Search

Abstract Background Danggui Shaoyao San (DSS), a frequently prescribed Chinese medicine formula, has demonstrated clinical efficacy in the treatment of Alzheimer’s disease (AD). This study aims to explore the differences in therapeutic effects of DSS and its disassembled prescriptions, Suangan (SG) and Xingan (XG), in treating Alzheimer’s Disease and the mechanism of DSS recovering autophagy in AD. Methods A network pharmacology strategy was employed to delineate the bioactive constituents, associated targets, and regulatory mechanisms of DSS in AD, encompassing in silico target forecasting, the generation and scrutiny of PPI networks, alongside GO and KEGG-based pathway elucidation. An AD mouse model, induced by intracerebroventricular injection of Aβ1–42, was used to evaluate the therapeutic effects of DSS and its disassembled prescriptions on AD. Cognitive function was evaluated using the Morris water maze. Expression levels of inflammatory cytokines were quantified via RT-qPCR and ELISA. Western blotting was used to detect the expression of proteins related to AD pathological markers and the AMPK/mTOR signaling pathway. Results 50 active compounds and 718 HUB genes were screened from relevant databases and literature. KEGG and GO analyses indicated that DSS’s potential mechanisms against AD involved the AMPK/mTOR signaling pathway and mitophagy. In vivo animal model, the results demonstrated that DSS, SG, and XG treatments improved cognitive function and ameliorated neuroinflammation in mice. Additionally, they alleviated the pathological changes of neuronal cells. These treatments also increased the protein level of PSD-95, and decreased levels of APP and p-Tau. Among them, DSS exhibited the best efficacy. Furthermore, DSS, SG, and XG upregulated the expression of LC3, Beclin1, and p-AMPK, while decreasing the expression of P62 and p-mTOR. Conclusions DSS, SG, and XG were found to ameliorate AD-related pathological symptoms in Aβ1−42-injected mice, likely through the AMPK/mTOR autophagy signaling pathway.

Industrialization and urbanization produce hazardous particulate matter (PM), including ammonium compounds like (NH4)2SO4 and NH4NO3, which comprise around 50 % of PM. Despite this, the influence of ammonium on intestinal inflammation remains unclear. We studied an ammonium mixture’s effects on the intestine, finding elevated pro-inflammatory cytokines and oxidative stress in exposed mice, causing small intestine morphological changes. Investigating mitigation strategies, we assessed silibinin, an antioxidant from milk thistle seeds. Silibinin treatment in (NH4)2SO4- and NH4NO3-exposed mice significantly reduced inflammatory markers, alleviated oxidative stress, and preserved intestinal tissue integrity via the PI3K/AKT pathway. Our findings elucidate ammonium’s potential impact on intestinal inflammation and highlight silibinin’s therapeutic impact against PM-induced small intestine damage.

Abstract Introduction Conventional etiological detection and pathogenic antibody methods make it challenging to identify the atypical pathogens among the community‐acquired pneumonia (CAP). Metagenomic next‐generation sequencing (mNGS) could rapidly detect all potentially infectious diseases and identifies novel or potential pathogens. Methods Eighteen patients diagnosed with atypical CAP were enrolled in this retrospective study, including nine Chlamydia psittaci pneumonia (C. p), four Legionella pneumonia (L. p) and five Mycoplasma pneumonia (M. p). We simultaneously tested bronchoalveolar lavage fluid (BALF) samples for conventional microbiological methods and mNGS, and blood specimens were analysed. We also collected and compared baseline and clinical characteristics and treatment responses. Results Patients with C. p and L. p had similar symptoms, including fever, cough, headache, dyspnoea, asthenia, shivering and headache, compared with M. p, whose symptoms were slight. C. p and L. p usually showed multiple lobar distributions with pleural effusion. Serologic testing indicated that L. p had higher levels of white blood cells (WBCs), neutrophils, C‐reactive protein (CRP), procalcitonin (PCT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine compared with M. p and L. p (p

