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Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH. Methods We retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022. Results The mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH. Conclusions LT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.

Abstract Objectives In this study, we investigated whether neural precursor cell–expressed developmentally down-regulated gene 4-like (NEDD4L) is the E3 enzyme of angiotensin-converting enzyme 2 (ACE2) and whether NEDD4L degrades ACE2 via ubiquitination, leading to the progression of pulmonary arterial hypertension (PAH). Methods Bioinformatic analyses were used to explore the E3 ligase that ubiquitinates ACE2. Cultured pulmonary arterial smooth muscle cells (PASMCs) and specimens from patients with PAH were used to investigate the crosstalk between NEDD4L and ACE2 and its ubiquitination in the context of PAH. Results The inhibition of ubiquitination attenuated hypoxia-induced proliferation of PASMCs. The levels of NEDD4L were increased, and those of ACE2 were decreased in lung tissues from patients with PAH and in PASMCs. NEDD4L, the E3 ligase of ACE2, inhibited the expression of ACE2 in PASMCs, possibly through ubiquitination-mediated degradation. PAH was associated with upregulation of NEDD4L expression and downregulation of ACE2 expression. Conclusions NEDD4L, the E3 ubiquitination enzyme of ACE2, promotes the proliferation of PASMCs, ultimately leading to PAH.

Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin–proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.

Abstract Background Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. Methods This study included 6952 children aged 9–11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers

Abstract Prolonged mechanical ventilation (PMV) is commonly associated with increased post-operative complications and mortality. Nevertheless, the predictive factors of PMV after lung transplantation (LTx) using extracorporeal membrane oxygenation (ECMO) as a bridge remain unclear. The present study aimed to develop a novel nomogram for PMV prediction in patients using ECMO as a bridge to LTx. A total of 173 patients who used ECMO as a bridge following LTx from January 2022 to June 2023 were divided into the training (122) and validation sets (52). A mechanical ventilation density plot of patients after LTx was then performed. The training set was divided in two groups, namely PMV (95) and non-prolonged ventilation (NPMV) (27). For the survival analysis, the effect of PMV was assessed using the log-rank test. Univariate and multivariate logistic regression analyses were performed to assess factors associated with PMV. A risk nomogram was established based on the multivariate analysis, and model performance was further assessed in terms of calibration, discrimination, and clinical usefulness. Internal validation was additionally conducted. The difference in survival curves in PMV and NPMV groups was statistically significant (P

Abstract Purpose This study aims to provide a comprehensive overview of anesthesia management strategies employed in pediatric lung transplantation. Methods A retrospective analysis was conducted on data from 14 pediatric patients who underwent lung transplantation at the Wuxi Center between September 2019 and November 2022. Patient demographics, surgical particulars, airway management, utilization of extracorporeal support, fluid administration, blood gas and electrolyte profiles, and postoperative outcomes were systematically documented and subsequently summarized. Results Of the 14 patients, 7 received extracorporeal membrane oxygenation (ECMO) and 1 received cardiopulmonary bypass (CPB). The average operation time was 303 ± 53 min, with the median extubation time of 26 h. The entirety of pediatric lung transplant procedures was executed successfully, resulting in the discharge of thirteen patients postoperatively. Regrettably, one patient died due to infectious shock on the fourth postoperative day. Conclusion The achievement of successful pediatric lung transplantation necessitates effective perioperative anesthesia management, with a focal emphasis on circulatory control. Real-time measurements serve as the cornerstone for decision-making. Proactive administration of vasoactive agents is integral to sustaining hemodynamic stability. The judicious assessment of ECMO necessity is paramount, favoring central ECMO during the surgical intervention.

Abstract Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids’ biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.

Abstract. Background:. Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown. Methods:. GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice (Grk2ΔSM22), and littermate controls (Grk2flox/flox) were grouped into control and hypoxia mice (n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein (YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results:. The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2ΔSM22 mice compared with littermate controls. The amelioration of PH in Grk2ΔSM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion:. Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Mulberry has a long history of use as an edible fruit and medicine. Studies have shown that mulberry possesses several functional characteristics including antioxidation, anti-inflammation and anticancer. In recent years, mulberry wine has gained much attention from consumers due to its abundant bioactive components and distinctive sensory attributes. Based on the latest research, this review summarizes the health effects of mulberry wine from the perspective of bioactive components, clarifies the aroma composition of mulberry wine, discusses the main factors affecting the aroma quality of mulberry wine and prospected the future research trends. It is expected to provide new ideas for theoretical study and product development of mulberry wine, which will be helpful to promote the quality standardization of mulberry wine and enhance the economic value of mulberry wine industry.

With the increase of traffic flow in modern urban areas, traffic congestion has become a serious problem that affects people’s normal production and life. Using target detection technology instead of manual labor can quickly detect the road traffic situation and provide timely information about the traffic flow. However, when using drones to observe the traffic flow in the air, the perspective effect will cause the detected vehicles and pedestrians to be very small, and the scale difference between different categories of targets is large, which increases the detection difficulty of a single convolutional neural network model. In order to solve the problem of low accuracy of traditional single-stage target detection models, this study proposes an improved Yolov5 vehicle target detection model with Vision Transformer (VIT) backbone, You Only Look Once-HyperVision (YOLO-HV), which aims to solve the problem of poor multi-scale target recognition performance caused by the inability of traditional CNN networks to integrate contextual information, and help drones achieve more efficient and accurate traffic flow recognition functions. This study deeply integrates the Vision Transformer (VIT) backbone and Convolutional Neural Network (CNN), effectively combining the multi-scale detection advantages of Vision Transformer and the inductive bias ability of Convolutional Neural Network, and adds multi-scale residual modules and context correlation enhancement modules, which greatly improves the recognition accuracy of single-stage detectors for drone images. Through comparative experiments on the VisDrone dataset, it is found that the detection performance of this model is improved compared with several commonly used detection models. YOLO-HV can increase the mean average precision (mAP) by 3.3% compared with the pure convolutional network of the same model size. YOLO-HV model has achieved excellent performance in the task of traffic flow image detection taken by drones, and can more accurately identify and classify road vehicles than various target detection models.

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 μM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.

