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Despite recent progress in non‐small‐cell lung cancer (NSCLC) treatment, treatment outcomes remain poor, mainly because of treatment resistance or toxicity. Erastin is a ferroptosis inducer that has shown promising cytotoxic effects in various types of cancers, including NSCLC. Celastrol is a triterpene extracted from the Tripterygium wilfordii that exhibits potential anticancer activity. However, the side effects of celastrol are severe and limit its clinical application. Combination therapy is a promising strategy to overcome the compensatory mechanisms and unwanted off‐target effects. In the present study, we found that erastin synergized with celastrol to induce cell death at nontoxic concentrations. The combined treatment with celastrol and erastin significantly increased reactive oxygen species (ROS) generation, disrupted mitochondrial membrane potential, and promoted mitochondrial fission. Furthermore, cotreatment with erastin and celastrol initiated ATG5/ATG7‐dependent autophagy, PINK1/Parkin‐dependent mitophagy, and the expression of heat shock proteins (HSPs) in an HSF1‐dependent manner. HSF1 knockdown further enhanced cell death in vitro and inhibited tumor growth in vivo. Our findings indicate that the combination of celastrol with erastin may represent a novel therapeutic regimen for patients with NSCLC and warrants further clinical evaluation.

Abstract Background With the expanded utilization of transcatheter aortic valve implantation (TAVI) to younger and lower surgical risk patients with severe aortic stenosis (AS), optimal medical therapy after TAVI procedure has become the main concern. Renin-angiotensin system inhibitors (RASi) are widely utilized in the area of cardiovascular disease including heart failure and myocardial infarction and revealed the ability to reverse left ventricular (LV) remodeling. Interests have, thus, been drawn in investigating whether the prescription of RASi after the TAVI procedure can prevent or reverse cardiac remodeling and improve long-term clinical outcomes. No recommendation regarding the prescription of RASi after TAVI is proposed yet due to the lack of evidence from randomized controlled trials, especially in the Chinese population. We, therefore, designed this randomized controlled trial to explore the effect of adding fosinopril to standard care in patients who underwent a successful TAVI procedure on the LV remodeling. Methods A total of 200 post-TAVI patients from seven academic hospitals across China will be recruited and randomized with a ratio of 1:1 to receive standard care or standard care plus fosinopril. Follow-up visits will take place at 30 days, 3 months, 6 months, 12 months, and 24 months from randomization to assess the clinical symptoms, any adverse events, cardiac function, and quality of life. Cardiac magnetic resonance will be performed at baseline and repeated at the 24-month follow-up visit to assess LV remodeling. Discussion This study will provide evidence regarding medical therapy for AS patients who underwent TAVI and filling the gap in the Chinese population. Trial registration Chinese Clinical Trial Registry ChiCTR2100042266 . Registered on 17 January 2021

Summary Non‐tuberculous mycobacteria (NTM) can cause various respiratory diseases and even death in severe cases, and its incidence has increased rapidly worldwide. To date, it’s difficult to use routine diagnostic methods and strain identification to precisely diagnose various types of NTM infections. We combined systematic comparative genomics with machine learning to select new diagnostic markers for precisely identifying five common pathogenic NTMs (Mycobacterium kansasii, Mycobacterium avium, Mycobacterium intracellular, Mycobacterium chelonae, Mycobacterium abscessus). A panel including six genes and two SNPs (nikA, benM, codA, pfkA2, mpr, yjcH, rrl C2638T, rrl A1173G) was selected to simultaneously identify the five NTMs with high accuracy (> 90%). Notably, the panel only containing the six genes also showed a good classification effect (accuracy > 90%). Additionally, the two panels could precisely differentiate the five NTMs from M. tuberculosis (accuracy > 99%). We also revealed some new marker genes/SNPs/combinations to accurately discriminate any one of the five NTMs separately, which provided the possibility to diagnose one certain NTM infection precisely. Our research not only reveals novel promising diagnostic markers to promote the development of precision diagnosis in NTM infectious, but also provides an insight into precisely identifying various genetically close pathogens through comparative genomics and machine learning.

Abstract Study design This was a cross-sectional frequency-matched case–control study. Background and aim The serum lipid profile of lipoprotein(a) [Lp(a)] level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/Apo A1) ratio were found to be more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were found to be associated with symptomatic intervertebral disk herniation (IDH), no studies to date have evaluated the association of Apo AI, Apo B, Lp(a), and Apo B/Apo AI levels with symptomatic IDH. This study aimed to assess the link between blood lipid levels and symptomatic IDH. Method The study included 1839 Chinese patients. Of these, 918 patients were diagnosed with IDH and enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B, and Apo B/Apo AI were examined and analyzed. The control group comprised randomly selected patients who met the baseline levels of the aforementioned lipid molecules. Results Patients with IDH exhibited significantly higher TC, TG, LDL, Apo B, and Lp(a) levels than controls. The percentage of high TC, high TG, high LDL, high Apo B, and high Lp(a) were obviously higher in the IDH group than in the control group. However, hyperlipidemia had no relationship with the degenerated segment of the IDH (P = 0.201). The odds ratio (OR) for the incidence of IDH with elevated levels of LDL-C, TC, TG, Lp(a), Apo B, and Apo B/Apo AI was 1.583, 1.74, 1.62, 1.58, 1.49, and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a), and incidence of IDH was significant (R 2 LDL = 0.017; R 2 TC = 0.004; R 2 TG = 0.015; R 2 Apo B = 0.004; R 2 Lp(a) = 0.021) (P

Objective: Losartan and activation of the peroxisome proliferator-activated receptor-γ (PPARγ) have been previously reported to alleviate the progression of osteoarthritis (OA). However, the nature of the interaction between losartan and PPARγ in OA remains elusive. Therefore, we aimed to investigate the mechanism of the regulation of PPARγ by losartan in the context of OA. Methods: Clinical samples of OA patients were collected and the chondrocytes were further isolated, and used to construct OA chondrocyte model via induction with IL-1β. An OA mouse model was developed by the surgical destabilization of the medial meniscus (DMM). OA chondrocytes were treated with losartan, PPARγ siRNA and the PPAR-γ agonist GW1929 alone or in combination. Furthermore, the OA mice were treated with varying doses of losartan to determine the best mode of administration and treatment dose. Subsequently, the DMM mice were treated with losartan and GW9662. Expression of PPARγ, key proteins of the transforming growth factor-beta1 (TGF-β1) signaling pathway and the markers of OA degeneration were evaluated by the Western blot analysis, while effects on OA inflammatory factors were determined by ELISA. Results: The downregulation of PPARγ and the upregulation of TGF-β1 signaling pathway were detected in the OA cartilage tissues and chondrocytes. Losartan treatment or PPARγ activation contributes to reduced levels of IL-6, IL-1β, TNF-α, and COX-2, expression of TGF-β1, MMP-13, ADAMTS-4, ADAMTS-5, HtrA1, and iNOS, along with reduced Smad2 and Smad3 phosphorylation, but elevated PPARγ and Collagen II expression in vivo and in vitro. Additionally, the intraarticular injection of losartan into the knee joint proved to be the best mode of administration, and 10 ​mg/mL being the optimal treatment concentration. Conclusion: Our results show that losartan could arrest the progression of OA by upregulating PPARγ expression and inactivating the TGF-β1 signaling pathway.The translational potential of this article: Our results provide a biological rationale for the use of losartan as a potential candidate for OA treatment.