The diagnosis of invasive pulmonary aspergillosis (IPA) diseases in non-neutropenic patients remains challenging. It is essential to develop optimal non-invasive or minimally invasive detection methods for the rapid and reliable diagnosis of IPA. Metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) can be a valuable tool for identifying the microorganism. Our study aims to evaluate the performance of mNGS in BALF in suspected IPA patients and compare it with other detection tests, including serum/BALF galactomannan antigen (GM) and traditional microbiological tests (BALF fungal culture and smear and lung biopsy histopathology). Ninety-four patients with suspicion of IPA were finally enrolled in our study. Thirty-nine patients were diagnosed with IPA, and 55 patients were non-IPA. There was significance between the IPA and non-IPA groups, such as BALF GM (P < 0.001), history of glucocorticoid use (P = 0.004), and pulmonary comorbidities (P = 0.002), as well as no significance of the other demographic data including age, sex, BMI, history of cigarette, blood GM assay, T-SPOT.TB, and NEUT#/LYMPH#. The sensitivity of the BALF mNGS was 92.31%, which was higher than that of the traditional tests or the GM assays. The specificity of BALF mNGS was 92.73%, which was relatively similar to that of the traditional tests. The AUC of BALF mNGS was 0.925, which presented an excellent performance compared with other traditional tests or GM assays. Our study demonstrated the important role of BALF detection by the mNGS platform for pathogen identification in IPA patients with non-neutropenic states, which may provide an optimal way to diagnose suspected IPA disease.

Background: Nontuberculous mycobacterial (NTM) pulmonary disease (PD) has rapidly increased globally. The characteristics and comparison of rapidly growing mycobacteria PD (RGM-PD) and slowly growing mycobacteria PD (SGM-PD) are still unclear. Methods: Our study enrolled 31 NTM-PD patients. Clinical data, including baseline, symptoms, underlying disease, laboratory tests, metagenomic next-generation sequencing (mNGS) results, radiological images, treatment, and outcome were recorded and analyzed. Results: Of the 31 patients with NTM-PD, 22 patients were female and 9 were male. It included 11 RGM-PD and 20 SGM-PD. There was no difference in age (P = 0.425) and body mass index (P = 0.152) between the two groups. The common respiratory diseases in prevalence included bronchiectasis and chronic obstructive pulmonary disease. Three patients had positive results of T-SPOT tuberculosis (TB), and none had positive Xpert-Mycobacterium tuberculosis/rifampin results. On admission, patients were symptomatic and included cough/sputum production, fever, weight loss, fatigue, and hemoptysis. In comparison to RGM-PD, patients with SGM-PD had a greater chance of experiencing fatigue (P = 0.012). No significance was found in serum biomarkers between RGM and SGM-PD, including CD4/CD8 ratio, white blood cells, neutrophils, lymphocytes, procalcitonin, ferritin, C-reactive protein, and erythrocyte sedimentation rate. No liver or kidney impairment was found. Patients with RGM-PD were more likely to have right lower lobe (RLL) impairment (P = 0.021) and a cavity characteristic (P = 0.012). All 31 cases had positive mNGS results. The duration of mNGS was shorter than conventional methods (3.4 ± 0.7 vs. 26.4 ± 20.9, P < 0.001). Conclusions: Patients with SGM-PD were more likely to experience fatigue. The cavity and RLL involvement were more frequent in the RGM-PD. mNGS increases the identification of NTM specimens and complements the capabilities of conventional methods.

Abstract Background As a member of the Ephrin protein family that elicits short distance cell‐cell signaling, EphrinA3 has been shown to promote or inhibit tumorigenesis depending on tumor types, but its roles and the underlying mechanisms in lung adenocarcinoma (LUAD) have not been reported. Materials and Methods The TCGA database and Kaplan‐Meier Plotter database were used to analyze the differential expression of EphrinA3 between LUAD and para‐carcinoma tissues, and its effect on overall survival of LUAD patients. CCK‐8 assay, Edu assay, and flow cytometry were used to probe the effect of EphrinA3 on the proliferation of LUAD cells, and transwell assay was employed to examine its effect on migration and invasion. In addition, the effect of EphrinA3 on the growth of LUAD was further evaluated using a xenograft tumor model. Results EphrinA3 was expressed highly in LUAD, and its expression level was negatively correlated with the prognosis of LUAD patients. In addition, EphrinA3 promoted proliferation, migration, and invasion of LUAD cells, and accelerated tumor growth in a xenograft LUAD model. The reported EphrinA3 receptors, EphA1 and EphA10, were expressed in clinical LUAD tissues and co‐localized with EphrinA3 in LUAD cells. Mechanistically, EphrinA3/Eph signaling activated AKT, ERK, and p38MAPK, induced epithelial‐mesenchymal transition (EMT), and upregulated matrix metalloproteases‐2 and ‐9 (MMP‐2/−9). Conclusion EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.

