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Autonomic nerve dysfunction is a common non-motor symptom of Parkinson's disease (PD). It has a high incidence and involves multiple organ system disorders with various manifestations, seriously affecting the quality of life. Autonomic nerve dysfunction can be a major symptom of advanced PD and a major cause of disability. Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced PD, and its improvement of motor symptoms in PD patients has been widely recognized. However, the effect of STN - DBS on the symptoms of autonomic nerve dysfunction in PD patients is still unclear. Here, the efficacy of STN - DBS on PD autonomic nerve dysfunction is briefly reviewed. Therefore, we should pay more attention to the symptoms of autonomic nerve dysfunction in PD patients, and conduct preoperative evaluation of DBS in PD patients, so as to comprehensively consider the postoperative efficacy, target selection, stimulus parameter setting, drug adjustment, develop an individualized treatment plan.

Deep brain stimulation (DBS) has been widely used for Parkinson's disease, essential tremor, dystonia, drug - resistant epilepsy and other diseases. The operation procedure of this surgical method is complicated, and it also has certain complications in clinical application, including surgical complications such as intracranial hemorrhage and infection, hardware complications such as lead fracture and displacement, and stimulation complications such as paresthesia and muscle spasm, in which lead fracture and erosion and infection of the skin behind the ear are common and troublesome complications. In clinical practice, we found that lead fracture and erosion and infection of the skin were mainly located behind the ear. Since 2012, Beijing Tiantan Hospital, Capital Medical University had applied the retroauricular bone grinding groove technology in DBS, which significantly reduced the incidence of lead fracture and erosion and infection of the skin. Therefore, the retroauricular bone grinding groove technology can effectively solve the above problems. This paper mainly introduces the retroauricular bone grinding groove technology and the clinical application attention matters, providing references for colleagues.

Stroke can lead to long - term motor disorders and reduced quality of life. Despite advances in conventional rehabilitation, many patients are still faced with limited efficacy of rehabilitation. Neuromodulation techniques have shown breakthrough therapeutic potential. The purpose of this article is to provide an overview of the mechanism of poststroke neuroplasticity, to explore the mechanism of dentate nucleus deep brain stimulation (DN - DBS) to improve poststroke motor function, and to summarize the progress of the study, in order to provide a scientific basis and a new therapeutic perspective for clinical practice of DN-DBS.

Abstract Self-efficacy or perceived ability refers to the confidence an individual has in their ability to successfully perform a specific task. Previous researchers have demonstrated the importance of self-efficacy beliefs and its impact on predicting students’ mathematics performances. Specifically, gender has been regarded as an important moderator variable in the prediction of achievement from measures of affect. To this end, using data from High School Longitudinal Study of 2009, this study utilized the multi-group analysis under the framework of structural equation modeling to examine gender differences in the reciprocal relationship between mathematics self-efficacy and mathematics achievement. The results showed that there were statistically significant differences between male students and female students in the reciprocal relationship between mathematics self-efficacy and mathematics achievement; the impact of prior mathematics achievement on later mathematics achievement was stronger than the impact of prior mathematics self-efficacy on later mathematics self-efficacy. Significance of these findings were discussed in this paper.

Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair. Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications. Instead, imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration. Here, we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration. Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites. Nanofiber sheaths conveyed adequate elasticity and permeability, whilst exhibiting a barrier function against the infiltration of fibroblasts. We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models. At 12 months post-implant, the morphometric and histological recovery, gait recovery, electrophysiological function, and degree of muscle atrophy were assessed. The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls. Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.

Fugitive dust is an important source of total suspended particulate matter in urban ambient air. The existing segmentation methods for dust sources face challenges in distinguishing key and secondary features, and they exhibit poor segmentation at the image edge. To address these issues, this paper proposes the Dust Source U-Net (DSU-Net), enhancing the U-Net model by incorporating VGG16 for feature extraction, and integrating the shuffle attention module into the jump connection branch to enhance feature acquisition. Furthermore, we combine Dice Loss, Focal Loss, and Activate Boundary Loss to improve the boundary extraction accuracy and reduce the loss oscillation. To evaluate the effectiveness of our model, we selected Jingmen City, Jingzhou City, and Yichang City in Hubei Province as the experimental area and established two dust source datasets from 0.5 m high-resolution remote sensing imagery acquired by the Jilin-1 satellite. Our created datasets include dataset HDSD-A for dust source segmentation and dataset HDSD-B for distinguishing the dust control measures. Comparative analyses of our proposed model with other typical segmentation models demonstrated that our proposed DSU-Net has the best detection performance, achieving a mIoU of 93% on dataset HDSD-A and 92% on dataset HDSD-B. In addition, we verified that it can be successfully applied to detect dust sources in urban areas.

Abstract Background Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks. Methods By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs). Findings Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18–0.19) to 0.23 (95% CI 0.23–0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks. Interpretation Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of ‘Long COVID-19.’

Abstract Background Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone‐induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms. Methods C26 tumour‐bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF‐α‐induced C2C12 myotubes or ad‐mRFP‐GFP‐LC3B‐transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy‐lysosome system. The possible direct targets of CYA were searched using the biotin‐streptavidin pull‐down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay. Results The administration of CYA prevented body weight loss and muscle wasting in C26 tumour‐bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P

With the continuous expansion of their market size and scope of use, the monetary attribute of stablecoins has become a focal point. The identification of the monetary attribute of stablecoins is a prerequisite for their supervision. Based on the essence and macroeconomic effects of money, this paper analyzes the monetary attribute of stablecoins from theoretical and empirical perspectives. We find that in the traditional financial market, stablecoins are not widely accepted, and their increased supply competes with traditional financial assets. As new types of digital assets, they do not possess a monetary attribute. However, in the digital asset market, stablecoins are widely used. The increase in issuance pushes up asset prices and brings liquidity effects to the market. Therefore, stablecoins possess a monetary attribute in the digital asset market and play the role of "digital fiat currency". This private sector liquidity is not controlled by the government and tends to accumulate risk. Therefore, the government should clarify the legal attribute of stablecoins according to their monetary attribute, strengthen the supervision of stablecoin issuers and prevent the private sector from monopolizing the digital asset market transaction medium.

Waldenström macroglobulinemia (WM) rarely leads to pulmonary embolism. Due to its low incidence, the underlying pathophysiology, prognosis, and optimal treatment remain largely unexplored and uninvestigated. In this study, a patient with a double-clonal WM, a rare subtype, presented with pulmonary embolism. The patient had a small number of plasma cells without morphological abnormalities, and an effective therapeutic response was observed. Nonetheless, the clinical prognosis requires a long-term follow-up.

Introduction: Carnosol exhibited ameliorating effects on muscle atrophy of mice developed cancer cachexia in our previous research.Method: Here, the ameliorating effects of carnosol on the C2C12 myotube atrophy result from simulated cancer cachexia injury, the conditioned medium of the C26 tumor cells or the LLC tumor cells, were observed. To clarify the mechanisms of carnosol, the possible direct target proteins of carnosol were searched using DARTS (drug affinity responsive target stability) assay and then confirmed using CETSA (cellular thermal shift assay). Furthermore, proteomic analysis was used to search its possible indirect target proteins by comparing the protein expression profiles of C2C12 myotubes under treatment of C26 medium, with or without the presence of carnosol. The signal network between the direct and indirect target proteins of carnosol was then constructed.Results: Our results showed that, Delta-1-pyrroline-5-carboxylate synthase (P5CS) might be the direct target protein of carnosol in myotubes. The influence of carnosol on amino acid metabolism downstream of P5CS was confirmed. Carnosol could upregulate the expression of proteins related to glutathione metabolism, anti-oxidant system, and heat shock response. Knockdown of P5CS could also ameliorate myotube atrophy and further enhance the ameliorating effects of carnosol.Discussion: These results suggested that carnosol might ameliorate cancer cachexia-associated myotube atrophy by targeting P5CS and its downstream pathways.

