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BackgroundThere is no effective drug treatment for the organ failure (OF) caused by severe acute pancreatitis (SAP).ObjectiveWe aimed to evaluate the efficacy of cyclooxygenase-2 inhibitors (COX-2-Is) on the treatment of SAP and its safety.DesignIn this multicentre, double-blind, randomised, placebo-controlled, investigator-initiated trial, 348 patients with acute pancreatitis aged 18–75 years, <1 week from onset of illness to admission, and Acute Physiology and Chronic Health Evaluation II Score ≥7 or modified Marshall Score ≥2, were randomly assigned (1:1) to the COX-2-Is group (parecoxib sequential with imrecoxib) or the placebo group. SAP occurrence, duration of OF, local complications, clinical outcomes and serum inflammatory mediators were measured.ResultsCompared with the placebo group, SAP occurrence was reduced by 20.7% (77.6% vs 61.5%, p=0.001) and the persistent OF duration in SAP was shortened by 2 days (p<0.001) after COX-2-Is treatment. For patients enrolled within or after 48 hours from symptom onset, SAP occurrence was reduced by 23.8% (p=0.001) and 8.5% (p=0.202), and the persistent OF duration in SAP was shortened by 3 days (p=0.001) and 2 days (p=0.010) after COX-2-Is treatment, respectively. The occurrence of local complications in the COX-2-Is group was significantly lower than those in the placebo group, 33.7% vs 49.1%, p=0.004. The serum levels of inflammatory mediators and 30-day mortality (from 8.6% to 3.4%) were significantly reduced after COX-2-Is treatment, p<0.05. The incidence of adverse events was similar between the two treatment groups.ConclusionParecoxib sequential with imrecoxib was effective and well tolerated in reducing the occurrence and duration of SAP and local complications through suppression of systemic inflammatory response, leading to decreased morbidity.

Long non-coding RNAs (lncRNAs) Mirt2 and interferon-γ antisense RNA I (IFNG-AS1) play opposing roles in lipopolysaccharide (LPS)-induced inflammation, a key initiator of ulcerative colitis (UC). The present study aimed to analyze the potential interaction between Mirt2 and IFNG-AS1 in UC. Levels of IFNG-AS1 and Mirt2 in plasma samples from UC patients were measured using reverse transcription-quantitative PCR. Receiver operating characteristic curves were used to evaluate the diagnostic values of IFNG-AS1 and Mirt2 fr UC. The role of Mirt2 and IFNG-AS1 in colonic epithelial cell apoptosis was analyzed by cell apoptosis assay. In patients with UC, Mirt2 and IFNG-AS1 exhibited an inverse correlation, in which Mirt2 was downregulated while IFNG-AS1 was upregulated. Altered expression of IFNG-AS1 and Mirt2 separated patients with UC from healthy controls. In colonic epithelial cells, lipopolysaccharide treatment led to the downregulation of Mirt2 and the upregulation of IFNG-AS1. Furthermore, overexpression of Mirt2 in colonic epithelial cells resulted in downregulation of IFNG-AS1, and vice versa. Overexpression of Mirt2 led to a decreased rate of colonic epithelial cell apoptosis, while overexpression of IFNG-AS1 led to an increased rate of apoptosis. Moreover, IFNG-AS1 overexpression attenuated the effects of Mirt2 overexpression. Therefore, Mirt2 may interact with IFNG-AS1 during UC to participate in colonic epithelial cell apoptosis.

The use of halogen bond is widespread in drug discovery, design, and clinical trials, but is overlooked in drug biosynthesis. Here, the role of halogen bond in the nitrilase-catalyzed synthesis of ortho-, meta-, and para-chlorophenylacetic acid was investigated. Different distributions of halogen bond induced changes of substrate binding conformation and affected substrate selectivity. By engineering the halogen interaction, the substrate selectivity of the enzyme changed, with the implication that halogen bond plays an important role in biosynthesis and should be used as an efficient and reliable tool in enzymatic drug synthesis.