Abstract Background To reveal the function of protein tyrosine phosphatase‐L1 (PTPL1) in lung adenocarcinoma. Methods Lung cancer cell lines were transfected with short hairpin RNA against PTPL1 (shPTPL1 group) or negative control (shmock group). Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting were used to verify the transfection efficacy. Cell proliferation was analyzed by ethynyldeoxyuridine (EdU), Cell counting kit 8 (CCK8), and colony formation assay after PTPL1 or PTPL1 and yes‐associated protein (YAP1) knockdown. The effect of PTPL1 on tumor growth was examined in a xenograft lung cancer model. Results PTPL1 was downregulated in various types of lung cancer cell lines. The EdU, CCK8, colony formation assays and investigation using a xenograft lung cancer model indicated that PTPL1 knockdown increased the proliferation of lung cancer cells. Mechanistically, PTPL1 knockdown induced the activation of the Proto‐oncogene tyrosine‐protein kinase SRC (Src)/Extracellular regulated MAP kinase (ERK) pathway and thereby promoted yes‐associated protein (YAP1) nuclear translocation and activation. Conclusions In our study, PTPL1 played a crucial suppressive role in the pathogenesis of lung cancer potentially through counteracting the Src/ERK/YAP1 pathway.

The existing acoustic logging methods for evaluating the hydraulic fracturing effectiveness usually use the fracture density to evaluate the fracture volume, and the results often cannot accurately reflect the actual productivity. This paper studies the dynamic fluid flow through hydraulic fractures and its effect on borehole acoustic waves. Firstly, based on the fractal characteristics of fractures observed in hydraulic fracturing experiments, a permeability model of complex fracture network is established. Combining the dynamic fluid flow response of the model with the Biot-Rosenbaum theory that describes the acoustic wave propagation in permeable formations, the influence of hydraulic fractures on the velocity dispersion of borehole Stoneley-wave is then calculated and analyzed, whereby a novel hydraulic fracture fluid transport property evaluation method is proposed. The results show that the Stoneley-wave velocity dispersion characteristics caused by complex fractures can be equivalent to those of the plane fracture model, provided that the average permeability of the complex fracture model is equal to the permeability of the plane fracture. In addition, for fractures under high-permeability (fracture width 10~100 μm, permeability ~100 μm2) and reduced permeability (1~10 μm, ~10 μm2 as in fracture closure) conditions, the Stoneley-wave velocity dispersion characteristics are significantly different. The field application shows that this fluid transport property evaluation method is practical to assess the permeability and the connectivity of hydraulic fractures.

Abstract Cumulative evidence indicates that the abnormal regulation of the NEDD4 family of E3-ubiquitin ligases participates in the tumorigenesis and development of cancer. However, their role in lung adenocarcinoma (LUAD) remains unclear. This study comprehensively analyzed the NEDD4 family in LUAD data sets from public databases and found only NEDD4L was associated with the overall survival of LUAD patients. Gene set enrichment analysis (GSEA) indicated that NEDD4L might be involved in the regulation of mTORC1 pathway. Both cytological and clinical assays showed that NEDD4L inhibited the activity of the mTOR signaling pathway. In vivo and in vitro experiments showed that NEDD4L could significantly inhibit the proliferation of LUAD cells. In addition, this study also found that the expression of NEDD4L was regulated by EGFR signaling. These findings firstly revealed that NEDD4L mediates an interplay between EGFR and mTOR pathways in LUAD, and suggest that NEDD4L held great potential as a novel biomarker and therapeutic target for LUAD.

Abstract Background At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients. Methods Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance. Results A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score). Conclusions A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients. Trial registration: ClinicalTrials.gov (Identifier: NCT01417338).

Abstract In the weak current network environment, the existence of power network impedance will reduce the current control stability margin of LCL grid connected inverter, the stability margin will gradually deteriorate as the inductive component of the power network impedance increases, leading to system instability. In this paper, an improved weighted average current control strategy is proposed, which is based on the active damping control of the voltage feedforward of the charged network. In the new control strategy, with the zero-pole cancellation method, a new weighting coefficient related only to the parameters of LCL filter is obtained, which reduces the order of the system, suppresses the influence of power network impedance, and improves the stabilization of the system, getting better inverter output current quality. Then the influence of power network impedance on the control system of grid connected inverter is analyzed, and the feed-forward control of grid voltage is improved to improve the stability of inverter in weak current network. The Bode diagram analysis and MATLAB simulation results proved that the proposed control strategy is feasible.