Since the beginning of March 2022, the epidemic due to the Omicron variant has developed rapidly in Jilin Province. To figure out the key controlling factors and validate the model to show the success of the Zero-COVID policy in the province, we constructed a Recursive Zero-COVID Model quantifying the strength of the control measures, and defined the control reproduction number as an index for describing the intensity of interventions. Parameter estimation and sensitivity analysis were employed to estimate and validate the impact of changes in the strength of different measures on the intensity of public health preventions qualitatively and quantitatively. The recursive Zero-COVID model predicted that the dates of elimination of cases at the community level of Changchun and Jilin Cities to be on April 8 and April 17, respectively, which are consistent with the real situation. Our results showed that the strict implementation of control measures and adherence of the public are crucial for controlling the epidemic. It is also essential to strengthen the control intensity even at the final stage to avoid the rebound of the epidemic. In addition, the control reproduction number we defined in the paper is a novel index to measure the intensity of the prevention and control measures of public health.

Accurate comprehension of grassland fires is imperative for maintaining ecological stability. In this study, we propose a novel fire model that incorporates real-time meteorological conditions. Our methodology integrates key meteorological factors including relative humidity, temperature, degree of solidification of combustible materials, and wind speed. These factors are embedded into a comprehensive function that determines both the downwind and upwind spreading speeds of the fire. Additionally, the model accommodates fire spread in the absence of wind by incorporating the direction perpendicular to the wind, with wind speed set to zero. By precisely determining wind speed, the model enables real-time calculation of fire spread speeds in all directions. Under stable wind conditions, the fire spread area typically adopts an elliptical shape. Leveraging ellipse properties, we define the aspect ratio as a function related to wind speed. Consequently, with knowledge of the fire duration, the model accurately estimates the area of fire spread. Our findings demonstrate the effectiveness of this model in predicting and evaluating fires in the Hulunbuir Grassland. The model offers an innovative method for quantifying grassland fires, contributing significantly to the understanding and management of grassland ecosystems.

Greenhouse gas satellites can provide consistently global CO2 data which are important inputs for the top-down inverse estimation of CO2 emissions and their dynamic changes. By tracking greenhouse gas emissions, policymakers and businesses can identify areas where reductions are needed most and implement effective strategies to reduce their impact on the environment. Monitoring greenhouse gases provides valuable data for scientists studying climate change. The requirements for CO2 emissions monitoring and verification support capacity drive the payload design of future CO2 satellites. In this study, we quantitatively evaluate the performance of satellite in detecting CO2 plumes from power plants based on an improved Gaussian plume model, with focus on impacts of the satellite spatial resolution and the satellite-derived XCO2 precision under different meteorological conditions. The simulations of CO2 plumes indicate that the enhanced spatial resolution and XCO2 precision can significantly improve the detection capability of satellite, especially for small-sized power plants with emissions below 6 Mt CO2/yr. The satellite-detected maximum of XCO2 enhancement strongly varies with the wind condition. For a satellite with a XCO2 precision of 0.7 ppm and a spatial resolution of 2 km, it can recognize a power plant with emissions of 2.69 Mt CO2/yr at a wind speed of 2 m/s, while its emission needs be larger than 5.1 Mt CO2/yr if the power plant is expected to be detected at a wind speed of 4 m/s. Considering the uncertainties in the simulated wind field, the satellite-derived XCO2 measurements and the hypothesized CO2 emissions, their cumulative contribution to the overall accuracy of the satellite’s ability to identify realistic enhancement in XCO2 are investigated in the future. The uncertainties of ΔXCO2 caused by the uncertainty in wind speed is more significant than those introduced from the uncertainty in wind direction. In the case of a power plant emitting 5.1 Mt CO2/yr, with the wind speed increasing from 0.5 m/s to 4 m/s, the simulated ΔXCO2 uncertainty associated with the wind field ranges from 3.75 ± 2.01 ppm to 0.46 ± 0.24 ppm and from 1.82 ± 0.95 ppm to 0.22 ± 0.11 ppm for 1 × 1 km2 and 2 × 2 km2 pixel size, respectively. Generally, even for a wind direction with a higher overall uncertainty, satellite still has a more effective capability for detecting CO2 emission on this wind direction, because there is more rapid growth for simulated maximal XCO2 enhancements than that for overall uncertainties. A designed spatial resolution of satellite better than 1 km and a XCO2 precision higher than 0.7 ppm are suggested, because the CO2 emission from small-sized power plants is much more likely be detected when the wind speed is below 3 m/s. Although spatial resolution and observed precision parameters are not sufficient to support the full design of future CO2 satellites, this study still can provide valuable insights for enhancing satellite monitoring of anthropogenic CO2 emissions.

Abstract Water‐use efficiency (WUE), defined as the ratio of gross primary productivity (GPP) and evapotranspiration (ET), is a key indicator of the coupling of carbon and water cycles in terrestrial ecosystems. Diffuse radiation significantly affects WUE as diffuse radiation has stronger fertilization effects on GPP than ET. Remote sensing data‐driven (RS) models were widely used to estimate WUE. However, the performance of RS models in simulating diffuse radiation effect on WUE is poorly understood. We used GPP and ET products from MODIS, PML, BESS, and GLASS to explore the response of WUE to diffuse radiation across different vegetation types. We found that there was a large divergence among the RS models in estimating the response of WUE to FDP. PML model performed better than other RS models in simulating diffuse radiation effect on WUE. This research has significant implications for improving model simulations and understanding global carbon and water cycles.

Introduction: To repair cartilage defect as well as the calcified cartilage layer (CCL) and bone tissue, there is need to fabricate a three-phase complex that mimics the natural cartilage tissue. Materials and methods: SF/Col-Ⅱ/HA scaffolds were constructed by low-temperature 3D printing, and to prepare a three-phase complex. The microstructure were showed using a SEM image analysis program. To observe collagen and glycosaminoglycan expression and analyze morphometric parameters, HE staining was performed to reveal new cartilage. Immunohistochemical were performed to investigate the collagen content and defect repair status in the new cartilage group in vitro and vivo. Results: Physical and biochemical properties and biocompatibility of three-phase complex met the requirements of constructing tissue-engineered cartilage. The OD values increased gradually at different time points. With increasing culture time, the OD values showed an upward trend. The HE and immunohistochemical staining results showed that new cartilage had formed at the defect and new cartilage formation occurred during in vivo repair. Conclusion: 3DP-anchored three-phase complexes have good physical and biochemical properties and biocompatibility and thus represent an alternative cartilage tissue engineering material.

