, recovery, and matrix effect. Based on tissue distribution, LVFX could diffuse into all of the tested tissues, with significant differences in the content of each tissue between the coadministration group and single administration group. At 48 h after the combination was orally administered, the urinary cumulative excretion of LVFX decreased from 20.69% to 11.84% while its fecal cumulative excretion decreased from 26.08% to 13.28%. Our results suggest that a drug interaction exists between the two drugs in the process of distribution and excretion. This study provides important experimental evidence for further studies on the clinical efficacy and mechanism of the Polygonum capitatum extract and LVFX.

A rapid, reliable, and sensitive HPLC-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for simultaneous determination of militarine and its three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) in rat plasma. Plasma was acidified with formic acid, and protein was precipitated with methanol. MS/MS with ESI and multiple reaction monitoring at m/z 725.3→457.3, 457.1→127, 304.3→107.2, 189→129, and 417.1→267.1 was used for determination of militarine, gastrodin, α-isobutylmalic acid, gymnoside I, and puerarin (internal standard), respectively. Chromatographic separation was conducted using an ACE UltraCore SuperC18 (2.1 × 100 mm, 2.5 μm) column with gradient mobile phase (0.1% formic acid in water and acetonitrile). The lower limits of quantitation for militarine, gastrodin, α-isobutylmalic acid, and gymnoside I were 1.02, 2.96, 1.64, and 0.3 ng/mL, respectively. The relative standard deviations of intra- and interday measurements were less than 15%, and the method accuracy ranged from 87.4% to 112.5%. The extraction recovery was 83.52%-105.34%, and no matrix effect was observed. The three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) were synchronously detected at 0.83 h, suggesting that militarine was rapidly transformed to gastrodin, α-isobutylmalic acid, and gymnoside I. Moreover, the area under the curve (AUC) and Cmax of militarine were significantly lower than those of gastrodin and α-isobutylmalic acid, showing that militarine was largely metabolized to gastrodin and α-isobutylmalic acid in vivo. The studies on pharmacokinetics of militarine and its three metabolites were of great use for facilitating the clinical application of militarine and were also highly meaningful for the potential development of militarine.