Abstract The advanced biomimetic mineralization technology was applied to protect the Botulinum neurotoxin type D, and the processing of the mineralization granule of botulinum toxin type D was successfully screened. The loss of activity of the toxin protein at different temperatures and the destructive strength of the gastrointestinal tract against the toxin were determined biologically. The lethal toxicity of the mineralized toxin to wild rodents was determined by median lethal dose. Protective tests at different temperatures showed that the preservation period of botulinum toxin type D mineralized sample 2 was significantly higher than that of the control group at three different temperatures, and its toxicity loss was significantly reduced. The damage intensity of the mineralized toxin to the gastrointestinal contents of plateau zokor and plateau pika was significantly reduced. The minimum lethal doses of the mineralized toxin particles to plateau zokor, plateau pika, and mice were 5200, 8,600,000, and 25,000 MLD/kg. These results showed that biomimetic mineralization could greatly improve the thermal stability of botulinum toxin type D and reduce the damaging effect of the gastrointestinal contents of target animals to botulinum toxin type D. The mineralized toxin could be used to control the population density of urban rodents. This research provides new insights into the protection of toxin protein substances.

Methionine is a substrate for protein synthesis and participates in many other biological events via its metabolism. We have previously demonstrated significant differences in the metabolism of L-methionine (L-Met) and its precursor DL-2-hydroxy-4-methylthiobutyric acid (DL-HMTBA) in IPEC-J2 cells. When DL–HMTBA is added to the diet, intracellular methionine (Met) sources also contain the natural form of L-Met. Then, what is the effect on Met metabolism when these two Met sources exist simultaneously? Moreover, the effects of metabolic differences on cell function remain unclear. In this study, it was found that when the proportion of L-Met to DL–HMTBA was ≤ 40%:60%, Met transmethylation was promoted and when the proportion of L-Met to DL-HMTBA was ≤ 85%:15%, Met trans-sulfuration and regeneration were improved. In addition, DL-HMTBA improved the cell barrier function when the ratio of L-Met to DL-HMTBA was ≤ 40%:60%. This finding may be due to the decrease in the proportion of S-adenosylmethionine to S-adenosylhomocysteine and mRNA N6-methyladenosine (m6A) levels, which increase the mRNA stability and protein expression of tight junction zona occludens-1. To sum up, the effects of L-Met and DL–HMTBA on Met metabolism, especially transmethylation, suggest that DL–HMTBA has the potential to influence the intestinal barrier function of animals through epigenetic processes.

Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality, and so far patients have failed to benefit from therapeutics clinically available. Max interacting protein 1–0 (Mxi1-0) is one of the functional isoforms of Mxi1. Although it also binds to Max, Mxi1-0, unlike other Mxi1 isoforms, cannot antagonize the oncoprotein c-Myc because of its unique proline rich domain (PRD). While Mxi1-0 was reported to promote cell proliferation via largely uncharacterized mechanisms, it is unknown whether and how it plays a role in the pathogenesis of HPH.Methods: GEO database was used to screen for genes involved in HPH development, and the candidate players were validated through examination of gene expression in clinical HPH specimens. The effect of candidate gene knockdown or overexpression on cultured pulmonary arterial cells, e.g., pulmonary arterial smooth muscle cells (PASMCs), was then investigated. The signal pathway(s) underlying the regulatory role of the candidate gene in HPH pathogenesis was probed, and the outcome of targeting the aforementioned signaling was evaluated using an HPH rat model.Results: Mxi1 was significantly upregulated in the PASMCs of HPH patients. As the main effector isoform responding to hypoxia, Mxi1-0 functions in HPH to promote PASMCs proliferation. Mechanistically, Mxi1-0 improved the expression of the proto-oncogene c-Myc via activation of the MEK/ERK pathway. Consistently, both a MEK inhibitor, PD98059, and a c-Myc inhibitor, 10058F4, could counteract Mxi1-0-induced PASMCs proliferation. In addition, targeting the MEK/ERK signaling significantly suppressed the development of HPH in rats.Conclusion: Mxi1-0 potentiates HPH pathogenesis through MEK/ERK/c-Myc-mediated proliferation of PASMCs, suggesting its applicability in targeted treatment and prognostic assessment of clinical HPH.