Abstract T cell receptor (TCR)-engineered T cell therapy is a promising potential treatment for solid tumors, with preliminary efficacy demonstrated in clinical trials. However, obtaining clinically effective TCR molecules remains a major challenge. We have developed a strategy for cloning tumor-specific TCRs from long-term surviving patients who have responded to immunotherapy. Here, we report the identification of a TCR (10F04), which is human leukocyte antigen (HLA)-DRA/DRB1*09:01 restricted and human papillomavirus type 18 (HPV18) E784-98 specific, from a multiple antigens stimulating cellular therapy (MASCT) benefited metastatic cervical cancer patient. Upon transduction into human T cells, the 10F04 TCR demonstrated robust antitumor activity in both in vitro and in vivo models. Notably, the TCR effectively redirected both CD4+ and CD8+ T cells to specifically recognize tumor cells and induced multiple cytokine secretion along with durable antitumor activity and outstanding safety profiles. As a result, this TCR is currently being investigated in a phase I clinical trial for treating HPV18-positive cancers. This study provides an approach for developing safe and effective TCR-T therapies, while underscoring the potential of HLA class II-restricted TCR-T therapy as a cancer treatment.

Abstract The combination of macrocyclic chemistry with co-crystal engineering has promoted the development of materials with vapochromic behaviors in supramolecular science. Herein, we develop a macrocycle co-crystal based on hybrid[4]arene and 1,2,4,5-tetracyanobenzene that is able to construct vapochromic materials. After the capture of benzene and toluene vapors, activated hybrid[4]arene-based co-crystal forms new structures, accompanied by color changes from brown to yellow. However, when hybrid[4]arene-based co-crystal captures cyclohexane and pyridine, neither structures nor colors change. Interestingly, hybrid[4]arene-based co-crystal can separate benzene from a benzene/cyclohexane equal-volume mixture and allow toluene to be removed from a toluene/ pyridine equal-volume mixture with purities reaching 100%. In addition, the process of adsorptive separation can be visually monitored. The selectivity of benzene from a benzene/cyclohexane equal-volume mixture and toluene from a toluene/ pyridine equal-volume mixture is attributed to the different changes in the charge-transfer interaction between hybrid[4]arene and 1,2,4,5-tetracyanobenzene when hybrid[4]arene-based co-crystal captures different vapors. Moreover, hybrid[4]arene-based co-crystal can be reused without losing selectivity and performance. This work constructs a vapochromic material for hydrocarbon separation.

Objective To investigate the association between driving pressure (ΔP) and 90-day mortality in patients following lung transplantation (LTx) in patients who developed primary graft dysfunction (PGD). Methods This prospective, observational study involved consecutive patients who, following LTx, were admitted to our intensive care unit (ICU) from January 2022 to January 2023. Patients were separated into two groups according to ΔP at time of admission (i.e., low, ≤15 cmH 2 O or high, >15 cmH 2 O). Postoperative outcomes were compared between groups. Results In total, 104 patients were involved in the study, and of these, 69 were included in the low ΔP group and 35 in the high ΔP group. Kaplan-Meier analysis of 90-day mortality showed a statistically significant difference between groups with survival better in the low ΔP group compared with the high ΔP group. According to Cox proportional regression model, the variables independently associated with 90-day mortality were ΔP and pneumonia. Significantly more patients in the high ΔP group than the low ΔP group had PGD grade 3 (PGD3), pneumonia, required tracheostomy, and had prolonged postoperative extracorporeal membrane oxygenation (ECMO) time, postoperative ventilator time, and ICU stay. Conclusions Driving pressure appears to have the ability to predict PGD3 and 90-day mortality of patients following LTx. Further studies are required to confirm our results.

Abstract Loss of refreshment in nucleus pulposus (NP) cellularity leads to intervertebral disc (IVD) degeneration. Nevertheless, the cellular sequence of NP cell differentiation remains unclear, although an increasing body of literature has identified markers of NP progenitor cells (NPPCs). Notably, due to their fragility, the physical enrichment of NP‐derived cells has limited conventional transcriptomic approaches in multiple studies. To overcome this limitation, a spatially resolved transcriptional atlas of the mouse IVD is generated via the 10x Genomics Visium platform dividing NP spots into two clusters. Based on this, most reported NPPC‐markers, including Cathepsin K (Ctsk), are rare and predominantly located within the NP‐outer subset. Cell lineage tracing further evidence that a small number of Ctsk‐expressing cells generate the entire adult NP tissue. In contrast, Tie2, which has long suggested labeling NPPCs, is actually neither expressed in NP subsets nor labels NPPCs and their descendants in mouse models; consistent with this, an in situ sequencing (ISS) analysis validated the absence of Tie2 in NP tissue. Similarly, no Tie2‐cre‐mediated labeling of NPPCs is observed in an IVD degenerative mouse model. Altogether, in this study, the first spatial transcriptomic map of the IVD is established, thereby providing a public resource for bone biology.

Abnormalities in pulmonary vasculature or technical issues during lung procurement can lead to an insufficient left atrial (LA) cuff in donors. However, surgeons frequently need to reconfigure these less-than-ideal lungs for transplantation. This case report introduces a novel technique for such reconstruction. The patient was a 35-year-old male diagnosed with pneumoconiosis for over a year. Due to progressive worsening dyspnoea leading to respiratory failure on multiple occasions, he was deemed a candidate for lung transplantation. While obtaining the donor's lung, an inadvertent short cut of the LA cuff around the left inferior pulmonary vein orifice resulted in the residual vein retracting into the pulmonary hilum. To overcome this, we employed the aortic arch for reconstruction, enabling the successful completion of the lung transplantation. On post-transplantation day 2, extracorporeal membrane oxygenation was no longer required. Mechanical ventilation ceased after 13 days, with the subsequent removal of a tracheostomy. The patient spent 35 days in the intensive care unit and 58 days in the hospital. Post-transplantation complications included primary graft dysfunction, acute kidney failure, pneumothorax in the transplanted lung, the clots in the inferior vena cava, and pneumonia. Remarkably, over a year of follow-up (19 months after lung transplantation), the patient reported no adverse events and had successfully returned to work. In this case, the aortic arch is an alternative for reconstructing an insufficient LA cuff.