Industrial Park is a part of urban development and plays an indispensable role in promoting regional economic development. However, the high consumption of resources and the concentrated emission of pollution pose a great threat to the ecological balance and human health. Therefore, the future of industrial park needs to be balanced with economic growth while realizing resource conservation and environmental improvement as much as possible. However, there is still a research gap in analyzing the relationship between ecological environment quality (EEQ) and economic development (ED) at the industrial park scale. This paper first constructs the new remote sensing ecological index (RSEInew) model to measure the EEQ of Suzhou Industrial Park (SIP) from 2000 to 2020. Then this study constructs an ED index system to evaluate its economic situation. Finally, this paper utilizes the Environmental Kuznets Curve (EKC) model and the coupled coordination degree (CCD) model to deeply analyze the relationship between EEQ and ED. The results show that: (1) The average annual growth rate of EEQ in SIP is −1.50 %, with a general downward trend. Over the past 20 years, the ecological environment of SIP has not deteriorated extensively. (2) The ED of SIP is steady and rising, with an average annual growth rate of 10.17 %. (3) From 2000 to 2020, the EKC between EEQ and the ED of the SIP takes on an inverted “N” shape, with its CCD rising from barely coordinated to highly coordinated. This study can provide a reference for studying the quality development of areas at the industrial park level.

The extraction of species-specific calls from passive acoustic recordings is a common preliminary step in ecological analysis. But for many species, especially those occupying noisy, acoustically variable habitats, the call extraction process remains largely manual, a time-consuming, and increasingly unsustainable process. Deep neural networks have been shown to provide excellent performance in a range of acoustic classification applications. We take as an example the recognition of four songs of one of the rarest mammals in the world, the western black-crested gibbon (Nomascus concolors).The process of recognition in this paper which includes distributed BIC ambient sound segmentation based on the OpenPAI platform; DNN-based western black-crested gibbon song enhancement processing; data pre-processing, labeling samples; proposed DNN + ResNet34 + CBAM + GRU + Attention recognition model; comparing other classical neural network models.Our best model converts acoustic recordings into spectrogram images on the mel frequency scale and uses these images to train convolutional neural networks.Our proposed model proved to be very accurate in predicting the segmented western black-crested gibbon songs with an accuracy of 99.8%, and almost a few western black-crested gibbon songs were incorrectly identified when all segmented data were recognized. In the four consecutive years of the acoustic monitoring system deployed in the Ailao Mountain National Nature Reserve, the western black-crested gibbon was most active near the monitoring site from March to August each year, and least active in January and February. Based on call sound intensity analysis, we monitored a total of two different western black-crested gibbon groups (G1 and G2) during the monitoring cycle. We demonstrate that passive acoustic monitoring combined with CNN classifiers is an effective tool for the remote detection of one of the rarest and most threatened species in the world.

ObjectiveThis study sought to assess the efficacy and safety of immunotherapy combined with single-agent chemotherapy as a second- or later-line setting for metastatic non-small cell lung cancer (NSCLC) and to provide clinical evidence for this treatment regimen. The predictive value of extracellular vesicle (EV) membrane proteins was explored in patients who underwent this treatment.MethodsClinical data from patients diagnosed with metastatic NSCLC who received immunotherapy plus single-agent chemotherapy as a second- or later-line setting were retrospectively collected between March 2019 and January 2022. A total of 30 patients met the inclusion criteria, and all were pathologically confirmed to have NSCLC. Short-term efficacy, progression-free survival (PFS), EV markers for response prediction, and adverse events were assessed.ResultsEfficacy data were available for all 30 patients and included a partial response in 5 patients, stable disease in 18 patients, and disease progression in 7 patients. The objective response rate was 16.7%, the disease control rate was 76.7%, and the median PFS was 3.2 months. Univariate analysis showed that PFS was not associated with sex, age, smoking status, treatment lines, prior use of immunotherapy, or prior use of antiangiogenic drugs. The EV membrane proteins MET proto-oncogene, receptor tyrosine kinase (c-MET), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptor 2 (VEGFR2) at baseline were associated with poor prognosis and correlated with the efficacy of immunotherapy plus chemotherapy. According to the receiver operating characteristics and Kaplan–Meier curve analyses, patients with high c-MET, EGFR, and VEGFR2 expression at baseline had significantly shorter PFS than those with low expression. In addition, VEGFR2 expression was increased after combined immunotherapy in responders, which was decreased in non-responders. The most common grade 2 or higher adverse events were neutropenia, gastrointestinal reactions, and thyroid dysfunction, all of which were tolerated.ConclusionsImmunotherapy plus single-agent chemotherapy as a second- or later-line treatment is safe, effective, and tolerable for metastatic NSCLC. EV markers can be used as predictive markers of efficacy in patients with metastatic NSCLC treated with immunotherapy plus chemotherapy to help monitor treatment efficacy and guide treatment decisions.

The variation of nutrient supply not only leads to the differences in the phytoplankton biomass and primary productivity but also induces the long-term phenotypic evolution of phytoplankton. It is widely accepted that marine phytoplankton follows Bergmann's Rule and becomes smaller with climate warming. Compared with the direct effect of increasing temperature, the indirect effect via nutrient supply is considered to be an important and dominant factor in the reduction of phytoplankton cell size. In this paper, a size-dependent nutrient-phytoplankton model is developed to explore the effects of nutrient supply on the evolutionary dynamics of functional traits associated with phytoplankton size. The ecological reproductive index is introduced to investigate the impacts of input nitrogen concentration and vertical mixing rate on the persistence of phytoplankton and the distribution of cell size. In addition, by applying the adaptive dynamics theory, we study the relationship between nutrient input and the evolutionary dynamics of phytoplankton. The results show that input nitrogen concentration and vertical mixing rate have significant effects on the cell size evolution of phytoplankton. Specifically, cell size tends to increase with the input nutrient concentration, as does the diversity of cell sizes. In addition, a single-peaked relationship between vertical mixing rate and cell size is observed. When the vertical mixing rate is too low or too high, only small individuals are dominant in the water column. When the vertical mixing rate is moderate, large individuals can coexist with small individuals, so the diversity of phytoplankton is elevated. We predict that reduced intensity of nutrient input due to climate warming will lead to a trend towards smaller cell size and will reduce the diversity of phytoplankton.

Abstract Background Atractylenolide I (AI) is a natural sesquiterpene lactone isolated from Atractylodes macrocephala Koidz, known as Baizhu in traditional Chinese medicine. AI has been found to ameliorate cancer cachexia in clinic cancer patients and in tumour‐bearing mice. Here, we checked the influence of AI on biogenesis of IL‐6 and extracellular vesicles (EVs) in cancer cachexia mice and then focused on studying mechanisms of AI in inhibiting the production of tumour‐derived EVs, which contribute to the ameliorating effects of AI on cancer cachexia. Methods C26 tumour‐bearing BALB/c mice were applied as animal model to examine the effects of AI (25 mg/kg) in attenuating cachexia symptoms, serum IL‐6 and EVs levels. IL‐6 and EVs secretion of C26 tumour cells treated with AI (0.31–5 μM) was further observed in vitro. The in vitro cultured C2C12 myotubes and 3T3‐L1 mature adipocytes were used to check the potency of conditioned medium of C26 cells treated with AI (0.625–5 μM) in inducing muscle atrophy and lipolysis. The glycolysis potency of C26 cells under AI (0.31–5 μM) treatment was evaluated by measuring the extracellular acidification rate using Seahorse XFe96 Analyser. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms. STAT3 overexpression or knockout C26 cells were also used to confirm the effects of AI (5 μM). Results AI ameliorated cancer cachexia symptoms (P