Tryptophan decarboxylases (TDCs) are a group of pyridoxal 5′-phosphate-dependent enzymes involved in the enzymatic conversion of tryptophan into tryptamine, a critical biogenic amine. We herein mined and cloned a TDC-encoding gene, CaTDC3, from camptothecin-producing plant Camptotheca acuminata. The intact CaTDC3 was heterologously overexpressed in Escherichia coli and the recombinant CaTDC3 was purified to homogeneity. High-performance liquid chromatography (HPLC)-diode array detector (DAD) and high resolution mass spectrometry (HRMS) data analyses of the CaTDC3-catalyzed reaction mixture confirmed the catalytically decarboxylative activity of CaTDC3. CaTDC3 shows strict stereoselectivity for L-tryptophan. Homology modeling and molecular docking implied CaTDC3’s recognition of L-tryptophan derivatives and analogs. Substrate scope investigations revealed that the appropriate substituent groups on the indole ring, i.e., hydroxylated and halogenated L-tryptophans, could be recognized by CaTDC3 and the decarboxylation reactions generated the corresponding tryptamines. The Cβ -methyl-L-tryptophans were decarboxylated by CaTDC3 efficiently. 1-Thio-L-tryptophan, the NH group of the indole ring replaced by an S atom, could be decarboxylated by CaTDC3. CaTDC3 catalyzed the decarboxylation of 7-aza-L-tryptophan, an N displacement of the C on the aromatic ring, to afford 7-aza-tryptamine. L-Kynurenine, an L-tryptophan degradation product, could be decarboxylated by CaTDC3. The present works uncover a catalytically promiscuous TDC and the TDC is a versatile decarboxylase in synthetic biology for specialized pharmaceutically important substances.

Objective To investigate the effects of hand–foot syndrome (HFS) and fatigue on disease progression and survival in patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma. Methods A retrospective analysis of patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from 1 October 2018 to 31 October 2021 was performed, and clinical and pathological data and follow-up results were obtained. Patients were divided into groups according to the severity of HFS and fatigue. Survival analysis among the groups was performed using the Kaplan–Meier method, continuous variables were analyzed using the t -test, and factors associated with survival were evaluated using multivariate Cox regression analysis. Results The study included 150 men and 23 women with a mean age of 60.77 years (range: 40–85 years). The median overall survival (OS), progression-free survival (PFS), and time to tumor progression (TTP) increased with increasing severity of HFS. Conversely, the median OS, PFS, and TTP decreased with increasing severity of fatigue Conclusion HFS and fatigue were independent risk factors affecting TTP, PFS, and OS among patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma.

As a newly emerging Klebsiella pathogen, more and more Klebsiella michiganensis drug resistant strains have been reported in recent years, which posed serious threats to public health. Here we first reported a multidrug-resistant K. michiganensis strain 12084 with two blaSIM-1 and one mcr-9.2 genes isolated from the sputum specimen of a patient in the Second Affiliated Hospital of Zhejiang University School of Medicine and analyzed its genetic basis and drug-resistance phenotypes. Genetic analysis showed that this strain harbored three different incompatibility groups (IncHI2, IncHI5, and IncFIIpKPHS2:IncFIB-4.1) of plasmids (p12084-HI2, p12084-HI5, and p12084-FII). A total of 26 drug-resistance genes belonging to 12 classes of antibiotics were identified, most of which (24) were located on two plasmids (p12084-HI2 and p12084-HI5). Interestingly, two blaSIM-1 genes were identified to locate on p12084-HI2 and p12084-HI5, respectively, both of which were embedded in In630, indicating their genetic homogeny. It was noting that one blaSIM-1 gene was situated in a novel unit transposon (referred to as Tn6733) on the p12084-HI5 plasmid. We also discovered an mcr-9.2 gene on the p12084-HI2 plasmid. To the best of our knowledge, this is the first report of a blaSIM-1 and mcr-9.2 harboring K. michiganensis strain. We then investigated the population structure/classification, and antibiotic resistance for all 275 availably global K. michiganensis genomes. Population structure revealed that K. michiganensis could be divided into two main clades (Clade 1 and Clade 2); the most popular ST29 was located in Clade 1, while other common STs (such as ST50, ST27, and ST43) were located in Clade 2. Drug-resistance analysis showed 25.5% of the K. michiganensis strains (70/275) harboring at least one carbapenemase gene, indicating severe drug resistance of K. michiganensis beyond our imagination; this is a dangerous trend and should be closely monitored, especially for ST27 K. michiganensis with the most drug-resistant genes among all the STs. Overall, we reported a blaSIM-1 and mcr-9.2 harboring K. michiganensis strain, and further revealed the population structure/classification, and drug-resistance of K. michiganensis, which provided an important framework, reference, and improved understanding of K. michiganensis.

BackgroundNeoadjuvant anti-programmed death receptor-1 (PD-1) blockade has been reported to improve the prognosis of locally advanced esophageal squamous cell carcinoma (ESCC). This study was aimed to evaluate the efficacy and safety of neoadjuvant camrelizumab plus chemoradiotherapy in locally advanced ESCC.MethodsWe retrospectively enrolled ESCC patients who received camrelizumab plus chemoradiotherapy as neoadjuvant therapy before surgery from May 2019 to September 2021.ResultsA total of 38 eligible patients were enrolled. The neoadjuvant treatment was well tolerated with no serious treatment-related adverse events. 36 (94.7%) patients achieved a R0 resection without hospital mortality or any other serious intraoperative complications. The objective response rate (ORR) was 63.2% and the disease control rate (DCR) was 100.0%. The major pathological response (MPR) was 50.0% and the complete pathological response (pCR) was 39.5%. With a median follow-up of 18.5 months, 6 (15.8%) patients had died. The overall survival (OS) and disease-free survival (DFS) at 12 months were 87.6% and 78.7%, respectively. Subgroup analysis demonstrated that patients who got MPR or pCR achieved improved survival, while PD-L1 expression did not reach statistically difference in predicting survival.ConclusionsNeoadjuvant camrelizumab plus chemoradiotherapy is safe and efficacious in treating patients with locally advanced ESCC.

Urban land-use scene classification from high-resolution remote-sensing imagery at high quality and accuracy is of paramount interest for urban planning, government policy-making and urban change detection. In recent years, urban land-use classification has become an ongoing task in areas addressable primarily by remote sensing, and numerous deep learning algorithms have achieved high performance on this task. However, both dataset and methodology problems still exist in the current approaches. Previous studies have relied on limited data sources, resulting in saturated classification results, and they have difficulty achieving comprehensive classification results. The previous methods based on convolutional neural networks (CNNs) focused primarily on model architecture rather than on the hyperparameters. Therefore, to achieve more accurate classification results, in this study, we constructed a new large dataset for urban land-use scene classification. More than thirty thousand remote sensing scene images were collected to create a dataset with balanced class samples that includes both higher intra-class variations and smaller inter-class dissimilarities than do the previously available public datasets. Then, we analysed two possible strategies for exploiting the capabilities of three existing popular CNNs on our datasets: full training and fine tuning. For each strategy, three types of learning rate decay were applied: fixed, exponential and polynomial. The experimental results indicate that fine tuning tends to be the best-performing strategy, and using ResNet-V1-50 and polynomial learning rate decay achieves the best results for the urban land-use scene classification task.

