Aeroengine blades (AEBs) are critical components of aircraft engines that require consistent monitoring and inspection to ensure airworthiness and operational safety. The aerospace industry relies heavily on maintenance, repair, and overhaul (MRO) procedures, where surface inspection of AEBs plays a pivotal role. Traditional manual or borescope-based inspection methods are time consuming, labor intensive, and susceptible to human error. In this work, a deep learning enabled intelligent robotic system is proposed for the autonomous inspection of AEBs, addressing key MRO requirements. Two distinct datasets were collected, one for aeroengine blade localization and another for surface defect detection. A robust deep learning model is trained separately on each dataset to perform their respective tasks with high accuracy. The trained models were integrated into an intelligent robotic system to automate the inspection workflow. In real time operation, a container filled with aeroengine blades is placed in front of the intelligent system, which autonomously localizes each blade, picks it up, places it in an image acquisition box, detects any surface defects, and returns the blade to its original position. The system provides real time feedback and accelerates decision making processes. Experimental results demonstrate that the proposed approach significantly reduces inspection time and enhances defect detection accuracy compared to conventional methods. By seamlessly combining vision based deep learning with robotic automation, the system offers a reliable solution for controlled industrial inspection environments for modern aerospace MRO processes, overcoming the limitations associated with manual inspection techniques. Experimental results demonstrate that the proposed approach achieves an mAP of 88.2% and reduces inspection cycle time to approximately 4 seconds per blade, significantly improving efficiency compared to conventional methods.
Managing skin infections requires both pathogen eradication and tissue regeneration, yet current therapeutics rarely address these sequential needs. Here, we designed a biomimetic catalytic system (MBC) to recapitulate the dynamic, dual-phase functionality of the innate immune response. In the infectious microenvironment, MBC mimics neutrophil-mediated killing by using CeO2 nanoparticles (NPs) and Br ions to exert haloperoxidase-like activity, generating HBrO from endogenous H2O2 to eliminate MRSA biofilms. Upon infection clearance, the system autonomously transitioned to a healing phase. CeO2 NPs switch to macrophage-like antioxidant functions, scavenging reactive oxygen species, resolving inflammation, and restoring immune homeostasis. In three murine infection models of MRSA-infected wounds, pressure ulcers, and subcutaneous abscesses, MBC achieves comprehensive therapeutic efficacy.
This study aimed to evaluate the relationship between mild autonomous cortisol secretion (MACS) caused by adrenal adenomas and hepatic fat fraction (HFF) measured by dual-echo Dixon chemical shift-encoded MRI (dual-echo CSE-MRI). This retrospective study included 151 patients with 169 adrenal adenomas evaluated between November 2023 and November 2025. According to post-1 mg dexamethasone suppression test (DST) cortisol levels, patients were classified as having MACS or non-functioning adrenal incidentalomas (NFAI). HFF was quantitatively assessed using dual-echo CSE-MRI. Clinical, biochemical, and imaging findings were analyzed. Correlation analyses and multivariate regression models were used to identify factors associated with hepatic fat fraction and MACS. Forty-five adrenal adenomas (26.6%) were classified as MACS. HFF was significantly higher in patients with MACS compared with those with NFAI (16.0% ± 13.3% vs. 7.1% ± 7.6%, p < 0.001). HFF showed a significant positive correlation with post-DST cortisol levels (r = 0.316, p < 0.001) and fasting glucose levels (r = 0.312, p < 0.001). In multivariate logistic regression analysis, hepatic fat fraction remained independently associated with MACS (OR: 1.084, p < 0.001). Multivariate linear regression analysis demonstrated that post-DST cortisol levels, fasting glucose levels, and age were independently associated with HFF. Hepatic fat fraction measured by dual-echo CSE-MRI is increased in patients with MACS and is associated with cortisol excess.