This study explored the active ingredients and mechanism of action of Crataegi Fructus in the treatment of coronary heart disease through network pharmacology and molecular docking technology. With the help of TCMSP, Gene Cards, OMIM and other databases to collect target information, the STRING database was used to construct a PPI network diagram, perform GO and KEGG pathway enrichment analysis on the common target, and finally molecularly dock the active ingredient with the core target to initially verify the network pharmacology results. In this study, a total of 6 Crataegi Fructus active ingredients (sitosterol, kaempferol, stigmasterol, quercetin, ent-Epicatechin, isorhamnetin) and 10 Crataegi Fructus core targets for the treatement of coronary heart disease (JUN, AKT1, TNF, MAPK1, TP53, RELA, IL6, MAPK8, MAPK14, EGFR) were screened; KEGG pathway enrichment results showed that Crataegi Fructus prevention and treatment of coronary heart disease pathway involved pathway in cancer, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, MAPK signaling pathway, etc.; Molecular docking results showed that quercetin, isorhamnetin and kaempferol all had good binding to the core target. It is speculated that these components may be the main active components for the treatment of coronary heart disease. This study revealed that Crataegi Fructus may treat coronary heart disease through multiple components (isorhamnetin, kaempferol, quercetin), acting on key targets such as MAPK8, MAPK1, RELA, and regulating multiple signaling pathways such as MAPK. It preliminarily revealed the potential mechanism of Crataegi Fructus in the treatment of coronary heart disease.

Abstract Background Countries that aimed for eliminating the cases of COVID-19 with test-trace-isolate policy are found to have lower infections, deaths, and better economic performance, compared with those that opted for other mitigation strategies. However, the continuous evolution of new strains has raised the question of whether COVID-19 eradication is still possible given the limited public health response capacity and fatigue of the epidemic. We aim to investigate the mechanism of the Zero-COVID policy on outbreak containment, and to explore the possibility of eradication of Omicron transmission using the citywide test-trace-isolate (CTTI) strategy. Methods We develop a compartmental model incorporating the CTTI Zero-COVID policy to understand how it contributes to the SARS-CoV-2 elimination. We employ our model to mimic the Delta outbreak in Fujian Province, China, from September 10 to October 9, 2021, and the Omicron outbreak in Jilin Province, China for the period from March 1 to April 1, 2022. Projections and sensitivity analyses were conducted using dynamical system and Latin Hypercube Sampling/ Partial Rank Correlation Coefficient (PRCC). Results Calibration results of the model estimate the Fujian Delta outbreak can end in 30 (95% confidence interval CI: 28–33) days, after 10 (95% CI: 9–11) rounds of citywide testing. The emerging Jilin Omicron outbreak may achieve zero COVID cases in 50 (95% CI: 41–57) days if supported with sufficient public health resources and population compliance, which shows the effectiveness of the CTTI Zero-COVID policy. Conclusions The CTTI policy shows the capacity for the eradication of the Delta outbreaks and also the Omicron outbreaks. Nonetheless, the implementation of radical CTTI is challenging, which requires routine monitoring for early detection, adequate testing capacity, efficient contact tracing, and high isolation compliance, which constrain its benefits in regions with limited resources. Moreover, these challenges become even more acute in the face of more contagious variants with a high proportion of asymptomatic cases. Hence, in regions where CTTI is not possible, personal protection, public health control measures, and vaccination are indispensable for mitigating and exiting the COVID-19 pandemic. Graphical Abstract

Mercury (Hg) emissions from open biomass burning represent one of the largest Hg inputs to the atmosphere, with considerable effects on the atmospheric Hg budget. However, there is currently large uncertainty in the inventory of Hg emissions from open biomass burning in China due to limitations on the coarse resolution of burned area products, rough biomass data, and the unavailability of suitable emission factors (EFs). In this study, we developed high tempo-spatial resolution (30 m) and long time-series (2000–2019) atmospheric Hg emission inventories from open biomass burning using the Global Annual Burned Area Map (GABAM) product, high-resolution biomass map, Landsat-based tree cover datasets as well as local EFs in China. The results showed that the average annual Hg emission from open biomass burning in China amounted to 172.6 kg during 2000–2019, with a range of 63–398.5 kg. The largest Hg emissions were found in cropland (72%), followed by forest (25.9%), and grassland (2.1%). On a regional level, Northeast China (NE) and Southwest China (SW) were the two main contributors, together accounting for more than 60% of total Hg emissions. The temporal distribution of Hg emissions showed that the peaks occurred in 2003 and 2014. This is a comprehensive estimation of Hg emissions from open biomass burning in China by integrating various high-resolution remotely sensed data and nationwide localized EFs, which has important implications for understanding the role of open biomass burning in China in regional and global atmospheric Hg budget.

Intracranial atherosclerotic ischemic stroke dramatically impacts the quality of life among the elderly. Statins therapy has been proven to be effective in plaque stabilization and alleviation in patients with intracranial atherosclerotic ischemic stroke. According to recent studies, these effects may be directly related to lipid levels rather than specific lipid-lowering drugs. Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK-9 inhibitor) are newer effective lipid-lowering drugs increasingly prescribed to patients at high cardiovascular risk to lower LDL cholesterol. Studies have provided evidence that PCSK9 inhibitor combined with statin therapy can lead to a decrease in the plaque volume measured by intravascular ultrasound in coronary heart disease patients. But the efficacy of combination of the two drugs in symptomatic intracranial artery stenosis has been unknown. Here we provide a case which was reported to suggest that a combination of Evolocumab and intensive statin therapy might reverse or alleviate symptomatic intracranial artery stenosis.

This study employs an ensemble Kalman filter assimilation method to validate and update the pollutant emission inventory to mitigate the impact of uncertainties on the forecasting performance of air quality numerical models. Based on nationwide ground-level pollutant monitoring data in China, the emission inventory for the entire country was inverted hourly in 2022. The emission rates for PM2.5, CO, NOx, SO2, NMVOCs, BC, and OC updated by the inversion were determined to be 6.6, 702.4, 37.2, 13.4, 40.3, 3, and 18.2 ng/s/m2, respectively. When utilizing the inverted inventory instead of the priori inventory, the average accuracy of all cities’ PM2.5 forecasts was improved by 1.5–4.2%, especially for a 7% increase on polluted days. The improvement was particularly remarkable in the periods of January–March and November–December, with notable increases in the forecast accuracy of 12.5%, 12%, and 6.8% for the Northwest, Northeast, and North China regions, respectively. The concentration values and spatial distribution of PM2.5 both became more reasonable after the update. Significant improvements were particularly observed in the Northwest region, where the forecast accuracy for all preceding days was improved by approximately 15%. Additionally, the underestimated concentration of PM2.5 in the priori inventory compared to the observation value was notably alleviated by the application of the inversion.