Abstract Interactions between gut microbiota not only regulate physical health, but also form a vital bridge between the environment and the host, thus helping the host to better adapt to the environment. The improvement of modern molecular sequencing techniques enables in‐depth investigations of the gut microbiota of vertebrate herbivores without harming them. By sequencing the 16S rRNA V4‐V5 region of the gut microbiota of both the captive and wild kiang in winter and summer, the diversity and function of the microbiota could be compared. The reasons for observed differences were discussed. The results showed that the dominant phyla of the kiang were Bacteroidetes and Firmicutes, and the structure and abundance of the gut microbiota differed significantly between seasons and environments. However, the relatively stable function of the gut microbiota supplies the host with increased adaptability to the environment. The diversity of the intestinal flora of the kiang is relatively low in captivity, which increases their risk to catch diseases to some extent. Therefore, importance should be attached to the impact of captivity on wildlife.

As large-scale direct-drive wind turbine generator set is connected to the grid, the power system will face problems such as reduced inertia and insufficient frequency modulation capability. The control of wind turbine virtual inertia is an important way to solve this problem. Therefore, this paper takes the direct-drive wind power generation system as the research object, draws lessons from the multi-time scale modeling idea, and based on the electrical torque analysis, establishes the DC voltage time model with the wind turbine virtual inertia control. Based on this, inertia damping characteristics of direct-drive wind power grid-connected system are analyzed. The results show that the dynamic characteristic parameters of the system are affected by many factors, among which the equivalent inertia coefficient of the system is mainly affected by DC capacitance, DC bus voltage and wind turbine virtual inertia control parameters. Damping coefficient is mainly affected by steady-state operating point and DC voltage proportional control parameter Kpu. The synchronization coefficient is mainly affected by steady-state operating point and DC voltage integration control parameter Kiu. The correctness of mechanism analysis of inertia damping characteristics of the whole system is verified by simulation, which provides a certain theoretical reference for inertia damping research of electronic power system.

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

Many oil and gas fields, especially non-conventional shale and compacted sand reservoirs, have formation anisotropy. The acoustic anisotropy measurement of cores in these reservoirs can guide drilling, well logging, and exploitation. However, almost all core holders are designed for cylinder cores, which are not suitable for all-directional measurements. A three-dimensional measurement device was designed on the basis of the cross-hole sonic logging method. This device mainly consisted of two pairs of transducers, a signal generator, an oscillograph, an omnidirectional positioning system, and a computer control system. By adjusting the measurement latitude and longitude circle automatically, this device scanned spherical sample rocks and obtained full-wave waveforms in all directions. Experiments were performed taking granite from the Jiaodong Peninsula, China, as an example, and the arrival times and velocities of the longitudinal and shear waves were calculated based on the full-wave waveforms. Thereafter, anisotropic physical characterizations were carried out on the basis of these velocities. These data play an important role in guiding formation fracturing and analyzing the stability of borehole walls.

Well logging is performed in oil and gas exploration wells to obtain the physical characteristics of underground formations. Thereafter, these wells are cased. Through-casing logging is important in mature fields and for wells that are cased without logging due to borehole stability issues. Acoustic through-casing logging is a challenging issue due to the strong interference of casing waves in formation waves, especially when the casing and formation are poorly bonded. An acoustic tool with dual-source transmitters is developed, in which an additional transducer is added to suppress casing waves. First, the operation principle and the overall design of the tool are carried out, including the span distance between the two transmitting transducers and the spacing distance between the transmitting transducer and the receiving transducers. Thereafter, a dual-source transmitting circuit is designed to send out two excitation signals of opposite polarities. These signals possess good consistency, high emission power, and precise signal adjustment. Lastly, the tool is tested in cased exploration wells in China. The experiment endings show that about 90% of the casing waves are canceled. By suppressing the casing wave amplitude, the cased-hole acoustic logging can be used commercially to obtain trustworthy formation information.