Urban-rural disparities may hinder HPV vaccination in Tibetan regions. This study quantified disparities in HPV vaccine knowledge, willingness, and uptake among women in Tibetan settings. A multi-center cross-sectional survey of women aged 18 to 45 years was conducted. HPV knowledge was measured using a 10-item score (range 0-10). Vaccination uptake was defined as self-reported receipt of at least 1 dose. Among unvaccinated participants, willingness was dichotomized as willing versus unwilling or undecided. Multivariable linear and logistic regression models accounted for within-site correlation using cluster-robust standard errors by survey site. Among 812 participants (568 urban, 244 rural), overall uptake was 29.8% (242/812) and was higher among urban than rural residents (35.2% vs. 17.2%, p < 0.001). The median knowledge score was 6 (IQR 2 to 7) overall; urban residents had higher knowledge than rural residents (median 6 [IQR 3 to 8] vs. 3 [IQR 0 to 6]; p < 0.001). Among unvaccinated participants (n = 570), willingness was associated with urban residence (adjusted OR 1.32, 95% CI 1.01 to 1.73), knowledge (per 2-point increase: 1.46, 1.28 to 1.67), Bachelor's-or-higher education (1.83, 1.28 to 2.62), and prior HPV testing (1.62, 1.08 to 2.44). In the base uptake model, urban residence (1.67, 1.21 to 2.30) and knowledge (per 2-point increase: 1.34, 1.23 to 1.46) were associated with uptake. In the staged model adding prevention-service contact, Pap smear history (1.88, 1.39 to 2.56) and HPV testing history (2.41, 1.55 to 3.75) were strong predictors and the urban association attenuated (1.26, 0.93 to 1.71). Among unvaccinated participants, cost (46.7%) and safety concerns (33.7%) were common; rural residents reported substantially higher access or travel burden (47.5% vs. 7.1%) and supply or availability constraints (45.0% vs. 2.7%). The most common maximum willingness-to-pay category was 300 to 999 CNY (37.5%). Large urban-rural gaps in knowledge and vaccination uptake persist despite high willingness among unvaccinated women, indicating a substantial intention-to-behavior gap driven by affordability and delivery constraints. Interventions should pair education with financing and service delivery strategies that reduce travel burden and improve reliable vaccine availability in rural Tibetan settings.
IGLV3-21R110 is a point mutation enabling autonomous B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL). It has been associated with shorter time to first treatment and overall survival, but its effects have not been evaluated in phase 3 clinical trials or in patients treated with Bruton tyrosine kinase inhibitors. Here, we analyzed samples from the phase 3 CLL12 study that compared ibrutinib vs. placebo in untreated early-stage CLL patients with intermediate to very high risk of disease progression, while patients with low risk of disease progression were allocated to watch-and-wait (w&w). Four detection methods (targeted next-generation sequencing, Sanger sequencing, multiplex IGLV3-21R110-specific PCR, and flow cytometry) were compared, yielding highly consistent results. Overall, 34/515 (6.6%) patients had productive IGLV3-21 rearrangements: 5/152 (3.3%) in w&w, 15/181 (8.3%) in placebo, and 14/182 (7.7%) in the ibrutinib group. Of these, 25 were IGLV3-21R110-positive (3/5, 12/15, and 10/14). IGLV3-21R110 was associated with shorter event-free survival (EFS) across all arms: w&w (hazard ratio [HR] 17.03, 95% confidence interval [CI 95%]: 4.99-58.13, P < 0.001), placebo (HR 2.31, CI 95%: 1.16-4.6, P = 0.017), and ibrutinib (HR 2.99, CI 95%: 1.17-7.65, P = 0.023). Multivariable analysis identified IGLV3-21R110 as an independent prognostic factor for shorter EFS (HR 3.18, CI 95%: 1.73-5.83, P < 0.001). Notably, IGLV3-21R110 was associated with reduced clinical effectiveness of ibrutinib. Ca2+-flux and cell viability assays using patient-derived BCRs expressed in murine B-cells confirmed reduced ibrutinib efficacy in IGLV3-21R110 cases, especially regarding inhibition of antigen-stimulated signaling. In summary, IGLV3-21R110 is an independent prognostic factor for shorter EFS in early-stage CLL and reduces ibrutinib effectiveness clinically and in vitro.