Abstract Intra‐ and inter‐organismal interactions play a crucial role in the maintenance and function of individuals, as well as communities. Extracellular vesicles (EVs) have been identified as effective mediators for the communication both within and between species. They can carry and transport molecular cargoes to transmit biological messages. Several databases (ExoBCD, ExoCarta, EVpedia, EV‐TRACK, Vesiclepedia) complied the cargoes information including DNA, RNA, protein, lipid and metabolite associated with EVs. Databases that refer to the complete records on both donor and recipient information are warranted to facilitate the understanding of the interaction across cells and species. In this study, we developed a database that compiled the records equipped with a structured process of EV‐mediated interaction. The sources of donor and recipient were classified by cell type, tissues/organs and species, thus providing an extended knowledge of cell‐cell, species‐species interaction. The isolation and identification methods were presented for assessing the quality of EVs. Information on functional cargoes was included, where microRNA was linked to a prediction server to broaden its potential effects. Physiological and pathological context was marked to show the environment where EVs functioned. At present, a total of 1481 data records in our database, including 971 cell‐cell interactions belonging to more than 40 different tissues/organs, and 510 cross‐species records. The database provides a web interface to browse, search, visualize and download the interaction records. Users can search for interactions by selecting the context of interest or specific cells/species types, as well as functional cargoes. To the best of our knowledge, the database is the first comprehensive database focusing on interactions between donor and recipient cells or species mediated by EVs, serving as a convenient tool to explore and validate interactions. The Database, shorten as EV‐COMM (EV mediated communication) is freely available at http://sdc.iue.ac.cn/evs/list/ and will be continuously updated.

Abstract Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease primarily affects populations in economically underdeveloped tropical regions, earning it the title of “neglected tropical disease”. Schistosomiasis is difficult to eradicate globally if medication alone is used. One of the essential elements of thorough schistosomiasis prevention and control is the management and disruption of the life cycle of intermediate host snails. The key approach to controlling the transmission of schistosomiasis is to control the intermediate hosts of the schistosome to disrupt its life cycle. We believe that approaching it from the perspective of the intermediate host’s immunity could be an environmentally friendly and potentially effective method. Currently, globally significant intermediate host snails for schistosomes include Oncomelania hupensis, Biomphalaria glabrata, and Bulinus truncatus. The immune interaction research between B. glabrata and Schistosoma mansoni has a history of several decades, and the complete genome sequencing of both B. glabrata and B. truncatus has been accomplished. We have summarized the immune-related factors and research progress primarily studied in B. glabrata and B. truncatus and compared them with several humoral immune factors that O. hupensis research focuses on: macrophage migration inhibitory factor (MIF), Toll-like receptors (TLRs), and thioredoxin (Trx). We believe that continued exploration of the immune interactions between O. hupensis and Schistosoma japonicum is valuable. This comparative analysis can provide some direction and clues for further in-depth research. Comparative immunological studies between them not only expand our understanding of the immune defense responses of snails that act as intermediaries for schistosomes but also facilitate the development of more comprehensive and integrated strategies for schistosomiasis prevention and control. Furthermore, it offers an excellent opportunity to study the immune system of gastropods and their co-evolution with pathogenic organisms. Graphical Abstract

Abstract Bergenia purpurascens is an important medicinal, edible and ornamental plant. It generally grows in high-altitude areas with complex climates. There have been no reports about how B. purpurascens survives under cold stress. Here, the B. purpurascens under low temperature were subjected to transcriptomics analysis to explore the candidate genes and pathways that involved in the cold tolerance of B. purpurascens. Compared with the control treatment, we found 9,600 up-regulated differentially expressed genes (DEGs) and 7,055 down-regulated DEGs. A significant number of DEGs were involved in the Ca2+ signaling pathway, mitogen-activated protein kinase (MAPK) cascade, plant hormone signaling pathway, and lipid metabolism. A total of 400 transcription factors were found to respond to cold stress, most of which belonged to the MYB and AP2/ERF families. Five novel genes were found to be potential candidate genes involved in the cold tolerance of B. purpurascens. The study provide insights into further investigation of the molecular mechanism of how B. purpurascens survives under cold stress.

The Tongnan secondary negative structure in central Sichuan Basin has controls and influences on the structural framework and petroleum geological conditions in the Gaoshiti-Moxi area. To clarify the controls and influences, the deformation characteristics, structural attributes and evolution process of the Tongnan negative structure were investigated through a series of qualitative and quantitative methods such as balanced profile restoration, area-depth-strain (ADS) analysis, and structural geometric forward numerical simulation, after comprehensive structural interpretation of high-precision 3D seismic data. The results are obtained in three aspects. First, above and below the P/AnP (Permian/pre-Permian) unconformity, the Tongnan negative structure demonstrates vertical differential structural deformation. It experiences two stages of structural stacking and reworking: extensional depression (from the Sinian Dengying Formation to the Permian), and compressional syncline deformation (after the Jurassic). The multi-phase trishear deformation of the preexisting deep normal faults dominated the extensional depression. The primary depression episodes occurred in the periods from the end of Late Proterozoic to the deposition of the 1st–2nd members of the Dengying Formation, and from the deposition of Lower Cambrian Longwangmiao Formation–Middle–Upper Cambrian until the Ordovician. Second, the multi-stage evolution process of the Tongnan negative structure controlled the oil and gas migration and adjustment and present-day differential gas and water distribution between the Tongnan negative structure and the Gaoshiti and Moxi-Longnüsi structural highs. Third, the Ordovician, which is limitedly distributed in the Tongnan negative structure and is truncated by the P/AnP unconformity on the top, has basic geological conditions for the formation of weathering karst carbonate reservoirs. It is a new petroleum target deserving attention.

Edge servers frequently manage their own offline digital twin (DT) services, in addition to caching online digital twin services. However, current research often overlooks the impact of offline caching services on memory and computation resources, which can hinder the efficiency of online service task processing on edge servers. In this study, we concentrated on service caching and task offloading within a collaborative edge computing system by emphasizing the integrated quality of service (QoS) for both online and offline edge services. We considered the resource usage of both online and offline services, along with incoming online requests. To maximize the overall QoS utility, we established an optimization objective that rewards the throughput of online services while penalizing offline services that miss their soft deadlines. We formulated this as a utility maximization problem, which was proven to be NP-hard. To tackle this complexity, we reframed the optimization problem as a Markov decision process (MDP) and introduced a joint optimization algorithm for service caching and task offloading by leveraging the deep Q-network (DQN). Comprehensive experiments revealed that our algorithm enhanced the utility by at least 14.01% compared with the baseline algorithms.