Background and aimsChildren with spinal muscular atrophy (SMA) have a high rate of dyslipidaemia, which is a risk factor of vital importance for cardiovascular diseases in adulthood. Studies have demonstrated that the serum zinc level is associated with lipid profiles in the general population as well as in individuals diagnosed with obesity or diabetes. The purpose of this study was to evaluate the relationship between serum zinc level and lipid profiles in children with SMA.MethodsThis cross-sectional study was launched in a tertiary children's medical center in China and involved pediatric patients with SMA under the management of a multidisciplinary team of outpatient services from July 2019 to July 2021. Anthropometric information, general clinical data, serum zinc level, lipid profiles, and body composition data were collected. Multivariate analysis was used for a thorough inquiry on the association between the serum zinc level and lipid profiles.ResultsAmong the 112 patients with SMA [median (IQR) age 5.54 years (2.75–8.29), 58.04% female], who fulfilled the inclusion criteria of the study, dyslipidaemia was detected in 60 patients (53.57%). Based on multivariable linear regression, serum zinc level was positively associated with high-density lipoprotein cholesterol (HDL-C; β = 1.63, 95% CI = 0.44–3.22) and apolipoprotein A1 (APO A1; β = 2.94, 95% CI = 0.03–5.85) levels, independently of age, sex, type, activity, percentage of body fat, and body mass index. As the serum zinc level increased by 10 μmol/L, the risk of low APO A1 levels decreased by 35% (OR = 0.65, 95% CI = 0.44–0.97) according to multivariable logistic regression analyses.ConclusionSerum zinc concentration was positively correlated with HDL-C and APO A1 levels among children with SMA. We suggest measures to correct the lower level of serum zinc to improve HDL-C and APO A1 levels.

Biological pattern formation ensures that tissues and organs develop in the correct place and orientation within the body. A great deal has been learned about cell and tissue staining techniques, and today’s microscopes can capture digital images. A light microscope is an essential tool in biology and medicine. Analyzing the generated images will involve the creation of unique analytical techniques. Digital images of the material before and after deformation can be compared to assess how much strain and displacement the material responds. Furthermore, this article proposes Development Biology Patterns using Digital Image Technology (DBP-DIT) to cell image data in 2D, 3D, and time sequences. Engineered materials with high stiffness may now be characterized via digital image correlation. The proposed method of analyzing the mechanical characteristics of skin under various situations, such as one direction of stress and temperatures in the hundreds of degrees Celsius, is achievable using digital image correlation. A DBP-DIT approach to biological tissue modeling is based on digital image correlation (DIC) measurements to forecast the displacement field under unknown loading scenarios without presupposing a particular constitutive model form or owning knowledge of the material microstructure. A data-driven approach to modeling biological materials can be more successful than classical constitutive modeling if adequate data coverage and advice from partial physics constraints are available. The proposed procedures include a wide range of biological objectives, experimental designs, and laboratory preferences. The experimental results show that the proposed DBP-DIT achieves a high accuracy ratio of 99,3%, a sensitivity ratio of 98.7%, a specificity ratio of 98.6%, a probability index of 97.8%, a balanced classification ratio of 97.5%, and a low error rate of 38.6%.

Abstract The Carbonate rock weathering Carbon Sink (CCS) and Silicate rock weathering Carbon Sink (SCS) play a significant role in the carbon cycle and global climate change. However, the spatial‐temporal patterns and trends of the CCS and SCS from 1950 to 2099 have not been systematically quantified. Thus, Supported by long‐term hydrometeorological data under the RCP8.5, we use the accepted Suchet and Hartmann models to determine the following. First, we found except for the difference in their weathering rates, the SCS covers 37.2 million km2 more area than the CCS. The CCS Flux (CCSF) and SCS Flux (SCSF) are 5.36 and 1.22 t/km2/yr, respectively. Similarly, the Full CCS (FCCS, 0.3 Pg/yr) is more than the Full SCS (FSCS, 0.08 Pg/yr). Furthermore, the CCS (7.01 kg/km2) and SCS (3.95 kg/km2) are in a state of overall increase. In addition, the mid‐to‐high latitudes of the northern hemisphere are aggravated by warming (0.03°C) and humidity (0.65 mm), while the decrease in runoff in the mid‐latitudes of the southern hemisphere reduces karstification. Specifically, by 2099, the CCSF in the mid‐latitudes of the southern hemisphere will decrease by 5.72%. Instead, the CCSF in the northern hemisphere and lower latitudes of the southern hemisphere will exhibit a gentle upward slope. Particularly, the peak regions of the global FCCS (65.63 Tg/yr) and FSCS (33.01 Tg/yr) are the tropical zone. In conclusion, this study contributes a high‐resolution and long‐time series CS datasets for the CCS and SCS. We provide data and a theory for solving terrestrial carbon sink loss.

BackgroundThe current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems.ResultsPositive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models.ConclusionsA positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.

Droughts are the most expensive natural disasters on the planet. As a result of climate change and human activities, the incidence and impact of drought have grown in China. Timely and effective monitoring of drought is crucial for water resource management, drought mitigation, and national food security. In this study, we constructed a comprehensive drought index (YCDI) suitable for the Yellow River Basin using principal component analysis and the entropy weight-AHP method, which integrated a standardized precipitation evapotranspiration index (SPEI), self-calibrating Palmer drought severity index (scPDSI), vegetation condition index (VCI), and standardized water storage index (SWSI). SWSI is calculated by the terrestrial water storage anomaly (TWSA), which can more comprehensively reflect the impact of surface water resources on drought (as compared with soil moisture-based indexes). The study results showed that: (1) compared with single drought index, YCDI has stronger ability to monitor drought process. In terms of time scale and drought degree, the monitoring results based on YCDI were similar with data presented in the China Flood and Drought Bulletin and Meteorological Drought Yearbook, reaching ~87% and ~69%, respectively. The correlation between drought intensity and crop harvest area was 0.56. (2) By the combined analysis of the Mann-Kendall test and Moving T test, it was found that the abrupt change of YCDI index at the time of 2009, mainly due to the precipitation in 2009 reached the lowest value in the past 30 years in northern China and extreme high temperature weather. (3) The YCDI of Henan and Shandong provinces in the middle and lower reaches of the basin decreased more significantly, with the maximum value reaching 0.097/yr, while the index in the upper reaches showed an increasing trend with the maximum rate of 0.096/yr. (4) The frequency of mild drought, moderate drought, severe drought and extreme drought in the Yellow River basin during the study period was 15.84%, 12.52%, 4.03% and 0.97%, respectively. Among them, the highest frequency of droughts occurred in Ningxia, Inner Mongolia and central Shaanxi provinces. Drought causation in the Yellow River basin is more influenced by human activities than climate change in the middle and lower reaches, while climate change is the main factor in the upper reaches. Overall, YCDI is a reliable indicator for monitoring the spatial and temporal evolution of drought in the Yellow River basin, and it can be used for monitoring soil moisture changes and vegetation dynamics, which can provide scientific guidance for regional drought governance.

Introduction Non-cystic fibrosis bronchiectasis (NCFB) brought a heavy healthcare burden worldwide. Macrolide maintenance therapy was proved to be helpful in reducing exacerbation of NCFB. However, the optimal dosing regimens of macrolides have not been determined, and its efficacy in Chinese NCFB population has not been validated. This protocol describes a head-to-head clinical trial designed to compare the efficacy of two dosing regimens of azithromycin in Chinese NCFB population.Methods and analysis This prospective, open-label and randomised controlled trial will be conducted in the First People’s Hospital of Jiashan, China. Eligible patients with high-resolution CT defined NCFB will be randomly divided into three groups, which will receive either 250 mg daily azithromycin, or 500 mg three-times-weekly azithromycin or no treatment for 6 months. They will be followed up for another 6 months without treatment. The primary outcome is the mean rate of protocol-defined pulmonary exacerbation at 6 months.Ethics and dissemination Ethical approval was obtained from the First People’s Hospital of Jiashan Ethics Committee. The findings will be disseminated in peer-reviewed publications.Trial registration number ChiCTR2100052906.

Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies. Methods: Within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case–control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. We further assessed the effect modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population. Results: The PRS was evaluated in 31,925 cases and 490,507 controls, including men from European (22,049 cases, 414,249 controls), African (8794 cases, 55,657 controls), and Hispanic (1082 cases, 20,601 controls) populations. Comparing men in the top decile (90–100% of the PRS) to the average 40–60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62–3.96), 2.8-fold in African ancestry men (95% CI = 2.59–3.03), and 3.2-fold in Hispanic men (95% CI = 2.64–3.92). The PRS did not discriminate risk of aggressive versus nonaggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55–60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40–60% PRS category. Conclusions: Our findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. A clinical study of PRS is warranted to determine whether the PRS could be used for risk-stratified screening and early detection. Funding: This work was supported by the National Cancer Institute at the National Institutes of Health (grant numbers U19 CA214253 to C.A.H., U01 CA257328 to C.A.H., U19 CA148537 to C.A.H., R01 CA165862 to C.A.H., K99 CA246063 to B.F.D, and T32CA229110 to F.C), the Prostate Cancer Foundation (grants 21YOUN11 to B.F.D. and 20CHAS03 to C.A.H.), the Achievement Rewards for College Scientists Foundation Los Angeles Founder Chapter to B.F.D, and the Million Veteran Program-MVP017. This research has been conducted using the UK Biobank Resource under application number 42195. This research is based on data from the Million Veteran Program, Office of Research and Development, and the Veterans Health Administration. This publication does not represent the views of the Department of Veteran Affairs or the United States Government.

In tone languages, some case studies showed that the word-level tonal representation was closely related to the underlying metrical pattern. Based on different tonal patterns in prosodic units, the metrical structures could generally be divided into the left- and right-dominant types in Chinese dialects. Yet the cross-dialectal phonetic realizations (e.g., duration and pitch) between or within these two metrical structures were still unrevealed. The current study investigated the duration and pitch realizations of disyllabic prosodic words in Changsha and Chengdu dialects (the left-dominant structure), and in Fuzhou and Xiamen dialects (the right-dominant structure). Results showed that not all the duration patterns across four Chinese dialects were sensitive to different metrical structures, indicating that the duration might not be the universal cue for metrical prominence in Chinese dialects. In terms of pitch realization across all the four Chinese dialects, level tones (sometimes falling tones) generally appeared in the metrically weak unit, while underlying pitch forms appeared in the metrically strong unit. Compared with duration, pitch might be more robust for prosodic realizations of metrical structures in Chinese dialects. Furthermore, there was an interaction between duration and pitch patterns in Chinese dialects, which could shed new light on the phenomenon of “metrical tone sandhi”. Meanwhile, this study also provides some references for the judgment of the metrical stress and prosodic realizations in other Chinese dialects.

PurposeTo investigate the dosimetric impact on target volumes and organs at risk (OARs) when unmodified auto-segmented OAR contours are directly used in the design of treatment plans. Materials and MethodsA total of 127 patients with cervical cancer were collected for retrospective analysis, including 105 patients in the training set and 22 patients in the testing set. The 3D U-net architecture was used for model training and auto-segmentation of nine types of organs at risk. The auto-segmented and manually segmented organ contours were used for treatment plan optimization to obtain the AS-VMAT (automatic segmentations VMAT) plan and the MS-VMAT (manual segmentations VMAT) plan, respectively. Geometric accuracy between the manual and predicted contours were evaluated using the Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), and Hausdorff distance (HD). The dose volume histogram (DVH) and the gamma passing rate were used to identify the dose differences between the AS-VMAT plan and the MS-VMAT plan.Results Average DSC, MDA and HD95 across all OARs were 0.82–0.96, 0.45–3.21 mm, and 2.30–17.31 mm on the testing set, respectively. The D99% in the rectum and the Dmean in the spinal cord were 6.04 Gy (P = 0.037) and 0.54 Gy (P = 0.026) higher, respectively, in the AS-VMAT plans than in the MS-VMAT plans. The V20, V30, and V40 in the rectum increased by 1.35% (P = 0.027), 1.73% (P = 0.021), and 1.96% (P = 0.008), respectively, whereas the V10 in the spinal cord increased by 1.93% (P = 0.011). The differences in other dosimetry parameters were not statistically significant. The gamma passing rates in the clinical target volume (CTV) were 92.72% and 98.77%, respectively, using the 2%/2 mm and 3%/3 mm criteria, which satisfied the clinical requirements.ConclusionsThe dose distributions of target volumes were unaffected when auto-segmented organ contours were used in the design of treatment plans, whereas the impact of automated segmentation on the doses to OARs was complicated. We suggest that the auto-segmented contours of tissues in close proximity to the target volume need to be carefully checked and corrected when necessary.

This study explored the performance of Chinese college students with different severity of trait depression to process English emotional speech under a complete semantics–prosody Stroop effect paradigm in quiet and noisy conditions. A total of 24 college students with high-trait depression and 24 students with low-trait depression participated in this study. They were required to selectively attend to either the prosodic emotion (happy, sad) or semantic valence (positive and negative) of the English words they heard and then respond quickly. Both prosody task and semantic task were performed in quiet and noisy listening conditions. Results showed that the high-trait group reacted slower than the low-trait group in the prosody task due to their bluntness and insensitivity toward emotional processing. Besides, both groups reacted faster under the consistent situation, showing a clear congruency-induced facilitation effect and the wide existence of the Stroop effect in both tasks. Only the Stroop effect played a bigger role during emotional prosody identification in quiet condition, and the noise eliminated such an effect. For the sake of experimental design, both groups spent less time on the prosody task than the semantic task regardless of consistency in all listening conditions, indicating the friendliness of basic emotion identification and the difficulty for second language learners in face of semantic judgment. These findings suggest the unneglectable effects of college students’ mood conditions and noise outside on emotion word processing.

PurposeComitant exotropia (CE) is a common eye disorder characterized by impaired stereoscopic vision and eye deviation. Previous neuroimaging studies demonstrated that patients with CE were accompanied by specific functional and structural abnormalities of the brain. However, the effect of impaired stereoscopic vision and eye deviation on interhemispheric homotopic connectivity remains unknown.MethodsA total of thirty-six patients with CE (25 males and 11 females) and 36 well-matched healthy controls underwent magnetic resonance imaging scanning. The voxel-mirrored homotopic connectivity (VMHC) method was applied to assess the interhemispheric homotopic connectivity changes in patients with CE. Furthermore, the support vector machine method was applied to assess to differentiate patients with CE from healthy controls (HCs) with the VMHC maps as a feature.ResultsCompared with HCs, patients with CE showed significantly increased VMHC values in the bilateral cerebelum_ 8 and cerebelum_4_5. Moreover, we found that the VMHC maps showed an accuracy of 81.94% and an area under the curve of 0.87 for distinguishing the patients with CE from HCs.ConclusionOur study demonstrates that patients with CE showed interhemispheric homotopic connectivity changes in the cerebellum, which might reflect the neurological mechanisms of impaired stereoscopic vision and eye deviation in patients with CE.