Benzodiazepines are widely used to treat anxiety; however, their influence on defensive behavior when threats compete with rewards remains unclear. Here, we tested the effects of diazepam on reactive avoidance (no conflict), threat-reward conflict resolution, and re-expression of avoidance following conflict. Using an integrated platform-mediated avoidance paradigm in female and male rats, we assessed the effects of a low dose systemically administered diazepam (1 mg/kg). Diazepam did not alter the reactive avoidance memory expression when threat cues were presented without a concurrent reward cue. In contrast, during the cued threat-reward conflict, diazepam reduced platform avoidance and increased reward engagement, shifting the avoidance/approach balance toward the approach. Diazepam also impaired the re-expression of avoidance following conflict training, maintaining a more approach-dominant behavioral allocation. Sex differences emerged selectively during post-conflict re-expression of avoidance, where diazepam produced a clearer shift toward reward engagement in males, whereas the effect in females was weaker and not clearly detectable under the present conditions. Control assays showed no significant effects of diazepam on threat or reward memory retrieval, sucrose intake, open-field locomotion, or anxiety-like behavior. These findings indicate that diazepam shifts behavioral allocation toward reward during threat-reward conflict and alters post-conflict avoidance re-expression, with effects that were more apparent in males than in females, while sparing reactive avoidance under no-conflict conditions.
Organ transplants are currently the most effective treatment for end-stage organ failure and are sometimes the only option. They can affect the life expectancy of patients who depend on treatments that seriously compromise their quality of life. Various studies have been conducted to ascertain opinions, perceptions and attitudes toward organ donation among different sectors of society, including healthcare professionals. It was therefore deemed appropriate to extend these questions to undergraduate students, who will soon be responsible for these tasks. This exploratory qualitative study was conducted with 120s-year nursing students who participated from a cohort of 152 students enrolled in Adult Nursing I at the University of Málaga. Twelve focus groups were conducted after a specific seminar on organ donation. The study therefore explored students' postseminar perceptions, knowledge, and attitudes toward organ donation. Transcripts were analysed using inductive thematic analysis. The results revealed a significant perceived knowledge gap regarding the donation process, despite participants expressing positive attitudes toward donation. Most students considered that training on this subject was insufficient within the university curriculum and requested more formal, practical education on organ donation and transplantation. Generosity, solidarity, and the idea of leaving a legacy emerged as key motivations for donating. Gender-related perceptions were also identified, particularly the view that women may be more willing to donate during life. These findings suggest that organ donation education could strengthen nursing students' preparedness and may inform future educational interventions; however, effects on family refusal rates or transplant-system outcomes should be examined in subsequent studies rather than inferred directly from this exploratory qualitative work. No formal patient or public involvement was undertaken in the design, conduct, analysis, or reporting of this study. Nursing students participated solely as research participants in the focus groups, not as formal patient or public contributors. Their perspectives, however, provide relevant insight into how future nurses perceive organ donation, the educational gaps they identify, and the type of training they consider necessary to support future clinical nursing practice, particularly in communication with patients and families, health education, and professional involvement in the organ donation process.