Summary: LncRNA associated with immune cell infiltration in tumor microenvironment (TME) may be a potential therapeutic target for lung adenocarcinoma. We established a machine learning (ML) model based on 3896 samples characterized by the degree of immune cell infiltration, and further screened the key lncRNA. In vitro experiments were applied to validate the prediction. Treg is the key immune cell in the TME of lung adenocarcinoma, and the degree of infiltration is negatively correlated with the prognosis. PCBP1-AS1 may affect the infiltration of Tregs by regulating the TGF-β pathway, which is a potential predictor of clinical response to immunotherapy. PCBP1-AS1 regulates cell proliferation, cell cycle, invasion, migration, and apoptosis in lung adenocarcinoma. The results of clinical sample staining and in vitro experiments showed that PCBP1-AS1 was negatively correlated with Treg infiltration and TGF-β expression. Tregs and related lncRNA PCBP1-AS1 can be used as targets for the diagnosis and treatment of lung adenocarcinoma.

Mitochondrial dysfunction is one of the hallmarks of cardiovascular aging. The leakage of mitochondrial DNA (mtDNA) is increased in senescent cells, which are resistant to programmed cell death such as apoptosis. Due to its similarity to prokaryotic DNA, mtDNA could be recognized by cellular DNA sensors and trigger innate immune responses, resulting in chronic inflammatory conditions during aging. The mechanisms include cGAS-STING signaling, TLR-9 and inflammasomes activation. Mitochondrial quality controls such as mitophagy could prevent mitochondria from triggering harmful inflammatory responses, but when this homeostasis is out of balance, mtDNA-induced inflammation could become pathogenic and contribute to age-related cardiovascular diseases. Here, we summarize recent studies on mechanisms by which mtDNA promotes inflammation and aging-related cardiovascular diseases, and discuss the potential value of mtDNA in early screening and as therapeutic targets.

Cardiac dysfunction frequently emerges in the initial stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model. Concurrently, these mice underwent a low-intensity exercise regimen to investigate its potential role in cardiac function during cachexia. Our findings indicate that exercise training can help prevent metastatic melanoma-induced muscle loss without significant alterations to body and fat weight. Moreover, exercise improved the melanoma-induced decline in left ventricular ejection fraction and fractional shortening, while also mitigating the increase in high-sensitive cardiac troponin T levels caused by metastatic melanoma in mice. Transcriptome analysis revealed that exercise significantly reversed the transcriptional alterations in the heart induced by melanoma, which were primarily enriched in pathways related to heart contraction. These results suggest that exercise can improve systolic heart function and directly influence the transcriptome of the heart during metastatic melanoma-induced cachexia.

Background: Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients.Objective: This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs.Methods: This retrospective cross-sectional study included lung transplant recipients from January 2018 to December 2021. Pertinent information was retrieved from medical records. All prescribed medications were screened for pDDIs using the Lexicomp® drug interaction software. According to this interaction software, pDDIs were classified as C, D, or X (C = monitor therapy, D = consider therapy modification, X = avoid combination). The Drug Interaction Probability Scale was used to determine the causation of DDIs. All statistical analysis was performed in SPSS version 26.0.Results: 114 patients were qualified for pDDI analysis, and total pDDIs were 4051. The most common type of pDDIs was category C (3323; 82.0%), followed by D (653; 16.1%) and X (75; 1.9%). Voriconazole and posaconazole were the antifungal medicine with the most genuine DDIs. Mean tacrolimus concentration/dose (Tac C/D) before or after co-therapy was considerably lower than the Tac C/D during voriconazole or posaconazole co-therapy (p < 0.001, p = 0.027). Real DDIs caused adverse drug events (ADEs) in 20 patients. Multivariable logistic regression analyses found the number of drugs per patient (OR, 1.095; 95% CI, 1.048–1.145; p < 0.001) and the Acute Physiology and Chronic Health Evaluation II (APACHE Ⅱ) score (OR, 1.097; 95% CI, 1.021–1.179; p = 0.012) as independent risk factors predicting category X pDDIs.Conclusion: This study revealed a high incidence of both potential and real DDIs in ICU lung transplant recipients. Immunosuppressive drugs administered with azole had a high risk of causing clinically significant interactions. The number of co-administered drugs and APACHE Ⅱ score were associated with an increased risk of category × drug interactions. Close monitoring of clinical and laboratory parameters is essential for ensuring successful lung transplantation and preventing adverse drug events associated with DDIs.

Flexible thermoelectric generators (FTEGs) offer a promising solution for powering wearable electronics, while their practical applications are mainly obstructed by the moderate properties of flexible thermoelectric (TE) materials. Here, flexible Ag2Se nanowire (NW)/methyl cellulose (MC) composite films were developed via facile screen-printing technology combined with cold pressing and annealing treatment, and a highest power factor of 1,641.58 μW m−1 K−2 at 360 K was achieved. The reasons for the high TE performance of the Ag2Se NW/MC composite films were because, after the annealing treatment, the Ag2Se NWs were sintered to form conductive network structures, the crystallinity of Ag2Se was markedly enhanced, and the content of insulating phase MC in the composite film was decreased. The Ag2Se NW/MC composite film held appreciable flexibility, as its room-temperature power factor (1,312.08 μW m−1 K−2) can retain ~93% after bending for 1,000 cycles at a radius of 4 mm. Furthermore, the assembled FTEG consisting of 4 strips can generate a maximal power density of 3.51 W m−2 at a temperature difference of 14.1 K. Our results open an effective and large-scale strategy for fabricating high-performance flexible TE materials and energy-harvesting devices.