Global temperatures are continuing to rise as atmospheric carbon dioxide (CO2) concentrations increase, and climate warming has become a major challenge to global sustainable development. The Cross-Track Infrared Sounder (CrIS) instrument is a Fourier transform spectrometer with 0.625 cm−1 spectral resolution covering a 15 μm CO2-absorbing band, providing a way of monitoring CO2 with on a large scale twice a day. This paper proposes a method to predict the concentration of column-averaged CO2 (XCO2) from thermal infrared satellite data using ensemble learning to avoid the iterative computations of radiative transfer models, which are necessary for optimization estimation (OE). The training data set is constructed with CrIS satellite data, European Centre for Medium-Range Weather Forecasts (ECMWF) Reanalysis v5 (ERA5) meteorological parameters, and ground-based observations. The training set was processed using two methods: correlation significance analysis (abbreviated as CSA) and principal component analysis (PCA). Extreme Gradient Boosters (XGBoost), Extreme Random Trees (ERT), and Gradient Boost Regression Tree (GBRT) are used for training and learning to develop the new retrieval model. The results showed that the R2 of XCO2 prediction built from the PCA dataset was bigger than that from the CSA dataset. These three learning models were verified by validation sets, and the ERT model showed the best agreement between model predictions and the truth (R2 = 0.9006, RMSE = 0.7994 ppmv, MAE = 0.5804 ppmv). The ERT model was finally selected to estimate the concentrations of XCO2. The deviation of XCO2 predictions of 12 TCCON sites in 2019 was within ±1 ppm. The monthly averages of XCO2 concentrations in close agreement with TCCON ground observations were grouped into four regions: Asia (R2 = 0.9671, RMSE = 0.7072 ppmv), Europe (R2 = 0.9703, RMSE = 0.8733 ppmv), North America (R2 = 0.9800, RMSE = 0.6187 ppmv), and Oceania (R2 = 0.9558, RMSE = 0.4614 ppmv).

Background: Strategies to stabilize and support overall infant health by increasing the number of Bifidobacterium longum in the infant gut are of interest, but few studies have systematically addressed this issue. We aimed to evaluate the efficacy and safety of Bifidobacterium longum use in infants using meta-analysis. Methods: We searched PubMed, EMBASE, Cochrane Library of Systematic Reviews, and SinoMed for publications until 27 July 2022. The main outcomes of interest were weight gain, risk of necrotizing enterocolitis (NEC), and adverse events. Two authors independently performed study screening, risk of bias assessment, and data extraction. Outcome data were extracted from each included study and combined using mean difference (MD) or risk ratio (RR) and finally combined using a fixed-effect model or random-effect model. Results: A total of 4481 relevant studies were identified, of which 15 were found to be eligible for randomized controlled trials and were included in the meta-analysis. The combined extracted data showed that the intervention group containing Bifidobacterium longum had a significantly lower risk of NEC (RR = 0.539, 95% CI: 0.333, 0.874) compared to the control group. There was no statistical difference between the intervention and control groups regarding weight gain (MD = 0.029, 95% CI: −0.032, 0.090), the occurrence of adverse events (RR = 0.986, 95% CI: 0.843, 1.153), and serious adverse events (RR = 0.881, 95% CI: 0.493, 1.573). Conclusions: Bifidobacterium longum may significantly reduce the risk of NEC in infants as well as being safe; thus, further research evidence is needed on whether there is a benefit on weight gain.

Oil wells play an important role in the extraction of oil and gas, and their future potential extends beyond oil and gas exploitation to include the development of geothermal resources for sustainable power generation. Identifying and detecting oil wells are of paramount importance given the crucial role of oil well distribution in energy planning. In recent years, significant progress has been made in detecting single oil well objects, with recognition accuracy exceeding 90%. However, there are still remaining challenges, particularly with regard to small-scale objects, varying viewing angles, and complex occlusions within the domain of oil well detection. In this work, we created our own dataset, which included 722 images containing 3749 oil well objects in Daqing, Huatugou, Changqing oil field areas in China, and California in the USA. Within this dataset, 2165 objects were unoccluded, 617 were moderately occluded, and 967 objects were severely occluded. To address the challenges in detecting oil wells in complex occlusion scenarios, we propose the YOLOv5s-seg CAM NWD network for object detection and instance segmentation. The experimental results show that our proposed model outperforms YOLOv5 with F1 improvements of 5.4%, 11.6%, and 23.1% observed for unoccluded, moderately occluded, and severely occluded scenarios, respectively.

In the last decade, low-quality unconventional oil and gas resources have become the primary source for domestic oil and gas storage and production, and hydraulic fracturing has become a crucial method for modifying unconventional reservoirs. This paper puts forward a framework for predicting hydraulic fracture parameters. It combines eXtreme Gradient Boosting and Bayesian optimization to explore data-driven machine learning techniques in fracture simulation models. Analyzing fracture propagation through mathematical models can be both time-consuming and costly under conventional conditions. In this study, we predicted the physical parameters and three-dimensional morphology of fractures across multiple time series. The physical parameters encompass fracture width, pressure, proppant concentration, and inflow capacity. Our results demonstrate that the fusion model applied can significantly improve fracture morphology prediction accuracy, exceeding 0.95, while simultaneously reducing computation time. This method enhances standard numerical calculation techniques used for predicting hydraulic fracturing while encouraging research on the extraction of unconventional oil and gas resources.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as Erlotinib, have demonstrated remarkable efficacy in the treatment of non-small cell lung cancer (NSCLC) patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type (wt) EGFR tumours has been shown to be marginal. Methods that can sensitize Erlotinib to EGFR wild-type NSCLC remain rare. Herein, we developed a multifunctional superparamagnetic nanotheranostic agent as a novel strategy to potentiate Erlotinib to EGFR-wt NSCLCs. Our results demonstrate that the nanoparticles can co-escort Erlotinib and a vascular epithermal growth factor (VEGF) inhibitor, Bevacizumab (Bev), to EGFR-wt tumours. The nanotheranostic agent exhibits remarkable effects as an inhibitor of EGFR-wt tumour growth. Moreover, Bev normalizes the tumour embedded vessels, further promoting the therapeutic efficacy of Erlotinib. In addition, the tumour engagement of the nanoparticles and the vascular normalization could be tracked by magnetic resonance imaging (MRI). Collectively, our study, for the first time, demonstrated that elaborated nanoparticles could be employed as a robust tool to potentiate Erlotinib to EGFR-wt NSCLC, paving the way for imaging-guided nanotheranostics for refractory NSCLCs expressing EGFR wild-type genes.

Abstract Background The majority of lung cancer(LC) patients are diagnosed at advanced stage with a poor prognosis. However, there is still no ideal diagnostic and prognostic prediction model for lung cancer. Methods Data of CEA, CYFRA21-1 and NSE test of patients with LC and benign lung diseases (BLDs) or healthy people from Physical Examination Center was collected. Samples were divided into three data sets as needed. Reassign three kinds of tumor markers (TMs) according to their distribution characteristics in different populations. Diagnostic and prognostic models were thus established, and independent validation was conducted with other data sets. Results The diagnostic prediction model showed good discrimination ability: the area under the receiver operating characteristic curve (AUC) differentiated LC from healthy people and BLDs (diagnosed within 2 months), being 0.88 and 0.84 respectively. Meanwhile, the prognostic prediction model did great in prediction: AUC in training data set and test data set were 0.85 and 0.8 respectively. Conclusion Reassigned CEA, CYFRA21-1 and NSE can effectively predict the diagnosis and prognosis of LC. Compared with the same TMs that were considered individually, this diagnostic prediction model can identify high-risk population for LC screening more accurately. The prognostic prediction model could be helpful in making more scientific treatment and follow-up plans for patients.