ObjectiveThis study was conducted to determine the safety and efficacy of the Esperance® Distal Access Catheter (0.071”), a novel large bore aspiration catheter in treating acute ischemic stroke (AIS) with large vessel occlusion (LVO).MethodsA prospective multicenter clinical trial involving 15 stroke centers was performed. Baseline characteristics, procedural data, and angiographic and clinical outcomes of all acute stroke procedures (from May 2020 to March 2021) using the novel large bore aspiration catheter were analyzed.ResultsDuring the study period, 160 consecutive patients were recruited. The mean age and median baseline NIHSS were 65.4 years and 16, respectively. Successful reperfusion was achieved in 147 (91.9%) cases [at least modified Thrombolysis in Cerebral Infarction (mTICI) 2b] with aspiration alone, with complete reperfusion (mTICI 3) in 94 (58.8%) cases. Successful/complete first pass reperfusion was achieved in 104 (64.60%) cases, including mTICI 2b in 34 (21.1%) cases and mTICI 3 in 70 (43.5%) cases. The time from groin puncture to successful reperfusion was 44 (33, 62) min. There were 16 (9.9%) cases requiring rescue therapy using stent-retriever. Procedure-related complications included 2 (1.3%) cases of arterial perforation, 2 (1.3%) cases of arterial dissection, 12 (7.5%) cases of distal embolization, and 1(0.6%) case of puncture site infection. The rate of symptomatic intracranial hemorrhage (sICH) was 3.8% and mortality rate was 13.8%. A total of 99 (62.3%) cases had a favorable outcome (mRS 0–2) at 90 days.ConclusionsIn current practice, the first-line aspiration approach with the Esperance® Distal Access Catheter is safe and efficacious. This device may achieve high reperfusion rates with lower instances of rescue stent retriever therapy.

Hepatocellular carcinoma (HCC) is a cancer that is sensitive to ferroptosis, and immunotherapy has emerged as a promising treatment for HCC patients. However, the prognostic potential of ferroptosis-related genes (FRGs) and the effect of ferroptosis on the tumor immune microenvironment in HCC remain largely obscure. Here, we analyzed the expression pattern of FRGs using the TCGA, ICGC and GEO databases. The expression of most FRGs was upregulated in HCC tissues compared with normal liver tissues. Three independent clusters were determined by consensus clustering analysis based on FRG expression in HCC. Cluster 3 exhibited higher expression, unfavorable prognosis, and higher histological tumor stage and grade than clusters 1 and 2. CIBERSORT analysis indicated different infiltrating levels of various immune cells among the three clusters. Moreover, most immune checkpoint genes were highly expressed in cluster 3. Univariate Cox regression and LASSO regression analyses were performed to develop a five FRG-based prognostic risk model using the TCGA and ICGC datasets. Kaplan–Meier analysis and ROC curves were performed to verify the prognostic potential of the risk model. A nomogram containing independent prognostic factors was further developed. Compared with low-risk patients, high-risk HCC patients exhibited worse overall survival (OS). In addition, this risk model was significantly correlated with the infiltrating levels of six major types of immune cells in HCC. Finally, the relationships between the five FRGs and drug sensitivity were investigated. The present study suggests that the five FRGs could elucidate the molecular mechanisms of HCC and lead to a new direction for the improvement of predictive, preventive, and personalized medicine for HCC.

Aims: This study aims to evaluate ECM-coated micropattern arrays derived from decellularization of native porcine lungs as a novel three-dimensional cell culture platform. Methods: ECM derived from decellularization of native porcine lungs was exploited to prepare hydrogels. Then, dECM-coated micropattern arrays were fabricated at four different diameters (50, 100, 150 and 200 ​μm) using polydimethylsiloxane (PDMS). Two lung cancer cell lines, A549 and H1299, were tested on a dECM-coated micropattern array as a novel culture platform for cell adhesion, distribution, proliferation, viability, phenotype expression, and drug screening to evaluate the cytotoxicity of paclitaxel, doxorubicin and cisplatin. Results: The ECM derived from decellularization of native porcine lungs supported cell adhesion, distribution, viability and proliferation better than collagen I and Matrigel as the coated matrix on the surface. Moreover, the optimal diameter of the micropattern arrays was 100–150 ​μm, as determined by measuring the morphology, viability, proliferation and phenotype of the cancer cell spheroids. Cell spheroids of A549 and H1299 on dECM-coated micropattern arrays showed chemoresistance to anticancer drugs compared to that of the monolayer. The different distributions of HIF-1α, MCL-1 (in the center) and Ki-67 and MRP2 (in the periphery) of the spheroids demonstrated the good establishment of basal-lateral polarity and explained the chemoresistance phenomenon of spheroids. Conclusions: This novel three-dimensional cell culture platform is stable and reliable for anticancer drug testing. Drug screening in dECM-coated micropattern arrays provides a powerful alternative to existing methods for drug testing and metabolic profiling in the drug discovery process.

BackgroundAcute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.MethodsTen AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.ResultsWe identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell–cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.ConclusionsOur studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

Much of early western research has focused on identity. A primed identity can inhibit the priming of other alternative identities, and also negatively affect the intention to purchase products related to those alternative identities. In western culture, individuals operate within a cultural framework that makes them more likely to prioritize their own goals and less likely to rely on environmental factors when evaluating others. Individuals are more likely to choose products that fit their primed identity. In this study, we suggest that in collectivist Chinese culture, individuals may give priority to group-level goals and attach more importance to situational factors when evaluating others. Therefore, a primed identity may not necessarily inhibit the priming of alternative identities. In this research, we examine the association between a focal identity and alternative identities, with particular emphasis on the accessibility, discrepancies, and effects on purchase intention of alternative identities. We also examine the intent to purchase products related to the alternative identity vs. the focal identity, developing a model with which to explore this construct. We test four hypotheses through experiments using an online questionnaire and analyzing the resulting data using statistical product service solutions (SPSS) 22.0 and the PROCESS macro modeling tool. The results are as follows: First, the association between a focal identity and alternative identity has a positive impact on the accessibility of the alternative identity. The clearer the alternative identity is, the greater the impact of the association between the focal identity and alternative identity on the latter’s accessibility. Second, the accessibility of the alternative identity has a positive impact on the intent to purchase alternative identity vs. focal identity-related products. The greater the discrepancy between the focal identity and the alternative identity, the greater the impact on the intent to purchase alternative identity vs. focal identity-related products. The results of this study confirmed the interaction between identity association and the clarity of the alternative identity, as well as the influence of the accessibility of the alternative identity on the intent to purchase alternative identity vs. focal identity-related products. We contribute to the development of a theory on intention to purchase identity-related products.

Purpose: To compare the consistency of one-dimensional Response Evaluation Criteria in Solid Tumors (1D-RECIST), two-dimensional WHO criteria (2D-WHO), and three-dimensional (3D) measurement for therapeutic response assessment of nasopharyngeal carcinoma (NPC). Materials and methods: Retrospective data of 288 newly diagnosed NPC patients were reviewed. Tumor size was assessed on magnetic resonance imaging (MRI) according to the 1D-RECIST, 2D-WHO, and 3D measurement criteria. Agreement between tumor responses was assessed using unweighted k statistics. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point of the PTV. The Kaplan–Meier method and Cox regression were used for the survival analysis. Results: The optimal cut-off point of the PTV for progression-free survival (PFS) was 29.6%. Agreement with PTV measurement was better for 1D measurement than for 2D and 3D measurements (kappa values of 0.646, 0.537, and 0.577 for 1D, 2D, and 3D measurements, respectively; P

Abstract Introduction The prognosis of new-onset atrial fibrillation (AF) compared with that of preexisting and non-AF remains controversial. The purpose of this study was to evaluate the effect of new-onset AF compared with preexisting and non-AF on hospital and 90-day mortality. Methods A retrospective cohort study was performed using data obtained from the Medical Information Mart for Intensive Care III database. The primary outcome was 90-day mortality. Secondary outcomes included hospital mortality, hospital and intensive care unit (ICU) length of stay, and acute kidney injury. Logistic and Cox regression analyses were performed to evaluate the relationship between new-onset AF and study outcomes. Results A total of 38,159 adult patients were included in the study. The incidence of new-onset AF was 9.4%. Ninety-day mortality, hospital mortality, and hospital and ICU length of stay in patients with new-onset and preexisting AF were significantly increased compared with those in patients with non-AF patients (all p