Abstract Upland buzzard (Buteo hemilasius), Saker falcon (Falco cherrug), and Himalayan vulture (Gyps himalayensis) are three common large raptors in the Sanjiangyuan National Park (SNP), China's first national park. Among them, Upland buzzard and Saker falcon play a significant role in controlling plateau rodent populations and reducing the transmission of pathogens carried by rodents. The Himalayan vulture can provide services for the redistribution and recycling of nutrients in the ecosystem, and play an irreplaceable role in the celestial burial culture of Tibetans in China. Exploring their habitat suitability is important for the protection of the three raptors. Our research was based on the current distribution of Upland buzzard, Saker falcon, and Himalayan vulture that we had extensively surveyed in the Sanjiangyuan National Park from 2016 to 2017. Combined with the correlation analysis of environmental variables, we utilized maximum entropy model (MaxEnt) to evaluate and compare the habitat suitability of the three species in the Sanjiangyuan National Park. Elevation, climate, and human disturbance factors, which had direct or indirect effects on species survival and reproduction, were all included in the model. Among them, elevation was the most important environmental variables affecting the suitability of habitats of three species. Temperature‐related factor was another important predictor. The high (>60%) suitable habitat areas for Upland buzzard, Saker falcon, and Himalayan vulture were 73,017.63, 40,732.78, and 61,654.33 km2, respectively, accounted for 59.32%, 33.09%, and 50.08% of the Sanjiangyuan National Park and their total suitable area (i.e., the sum area of high and moderate habitats) reached 96.07%, 60.59%, and 93.70%, respectively. Besides, the three species have overlapping areas for the suitable habitats, which means that overlapping areas should be highly valued and protected. Therefore, understanding the distribution of suitable habitats of the three raptors can provide useful information and reasonable reference for us to put forward suggestions for their protection and regional management.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammatory processes, and exacerbation of COPD represents a critical moment in the progression of COPD. Several biomarkers of inflammation have been proposed to have a predictive function in acute exacerbation. However, their use is still limited in routine clinical practice. The purpose of our study is to explore the prognostic efficacy of novel inflammatory hemogram indexes in the exacerbation among stable COPD patients.Method: A total of 275 stable COPD patients from the Shanghai COPD Investigation Comorbidity Program were analyzed in our study. Blood examinations, especially ratio indexes like platelet–lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio [systemic immune-inflammation index (SII)], and monocyte × neutrophil/lymphocyte ratio [systemic inflammation response index (SIRI)], lung function test, CT scans, and questionnaires were performed at baseline and routine follow-ups. Clinical characteristics and information of exacerbations were collected every 6 months. The relationship between hemogram indexes and diverse degrees of exacerbation was assessed by logistic regression. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the ability of hemogram indexes to predict exacerbation of COPD. Furthermore, the discrimination and accuracy of combined indexes were measured by ROC and calibration curve.Result: There was a significant positive correlation between PLR levels and total exacerbation of COPD patients in a stable stage in a year. Also, the predictive ability of PLR exceeded any other ratio indexes, with an AUC of 0.66. SII and SIRI ranked second only to PLR, with an AUC of 0.64. When combining PLR with other indexes (sex, COPD year, and St. George's Respiratory Questionnaire scores), they were considered as the most suitable panel of index to predict total exacerbation. Based on the result of the ROC curve and calibration curve, the combination shows optimal discrimination and accuracy to predict exacerbation events in COPD patients.Conclusion: The hemogram indexes PLR, SII, and SIRI were associated with COPD exacerbation. Moreover, the prediction capacity of exacerbation was significantly elevated after combining inflammatory hemogram index PLR with other indexes, which will make it a promisingly simple and effective marker to predict exacerbation in patients with stable COPD.

Elephants are the largest extant terrestrial animals and are important for maintaining regional ecosystem balance and community diversity. However, poaching, population growth, habitat fragmentation, and viruses are major threats to global elephant populations. Foot-and-mouth disease (FMD) is one of the major threats to the health of elephants. Global warming has a serious impact on wildlife and accelerates the spread of viruses. In this study, the effects of climate change on the risk of disease in elephants were evaluated based on 1833 sites with reported FMD cases. Maximum entropy (MaxEnt) was used to model the current and future geographic distributions of FMD and to assess the risk of FMD in elephants under climate change. The results showed that the average annual temperature and annual precipitation were higher in elephant habitats than in the range of the FMD virus. The mean temperature in the driest quarter, temperature seasonality, annual mean temperature, and precipitation in the driest month had relatively large contributions to the risk of FMD, with a cumulative contribution rate of 82.8%. Both Asian elephants and African elephants had high overlap with the FMD virus with respect to altitude, annual mean temperature, and annual precipitation. An overall high risk of disease was detected at a certain band, mainly concentrated from 10°N to 50°N in the northern hemisphere and from 10°S to 35°S in the southern hemisphere. The risk of FMD was higher for the Asian elephant than the African elephant. The FMD risk increased gradually from the southeast to northwest in habitats of the Asian elephant, and presented a pattern of high north–south risk and low intermediate risk in the habitats of the African elephant. The area proportions of high risk, medium risk, and low risk in the distribution of both the Asian elephant and African elephant were all higher than the proportions of all risk types worldwide. Under global warming, the FMD risk was not expected to change significantly in most of the habitat areas of the Asian elephant or the African elephant in the 2050s and 2070s. Moreover, the areas and proportions of high risk, medium risk, and low risk were likely to change slightly. These results could benefit the conservation of elephants and provide relevant data for the prevention of FMD in high-risk areas under climate change.