To compare the effects of liposomal bupivacaine and ropivacaine for ultrasound-guided parasternal block combined with rectus sheath block (PSB + RSB) on acute and chronic postoperative pain in patients undergoing cardiac sternotomy, so as to provide an evidence-based basis for optimizing the multimodal analgesia regimen for such surgeries. A total of 90 patients scheduled for elective median sternotomy cardiac and great vessel surgery at the Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University from April 2024 to February 2025 were enrolled. They were divided into the liposomal bupivacaine group (group LB, n=45) and the ropivacaine group (group ROP, n=45) using the random number table method. After endotracheal intubation under general anesthesia, group LB was given 40 mL of 266 mg liposomal bupivacaine injection for bilateral PSB+RSB, while group ROP was administered 40 mL of 0.375% ropivacaine injection for the same block regimen.The following outcomes were recorded at different postoperative time points: cumulative consumption of analgesic drugs (calculated as morphine milligram equivalents, MMEs), scores of Numeric Rating Scale (NRS, 0-10 points) for pain assessment, scores of Quality of Recovery-15 (QoR-15) scale, and the incidence of adverse events. A total of 88 patients completed the study (2 patients in group LB were excluded due to surgical duration exceeding 8 hours). At 24 h and 48 h after the first postoperative awakening, the cumulative MMEs consumption in group LB was significantly lower than that in group ROP [55.30(47.80,62.10) vs 68.00(48.40,80.00) mg, 76.30(68.80.83.10) mg vs 86.00(63.40,119.60), all P < 0.05]. At 4 h and 12 h post-extubation, the activity-related NRS scores in group LB were significantly lower than those in group ROP [2.00(2.00.2.00) points vs 2.00(2.00,3.00) points, 2.00(2.00,3.00) points vs 3.00(2.00,4.00) points, all P < 0.05]. At 24 h, 48 h and 72 h post-extubation, the QoR-15 scores in group LB were significantly higher than those in group ROP [(85.4±11.78) points vs (74.7±9.89) points, (91.6±10.4) points vs (86.8±8.6) points, (107.1±9.87) points vs (100.0±9.15) points, all P < 0.05]. The incidence of postoperative nausea and vomiting in group LB (16.3%, 7/43) was significantly higher than that in group ROP (2.2%, 1/45) (P < 0.05). There were no significant differences between the two groups in postoperative endotracheal extubation time, ICU stay time, hospital stay, and the incidence of chronic postsurgical pain (CPSP) at 3 months after surgery . The use of liposomal bupivacaine for PSB+RSB block in patients undergoing cardiac sternotomy can significantly reduce postoperative analgesic consumption, optimize early analgesic effect, and improve postoperative recovery quality. However, attention should be paid to the risk of nausea and vomiting, and individualized selection should be made after balancing the benefits and risks in clinical application. Trial registration:This trial was registered in the Chinese Clinical Trial Registry (ChiCTR2400084078) on May 10, 2024 (https://www.chictr.org.cn/).
Fecal samples have been frequently used to investigate ulcerative colitis (UC)-related gut microbiota study due to their easy availability. However, whether fecal microbiota accurately represents the mucosal microbiome of UC patients remains controversial. This study aims to analyze the gut microbiota in feces and colonic tissue, and to demonstrate from different perspectives whether the gut microbiota in feces can fully characterize the gut microbiota in colonic tissue. We employed 16S rRNA sequencing and standardized microbiome analysis for fecal and colon tissue samples from 12 UC patients and 16 non-IBD controls (NIC). And we also integrates ELISA, functional analysis, and machine learning techniques to discuss the similarities and differences among differentially identified UC-related microorganisms screened from two sample types. As results, colonic tissue exhibited greater microbial diversity than feces. And some taxa were only detected in colonic tissue. In UC, α-diversity was higher in colonic tissue but lower in feces compared to NIC. Only two microbial genera (Ligilactobacillus and Intestinimonas) showed consistent differential abundance across both sample types. At the functional pathway level, both fecal and colonic microbiota were primarily associated with metabolic pathways; however, colonic microbiota were additionally linked to immune-related pathways, such as the NOD-like receptor signaling pathway. IL-1β, IL-17 and IL-22 were significantly overexpressed in UC. Most fecal differential microbes were negatively correlated with those three cytokines. Regarding the two shared differentially expressed genera, abundance of Ligilactobacillus in tissues was more strongly correlated with the expression of inflammatory cytokines. The correlation between the abundance of Intestinimonas and the expression levels of inflammatory cytokines showed opposite trends in tissues and feces. The combined SHAP and random forest algorithms shown that the UC classification model based on tissue markers was more stable and exhibited weaker overfitting than the model based on fecal markers. In general, fecal microbiota profiles did not adequately represent the microbial landscape of colonic tissue in patients with UC. For studies investigating disease mechanisms, colonic tissue was the more appropriate sample type. However, due to its accessibility, fecal samples remained a promising source for microbial biomarker discovery and the development of diagnostic models.