Excitotoxicity represents the primary cause of neuronal death following spinal cord injury (SCI). While autophagy plays a critical and intricate role in SCI, the specific mechanism underlying the relationship between excitotoxicity and autophagy in SCI has been largely overlooked. In this study, we isolated primary spinal cord neurons from neonatal rats and induced excitotoxic neuronal injury by high concentrations of glutamic acid, mimicking an excitotoxic injury model. Subsequently, we performed transcriptome sequencing. Leveraging machine learning algorithms, including weighted correlation network analysis (WGCNA), random forest analysis (RF), and least absolute shrinkage and selection operator analysis (LASSO), we conducted a comprehensive investigation into key genes associated with spinal cord neuron injury. We also utilized protein-protein interaction network (PPI) analysis to identify pivotal proteins regulating key gene expression and analyzed key genes from public datasets (GSE2599, GSE20907, GSE45006, and GSE174549). Our findings revealed that six genes-Anxa2, S100a10, Ccng1, Timp1, Hspb1, and Lgals3-were significantly upregulated not only in vitro in neurons subjected to excitotoxic injury but also in rats with subacute SCI. Furthermore, Hspb1 and Lgals3 were closely linked to neuronal autophagy induced by excitotoxicity. Our findings contribute to a better understanding of excitotoxicity and autophagy, offering potential targets and a theoretical foundation for SCI diagnosis and treatment.

The development of micro/nanorobots and their application in medical treatment holds the promise of revolutionizing disease diagnosis and treatment. In comparison to conventional diagnostic and treatment methods, micro/nanorobots exhibit immense potential due to their small size and the ability to penetrate deep tissues. However, the transition of this technology from the laboratory to clinical applications presents significant challenges. This paper provides a comprehensive review of the research progress in micro/nanorobotics, encompassing biosensors, diagnostics, targeted drug delivery, and minimally invasive surgery. It also addresses the key issues and challenges facing this technology. The fusion of micro/nanorobots with medical treatments is poised to have a profound impact on the future of medicine.

Abstract Background The Procalcitonin (PCT) and C-reactive protein (CRP)/albumin ratio have recently been used to predict early prognosis for intensive care unit (ICU) patients and patients undergoing major surgery. But there were few clinical studies in patients after lung transplantation (LTX). Aim/Purpose The purpose of this study was to identify the association between PCT combined with CRP/albumin ratio and 30-day mortality and predict the accuracy of PCT combined with CRP/albumin ratio for 30-day mortality in patients after LTX. Method From January 1, 2016 to December 1, 2020, the clinical data of 77 patients undergoing LTX who died within 30 days were retrospectively collected, we randomly collected 87 patients survived more than 30 days after LTX. ROC curve was used to evaluate the prognostic value of PCT combined with CRP/albumin in predicting mortality at 30 days after ICU admission, Cox proportional hazard model analysis was used to identify risk factors, subgroup analyses was conducted. Results Postoperative PCT, CRP, albumin, CRP/albumin ratio, atrial fibrillation, primary graft dysfunction (PGD) grade, the hours of postoperative mechanical ventilation (MV) and length of ICU stay between survivor and non-survivor had a significant difference. On Cox proportional hazard regression analysis, both PCT [HR 1.02 (1.00–1.05), P = 0.037] and CRP/albumin ratio [HR 1.438 (1.26–1.65), P

The two-part tariff (TPT) policy is implemented as an important initiative to accelerate the marketization of the pumped storage industry and promote its high-quality development. However, it is not clear exactly how the TPT policy affects the productivity of the pumped storage industry. Using the EBM-GML method and the DID model, this paper measures the total factor productivity of the pumped storage industry and explores the impact of the Two-Part Tariff (TPT) policy on its total factor productivity. Based on the samples of 16 provinces in China from 2004 to 2020, we find the following: (1) At present, the total factor productivity of China’s pumped storage industry is still at a low level. (2) TPT policy can promote the improvement of total factor productivity, which was strongly supported by the robustness test. Innovation incentive is one of the main mechanisms. (3) The impact of TPT policy on total factor productivity has obvious regional heterogeneity. By geographic location, the TPT policy has little effect on the pumped storage industry’s TFP in the eastern region, but it exerts a significant positive role in the central region. By energy affluence, TPT policy effect is stronger in provinces with low energy dependence. By environmental governance, the role of this policy is more obvious in provinces with low environmental regulation but developed green financial market. Finally, some corresponding policy implications have been put forward.

Abstract Background Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. Results Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. Conclusion Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

Abstract Objective To explore whether narrow‐band imaging (NBI) endoscopy is accurate in the diagnosis of malignant transformation of vocal cord leukoplakia. Methods The PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect data on studies reporting the use of NBI endoscopy as a diagnostic test for diagnosing vocal cord leukoplakia from January 2015 to December 2021. Study design, analysis method, and extraction results were performed according to the PRISMA guidelines. The sensitivity, specificity, pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) were used to summarize the performance metrics of the meta‐analysis. Risk of bias data and the quality of the included studies was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies‐2 tool (QUADAS‐2). Results Nine studies were finally included in the analysis. The results of the meta‐analysis showed that the pooled sensitivity and specificity of NBI endoscopy for diagnosing leukoplakia lesions were 0.76 (95% CI: 0.72–0.8) and 0.93 (95% CI: 0.91–0.95), respectively. The PLR and NLR were 10.09 (95% CI: 6.53–15.59) and 0.22 (95% CI: 0.13–0.38), respectively. The comprehensive diagnostic odds ratio (DOR) was 54.96 (95% CI: 24.32–124.17), and the area under the curve was 0.9584. The eight articles had a low risk of bias risk and one article was unclear. Conclusion NBI likely has good accuracy for diagnosing malignant transformation of vocal cord leukoplakia. However, multicenter studies and large samples are still needed.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma in adults. CDGSH iron sulfur domain 2 (CISD2) is an iron–sulfur protein and plays a critical role of cell proliferation. The aberrant expression of CISD2 is associated with the progression of multiple cancers. However, its role in DLBCL remains unclear.MethodsThe differential expression of CISD2 was identified via public databases, and quantitative real-time PCR (qRT-PCR) and western blot were used to identifed the expression of CISD2. We estimated the impact of CISD2 on clinical prognosis using the Kaplan-Meier plotter. Meanwhile, the drug sensitivity of CISD2 was assessed using CellMiner database. The 100 CISD2-related genes from STRING obtained and analyzed using the LASSO Cox regression. A CISD2 related signature for risk model (CISD2Risk) was established. The PPI network of CISD2Risk was performed, and functional enrichment was conducted through the DAVID database. The impacts of CISD2Risk on clinical features were analyzed. ESTIMATE, CIBERSORT, and MCP-counter algorithm were used to identify CISD2Risk associated with immune infiltration. Subsequently, Univariate and multivariate Cox regression analysis were applied, and a prognostic nomogram, accompanied by a calibration curve, was constructed to predict 1-, 3-, and 5-years survival probabilities.ResultsCISD2 was upregulated in DLBCL patients comparing with normal controls via public datasets, similarly, CISD2 was highly expressed in DLBCL cell lines. Overexpression of CISD2 was associated with poor prognosis in DLBCL patients based on the GSE31312, the GSE32918, and GSE93984 datasets (P