Due to the increased economic demand for livestock, the number of livestock is increasing. Because of human interference, the survival of wild animals is threatened in the face of competition, particularly in co-inhabited grazing pastures. This may lead to differences in the adaptability between wild and domestic animals, as well as nutritional deficiencies in wild animals. The gut microbiota is closely associated with host health, nutrition, and adaptability. However, the gut microbiota diversity and functions in domestic and wild animals in co-inhabited areas are unclear. To reveal the adaptability of wild and domestic animals in co-inhabited areas based on gut microbiota, we assessed the gut microbiota diversity. This study was based on the V3–V4 region of 16S rRNA and gut microbiota functions according to the metagenome analysis of fresh fecal samples in wild goitered gazelles (Gazella subgutturosa) and domestic sheep (Ovis aries) in the Qaidam Basin. The wild and domestic species showed significant differences in alpha- and beta-diversities. Specifically, the alpha-diversity was lower in goitered gazelles. We speculated that the nutritional and habitat status of the goitered gazelles were worse. The gut microbiota functions in the gazelles were enriched in metabolism and cellular processes based on the KEGG database. In summary, we reasoned that gut microbiota can improve the adaptability of goitered gazelles through energy maintenance by the functions of gut microbiota in the face of nutritional deficiencies. These findings highlight the importance of gut microbiota diversity to improve the adaptability of goitered gazelles, laying a foundation for the conservation of wild goitered gazelles. In addition, we further provide management suggestions for domestic sheep in co-inhabited grazing pastures.

Abstract Background Crizotinib is recommended as first-line therapy in ROS1-driven lung adenocarcinoma. However, the optimal first-line therapy for this subgroup of lung cancer is controversial according to the available clinical data. Case presentation Here, we describe a 57-year-old man who was diagnosed with stage IIIB lung adenocarcinoma and EGFR/KRAS/ALK-negative tumors. The patient received six cycles of pemetrexed plus cisplatin as first-line therapy and then pemetrexed as maintenance treatment, with a progression-free survival (PFS) of 42 months. The patient relapsed and underwent re-biopsy. EZR-ROS1 fusion mutation was detected by next-generation sequencing (NGS). The patient was prescribed crizotinib as second-line therapy and achieved a PFS of 6 months. After disease progression, lorlatinib was administered as third-line therapy, with a favorable response. Conclusions Prolonged PFS in patients receiving pemetrexed chemotherapy might be related to the EZR-ROS1 fusion mutation. Lorlatinib is an optimal choice in patients showing crizotinib resistance.

Objective: To explore the experience with and complications of extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) for treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. Methods: The data on critically ill COVID-19 patients who received ECMO/CRRT at Tongji Hospital, which is affiliated with Huazhong University of Science and Technology, in February and March 2020 were collected and analyzed. All three patients were male, and the mean age was 50.6 years (range 44–58 years). The indications for ECMO in critically ill SARS-CoV-2 pneumonia patients at our center were severe acute respiratory distress syndrome with Pao 2 /Fio 2 below 100 mmHg under an effective protective pulmonary ventilation strategy and inflammatory storm accompanied by acute kidney injury. One patient, with severe heart failure, was selected for venoarterial ECMO, and the other two patients were selected for venovenous ECMO. Results: In the three patients who received ECMO combined with bedside CRRT, the mean duration was 9.7 days (range 7–13 days). Four complications occurred during ECMO/CRRT, especially thrombocytopenia. Laboratory testing showed increased counts of leukocytes and lymphocytes and decreased levels of inflammatory factors. Lung CT was suggestive of significantly absorbed and reduced lesions and interstitial fibrosis. Conclusions: The survival rate of patients with cardiopulmonary failure treated with ECMO/CRRT in whom conventional treatment failed in this group was 100%, which indicates that combined treatment with ECMO and CRRT is an important treatment technique.