Reduced kidney function is strongly associated with higher mortality, but most evidence is from high-income populations. This study evaluated the relevance of kidney function to cause-specific mortality in Mexico, a country where diabetes is common and chronic kidney disease (CKD) is a major cause of morbidity and mortality. Prospective study of Mexican adults aged ≥35 years at recruitment (1998-2004) who were followed until October 2022. Participants recruited into the Mexico City Prospective Study. Analyses focused on 126,245 participants aged 35-74 years at recruitment without prior disease (except diabetes or CKD). Estimated glomerular filtration rate (eGFR). Cause-specific mortality. Cox regression was used to relate eGFR to cause-specific mortality. Analyses were adjusted for sociodemographic and lifestyle factors, anthropometry, and diabetes. Among 40,996 men and 85,249 women aged 35-74 years, median eGFR was 102 (IQR, 91-110) mL/min/1.73 m2, mean body mass index was 29.1 (SD 4.9) kg/m2, 1% had self-reported CKD, 13% had previously diagnosed diabetes, and 12,590 died at ages 35-74 years over a median follow-up of 20.4 years. For those with eGFR <105 mL/min/1.73 m2, each 15-mL/min/1.73 m2 lower eGFR was associated with 32% higher all-cause mortality (RR, 1.32; 95% CI, 1.30-1.35). The strongest associations were for kidney (RR, 1.75; 95% CI, 1.69-1.80), infective (RR, 1.34; 95% CI, 1.24-1.44), and vascular deaths (RR, 1.28; 95% CI, 1.24-1.33). Compared with participants with eGFR 90-104 mL/min/1.73 m2, those with eGFR <30 mL/min/1.73 m2 had almost 7 times the all-cause mortality rate (RR, 6.5; 95% CI, 5.7-7.3). For participants with eGFR >105 mL/min/1.73 m2, higher eGFR was associated with higher mortality. The absolute excess mortality risk associated with reduced eGFR was particularly high for those with diabetes. Data on urinary albumin and nonfatal disease outcomes were unavailable. In Mexico, decreased kidney function is strongly associated with premature mortality, mainly from vascular, kidney, and infective causes. Prevention and management of CKD, particularly in individuals with diabetes, should be central to disease-prevention policies. Evidence of the impact of decreased kidney function on the risk of death is lacking in Mexico, a country where diabetes and kidney disease are major causes of death. Between 1998 and 2004, the Mexico City Prospective Study recruited 150,000 adults aged ≥35 years and tracked their causes of death for over 20 years. This study found that decreased kidney function was linked with a higher risk of death, mainly because of heart disease, kidney disease, and infections. Individuals with substantially decreased kidney function were about 7 times more likely to die than those with apparently healthy kidney function. Having both diabetes and decreased kidney function resulted in an extremely high risk of death. Increasing the use of kidney and heart-protective drugs in people with diabetes, elevated blood pressure, or chronic kidney disease and expanding access to dialysis and kidney transplantation will likely reduce premature mortality in Mexico.
Candida albicans (C. albicans) is among the most common opportunistic fungal pathogens and causes superficial infections and life-threatening invasive candidiasis in immunocompromised individuals. In recent years, C. albicans has become resistant to a wide range of clinical drugs, and the identification of effective antifungal drugs is an extremely urgent medical need. Acetylshikonin (ASK) is a naphthoquinone compound extracted from Lithospermum erythrorhizon that exhibits potent antibacterial activity. However, its efficacy against C. albicans and antimicrobial mechanisms, especially against drug-resistant C. albicans, are unclear. The antifungal activity of ASK was evaluated based on minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) measured in vitro and in mouse models of vulvovaginal candidiasis and oropharyngeal candidiasis to assess its efficacy in vivo. Mechanistic investigations included assessments of cell membrane and cell wall damage, adhesion ability, oxidative stress evaluation, protein expression, and target identification (including RT‒qPCR, molecular docking, and related methods). The main active ingredient from Lithospermum erythrorhizon that targets C. albicans was identified as ASK. It exhibits significant activity against drug-resistant fungi both in vitro and in vivo. Moreover, ASK can reduce the adhesion of C. albicans and damage to cell membrane and cell wall and induce apoptosis-like cell death-like cell death. In addition, ASK may directly bind to Malate Synthase 1 (Mls1) and effectively downregulate its expression and inhibit the glyoxylate cycle, leading to the generation and accumulation of large amounts of ROS, and damage to DNA to achieve its antifungal effects. ASK can treatment drug-resistant C. albicans infections, its mechanism of action is related to the inhibition of Mls1.