In addition to dispersed nanoparticles in the binder phase, the effect of Ni3Al on the growth mechanism of tungsten carbide (WC) grains is also essential for the fabrication of high-quality of cemented carbides. In this work, WC–Co–Ni3Al cemented carbides with different combinations of Co and Ni3Al binders was studied by using the original artificial bimodal WC grain size distribution. The WC particle sizes of medium 4 μm, fine 1 μm and ultrafine 0.2 μm were adopted. A series of WC–Co–Ni3Al alloys were firstly designed based on thermodynamic calculations and then liquid-sintered at 1450 °C for 1 h. Subsequently, the morphology and grain size distribution of WC grains were studied. By increasing the proportion of Ni3Al in the Co–Ni3Al composite binder phase, the solid–liquid interfacial energy increases significantly, which may provide a higher driving force for abnormal grain growth (AGG) through 2-dimension (2D) nucleation. However, the increase of Ni3Al proportion conversely greatly raises the energy barrier for the migration of W and C atoms into liquid binder phase, which finally retards the AGG of WC. Consequently, the AGG of WC decreases and the number of crystallites with blunt faces increases on WC particles with the increase of Ni3Al proportion, which can be well accounted for by the presently detected WC morphology evolution.

The vibration signal of crane gearbox has the characteristics of low signal-to-noise ratio and nonlinearity，so it needs some professional knowledge and experience to realize fault diagnosis. In order to realize intelligent fault diagnosis of crane gearbox，an intelligent fault diagnosis method based on variational modal decomposition（VMD） improved wavelet denoising and particle swarm optimization（PSO） support vector machine（SVM） is proposed. Firstly， VMD is used to decompose the vibration signal to obtain the intrinsic mode function（IMF） of different scales. The decomposed high frequency component is improved after wavelet de-noising and the low frequency component is reconstructed. Then the feature parameters of reconstructed signal are extracted to construct the feature vector， and kernel principal component analysis（KPCA） is used to realize the feature information fusion. Finally， the PSO optimized SVM is used for fault identification and classification. The experimental results show that the SVM model based on VMD improved wavelet signal preprocessing and PSO algorithm has high recognition accuracy and can effectively and accurately identify and classify the fault types of the crane gearbox.

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by incomplete reversible airflow limitation and chronic inflammatory response lesions. This study mainly explored whether FGFR2 and MGAT5 polymorphisms affected the risk of COPD in the Chinese people. Methods Five variants in FGFR2 and MGAT5 were chosen and genotyped using Agena MassARRAY platform from 315 COPD patients and 314 healthy controls. The correlation of FGFR2 and MGAT5 with COPD susceptibility was evaluated with odds ratio (OR) and 95% confidence interval (CI) via logistic regression. Results We found rs2420915 enhanced the risk of COPD, while rs6430491, rs2593704 reduced the susceptibility of COPD (p

Abstract Background In nonneutropenic patients with underlying respiratory diseases (URD), invasive pulmonary aspergillosis (IPA) is a life-threatening disease. Yet establishing early diagnosis in those patients remains quite a challenge. Methods A retrospective series of nonneutropenic patients with probable or proven IPA were reviewed from January 2014 to May 2018 in Department of Respiratory Medicine of two Chinese hospitals. Those patients were suspected of IPA and underwent lung computed tomography (CT) scans twice within 5–21 days. The items required for IPA diagnosis were assessed by their host factors, mycological findings and CT scans according to the European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria (EORTC/MSG criteria). Results Together with the risk factors, mycological findings and nonspecific radiological signs on first CT, ten patients were suspected of IPA. With the appearance of cavities on second CT scan in the following days, all patients met the criteria of probable or possible IPA. Except one patient who refused antifungal treatment, nine patients received timely antifungal treatment and recovered well. One of the nine treated IPA cases was further confirmed by pathology, one was confirmed by biopsy. Conclusions Dynamic monitor of CT scan provided specific image evidences for IPA diagnosis. This novel finding might provide a noninvasive and efficient strategy in IPA diagnosis with URD.

Abstract Hydraulic fracturing is an important technical means to improve the development effect of low-permeability oil and gas reservoirs. However, for low pressure, low-permeability, tight, and high-clay sandstone gas reservoirs, conventional propped fracturing can cause serious damage to the reservoir and restrict the fracturing effect. The pre-acid fracturing technology combines acid treatment technology with sand-fracturing technology. A pre-acid system that meets special performance requirements is injected before fracturing. The pre-acid reduces the formation fracture pressure and removes clay damage. During acid flowback, the fracturing fluid is promoted to break the gel, dissolve the fracturing fluid residue and polymer filter cake, clean the supporting cracks, and effectively improve the fracturing effect. This study analyzes the process principle and technical advantages of the pre-acid fracturing technology based on the laboratory evaluation of the fracturing damage mechanism of low-permeability tight gas reservoirs. To meet the performance requirements of low-permeability tight gas reservoirs and pre-acid fracturing technology, a set of polyhydrogen acid system with long-lasting slow reactivity, low damage, and low corrosion was developed and used as the pre-fracturing acid. The acid system is mainly composed of the main agent SA601 and the auxiliary agent SA701. Then, on the basis of laboratory experiments, this acid system is used as the fracturing pre-acid to evaluate the fracturing improvement effect. The results show that the fracturing fluid system can better dissolve the fracturing fluid filter cake and remove the fracturing fluid damage.

Abstract In situ heat systems are a technology that effectively solves paraffin deposition and improves oil recovery. Generally, the oxidation–reduction reaction of sodium nitrite and ammonium chloride generates a large amount of heat to promote the melting of paraffin. An in situ heat system combined with an acid-resistant fracturing fluid system can form an in situ heat fracturing fluid system, which solves the problem of the poor reformation effect caused by cold damage during the fracturing process of low-pressure and high-pour-point oil reservoirs. In this paper, with the goals of system heating up to 50 °C, a low H+ concentration, a high exotherm, and reduction of the toxic and harmful by-product NOX, the preferred in situ heat system was found to comprise 1.6 mol/L ammonium chloride, 1.0 mol/L sodium nitrite, and 0.8% hydrochloric acid. The effect of five factors on the heat production of the reaction was studied experimentally, and a reaction kinetic equation for the in situ heat system was proposed based on the results. The results showed that increasing the concentration of the reactants and lowering the ambient temperature produced more heat. The in situ heat system was used to conduct a crude oil cold damage elimination experiment, and the results of the removal experiments verified that the system could effectively but not completely reduce the cold damage. Overall, the in situ heat fracturing fluid system formed by the preferred in situ heat system combined with an acid-resistant fracturing fluid system could avoid cold damage in the formation during construction and increase the output.

Abstract Introduction The ubiquitously expressed nonhistone nuclear protein high‐mobility group box protein 1 (HMGB1) has different functions related to posttranslational modifications and cellular localization. In the nucleus, HMGB1 modulates gene transcription, replication and DNA repair as well as determines chromosomal architecture. When the post‐transcriptional modified HMGB1 is released into the extracellular space, it triggers several physiological and pathological responses and initiates innate immunity through interacting with its reciprocal receptors (i.e., TLR4/2 and RAGE). The effect of HMGB1‐mediated inflammatory activation on different systems has received increasing attention. HMGB1 is now considered to be an alarmin and participates in multiple inflammation‐related diseases. In addition, HMGB1 also affects the occurrence and progression of tumors. However, most studies involving HMGB1 have been focused on adults or mature animals. Due to differences in disease characteristics between children and adults, it is necessary to clarify the role of HMGB1 in pediatric diseases. Methods and Results Through systematic database retrieval, this review aimed to first elaborate the characteristics of HMGB1 under physiological and pathological conditions and then discuss the clinical significance of HMGB1 in the pediatric diseases according to different systems. Conclusions HMGB1 plays an important role in a variety of pediatric diseases and may be used as a diagnostic biomarker and therapeutic target for new strategies for the prevention and treatment of pediatric diseases.