Aiming at the problem of large magnitude and high frequency of common-mode voltage (CMV) when space vector pulse width modulation (SVPWM) is used in a three-phase motor fed by a two-level voltage source inverter, a common-mode reduction SVPWM (CMRSVPWM) is studied. In this method, six new sectors are obtained by rotating six sectors of conventional SVPWM by 30°. In odd-numbered sectors, only three non-zero vectors with odd subscripts are used for synthesis, while in even-numbered sectors, only three non-zero vectors with even subscripts are used for synthesis. The actuation durations of three non-zero vectors in each switching period in each sector are given. Simulation and experimental results show that, compared with the conventional SVPWM, the CMV magnitude of CMRSVPWM is reduced by 66.67% and the CMV frequency of CMRSVPWM is reduced from the original switching frequency to the triple fundamental frequency. At the same time, the current, torque and speed of the motor are still good.

Prostacyclin receptor (IP) and peroxisome proliferator-activated receptor-gamma (PPARγ) are both potential targets for treatment of pulmonary arterial hypertension (PAH). Expression of IP and PPARγ decreases in PAH, suggesting that screening of dual agonists of IP and PPARγ might be an efficient method for drug discovery. Virtual screening (VS) of potential IP–PPARγ dual-targeting agonists was performed in the ZINC database. Ten of the identified compounds were further screened, and cefminox was found to dramatically inhibit growth of PASMCs with no obvious cytotoxicity. Growth inhibition by cefminox was partially reversed by both the IP antagonist RO113842 and the PPARγ antagonist GW9662. Investigation of the underlying mechanisms of action demonstrated that cefminox inhibits the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway through up-regulation of the expression of phosphatase and tensin homolog (PTEN, which is inhibited by GW9662), and enhances cyclic adenosine monophosphate (cAMP) production in PASMCs (which is inhibited by RO113842). In a rat model of hypoxia-induced pulmonary hypertension, cefminox displayed therapeutic efficacy not inferior to that of the prostacyclin analog iloprost or the PPARγ agonist rosiglitazone. Our results identified cefminox as a dual agonist of IP and PPARγ that significantly inhibits PASMC proliferation by up-regulation of PTEN and cAMP, suggesting that it has potential for treatment of PAH.

The title coordination polymer, poly[[μ-aqua-triaqua(μ3-benzene-1,3,5-tricarboxylato)sodiumzinc] sesquihydrate], {[NaZn(C9H3O6)(H2O)4]·1.5H2O}n, was obtained in ionic liquid microemulsion at room temperture by the reaction of benzene-1,3,5-tricarboxylic acid (H3BTC) with Zn(NO3)2·6H2O in the presence of NaOH. The asymmetric unit comprises two Na+ ions (each located on an inversion centre), one Zn2+ ion, one BTC ligand, four coordinating water molecules and two solvent water molecules, one of which is disordered about an inversion centre and shows half-occupation. The Zn2+ cation is five-coordinated by two carboxylate O atoms from two different BTC ligands and three coordinating H2O molecules; the Zn—O bond lengths are in the range 1.975 (2)–2.058 (3) Å. The Na+ cations are six-coordinated but have different arrangements of the ligands: one is bound to two carboxylate O atoms of two BTC ligands and four O atoms from four coordinating H2O molecules while the other is bound by four carboxylate O atoms from four BTC linkers and two O atoms of coordinating H2O molecules. The completely deprotonated BTC ligand acts as a bridging ligand binding the Zn2+ atom and Na+ ions, forming a layered structure extending parallel to (100). An intricate network of O—H...O hydrogen bonds is present within and between the layers.

An effective ultra-performance liquid chromatography coupled with the quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF/MS) method was developed for analysing the chemical constituents in rat plasma and urine after the oral administration of Rubia cordifolia L. extract. Under the optimized conditions, nine of 11 prototypes in rat plasma and four prototypes in urine were identified or characterized by comparing the retention time, accurate mass, fragmentation patterns, reference compounds, and literature data. In total, six metabolites, including alizarin-1-O-β-glucuronide, alizarin-2-O-β-glucuronide, alizarin-1-O-sulfation, alizarin-2-O-sulfation, purpurin-1-O-β-glucuronide, and purpurin-3-O-β-glucuronide, were identified in rat plasma, which were confirmed by lavaging standard solutions. Purpurin was found to be able to be transformed into alizarin based on the results in which alizarin was detected in rat plasma after the oral administration of a purpurin solution. In total, four metabolites were found in rat urine, but their chemical structures were not confirmed. The results indicate that the metabolic pathway of alizarin involves glucuronidation and sulfation, with the purpurins having undergone glucuronidation. The components absorbed into the blood, and the metabolites have the opportunity to become bioactive constituents. The experimental results would supply a helpful chemical basis for further research on the mechanism of actions of Rubia cordifolia L.