The PA gene of the 2009 pandemic H1N1 (pdm09/H1N1) lineage is derived from avian influenza virus (AIV). Together with other polymerase subunits, it enhances the adaptation of avian-origin influenza virus to mammals. However, the functional region of the PA protein remains unclear. Using reverse genetics, we mapped functional domains of pdm09/H1N1 PA in an avian-origin H9N2 canine influenza virus (CIV) background. The N-terminal 169-252 region conferred high intrinsic polymerase activity yet failed to support efficient viral replication alone, revealing a dissociation between catalytic potential and replicative fitness. In contrast, the 85-168 region enabled robust replication despite lower activity. Importantly, synergy between the 169-252 region and its cognate pdm09/H1N1 NP drove high polymerase activity and replication. This pairing also enhanced viral growth in vitro, increased viral titers in mouse lungs and nasal turbinate, and induced pulmonary damage. Mechanistically, the 169-252 region interacts with NP, accelerating nuclear import and cRNA synthesis, thereby optimizing viral RNA replication timing. Thus, PA-NP co-evolution is a key driver of mammalian adaptation, moving beyond single mutations and highlighting internal gene compatibility as a determinant of viral fitness and pandemic potential.
Low back pain affects a large population globally, and intervertebral disc degeneration (IVDD) is one of its major causes. This review aims to summarize the roles and molecular mechanisms of hypoxia-inducible factors (HIFs) in IVDD progression, and provide theoretical support for developing precise treatment strategies for IVDD. We systematically retrieved, sorted and analyzed recent peer-reviewed studies concerning the association between HIF family members and IVDD. IVDD involves complex pathological changes including hypoxic microenvironment imbalance, inflammatory responses, extracellular matrix (ECM) dysfunction and altered autophagy. HIFs, key oxygen-sensing regulators, exert bidirectional effects on IVDD: they can either alleviate or accelerate disc degeneration under different conditions. HIFs play a central regulatory role in IVDD. Targeting HIF-related pathways holds great potential for clinical translation, and further research is still required to clarify unresolved mechanisms.
This study evaluates a synergistic treatment combining coagulation-flocculation with a UV254 photo-assisted electrochemical advanced oxidation process (AOP) producing HOCl-•OH for domestic wastewater collected from the influent of a municipal wastewater treatment plant in Mexico, and fortified with ciprofloxacin (CIP), cefadroxil (CFX), sulfamethoxazole (SMX), and carbamazepine (CBZ) at 20 mg L-1 each. Coagulation/flocculation with a coagulant/biopolymer at a 1:1 ratio achieved substantial primary removal efficiencies (80.64% turbidity, 73% Chemical Oxygen Demand (COD), and 82.08% Total Organic Carbon (TOC)), with removal mechanisms strongly influenced by pharmaceutical speciation. Subsequent UV254 photo-assisted electrochemical treatment in a filter-press FM01-LC reactor equipped with a Ti/RuO2-ZrO2-Sb2O3 anode enabled active chlorine electrogeneration and photolytic radical formation. Standalone photolysis, and pure electrocatalysis (77.76% TOC elimination) resulted in negligible mineralization, confirming the necessity of the hybrid method. Optimal degradation and mineralization (99.19% turbidity, 98.36% COD, 95.65% TOC) was achieved at 30 mA cm-2, 0.2 M NaCl, 1 L min-1, and pH 4.5 (1 h) in the fortified municipal wastewater; while a TOC decrease of 94.60% was achieved in the untreated sewage influent without fortification. These results demonstrate that pH control is more critical than increasing current density, as predominance of HOCl induces UV homolysis into highly reactive •OH and Cl• radicals. Active species trapping tests confirmed the dominant role of •OH in contaminant mineralization, while energy consumption remained low (0.04-0.05 kWh m-3), indicating competitive operational performance. Complete elimination of total coliforms was achieved; while Daphnia magna bioassays revealed null toxicity at shorter treatment times than 0.5 h. Overall, this hybrid process demonstrates high mineralization efficiency for municipal wastewater conditions while identifying operational constraints relevant for pilot-scale implementation.