Purpose: This study aimed to clarify the effect of donor and recipient age combinations on the short-term survival rates of patients undergoing lung transplantation. Patients and methods: We retrospectively reviewed the 2017–2020 data of the Affiliated Wuxi People’s Hospital of Nanjing Medical University database for all adults (≥18 years), lung transplant recipients, and their associated donors. The impact of donor and recipient ages on survival was analyzed using a multivariable Cox proportional hazards regression model. Subgroup analysis was also performed based on recipient and donor ages. Results: Different donor and recipient age combinations affected the short-term postoperative survival rates. When recipients were ≤55 years, the survival rates of the younger donor age group were significantly higher than the older donor age group at 30 days after surgery (P = 0.040); when the donors were ≤40 years, the postoperative survival rates of the younger recipient age group were significantly higher than the older recipient age group (P = 0.031, P = 0.026, P = 0.034, and P = 0.018 for 30 days, 90 days, 180 days, and 1 year after surgery, respectively). Conclusion: Younger recipients had a higher survival rate after transplantation than older recipients, and this benefit could be compromised by older donors. Furthermore, the influence of donor age on patient survival rate was limited and more pronounced in younger recipients and shortly after surgery.

Immune effector cells in the microenvironment tend to be depleted or remodeled, unable to perform normal functions, and even promote the malignant characterization of tumors, resulting in the formation of immunosuppressive microenvironments. The strategy of reversing immunosuppressive microenvironment has been widely used to enhance the tumor immunotherapy effect. Signal transducer and activator of transcription 3 (STAT3) was found to be a crucial regulator of immunosuppressive microenvironment formation and activation as well as a factor, stimulating tumor cell proliferation, survival, invasiveness and metastasis. Therefore, regulating the immune microenvironment by targeting the STAT3 oncogenic pathway might be a new cancer therapy strategy. This review discusses the pleiotropic effects of STAT3 on immune cell populations that are critical for tumorigenesis, and introduces the novel strategies targeting STAT3 oncogenic pathway for cancer immunotherapy. Lastly, we summarize the conventional drugs used in new STAT3-targeting anti-tumor applications.

Brain hemorrhage: Causes of fluid build-up on the brain Inhibiting a key inflammatory protein and thereby protecting the blood-brain barrier following brain hemorrhage may prevent the build-up of fluid on the brain (hydrocephalus). Using rat models and cell cultures, Yujie Chen and Hua Feng at the Third Military Medical University in Chongqing, China, and co-workers examined how posthemorrhagic hydrocephalus occurs. They found that the acute inflammatory response activated immediately after a brain hemorrhage, which is driven by a critical protein complex involved in innate immunity called the NLRP3 inflammasome, triggers the formation of lipid droplets in the choroid plexus, a part of the brain adjacent to the blood-brain barrier. The lipid droplets interact with mitochondria, increasing the release of reactive oxygen species and damaging the blood-brain barrier. This barrier dysfunction triggers hydrocephalus. Blocking NLRP3 activity improved the function of the barrier following hemorrhage.

Abstract Background The pristane-induced lupus (PIL) model is a useful tool for studying environmental-related systemic lupus erythematosus (SLE). However, neuropsychiatric manifestations in this model have not been investigated in detail. Because neuropsychiatric lupus (NPSLE) is an important complication of SLE, we investigated the neuropsychiatric symptoms in the PIL mouse model to evaluate its suitability for NPSLE studies. Results PIL mice showed olfactory dysfunction accompanied by an anxiety- and depression-like phenotype at month 2 or 4 after pristane injection. The levels of cytokines (IL-1β, IFN-α, IFN-β, IL-10, IFN-γ, IL-6, TNF-α and IL-17A) and chemokines (CCL2 and CXCL10) in the brain and blood–brain barrier (BBB) permeability increased significantly from week 2 or month 1, and persisted throughout the observed course of the disease. Notably, IgG deposition in the choroid plexus and lateral ventricle wall were observed at month 1 and both astrocytes and microglia were activated. Persistent activation of astrocytes was detected throughout the observed course of the disease, while microglial activation diminished dramatically at month 4. Lipofuscin deposition, a sign of neuronal damage, was detected in cortical and hippocampal neurons from month 4 to 8. Conclusion PIL mice exhibit a series of characteristic behavioral deficits and pathological changes in the brain, and therefore might be suitable for investigating disease pathogenesis and for evaluating potential therapeutic targets for environmental-related NPSLE.