Deep brain stimulation (DBS) is one of the most effective treatment methods for movement disorders, but there are still limitations in efficacy and adverse reactions, which may be due to the existing stimulation mode is too fixed to adjust according to the individual situation of patients. Adaptive deep brain stimulation (aDBS) based on the level of brain electrophysiological activity can adjust the stimulation mode with the change of clinical symptoms, which is more effective. The preliminary study of aDBS confirms its effectiveness. This article describes the electrophysiological signals involved in aDBS and its application progress in movement disorders.

(1) Background: Previous studies suggest that exposure to nitrogen dioxide (NO2) has a negative impact on health. But few studies have explored the association between NO2 and blood lipids or fasting plasma glucose (FPG), as well as gene–air pollution interactions. This study aims to fill this knowledge gap based on a pedigree cohort in southern China. (2) Methods: Employing a pedigree-based design, 1563 individuals from 452 families participated in this study. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and FPG were measured. We investigated the associations between short-term NO2 exposure and lipid profiles or FPG using linear mixed regression models. The genotype–environment interaction (GenoXE) for each trait was estimated using variance component models. (3) Results: NO2 was inversely associated with HDLC but directly associated with TG and FPG. The results showed that each 1 μg/m3 increase in NO2 on day lag0 corresponded to a 1.926% (95%CI: 1.428–2.421%) decrease in HDLC and a 1.400% (95%CI: 0.341–2.470%) increase in FPG. Moreover, we observed a significant genotype–NO2 interaction with HDLC and FPG. (4) Conclusion: This study highlighted the association between NO2 exposure and blood lipid profiles or FPG. Additionally, our investigation suggested the presence of genotype–NO2 interactions in HDLC and FPG, indicating potential loci-specific interaction effects. These findings have the potential to inform and enhance the interpretation of studies that are focused on specific gene–environment interactions.

Satellite aerosol products are pivotal in studies of regional air quality and global climate change. Compared with accurate in situ observations, satellite measurements provide valuable large-scale atmospheric information. However, limitations such as clouds and retrieval assumptions result in a significant number of missing values in satellite aerosol optical depth (AOD) products, which severely hampers the representativeness. To address this issue, spatial interpolation of the AOD data is necessary to improve data coverage. In this study, one year of AOD observation data from the MODIS C6.1 version was applied to analyze the spatiotemporal correlated characteristics. The statistical parameters were used as dynamic interpolation weights to develop a novel interpolation method called empirical correlation weighting (ECW) based on MODIS AOD over Northern China in 2016. The ECW interpolation results were obtained at a 0.05° resolution (~5 km). The results showed that the spatial coverage of the Deep Blue (DB) and Dark Target (DT) products increased from 43.88% to 70.65% and from 15.04% to 32.62%, respectively. The reconstruction of the ECW method illustrated good agreement with original values in three cases and in two experimental areas. The mean absolute error (MAE) and root mean square error (RMSE) in the two experiments were 0.1171 and 0.0809, and 0.1212 and 0.0838, respectively, indicating that the ECW exhibited the better accuracy than ordinary Kriging (OK) and Thin Plate Spline (TPS). The AERONET validation results indicated that the values of RMSE and MAE were slightly higher after interpolation compared with those before interpolation, maintaining relatively low values, 0.241 and 0.257, 0.140 and 0.150, respectively.

Abstract Background Increasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized. Methods The expression levels of TUG1, miR-524-5p, and sine oculis homeobox homolog 1 (SIX1) were determined using quantitative real-time PCR. The regulatory relationships were confirmed by dual-luciferase reporter assay. Cell proliferation and invasion were assessed using Cell Counting Kit 8 and transwell assays. Glucose uptake, cellular levels of lactate, lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) were detected using commercially available kits. Silencing of TUG1 or SIX1 was performed by lentivirus transduction. Protein levels were measured by immunoblotting. Results Cancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, and glycolysis in HepG2 cells by releasing TUG1. The promotive effects of CAFs-secreted exosomes were attenuated by silencing of TUG1. TUG1 and SIX1 are targets of miR-524-5p. SIX1 knockdown inhibited the promotive effects of miR-524-5p inhibitor. Silencing of TUG1 suppressed tumor growth and lung metastasis and therefore increased survival of xenograft model mice. We also found that TUG1 and SIX1 were increased in HCC patients with metastasis while miR-524-5p was decreased in HCC patients with metastasis. Conclusions CAFs-derived exosomal TUG1 promoted migration, invasion, and glycolysis in HCC cells via the miR-524-5p/SIX1 axis. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for HCC in future.

BackgroundThe posterior cruciate ligament (PCL) plays an important role in maintaining the stability of the knee joint. To date, researchers have not reached agreement on which type of fixation material should be used to treat PCL tibial avulsion fractures. The aim of this study was to investigate the effects of double button plate and cannulated screw fixation in the treatment of PCL avulsion fractures.MethodsWe retrospectively reviewed our database, which was collected prospectively. From January 2019 to January 2020, 46 patients with posterior cruciate ligament avulsion fractures who were treated with double button plate and cannulated screw fixation. The primary outcomes of this study were surgical complications (fixation failure/displacement, implant breakage, nonunion, infection), radiological parameters, and knee function and secondary outcomes included reoperation rates for the fixation methods and the prevalence of symptomatic hardware causing soft tissue irritation outcomes were included. Values were analysed using multiple comparisons, where P-values of 0.05 or less were considered significant.ResultsDouble button plate fixation had significantly higher values than cannulated screw fixation. The results showed that double button plate fixation was related to greater decreases in the length of surgery, intraoperative blood loss, hospital days, full weight bearing time, and incidence of complications, as well as greater increases in postoperative range of motion and Knee Society Score function and Lysholm scores.ConclusionCompared with cannulated screw fixation, the use of double button plate fixation technology has the following advantages: less trauma, shorter operation time, convenient use of instruments and fixtures, and it does not need to be removed, thus avoiding secondary trauma. Moreover, double button plate fixation under direct vision is safe and reliable without the need for additional equipment.

Abstract Background Non-small cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with an unfavorable prognosis. Ferroptosis is involved in the development of multiple cancers. Whereas, the prognostic value of ferroptosis-related lncRNAs in NSCLC remains uncertain. Methods Gene expression profiles and clinical information of NSCLC were retrieved from the TCGA database. Ferroptosis-related genes (FRGs) were explored in the FerrDb database and previous studies, ferroptosis-related lncRNAs (FRGs-lncRNAs) were identified by the correlation analysis and the LncTarD database. The differentially expressed FRGs-lncRNAs were screened and FRGs-lncRNAs associated with the prognosis were explored by univariate Cox regression analysis and Kaplan–Meier survival analysis. Then, an FRGs-lncRNAs signature was constructed and verified by the Lasso-penalized Cox analysis. Finally, the potential correlation between risk score, immune checkpoint genes, and chemotherapeutic sensitivity was further investigated. Results 129 lncRNAs with a potential regulatory relationship with 59 differentially expressed FRGs were found in NSCLC, of which 10 were related to the prognosis of NSCLC (P