This study aims to analyze the equity and efficiency of health resource allocation in underdeveloped county areas, providing a reference for improving health resource policies in such regions. Focusing on eight underdeveloped counties in Guangxi, China, this research evaluates the fairness of health resource distribution using the Gini coefficient and Lorenz curve, and assesses allocation efficiency through the Data Envelopment Analysis model. In terms of equity in health resource allocation from 2015 to 2021, the Gini coefficients for health resources per capita were between 0.07 and 0.23, indicating the highest level of equity; the fairness in the distribution of healthcare human resources was lower than that of medical institutions and hospital beds, with particularly low equity observed in the distribution of licensed (assistant) physicians. Regarding efficiency, the overall efficiency of health resource allocation averaged between 0.899 and 0.933, with the number of counties achieving efficiency fluctuating between three and five. There were inefficiencies observed, particularly in technical and scale efficiency, with low scale efficiency being a significant factor affecting the efficiency of health resource allocation in underdeveloped counties. The distribution of health resources based on population and GDP demonstrates greater equity compared to distribution based on geographic areas. The equity of institutions and beds is superior to that of healthcare human resources. Overall, the efficiency of health resource allocation is not high, and there are regional disparities in efficiency. Recommendations include increasing the focus on health resource allocation in underdeveloped areas, optimizing the management of healthcare human resources, and coordinating planning to improve the precision and rationality of resource investment, thereby enhancing the efficiency of health resource utilization.
Cobalamin (vitamin B₁₂) is synthesized only by certain bacteria and archaea and is rarely found in plant-derived foods because plants neither synthesize nor require this cofactor. The edible duckweed Wolffia globosa Mankai is unusual in containing bioavailable cobalamin, suggesting a microbial origin. However, how cobalamin biosynthetic capacity is organized within angiosperm-associated microbiomes remains largely unresolved. Here, we investigated bacterial community structure and cobamide biosynthetic potential across the cultivation medium, plant surface, and internal tissues of Mankai to determine how cobalamin production is maintained in this aquatic plant microbiome. Bacterial communities differed significantly among compartments, with the endosphere forming a low-diversity, host-filtered microbiome enriched in specialized taxa. Genome-resolved metagenomics showed that only a minority of endophytic bacteria encoded near-complete cobamide biosynthesis pathways consistent with de novo synthesis. In contrast, many co-occurring taxa lacked multiple biosynthetic steps but were enriched in genes associated with cobamide precursor salvage and remodeling. Network analysis identified putative producer taxa as highly connected hubs linked to salvager populations, consistent with metabolite cross-feeding. Comparative genomic analysis demonstrated reduced cobamide biosynthetic gene complements in endophytic genomes relative to closely related free-living strains, supporting adaptive pathway reduction in the host-associated niche. Cobalamin production in the Mankai endosphere appears to arise from a metabolically interdependent bacterial consortium rather than from single autonomous producers. These findings identify cooperative micronutrient biosynthesis as an organizing principle in plant-associated microbiomes and position Mankai as a tractable model for studying cobamide-mediated microbial cooperation in aquatic crops. Understanding these interactions may support microbiome-informed strategies to stabilize micronutrient production and functional resilience in controlled aquatic plant cultivation systems.
