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The contribution of Cutibacterium acnes (C. acnes) infection to intervertebral disc degeneration (IDD) and the antibiotic therapy has evoked several controversies in recent years. While some microbiology studies report bacterial disc infection within IDD patients, others attribute the positive results to contamination during prolonged cultures. In addition to the clinical controversy, little was known about the mechanism of C. acnes-caused Modic changes (MCs) if C. acnes was the pathogenic factor. This study aimed to investigate the inflammatory mechanism of MCs induced by different phylotypes of C. acnes in patients with IDD. Specimens from sixty patients undergoing microdiscectomy for disc herniation were included, C. acnes were identified by anaerobic culture, followed by biochemical and PCR-based methods. The identified species of C. acnes were respectively inoculated into the intervertebral discs of rabbits. MRI and histological change were observed. Additionally, we detected MMP expression in the rabbit model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Of the 60 cases, 18 (30%) specimens were positive for C. acnes, and we identified 4 of 6 defined phylogroups: IA, IB, II and III. The rabbits that received Type IB or II strains of C. acnes showed significantly decreased T1WI and higher T2WI at eighth weeks, while strain III C. acnes resulted in hypointense signals on both T1WI and T2WI. Histological examination results showed that all of the three types of C. acnes could cause disc degeneration and endplates rupture. Moreover, endplate degeneration induced by type IB or II strains of C. acnes is related with MMP13 expression. Meanwhile, strain III C. acnes might upregulated the level of MMP3. This study suggested that C. acnes is widespread in herniated disc tissues. Different types of C. acnes could induce different MCs by increasing MMP expression.

Eye diseases and injuries impose a significant clinical problem worldwide. Safe and effective ocular drug delivery is, however, challenging due to the presence of ocular barriers. Here we report a strategy using an eye patch equipped with an array of detachable microneedles. These microneedles can penetrate the ocular surface tissue, and serve as implanted micro-reservoirs for controlled drug delivery. The biphasic drug release kinetics enabled by the double-layered micro-reservoirs largely enhances therapeutic efficacy. Using corneal neovascularization as the disease model, we show that delivery of an anti-angiogenic monoclonal antibody (DC101) by such eye patch produces ~90% reduction of neovascular area. Furthermore, quick release of an anti-inflammatory compound (diclofenac) followed by a sustained release of DC101 provides synergistic therapeutic outcome. The eye patch application is easy and minimally invasive to ensure good patient compliance. Such intraocular drug delivery strategy promises effective home-based treatment of many eye diseases. Treatment for eye injuries and diseases is most efficient when delivered directly into the eye. Here, the authors developed a patient-friendly eye patch equipped with an array of detachable microneedles, through which drugs can be delivered through the cornea for an extended period of time.

Background Prediction scoring systems for coronary artery bypass grafting (CABG) patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) have not yet been reported. This study was designed to develop a predictive score for in-hospital mortality for cardiogenic shock patients who received VA-ECMO after isolated CABG. Methods Retrospective cohort study of consecutive CABG patients supported with VA-ECMO ( n  = 166) at the Beijing Anzhen Hospital between February 2004 and March 2017. Results One hundred and six patients (64%) could be weaned from VA-ECMO, and 74 patients (45%) survived to hospital discharge. On the basis of multivariable logistic regression analyses, the pRedicting mortality in patients undergoing veno-arterial Extracorporeal MEMBrane oxygenation after coronary artEry bypass gRafting (REMEMBER) score was created with six pre-ECMO parameters: older age, left main coronary artery disease, inotropic score > 75, CK-MB > 130 IU/L, serum creatinine > 150 umol/L, and platelet count < 100 × 10 9 /L. Four risk classes, namely class I (REMEMBER score 0–13), class II (14–19), class III (20–25), and class IV (> 25) with their corresponding mortality (13%, 55%, 70%, and 94%, respectively), were identified. The area under the receiver operating characteristic curve 0.85(95% CI 0.79–0.91) for the REMEMBER score was better than those for the SOFA, SAVE, EuroSCORE, and ENCOURAGE scores in this population. Conclusions The REMEMBER score might help clinicians at bedside to predict in-hospital mortality for patients receiving VA-ECMO after isolated CABG for refractory cardiogenic shock. Prospective studies are needed to externally validate this scoring system.

Objective This study aims to compare the clinical efficacy, ankle function, radiographic parameters, and lower limb alignment changes between supramalleolar osteotomy alone and that combined with fibular osteotomy in the treatment of varus ankle osteoarthritis, and to provide a reference for clinical decision-making. Materials and methods This was a continuous retrospective analytical single-center study performed in the orthopedic surgery unit of the Hospital. The American orthopedic foot and ankle society (AOFAS)ankle—hind score, and Visual Analogue Scale (VAS) were used for pre—and postoperative functional evaluation as well as the range of motion (ROM)of ankle on sagittal plane. The tibial anterior surface angle (TAS), talar tilt angle (TT), medial displacement of the talus (MDT), knee joint congruence (JLCA) angle and hip-knee-ankle (HKA) angle were evaluated pre—and postoperatively. Results The remaining 28 patients in Group I and 27 in Group II were included in the final analysis. fter surgery, the clinical and radiographic parameters of both groups were significantly improved compared with preoperative values ( P  < 0.05). The range of motion (ROM) of the ankle joint decreased postoperatively in both groups, but there was no significant difference in postoperative ROM between the two groups ( P  > 0.05). Compared with the SMOT alone group, the SMOT + FO group had significantly higher postoperative American Orthopaedic Foot and Ankle Society (AOFAS) scores, lower medial distal tibial angle (MDL), and more improved knee joint line convergence angle (JLCA) (all P  < 0.05). The significant correlations were found between the AOFAS and MDT changes( r =-0.341, P  = 0.011). Conclusion Both SMO alone and SMO + FO can effectively alleviate pain and improve ankle function in patients with varus ankle osteoarthritis. The SMO + FO approach has advantages in improving AOFAS scores, MDL, and JLCA, suggesting that it may be a more optimal surgical option for patients with specific indications.