Abstract Background Cancer cachexia is a multifactorial metabolic syndrome in which bile acid (BA) metabolism might be involved. The aim of the present study was to clarify the contribution of liver and gut microbiota to BA metabolism disturbance in cancer cachexia and to check the possibility of targeting BA metabolism using agents such as tauroursodeoxycholic acid (TUDCA) for cancer cachexia therapy. Methods The BA profiles in liver, intestine, and serum of mice with cancer cachexia induced by inoculation of colon C26 tumour cells were analysed using metabolomics methods and compared with that of control mice. Proteomic analysis of liver protein expression profile and 16S rRNA gene sequencing analysis of gut microbiota composition in cancer cachexia mice were conducted. Expression levels of genes related to farnesoid X receptor (FXR) signalling pathway in the intestine and liver tissues were analysed using RT–PCR analysis. The BA profiles in serum of clinical colon cancer patients with or without cachexia were also analysed and compared with that of healthy volunteers. The effects of TUDCA in treating cancer cachexia mice were observed. Results In the liver of cancer cachexia mice, expression of BA synthesis enzymes was inhibited while the amount of total BAs increased (P

Abstract Background Janus-activated kinase-1 (JAK1) plays a crucial role in many aspects of cell proliferation, differentiation, apoptosis and immune regulation. However, correlations of JAK1 with prognosis and immune infiltration in NSCLC have not been documented. Methods We analyzed the relationship between JAK1 expression and NSCLC prognosis and immune infiltration using multiple public databases. Results JAK1 expression was significantly decreased in NSCLC compared with that in paired normal tissues. JAK1 overexpression indicated a favourable prognosis in NSCLC. In subgroup analysis, high JAK1 expression was associated with a preferable prognosis in lung adenocarcinoma (OS: HR, 0.74, 95% CI from 0.58 to 0.95, log-rank P = 0.017), not squamous cell carcinoma. In addition, data from Kaplan–Meier plotter revealed that JAK1 overexpression was associated with a preferable prognosis in male and stage N2 patients and patients without distant metastasis. Notably, increased levels of JAK1 expression were associated with an undesirable prognosis in patients with stage 1 (OS: HR, 1.46, 95% CI from 1.06 to 2.00, P = 0.02) and without lymph node metastasis (PFS: HR, 2.18, 95% CI from 1.06 to 4.46, P = 0.029), which suggests that early-stage NSCLC patients with JAK1 overexpression may have a bleak prognosis. Moreover, multiple immune infiltration cells, including NK cells, CD8 + T and CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells (DCs), in NSCLC were positively correlated with JAK1 expression. Furthermore, diverse immune markers are associated with JAK1 expression. Conclusions JAK1 overexpression exhibited superior prognosis and immune infiltration in NSCLC.

Cancer cachexia is a kind of whole-body metabolic disorder syndrome accompanied by severe wasting of muscle tissue in which cancer exosomes may be involved. Analysis of clinical samples showed that the serum exosome concentrations were correlated with the development of cancer cachexia. Exosomes secreted by C26 cells could decrease the diameter of C2C12 myotubes in vitro and decrease mouse muscle strength and tibialis anterior (TA) muscle weight in vivo. GW4869, an inhibitor of exosome excretion, ameliorated muscle wasting in C26 tumor-bearing mice. MicroRNA (miRNA) sequencing (miRNA-seq) analysis suggested that miR-195a-5p and miR-125b-1-3p were richer in C26 exosomes than in exosomes secreted from MC38 cells (non-cachexic). Both miR-195a-5p and miR-125b-1-3p mimics could induce atrophy of C2C12 myoblasts. Downregulation of Bcl-2 and activation of the apoptotic signaling pathway were observed in C2C12 myoblasts transfected with miR-195a-5p and miR-125b-1-3p mimics, in the gastrocnemius muscle of C26 tumor-bearing mice and in the TA muscle injected with C26 exosomes. Results of dual-luciferase assay confirmed the targeting of miR-195a-5p/miR-125b-1-3p to Bcl-2. Overexpression of Bcl-2 successfully reversed atrophy of C2C12 myoblasts induced by the two miRNA mimics. These results suggested that cancer exosome enriched miRNAs might induce muscle atrophy by targeting Bcl-2-mediated apoptosis.

Objective To explore the pathophysiologic mechanism of SNCA gene in the early⁃stage of Parkinson's disease (PD). Methods Wild type (WT group, n=10) and SNCA Ala53Thr base substitution mice (TG group, n=10) were selected for further experiments. Endogenous metabolites in olfactory bulb (OB) of transgenic and wild type mice were detected and analyzed by high performance liquid chromatography⁃tandem mass spectrometry (HPLC⁃MS/MS). Then the endogenous metabolites were identified through mzCloud and determined by molecular formula and molecular weight. The differential endogenous metabolites were obtained by principal component analysis (PCA), partial least squares discrimination analysis (PLS⁃DA), orthogonal partial least squares discriminant analysis (OPLS⁃DA) and cluster analysis. Finally, the pathway and interaction network between the differential endogenous metabolites and corresponding pathways were constructed. Results Finally 29 variations were identified as differential metabolites. Among them, the relative expressions of phosphatidylcholine (PC), phosphatidylethanolamine (PE), vitamin C, sphingomyelin (SM), phosphatidylglycerol (PG) and glutamic acid were elevated in TG group (P＜0.05, for all) and the negative relationship was shown between elevated metabolite and decreased metabolite in relative expression, while the relative expressions of phosphalipids, taurine, ceramide valine and γ⁃aminobutyric acid (GABA) were decreased in TG group (P＜0.05, for all) and the relationship of relative expression among them was positive. The related metabolic pathways were mainly associated with the taurine and hypotaurine metabolism, glutamine and glutamate metabolism, ascorbate and aldarate metabolism, glycerophospholipid metabolism and alanine, aspartate and glutamate metabolism, included taurine, D⁃glutamate, vitamine C, phospholipid, LysoPC [18: 2 (9Z, 12Z)] and GABA all 6 significant metabolites. Conclusions The experiment verified pathological changes of OB in the early stage of PD. Meanwhile the differences in phosphatides could be a direct result of SNCA Ala53Thr mutation. Furthermore, malfunction of neurons in OB is also observed and may be contributed to the abnormal phosphatides' metabolism.

Abstract Background The skin is the largest organ of the body and has multiple functions. Wounds remain a significant healthcare problem due to the large number of traumatic and pathophysiological conditions patients suffer. Methods Gene expression profiles of 37 biopsies collected from patients undergoing split-thickness skin grafts at five different time points were downloaded from two datasets (GSE28914 and GSE50425) in the Gene Expression Omnibus (GEO) database. Principal component analysis (PCA) was applied to classify samples into different phases. Subsequently, differentially expressed genes (DEGs) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional enrichment analyses were performed, and protein–protein interaction (PPI) networks created for each phase. Furthermore, based on the results of the PPI, hub genes in each phase were identified by molecular complex detection combined with the ClueGO algorithm. Results Using principal component analysis, the collected samples were divided into four phases, namely intact phase, acute wound phase, inflammatory and proliferation phase, and remodeling phase. Intact samples were used as control group. In the acute wound phase, a total of 1 upregulated and 100 downregulated DEGs were identified. Tyrosinase (TYR), tyrosinase Related Protein 1 (TYRP1) and dopachrome tautomerase (DCT) were considered as hub genes and enriched in tyrosine metabolism which dominate the process of melanogenesis. In the inflammatory and proliferation phase, a total of 85 upregulated and 164 downregulated DEGs were identified. CHEK1, CCNB1 and CDK1 were considered as hub genes and enriched in cell cycle and P53 signaling pathway. In the remodeling phase, a total of 121 upregulated and 49 downregulated DEGs were identified. COL4A1, COL4A2, and COL6A1 were considered as hub genes and enriched in protein digestion and absorption, and ECM-receptor interaction. Conclusion This comprehensive bioinformatic re-analysis of GEO data provides new insights into the molecular pathogenesis of wound healing and the potential identification of therapeutic targets for the treatment of wounds.