The ultra-high-frequency (UHF) detection method is highly accurate and has a fault localization function. At present, most gas-insulated switchgear (GIS) installations are equipped with online UHF monitoring devices to detect partial discharges. In order to ensure the accuracy of the detection results, UHF sensors need to be verified regularly. UHF sensors used for online monitoring are usually installed at the handhole of the GIS and cannot be removed. Measuring the laboratory verification indexes (e.g., equivalent height, dynamic range, etc.) of the sensors directly is very difficult. However, it is easier to measure S11 of the sensor for verification and S21 between it and the neighboring sensors by injecting power signals. Accordingly, this paper proposes a degradation identification method for GIS UHF sensors using a cross-comparison of S-parameters. When sensor sensitivity decreases, S11 increases while S21 decreases, both serving as effective indicators of performance degradation. In this study, the equivalent S-parameter network and the variation mechanisms of S11 and S21 during sensor verification were first analyzed. Normal and typically degraded sensor models were then constructed and coupled in different GIS structures for electromagnetic simulation. The simulation and on-site verification results show that S11 is mainly affected by the sensor’s intrinsic performance and installation conditions at the inspection port, whereas S21 is predominantly influenced by sensor performance and the propagation characteristics of the GIS structure. Through cross-comparison of S11 and S21 at corresponding positions across three phases, sensor aging or failure can be effectively identified, enabling rapid on-site verification without removing the sensors. The proposed method was successfully validated on actual GIS equipment at the China Southern Power Grid Research Institute. It exhibits high accuracy, efficiency, and strong engineering applicability, enabling the early detection of degraded sensors and providing valuable support for condition assessment and maintenance decision-making in GIS online monitoring systems.

Lycium ruthenicum is an excellent eco-economic shrub. Numerous researches have been conducted for the function of its fruits but scarcely focused on the somaclonal variation and DNA methylation. An efficient micropropagation protocol from leaves and stems of L . ruthenicum was developed in this study, in which not only the leaf explants but also the stem explants of L . ruthenicum were dedifferentiated and produced adventitious buds/multiple shoots on one type of medium. Notably, the efficient indirect organogenesis of stem explants was independent of exogenous auxin, which is contrary to the common conclusion that induction and proliferation of calli is dependent on exogenous auxin. We proposed that sucrose supply might be the crucial regulator of stem callus induction and proliferation of L . ruthenicum . Furthermore, results of methylation-sensitive amplified polymorphism (MSAP) showed that DNA methylation somaclonal variation (MSV) of CNG decreased but that of CG increased after acclimatization. Three types of micropropagated plants (from leaf calli, stem calli and axillary buds) were epigenetically diverged more from each other after acclimatization and the ex vitro micropropagated plants should be selected to determine the fidelity. In summary, plants micropropagated from axillary buds and leaves of L . ruthenicum was more fidelity and might be suitable for preservation and propagation of elite germplasm. Also, leaf explants should be used in transformation. Meanwhile, plants from stem calli showed the highest MSV and might be used in somaclonal variation breeding. Moreover, one MSV hotspot was found based on biological replicates. The study not only provided foundations for molecular breeding, somaclonal variation breeding, preservation and propagation of elite germplasm, but also offered clues for further revealing novel mechanisms of both stem-explant dedifferentiation and MSV of L . ruthenicum .

Southern corn rust (SCR), caused by Puccinia polysora , is a major foliar disease that threatens global maize production. Current SCR management strategies prioritize genetic resistance and chemical control, but how foliar endophytic fungal communities modulate host susceptibility to P. polysora remains poorly understood. In this study, we profiled the endophytic communities in P. polysora -infected and non-infected maize leaves across 14 geographically distinct regions in eastern China. Our results revealed that P. polysora infection significantly altered the foliar endophytic community, with infected leaves exhibiting higher operational taxonomic unit (OTU) richness (722 vs. 572 OTUs) while reducing community evenness. Diversity metrics were significantly altered, with significant reductions in Shannon diversity and Chao1 index values for non-infected states. Network analysis revealed that infection caused a notable reduction in microbial connectivity and complexity, particularly in low- and medium-susceptibility regions, where positive intertaxon associations declined by 42.6% and 35.3%, respectively. High-susceptibility region networks retained greater stability, suggesting differential microbial resilience under pathogen pressure. Redundancy analysis further demonstrated that temperature was the dominant environmental factor shaping microbial assemblages, especially under infection conditions. Notably, correlation analysis further revealed that Alternaria was positively associated with host resistance ( r = 0.37, p = 0.05), underscoring its potential role in enhancing resistance to P. polysora . Conversely, Dioszegia and Naganishia were negatively correlated with resistance ( r = −0.36, p = 0.056; and r = −0.34, p = 0.074, respectively), implying potential roles in facilitating infection. This study reveals key mechanistic links between foliar endophytic communities and SCR infection, providing a basis for sustainable biocontrol interventions in maize.