Objective(s): Many persistent harmful stimuli can result in chronic liver diseases, which lead to about 2 million deaths per year in the whole world. Liver fibrosis was found to exist in all kinds of chronic liver diseases. Many studies suggested that DNA methylation was associated with the pathogenesis of liver fibrosis. This study aimed to quantitatively detect DNA methylation changes in the whole genome in fibrotic liver tissues of mice.Materials and Methods: Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) for 4 weeks. A genome-wide methylome analysis was performed using 850K BeadChips assays. The methylation status of 27 CpG dinucleotides located in 3 genes was detected by pyrosequencing to confirm chip data accuracy, and mRNA expressions of these 3 genes were examined by RT-qPCR methods.Results: A total of 130,068 differentially methylated sites (DMS, 58,474 hypermethylated, and 71,594 hypomethylated) between fibrotic liver tissues and control mice liver tissues were identified by the 850k BeadChips array. Consistency between pyrosequencing data and 850k BeadChips array data was observed (R=0.928; P

Noise-induced hearing loss (NIHL) is a prevalent form of adult hearing impairment, characterized by oxidative damage to auditory sensory hair cells. Although certain dihydropyridines, the L-type calcium channel blockers, exhibit protective properties against such damage, the ability of third-generation dihydropryidines like lercanidipine to mitigate NIHL remains unclear.We utilized glucose oxidase (GO)-treated OC1 cell lines and cochlear explants to evaluate the protective influence of lercanidipine on hair cells. To further investigate its effectiveness, we exposed noise-stimulated mice in vivo and analyzed their hearing thresholds. Additionally, we assessed the antioxidative capabilities of lercanidipine by examining oxidation-related enzyme expression and levels of oxidative stress markers, including 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE). Our findings demonstrate that lercanidipine significantly reduces the adverse impacts of GO on both OC-1 cell viability (0.3 to 2.5 µM) and outer hair cell (OHC) survival in basal turn cochlear explants (7 µM). These results are associated with increased mRNA expression of antioxidant enzyme genes (HO-1, SOD1/2, and Txnrd1), along with decreased expression of oxidase genes (COX-2, iNOS). Crucially, lercanidipine administration prior to, and following, noise exposure effectively ameliorates NIHL, as evidenced by lowered hearing thresholds and preserved OHC populations in the basal turn, 14 days post-noise stimulation at 110 dB SPL. Moreover, our observations indicate that lercanidipine’s antioxidative action persists even three days after simultaneous drug and noise treatments, based on 3-nitrotyrosine and 4-hydroxynonenal immunostaining in the basal turn. Based on these findings, we propose that lercanidipine has the capacity to alleviate NIHL and safeguard OHC survival in the basal turn, potentially via its antioxidative mechanism. These results suggest that lercanidipine holds promise as a clinically viable option for preventing NIHL in affected individuals.

Glucocorticoids (GCs), steroid hormones that depend on glucocorticoid receptor (GR) binding for their action, are essential for regulating numerous homeostatic functions in the body.GR signals are biased, that is, GR signals are various in different tissue cells, disease states and ligands. This biased regulation of GR signaling appears to depend on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly (recruitment of co-regulators) and intercellular differences. Based on the bias regulation of GR, selective GR agonists and modulators (SEGRAMs) were developed to bias therapeutic outcomes toward expected outcomes (e.g., anti-inflammation and immunoregulation) by influencing GR-mediated gene expression. This paper provides a review of the bias regulation and mechanism of GR and the research progress of drugs.

In this study, we used high-resolution optical satellite images on the Google Earth platform to map large-scale landslides in Xianyang City, Shaanxi Province, China. After mapping, a comprehensive and detailed large-scale landslide inventory that contains 2924 large-scale landslides was obtained. We analyzed the spatial distribution of landslides with seven influencing factors, including elevation, slope angle, aspect, curvature, lithology, distance to a river, and distance to the fault. Landslide Number, Landslide Area, Landslide Number Density (LND), and Landslide Area Percentage (LAP) were selected as indexes for the spatial distribution analysis. The results show that the number and area of landslides in the elevation range of 1000–1200 ​m is the highest. The highest number of landslides was observed in the slope angle of 25°–30°. North-facing slopes are prone to sliding. The area and number of landslides are the largest when the slope curvature ranges from −1.28 to 0. The LND and LAP reach their maxima when the slope curvature is less than −2.56. Areas covered by the Tertiary stratum with weakened fine-grained sandstone and siltstone show the highest LND and LAP values. Regarding distance to a river, the LAP peaks in the range of 300–600 ​m, whereas the LND peaks in an area larger than 2100 ​m. The values of LND and LNP rise as the distance from the faults increases, except for the locations 30 ​km away from active faults. This phenomenon is because active faults in this area pass through the plain areas, while landslides mostly occur in mountainous areas. The cataloging of landslide development in Xianyang City provides a significant scientific foundation for future research on landslides. In addition, the spatial distribution results are useful for landslide hazard prevention decisions and provide valuable references in this area.

Abstract Background Abdominal ultrasonography (AUS) has been suggested to be valuable in the early detection of necrotizing enterocolitis (NEC). Objective Here, we intended to assess the efficiency of abdominal ultrasound in terms of predicting bowel resection in infants with NEC. Methods From January 2018 to March 2021, 164 hospitalized children with NEC who underwent surgical management were enrolled. The enrolled infants were separated into two groups according to whether they underwent bowel resection. We reviewed the clinical data, as well as dynamic sonographic and abdominal radiographic (AR) parameters. The potential performance of AUS parameters was identified and compared with that of AR using a logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Results Several parameters were detected to be statistically significant in predicting the occurrence of bowel resection, including thick to thin transformation [p

Abstract Biodiversity in China coexists alongside large ethnically diverse rural human populations within linked ‘biocultural’ social–ecological systems. Cumulative and changing local anthropogenic pressures linked to human population growth and economic development are driving unsustainable resource exploitation, habitat loss and extensive species declines. However, these pressures vary between species and systems, and efforts to conserve regional biodiversity may also have unintended negative impacts on local communities and their long‐term relationship with nature. Based on our extensive experience working across China's diverse but vulnerable biocultural landscapes, we showcase a series of case studies that illustrate the differing interactions between biodiversity and local community use of natural resources, and the differing consequences of conservation management on local livelihoods. We highlight that some social–ecological relationships in China can maintain and support biodiversity, and we advocate for management underpinned by interdisciplinary conservation research that engages local communities, associated with robust evidence‐based assessment and evaluation frameworks to ensure effective monitoring and optimization of impacts. We frame a series of steps required to understand and mitigate local pressures on threatened species in China and identify potential ‘win–win’ approaches for the regional maintenance of biodiversity, ecosystem services and sustainable livelihoods, with directions proposed for future research, engagement and management. Read the free Plain Language Summary for this article on the Journal blog.

MYC activation can sensitise cells to apoptosis upon glutamine withdrawal. Here the authors show that MYC activation enhances global transcription and translation that creates a metabolic demand, while glutamine limitation causes a metabolic demand and supply imbalance through loss of TCA energetics and thus, sensitises cells to apoptosis.