Nanoplastics have recently been detected in human liver tissue, raising concerns about their potential impact on liver function. However, early hepatocyte responses associated with nanoplastics exposure remain poorly understood. Here, we combined high-throughput Cell Painting-based phenomics, untargeted metabolomics, and Seahorse mitochondrial functional assay to investigate the effects of 100 nm polystyrene nanoplastics on human HepaRG hepatocytes, a surrogate for primary human hepatocytes. At the tested concentrations (6.25-100 µg/mL), exposure did not induce overt cytotoxicity, enabling assessment of early sublethal cellular responses. Phenomics revealed widespread subcellular perturbations, with 16.4% of the measured phenotypic features significantly altered. Mitochondria-associated features represented the dominant altered phenotypic signature, showing pronounced changes in granularity, texture, and radial distribution, alongside alterations in endoplasmic reticulum- and cytoskeleton-associated features. Untargeted metabolomics of intracellular metabolites and the extracellular secretome revealed metabolic alterations, characterized by changes consistent with altered β-oxidation, lipid handling, membrane stress, and central carbon metabolism, including changes in the tricarboxylic acid (TCA) cycle and amino acid catabolism. Pathway analysis identified the TCA cycle as one of the most significantly affected pathways (FDR = 0.028). Integrated phenomic-metabolomic analysis revealed strong correlations between mitochondrial phenotypic features and metabolites involved in lipid and energy metabolism, indicating a coordinated structural-metabolic response to polystyrene nanoplastics exposure. Functional assessment using Seahorse assay showed reduced basal and maximal respiration and decreased ATP-linked O2 consumption. Together, these findings provide evidence that 100 nm polystyrene nanoplastics elicit early mitochondria-associated phenotypic, metabolic, and functional responses prior to overt cytotoxicity under the tested conditions. They also highlight the value of phenomic-metabolomic-functional integration for profiling sublethal nanotoxicological responses and guiding future targeted mechanistic studies.
Cardiac hypertrophy (CH) represents a key pathological process in cardiac remodeling and progression toward heart failure. Understanding its underlying molecular mechanisms is essential for developing novel therapeutic strategies. MicroRNAs (miRNAs) play crucial regulatory roles in cardiovascular diseases, however, their specific involvement in CH remains incompletely understood. Here, we demonstrate that miR-300-3p modulates angiotensin II (Ang II)-induced CH through the ACOX1/GPX4 pathway. Functionally, miR-300-3p directly targets ACOX1, leading to its downregulation and subsequent enhancement of ferroptosis. Overexpression of ACOX1 reversed these effects. Mechanistically, hypomethylation of the miR-300-3p promoter region, mediated by DNMT1, elevated miR-300-3p expression and contributed to Ang II-induced hypertrophic responses. Furthermore, ACOX1 exerted anti-hypertrophic effects via activation of the GPX4 signaling pathway. In conclusion, DNMT1-regulated promoter hypomethylation enhances miR-300-3p expression, suppresses ACOX1, and promotes ferroptosis in Ang II-induced CH. The miR-300-3p/ACOX1/GPX4 axis uncovers novel molecular pathways in CH and identifies potential therapeutic regulators.
Hepatic fibrosis (HF) is driven by hepatic stellate cell (HSC) activation. Although cyclic adenosine monophosphate (cAMP) is a key antifibrotic signal, whether pharmacological cAMP elevation acts through protein kinase A (PKA) or exchange protein directly activated by cAMP 1 (EPAC1) remains unclear. Alprostadil (PGE1) elevates intracellular cAMP, but its antifibrotic mechanism is undefined. Using CCl₄-induced HF in rats and primary HSCs, we found that Alprostadil markedly reduced liver injury, collagen deposition, and HSC activation. Fibrotic livers showed increased total cAMP but decreased PKA- and EPAC1-bound cAMP, indicating depletion of functional cAMP microdomains. Alprostadil restored effector-bound cAMP, increased EPAC1 expression, and enhanced PKA/CREB phosphorylation. Notably, EPAC1 inhibition-but not PKA inhibition-attenuated the antifibrotic effects of Alprostadil in vivo and in vitro. These findings identify EPAC1 as the dominant downstream effector through which Alprostadil restores localized cAMP signaling to suppress HSC activation and hepatic fibrosis.
The new HLA-DQA1*03:02:07 allele differs from its most closely related allele DQA1*03:02:01:02 in exon 3.