Objective: To investigate the activity concentration of tritium in urine of nuclear power plant (NPP) workers, in order to evaluate the occupational exposure levels. Methods: Three chosen NPPs were respectively located in southern, southeastern and northeastern China. Workers involved in operating, service, nuclear cleaning, chemical analysis, health physics, technical support, among others were randomly selected as the research targets, and 69 urine samples of no less than 50 ​mL were collected. The oxidative distillation method was used to pretreat the urine samples, and the activity concentration of tritium in distillate was then measured using liquid scintillation counter. The formula for the committed effective dose was also applied used to estimate the internal doses. Results: The highest tritium activity concentrations in urine samples from three NPPs were 2412.7, 6351.4, and 478.7 Bq/L, respectively. Correspondingly, the internal doses due to tritium intake were 1.8, 4.8 and 0.4 ​μSv, respectively. Conclusions: The urine tritium activity concentration of workers varied greatly dependent on their job categories. The values for urine tritium radioactivity concentrations of workers involved in health care, nuclear cleaning and maintenance were generally higher than those for other job categories. The difference in urine tritium activity concentration mainly came from the different exposure time and tritium concentrations. From the dose assessment results, the internal dose caused by tritium intake did not exceed the public annual effective dose limit.

Abstract Background Mesenchymal stem cells (MSCs) are derived from multiple tissues, including amniotic fluid (AF-MSCs) and the umbilical cord (UC-MSCs). Although the therapeutic effect of MSCs on sepsis is already known, researchers have not determined whether the cells from different sources require different therapeutic schedules or exert different curative effects. We assessed the biofunction of the administration of AF-MSCs and UC-MSCs in rats with caecal ligation and puncture (CLP)-induced sepsis. Methods CLP was used to establish a disease model of sepsis in rats, and intravenous tail vein administration of AF-MSCs and UC-MSCs was performed to treat sepsis at 6 h after CLP. Two phases of animal experiments were implemented using MSCs harvested in saline with or without filtration. The curative effect was measured by determining the survival rate. Further effects were assessed by measuring proinflammatory cytokine levels, the plasma coagulation index, tissue histology and the pathology of the lung, liver and kidney. Results We generated rats with medium-grade sepsis with a 30–40% survival rate to study the curative effects of AF-MSCs and UC-MSCs. MSCs reversed CLP-induced changes in proinflammatory cytokine levels and coagulation activation. MSCs ameliorated CLP-induced histological and pathological changes in the lung, liver and kidney. AF-MSCs and UC-MSCs functioned differently in different tissues; UC-MSCs performed well in reducing the upregulation of inflammatory cytokine levels in the lungs and inhibiting the inflammatory cell infiltration into the liver capsule, while AF-MSCs performed well in inhibiting cell death in the kidneys and reducing the plasma blood urea nitrogen (BUN) level, an indicator of renal function. Conclusions Our studies suggest the safety and efficacy of AF-MSCs and UC-MSCs in the treatment of CLP-induced sepsis in rats and show that the cells potentially exert different curative effects on the main sepsis-affected tissues.

Abstract Background To assess the indications and complications of late amniocentesis and the advanced genetic test results in a tertiary university fetal medical medicine unit. Methods In this retrospective study, women that underwent amniocentesis at 24+ 0 to 39+ 4 weeks, between January 2014 and December 2019, were recruited. Indications, complications, genetic test results, and pregnancy outcomes were reported for each pregnancy and compared with those who underwent the traditional amniocentesis at 16+ 0 to 23+ 6 weeks (control group). Information was retrieved from patient medical records, checked by research staff, and analyzed. Results Of the 1287 women (1321 fetuses) included in the late amniocentesis group, late detected sonographic abnormalities (85.5%) were the most common indication. The overall incidence of preterm birth and intrauterine demise after amniocentesis were 2.5 and 1.3%, respectively. Sixty-nine fetuses with aneuploidy (5.3%) and seventy-two fetuses with pathogenic copy number variations (5.5%) were identified by chromosomal microarray analysis. The maximal diagnostic yield (70%) was in the subgroup of fetuses with the abnormal diagnostic test results, followed by abnormal NIPT results (35.7%) and multiple abnormalities (23.8%). And 35.4% of the pregnancies were finally terminated. Conclusions Due to the high detection rates of advanced genetic technologies and the safety of the invasive procedure (3.9% vs 4.0%), it is reasonable to recommend late amniocentesis as an effective and reliable method to detect late-onset fetal abnormalities. However, chromosomal microarray and whole-exome sequencing may result in uncertain results like variants of uncertain significance. Comprehensive genetic counseling is necessary.

Identifying the response of runoff changes to extreme climate evolution was of great scientific significance for the rational regulation of watershed water resources and the prevention of hydrological disasters. However, the time–frequency response relationships were not clear. The Yinjiang River watershed, a typical watershed with karst trough valley areas, was chosen to identify the impact of different climatic driving factors on runoff changes from 1984 to 2015. Continuous wavelet transform (CWT), cross-wavelet transform (XWT), and wavelet coherence transform (WTC) were performed to study the response relationship and time–frequency effect between runoff changes and extreme climate change at different time scales. The main results showed that: (1) Twelve extreme climate indices (ECIs) were detected to have a significant impact on runoff changes, mainly on a 6-year time scale; (2) The R10 and Rx1day in extreme precipitation index and SU34.4 and TNx in the extreme temperature index were the main driving factors of runoff changes, which had relatively large impacts on runoff changes in high and low energy vibration regions. However, the remaining eight ECIs that passed the 0.05 confidence level showed relatively large impacts on runoff changes only in low energy vibration regions; (3) The transition of the interaction between ECIs and runoff changes in high and low time–frequency scales was related to the abrupt change characteristics of the ECIs. The correlation of abrupt change was an important reason for the emergence of highly correlated regions that trigger high and low energy vibrations; (4) As a whole, the extreme precipitation events were ahead of runoff changes at the high time–frequency scale and exhibited small lag effects at the low time–frequency scale, while extreme temperature events were mainly ahead of runoff changes. This study has effectively revealed the impact of climate factors at different scales on runoff changes, and provides a theoretical understanding for regulating and managing water resources in karst basins.

The progress in ultrahigh-resolution mass spectrometry (UHRMS) and related technologies has significantly promoted the development of petroleomics. The study of petroleomics has greatly broadened our knowledge of the composition of petroleum at the molecular level, especially heavy fractions that cannot be analyzed by gas chromatography (GC)-based methods. To date, heteroatom-containing (O, N, S, and metal atoms) compounds in petroleum have been studied extensively by UHRMS. Nevertheless, the main components of petroleum, hydrocarbon compounds, have remained out of reach of petroleomics characterization for a long time because they are too difficult to be softly and efficiently ionized for UHRMS analysis. It is undoubtedly the case that petroleum hydrocarbons should not be the missing part of petroleomics characterization since they play important roles not only as feeding pools for various high value-added petroleum products but also as critical biomarkers for geochemistry studies. Here, the most recent breakthroughs in petroleomics characterization of hydrocarbon compounds using UHRMS rather than conventional methods have been reviewed. Innovations of soft ionization methods can transform non-polar hydrocarbon molecules into molecular ions or quasi-molecular ions that are reachable for UHRMS without fragmentation. The development of data processing methods has assisted the decoding of the complicated UHRMS data to visualize the molecular composition and structure of hydrocarbon compounds. These advances make it possible to see the whole picture of petroleum compositions, from light distillation fractions to heavy distillation fractions, and from small volatile molecules to large non-volatile ones. The applications of UHRMS-based methods for petroleomics characterization of hydrocarbon compounds in crude oils and various petroleum samples including fuel oil, slurry, and even asphaltene have made a great contribution to petrochemistry and geochemistry studies, especially in the fields of molecular refining and biomarker discovery.