Conditioned taste aversion (CTA) is a survival mechanism that prevents consumption of harmful foods. Yet its neural circuits, especially those for solid food aversion, are poorly understood. Using a male mouse model where high-fat food (HFF) was paired with LiCl injections, we identified the median raphe region (MRR) as essential for CTA. Optogenetic activation of MRR glutamatergic neurons replaced LiCl injections, inducing robust HFF aversion. Calcium signaling in MRR neurons increased upon HFF approach post-CTA. We uncovered a necessary glutamatergic projection from the medial preoptic area (MPOA) to the MRR; stimulating this circuit mimicked LiCl, to elicit HFF aversion. Following CTA, synaptic changes in MRR neurons included an increased mEPSC frequency and an altered paired-pulse ratio in the MPOA VgluT2 -MRR pathway. Finally, MRR projections to the medial septum and lateral habenula differentially encode and retrieve CTA memory. These findings define a circuit for aversion learning, offering insights into maladaptive eating behaviors. Neural mechanisms underlying conditioned taste aversion are not fully understood. Here authors identified a brain circuit that drives learned aversion to high-fat food by associating it with nausea. This circuit’s learning and memory components offer insight into how the brain forms food avoidance behaviors.

Rapid population and economic growth have led to an increased demand for water and food, thereby exacerbating the water scarcity crisis. Therefore, an objective assessment of water usage in crop production is crucial for ensuring national food security and alleviating water scarcity. However, the city-scale crop production water footprint (CWF) in China remains incomplete, while grid-scale CWF data are plagued by the limitations of coarse crop statistics. To fill this knowledge gap, we propose a novel methodology for developing a high-resolution inventory of CWFs. Based on this methodology, we quantified the city-scale water footprint (WF) of three major crops (rice, wheat, and maize) in China and allocated the CWFs of individual cities to 3 km × 3 km grids through a top-down downscaling approach to create a high-resolution CWF inventory. The results show that the average annual CWF of the three crops from 2000 to 2020 was in the order of rice (2.50 × 10 12 m 3 ), maize (1.55 × 10 12 m 3 ) , and wheat (1.21 × 10 12 m 3 ). During the study period, the dependence on green water resources for crop production in China increased, especially for maize, which showed a relative increase of 106.76% in green water demand, in addition to optimal water use efficiency, with the dual advantages of combining high yield and low irrigation dependence. At a grid scale of 3 km × 3 km, the CWFs of the three crops followed the same order as at the city scale. Furthermore, the green water footprint (GWF) of each of the three crops increased at different rates during the study period, with maize showing a particularly significant increase of 59.26%. Meanwhile, the blue water footprint (BWF) per unit area for rice and wheat increased, while the BWF for maize decreased by 0.94%. This finding implies that maize cultivation is more efficient in utilizing rainwater resources, thereby reducing dependence on blue water. The inventory established in this study can assist in optimizing crop production in various regions of China, thereby mitigating the effects of water scarcity and facilitating sustainable agricultural development.

Under the current backdrop of increasingly variable climatic conditions, the distribution patterns and driving factors of fruit tree richness in North China remain insufficiently understood, yet fruit tree diversity is critical for agricultural biodiversity and regional food security, and systematic studies integrating both natural and anthropogenic drivers are lacking in this region. In this study, we integrated distribution data of 14 major fruit tree species with climate, terrain, soil, and anthropogenic variables, covering North China (Beijing, Tianjin, Hebei, Shanxi, Shandong, and Henan provinces, approximately 1.18 million km²). Potential suitable habitats were simulated using the MaxEnt model to estimate fruit tree richness, and the Geodetector together with structural equation modeling (SEM) was applied to disentangle the multi-factor driving mechanisms. The results indicated that: (1) the simulated distributions of the 14 fruit tree species achieve high accuracy, with most species exhibiting AUC values above 0.8; (2) high fruit tree richness in the North China region is mainly concentrated in hilly and mountainous areas such as the eastern Taihang Mountains, the Shandong Hills, and Jiaodong Peninsula; (3) among individual environmental contributions, population density, annual mean temperature and nighttime light most frequently rank among the top three contributors across 14 species, with anthropogenic and topographic variables jointly governing fruit-tree habitat suitability in North China; (4) the interaction between climate and anthropogenic was strongest, with anthropogenic factors showing both direct negative associations with fruit tree richness and indirect pathways via climate and soil, whereas climate is positively associated with fruit tree richness. These findings demonstrate that anthropogenic factors, rather than purely natural conditions, dominate the spatial patterns of fruit tree richness in this intensively managed agricultural region. This study enhances understanding of the distribution of fruit tree richness in North China, clarifies the multi-factor mechanisms shaping its spatial patterns, and provides a useful reference for understanding how multiple environmental and anthropogenic factors are associated with fruit tree distribution, which may inform future studies and region-specific management strategies.