Key messageThe deletion mutated rpoC2 leads to yellow stripes of Clivia miniata var. variegata by down regulating the transcription of 28 chloroplast genes and disturbing chloroplast biogenesis and thylakoid membrane development.Clivia miniata var. variegata (Cmvv) is a common mutant of Clivia miniata but its genetic basis is unclear. Here, we found that a 425 bp deletion mutation of chloroplast rpoC2 underlies the yellow stripes (YSs) of Cmvv. Both RNA polymerase PEP and NEP coexist in seed-plant chloroplasts and the β″ subunit of PEP is encoded by rpoC2. The rpoC2 mutation changed the discontinuous cleft domain required to form the PEP central cleft for DNA binding from 1103 to 59 aa. RNA-Seq revealed that 28 chloroplast genes (cpDEGs) were all down-regulated in YSs, of which, four involved in chloroplast protein translation and 21 of photosynthesis system (PS)I, PSII, cytochrome b6/f complex and ATP synthase are crucial for chloroplast biogenesis/development. The accuracy and reliability of RNA-Seq was verified by qRT-PCR. Moreover, the chlorophyll (Chl) a/b content, ratio of Chla/Chlb and photosynthetic rate (Pn) of YS decreased significantly. Meanwhile, chloroplasts of the YS mesophyll cells were smaller, irregular in shape, contain almost no thylakoid membrane, and even proplastid was found in YS. These findings indicate that the rpoC2 mutation down-regulated expression of the 28 cpDEGs, which disturb chloroplast biogenesis and its thylakoid membrane development. Thus, there are not enough PSI and II components to bind Chl, so that the corresponding areas of the leaf are yellow and show a low Pn. In this study, the molecular mechanism of three phenotypes of F1 (Cmvv ♀ × C. miniata ♂) was revealed, which lays a foundation for the breeding of variegated plants.

Aquaporin-8 (AQP8), a member of the aquaporin family, is strongly expressed in follicular granulosa cells, which could affect the hormone secretion level in females. AQP8, as a membrane protein, could mediate H 2 O 2 into cells, thereby triggering various biological events. The deficiency of Aqp8 increases female fertility, resulting from the decrease in follicular atresia. The low cell death rate is related to the apoptosis of granulosa cells. However, the mechanism by which AQP8 regulates the autophagy of granulosa cells remains unclear. Thus, this study aimed to explore the effect of AQP8 on autophagy in follicular atresia. We found that the expression of the autophagy marker light-chain protein 3 was significantly downregulated in the granulosa cells of Aqp8 -knockout ( Aqp8 −/− ) mice, compared with wild-type ( Aqp8 +/+ ) mice. Immunofluorescence staining and transmission electron microscopic examination indicated that the number of autophagosomes in the granulosa cells of Aqp8 −/− mice decreased. Using a follicular granulosa cell autophagy model, namely a follicular atresia model, we verified that the concentration of H 2 O 2 significantly increased during the autophagy of granulosa cells, consistent with the Aqp8 mRNA level. Intracellular H 2 O 2 accumulation was modulated by endogenous AQP8 expression level, indicating that AQP8-mediated H 2 O 2 was involved in the autophagy of granulosa cells. AQP8 deficiency impaired the elevation of H 2 O 2 concentration through phosphorylated tyrosine activation. In addition, we carried out the analysis of transcriptome sequencing datasets in the ovary and found there were obvious differences in principal components, differentially expressed genes (DEGs) and KEGG pathways, which might be involved in AQP8-regulated follicular atresia. Taken together, these findings indicated that AQP8-mediated H 2 O 2 transport could mediate the autophagy of granulosa cells. AQP8 might be a potential target for diseases related to ovarian insufficiency.