The Asian elephant (Elephas maximus) is a flagship species of tropical rainforests, and it has generated much concern. In this case, the gut bacterial communities of captive and wild Asian elephants are particularly noteworthy. We aim to compare the differences in bacterial diversity and antibiotic resistance gene (ARG) subtypes in fecal samples of Asian elephants from different habitats, which may affect host health. Analyses reveal that differences in the dominant species of gut bacteria between captive and wild Asian elephants may result in significant differences in ARGs. Network analysis of bacterial communities in captive Asian elephants has identified potentially pathogenic species. Many negative correlations in network analysis suggest that different food sources may lead to differences in bacterial communities and ARGs. Results also indicate that the ARG levels in local captive breeding of Asian elephants are close to those of the wild type. However, we found that local captive elephants carry fewer ARG types than their wild counterparts. This study reveals the profile and relationship between bacterial communities and ARGs in different sources of Asian elephant feces, providing primary data for captive breeding and rescuing wild Asian elephants.

Drought is one of the most destructive natural disasters in China and can cause serious environmental and socio-economic impacts. Based on monthly precipitation and temperature data from 571 meteorological stations, the Standardized Precipitation Evapotranspiration Index (SPEI) was calculated on a 12-month scale (SPEI-12) from 1985 to 2018 in mainland China, and it was compared with the records of the Bulletin of Flood and Drought Disasters in China to verify its drought monitoring accuracy. Then, run theory was used to explore in depth the spatiotemporal distribution of drought characteristics and trends in various climatic sub-regions. The results showed that: (1) the comparison with the Bulletin of Flood and Drought Disasters in China indicated that the results of SPEI-12 monitoring drought had high accuracy and could identify drought events in mainland China. (2) About 70% of the regions in mainland China experienced droughts more than 50 times, and about 43% of the regions had drought durations of between 100 and 110 months. Nearly 11% of the regions had drought severities of more than 130, which were mainly located in the Northwest Desert (NWC), the southern part of Northeast China (NEC), and the western part of North China (NC). (3) In the past 34 years, the droughts in the Northwest Desert (NWC), the western part of Inner Mongolia (IM), and the Qinghai-Tibet Plateau (TP) showed an aridity trend, while the droughts in South China (SC) and eastern Central and South China (CSC) presented a mitigation tendency. (4) Specifically, the droughts in South China (SC) were more influenced by precipitation, while those in the Northwest Desert (NWC) and Northeast China (NEC) were influenced by temperature and potential evapotranspiration, and the evolution of drought in North China (NC) and the Qinghai-Tibet Plateau (TP) was mainly influenced by soil moisture. The study could provide scientific guidance and a reference for drought response and sustainable development in China.

The prime objective of the cloud data storage process is to make the service, irrespective of being infinitely extensible, a more reliable storage and low-cost model that also encourages different data storage types. Owing to the storage process, it must satisfy the cloud users’ prerequisites. Nevertheless, storing massive amounts of data becomes critical as this affectsthe data quality or integrity. Hence, this poses various challenges for existing methodologies. An efficient, reliable cloud storage model is proposed using a hybrid heuristic approach to overcome the challenges. The prime intention of the proposed system is to store the data effectively in the cloud environment by resolving two constraints, which are general and specific (structural). The cloud data were initially gathered and used to analyze the storage performance. Since the data were extensive, different datasets and storage devices were considered. Every piece of data was specified by its corresponding features, whereas the devices were characterized by the hardware or software components. Subsequently, the objective function was formulated using the network’s structural and general constraints. The structural constraints were determined by the interactions between the devices and data instances in the cloud. Then, the general constraints regarding the data allocation rules and device capacity were defined. To mitigate the constraints, the components were optimized using the Hybrid Pelican–Billiards Optimization Algorithm (HP-BOA) to store the cloud data. Finally, the performance was validated, and the results were analyzed and compared against existing approaches. Thus, the proposed model exhibited the desired results for storing cloud data appropriately.

Acute coronary syndrome (ACS) is the most severe form of ischemic heart disease. Although it is caused by atherosclerotic plaque thrombosis or nonatherosclerotic causes, its pathophysiological mechanism of ACS is not fully understood, and its concept is constantly updated and developed. At present, the main pathophysiological mechanisms include plaque rupture, plaque erosion, calcified nodules (CN) and non-atherosclerotic causes such as coronary vasospasm and myocardial bridging (MB). These mechanisms may overlap and coexist in some ACS patients. Therefore, the pathophysiological mechanism of ACS is complex, and is of great significance for the diagnosis and treatment of ACS. This review will discuss the pathophysiological mechanisms of ACS to provide new thoughts on the pathogenesis, diagnosis and treatment of ACS.

The results of detailed studies on the beam quality of a non-chain pulsed electric discharged DF laser based on a compact inner cavity confocal positive branch unstable resonator were presented herein. The theoretical and experimental divergence angles for magnification M = 1.65, 1.85, 2.05, and 2.25 were calculated according to Fraunhofer diffraction and measured by the method of calibrated apertures. The smallest divergence of θ = 0.66 mrad was obtained with M = 2.25 in our experiment, which is 1.95 times the theoretical value. The corresponding far-field energy density at 10 km distance from the laser exit was 82.8 mJ/m2. The beam quality and energy density were increased by 11 and 91 times, respectively, compared with a similar stable resonator in our lab.

Foot-and-mouth disease (FMD) is one of the most contagious livestock diseases in the world, posing a constant global threat to the animal trade and national economies. The chemokine C-X-C motif chemokine ligand 13 (CXCL13), a biomarker for predicting disease progression in some diseases, was recently found to be increased in sera from mice infected with FMD virus (FMDV) and to be associated with the progression and severity of the disease. However, it has not yet been determined which cells are involved in producing CXCL13 and the signaling pathways controlling CXCL13 expression in these cells. In this study, the expression of CXCL13 was found in macrophages and T cells from mice infected with FMDV, and CXCL13 was produced in bone-marrow-derived macrophages (BMDMs) by activating the nuclear factor-kappaB (NF-κB) and JAK/STAT pathways following FMDV infection. Interestingly, CXCL13 concentration was decreased in sera from interleukin-10 knock out (IL-10-/-) mice or mice blocked IL-10/IL-10R signaling in vivo after FMDV infection. Furthermore, CXCL13 was also decreased in IL-10-/- BMDMs and BMDMs treated with anti-IL-10R antibody following FMDV infection in vitro. Lastly, it was demonstrated that IL-10 regulated CXCL13 expression via JAK/STAT rather than the NF-κB pathway. In conclusion, the study demonstrated for the first time that macrophages and T cells were the cellular sources of CXCL13 in mice infected with FMDV; CXCL13 was produced in BMDMs via NF-κB and JAK/STAT pathways; and IL-10 promoted CXCL13 expression in BMDMs via the JAK/STAT pathway.