IntroductionOsteonecrosis of the femoral head (ONFH) is a progressive and disabling disease with severe socioeconomic burdens. In the last 30 years, a growing number of publications have reported significant advances in understanding ONFH. However, only a few studies have clarified its global trends and current status. Thus, the purpose of our study was to summarize the global trends and current status in ONFH through bibliometrics.Materials and MethodsPublications related to ONFH from 1991 to 2020 were searched from the Web of Science (WOS) core collection database. The data were analyzed with bibliometric methods. Microsoft Excel was used for statistical analysis and to draw bar charts. SPSS was applied to perform linear regression analysis. VOSviewer was used to conduct bibliographic coupling analysis, co-authorship analysis, co-citation analysis and co-occurrence analysis.ResultsA total of 5,523 publications were covered. The United States consistently ranked first in total publications, sum of times cited, average citations per item and H-index. Kyushu University was the main contributor to ONFH. Clinical Orthopaedics and Related Research was the major publishing channels for ONFH-related articles. Takuaki Yamamoto published the most ONFH-related articles. Studies regarding ONFH could be divided into five clusters: 1) mechanism study, 2) treatment study, 3) complication study, 4) radiological study and 5) etiological study. Mechanism study might become a hot spot in the future.ConclusionsThe total number of publications in ONFH has generally increased over the last three decades. The United States was the leading country in ONFH research. Transplantation, engineering, cell and molecular biology, pharmacology and endocrinology have gradually increased and become hot topics in ONFH research. Mechanism study in ONFH including mesenchymal stem cells, apoptosis, oxidative stress, adipogenesis, osteogenic differentiation and endothelial progenitor cells, have attracted more attention and will become a hot spot in the future.

Abstract Background Cystic echinococcosis is one of the most severe helminth zoonosis with a drastic impact on human health and livestock industry. Investigating optimal control strategy and assessing the crucial factors are essential for developing countermeasures to mitigate this disease. Methods Two compartment models were formulated to study the dynamics of cystic echinococcosis transmission, to evaluate the effectiveness of various control measures, and to find the optimal control strategy. Sensitive analyses were conducted by obtaining PRCCs and contour plot was used to evaluate the effect of key parameters on the basic reproduction number. Based on forward–backward sweep method, numerical simulations were employed to investigate effects of key factors on the transmission of cystic echinococcosis and to obtain the optimal control strategy. Results The food resources of stray dog and invalid sheep vaccination rate, which are always neglected, were significant to the transmission and control of cystic echinococcosis. Numerical simulations suggest that, the implementation of optimal control strategy can significantly reduce the infections. Improving the cost of health education and domestic dog deworming could not decrease human infections. Conclusions Our study showed that only a long-term use of the optimal control measures can eliminate the disease. Meanwhile, during the intervention, sheep vaccination and stray dogs disposing should be emphasized ahead of domestic dogs deworming to minimize the control cost. Simultaneously reducing other wild intermediate hosts and strengthening the sheep vaccination as well as disposing the stray dogs would be most effective.

Large forest fires can cause significant damage to forest ecosystems and threaten human life and property. Heilongjiang Province is a major forested area in China with the highest number and concentration of lightning-caused forest fires in the country. This study examined the spatial and temporal distribution patterns of forest fires in Heilongjiang Province, as well as the ability of satellite remote sensing to detect these fires using VIIRS 375 m fire point data, ground history forest fire point data, and land cover dataset. The study also investigated the occurrence patterns of lightning-caused forest fires and the factors affecting satellite identification of these fires through case studies. Results show that April has the highest annual number of forest fires, with 77.6% of forest fires being caused by lightning. However, less than 30% of forest fires can be effectively detected by satellites, and lightning-caused forest fires account for less than 15% of all fires. There is a significant negative correlation between the two. Lightning-caused forest fires are concentrated in the Daxing’an Mountains between May and July, and are difficult to monitor by satellites due to cloud cover and lack of satellite transit. Overall, the trend observed in the number of forest fire pixels that are monitored by satellite remote sensing systems is generally indicative of the trends in the actual number of forest fires. However, lightning-caused forest fires are the primary cause of forest fires in Heilongjiang Province, and satellite remote sensing is relatively weak in monitoring these fires due to weather conditions and the timing of satellite transit.

Abstract Immune checkpoint inhibitor (ICI)‐based immunotherapy brought new hope for gastric cancer (GC) treatment. However, due to the lack of proper biomarkers, patient selection and outcome prediction for GC's immunotherapy remain unsatisfying. In this study, through applying an extracellular vesicle (EV) protein expression array, we assessed the correlation of plasma EV‐derived protein spectrum with outcomes of ICI‐related therapeutic combinations. Plasma from 112 GC patients received ICI‐related therapies were investigated retrospectively/prospectively as three cohorts. We identified four plasma EV‐derived proteins (ARG1/CD3/PD‐L1/PD‐L2) from 42 crucial candidate proteins and combined them as an EV‐score that robustly predicting immunotherapeutic outcomes at baseline and dynamically monitoring disease progression along with treatment. High EV‐score reflected microenvironmental features of stronger antitumour immunity, characterized by more activated CD8+ T/NK cells, higher TH1/TH2 ratio and higher expressions of IFN‐γ/perforin/granzymes in paired peripheral blood, which were verified by dataset analysis and in vivo experiments. EV‐score≥1 GC received more therapeutic benefits from ICIs, while EV‐score

BackgroundClinical and animal studies have shown that transcutaneous auricular vagus nerve stimulation (ta-VNS) exerts neuroprotection following cerebral ischemia. Studies have revealed that white matter damage after ischemia is related to swallowing defects, and the degree of white matter damage is related to the severity of dysphagia. However, the effect of ta-VNS on dysphagia symptoms and white matter damage in dysphagic animals after an ischemic stroke has not been investigated.MethodsMiddle cerebral artery occlusion (MCAO) rats were randomly divided into the sham, control and vagus nerve stimulation (VNS) group, which subsequently received ta-VNS for 3 weeks. The swallowing reflex was measured once weekly by electromyography (EMG). White matter remyelination, volume, angiogenesis and the inflammatory response in the white matter were assessed by electron microscopy, immunohistochemistry, stereology, enzyme-linked immunosorbent assay (ELISA) and Western blotting.Resultsta-VNS significantly increased the number of swallows within 20 s and reduced the onset latency to the first swallow. ta-VNS significantly improved remyelination but did not alleviate white matter shrinkage after MCAO. Stereology revealed that ta-VNS significantly increased the density of capillaries and increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) expression in the white matter. ta-VNS significantly alleviated the increase inTLR4, MyD88, phosphorylated MAPK and NF-κB protein levels and suppressed the expression of the proinflammatory factors IL-1β and TNF-α.ConclusionThese results indicated ta-VNS slightly improved dysphagia symptoms after ischemic stroke, possibly by increasing remyelination, inducing angiogenesis, and inhibiting the inflammatory response in the white matter of cerebral ischaemia model rats, implying that ta-VNS may be an effective therapeutic strategy for the treatment of dysphagia after ischemic stroke.