Pulmonary hypertension (PH) is a devastating disease characterized by irreversible pulmonary vascular remodeling (PVR) that causes right ventricular failure and death. The early alternative activation of macrophages is a critical event in the development of PVR and PH, but the underlying mechanisms remain elusive. Previously we have shown that N6-methyladenosine (m6A) modifications of RNA contribute to phenotypic switching of pulmonary artery smooth muscle cells and PH. In the current study, we identify Ythdf2, an m6A reader, as an important regulator of pulmonary inflammation and redox regulation in PH. In a mouse model of PH, the protein expression of Ythdf2 was increased in alveolar macrophages (AMs) during the early stages of hypoxia. Mice with a myeloid specific knockout of Ythdf2 (Ythdf2Lyz2 Cre) were protected from PH with attenuated right ventricular hypertrophy and PVR compared to control mice and this was accompanied by decreased macrophage polarization and oxidative stress. In the absence of Ythdf2, heme oxygenase 1 (Hmox1) mRNA and protein expression were significantly elevated in hypoxic AMs. Mechanistically, Ythdf2 promoted the degradation of Hmox1 mRNA in a m6A dependent manner. Furthermore, an inhibitor of Hmox1 promoted macrophage alternative activation, and reversed the protection from PH seen in Ythdf2Lyz2 Cre mice under hypoxic exposure. Together, our data reveal a novel mechanism linking m6A RNA modification with changes in macrophage phenotype, inflammation and oxidative stress in PH, and identify Hmox1 as a downstream target of Ythdf2, suggesting that Ythdf2 may be a therapeutic target in PH.

Objective Circulating tumor cells are complete tumor cells with multi-scale analysis values that present a high potential for lung cancer diagnosis. To enhance the accuracy of lung cancer diagnosis, we detected circulating tumor cells by the innovated conical micro filter integrated microfluidic system. Methods We recruited 45 subjects of study, including 22 lung cancer patients, 2 precancerous patients, the control group including 14 healthy participants, and 7 patients with lung benign lesions in this prospective study. We calculated the area under the receiver operating characteristic curve of circulating tumor cells, cytokeratin19 fragment, carcinoma embryonic antigen, squamous cell carcinoma, neuron-specific enolase, and their combination, respectively, while compared the circulating tumor cells levels between vein blood and arterial blood. A conical shape filter embedded in a microfluidic chip was used to improve the detection capability of circulating tumor cells. Results The study indicated that the sensitivity, specificity, positive predictive value, and negative predictive value of circulating tumor cells detection were 81.8%, 90.5%, 90.0%, and 82.6%, respectively. The circulating tumor cells level of lung cancer patient was significantly higher than that of the control group ( P

Background: This study aimed to investigate the effects of unilateral labyrinthectomy (UL) on monoamine neurotransmitters in the medial vestibular nucleus (MVN) of rats. Methods: Adult Sprague–Dawley rats were utilized for the vestibular impaired animal model through UL. The success of the model establishment and the recovery process were evaluated using vestibular behavioral tests, including spontaneous nystagmus, postural asymmetry, and balance beam test. Additionally, the expression levels of c-Fos protein in the MVN were assessed by immunofluorescence. Furthermore, changes in the expression levels of monoamine neurotransmitters, including 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), and histamine in the MVN, were analyzed using high-performance liquid chromatography (HPLC) at different time points after UL (4 h, 8 h, 1 day, 2 days, 4 days, and 7 days). Results: Compared to the sham control group, the UL group exhibited the most pronounced vestibular impairment symptoms at 4 h post-UL, which significantly decreased at 4 days and almost fully recovered by 7 days. Immunofluorescence results showed a notable upregulation of c-Fos expression in the MVN subsequent to the UL-4 h, serving as a reliable indicator of heightened neuronal activity. In comparison with the sham group, HPLC analysis showed that the levels of 5-HT and NE in the ipsilesional MVN of the UL group were significantly elevated within 4 days after UL, and peaked on 1 day and 2 days, respectively. DA showed an increasing trend at different time points up to 7 days post-UL, while histamine levels significantly increased only at 1 day post-UL. Conclusions: UL-induced dynamic changes in monoamine neurotransmitters during the early compensation period in the rat MVN may be associated with the regulation of the central vestibular compensation mechanism by the MVN.

We aimed to investigate the diagnostic utility of quantitative parameters of contrast-enhanced ultrasound (CEUS) for benign and malignant liver lesions in pediatric patients. This was a single-center retrospective analysis of children with liver lesions who underwent CEUS at our hospital between July 2019 and February 2023. The CEUS perfusion patterns for all lesions were qualitatively analyzed using histopathology, contrast-enhanced magnetic resonance imaging, contrast-enhanced computed tomography, or long-term clinical follow-up as reference standards. The CEUS images were quantitatively analyzed using SonoLiver® software (TomTec Imaging Systems, Munich, Germany) to obtain data regarding quantitative parameters and dynamic vascular pattern (DVP) parametric images, including rise time (RT), time to peak (TTP), mean transit time (mTT), and maximum intensity (IMAX). Statistical analysis was carried out using Student’s t-test and receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic value of quantitative parameters. A total of 53 pediatric cases were included in this study, and 88.57% (31/35) of malignant lesions exhibited hyper-enhancement with rapid washout patterns; the same proportion of DVP parametric images exhibited washout patterns. Conversely, 94.44% (17/18) of benign lesions showed hyper-enhancement with slow washout patterns, and the same proportion of DVP parametric images showed no-washout patterns. RT, TTP, and mTT were significantly shorter in the malignant group than in the benign group (p < 0.05), while IMAX showed no significant difference (p > 0.05). ROC analysis indicated that mTT < 113.34 had the highest diagnostic value, with an area under the curve of 0.82. CEUS quantitative analysis had an accuracy of 98.11%, while qualitative analysis had an accuracy of 92.45%, with no statistically significant difference (p > 0.05). Quantitative analysis of CEUS provides valuable assistance in differentiating benign and malignant liver lesions in children. Among all quantitative parameters, mTT holds promise as a potentially valuable tool for identifying liver tumors.