The objective of this study was to compare and analyze the representative opening and closing movement of Tai Chi elastic band exercise with the reverse fly movement of elastic band resistance training. The aim was to explore the biomechanical differences between the two exercises and provide theoretical support for the application of Tai Chi elastic band exercise in health intervention. A total of 26 male participants were recruited and randomly divided into two groups in a 1:1 ratio. There were 13 participants in each Tai Chi elastic band exercise group and elastic band resistance training group. Both groups of participants used an elastic band to perform movement in the experiment. Experimental data were collected using the Vicon infrared motion capture system and Delsys surface EMG system. The AnyBody software was utilized to simulate the creation of a musculoskeletal model for both exercises. The study found that the Tai Chi elastic band exercise group exhibited smaller horizontal abduction angle and flexion angle of the shoulder joint, as well as normalized RMS of the anterior deltoid and triceps brachii, compared to the elastic band resistance training group ( < 0.01); the Tai Chi elastic band exercise group exhibited greater elbow flexion angle, elbow flexion torque, and muscle strength of the infraspinatus, coracobrachialis, biceps brachii, brachialis and brachioradialis, compared to the elastic band resistance training group ( < 0.01); the Tai Chi elastic band exercise group exhibited smaller horizontal abduction angular velocity of the shoulder joint and a lower normalized RMS of the posterior deltoid, compared to the elastic band resistance training group ( < 0.05). (1) The opening and closing movement of Tai Chi elastic band exercise is characterized by a large elbow flexion angle, a small shoulder joint horizontal angle and flexion angle, and a slow and uniform speed of movement. The reverse fly movement of elastic band resistance training is characterized by a large horizontal abduction angle of the shoulder joint, a large flexion angle of the shoulder joint, a small flexion angle of the elbow joint, and a fast and uneven speed. (2) The opening and closing movement exerts a greater torque on the elbow flexion, while the reverse fly movement exerts a greater torque on the shoulder joint horizontal abduction and external rotation. (3) The opening and closing movement provide greater stimulation to the infraspinatus, coracobrachialis, and elbow flexor, while the reverse fly movement provides greater stimulation to the posterior deltoid, anterior deltoid, subscapularis, and elbow extensor. In summary, the variation in joint angle, joint angular velocity, and hand position could be the factor contributing to the differences in joint torque and muscle activity between the opening and closing movement of Tai Chi elastic band exercise and the reverse fly movement of elastic band resistance training.

Background Neuropsychiatric symptoms significantly impact surgical recovery, quality of life, and long‐term survival. To investigate the association between intraoperative dexmedetomidine administration and the incidence of postoperative depressive symptoms in noncardiac surgical patients. Methods A multicenter prospective observational study of older surgical patients over 65 years of age from April 2020 to April 2022. The primary outcome was the incidence of postoperative 7‐day depressive symptoms. Secondary outcomes were the incidence of postoperative 7‐day anxiety symptoms, sleep disturbance, and delirium. A logistic regression model based on the random effect was used to determine the association between dexmedetomidine administration and the outcomes. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were employed to address data imbalance. Subgroup analyses based on specific populations were performed to explore the relationship between dexmedetomidine and depressive symptoms. Results Of 5591 patients, 20.5% (1148) received intraoperative dexmedetomidine. The incidence of postoperative 7‐day depressive symptoms was significantly lower in the dexmedetomidine group compared to the nondexmedetomidine group (unadjusted: 7.6% vs. 26.7%, p < 0.001; PSM: 7.9% vs. 29.0%, IPTW: 8.7% vs. 25.8%, p < 0.001). Dexmedetomidine was significantly associated with the remission of postoperative 7‐day depressive symptoms (adjusted random‐effect model: risk ratio [RR] 0.104, 95% CI, 0.080–0.140, p < 0.001; PSM: RR 0.311, 95% CI, 0.242–0.415, p < 0.001; IPTW: RR 0.297, 95% CI, 0.253–0.343, p < 0.001). Additionally, dexmedetomidine demonstrated protective effects against postoperative anxiety symptoms, sleep disturbance, and delirium. In age, gender, cumulative comorbidity, frailty, ASA physical status, and inhaled anesthetic subgroups, we also found that dexmedetomidine was associated with a reduction in postoperative depressive symptoms in older noncardiac patients. Conclusion Intraoperative dexmedetomidine administration was associated with a reduction in postoperative 7‐day depressive symptoms, anxiety symptoms, sleep disturbances, and delirium in older patients undergoing noncardiac surgery. Trial Registration The clinical trial protocol of this study was registered in the Clinical Trial registry (NCT06362408). Prior Presentations The authors have nothing to report. This multicenter prospective observational study was conducted in China from April 2020 to April 2022, focusing on elderly surgical patients aged 65 years and older who underwent noncardiac surgery. The study revealed that the use of dexmedetomidine during the intraoperative phase significantly diminished the incidence of depressive and anxiety symptoms, sleep disturbances, and delirium within the first 7 days postoperatively. Through the application of adjusted random‐effects logistic regression analysis, propensity score matching (PSM), and inverse probability treatment weighting (IPTW) techniques, it was conclusively established that the administration of dexmedetomidine during surgery was robustly linked to a marked decrease in the manifestation of these postoperative neuropsychiatric symptoms at the 7‐day mark. Dexmedetomidine presents itself as a potentially groundbreaking approach and direction for the management of postoperative neuropsychiatric complications in elderly surgical patients. As a result, there is a compelling need for further randomized controlled trials to substantiate the therapeutic benefits of dexmedetomidine in mitigating postoperative neuropsychiatric symptoms in older adults undergoing noncardiac surgical procedures.