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ABSTRACT Tsukamurella species have been clinically regarded as rare but emerging opportunistic pathogens causing various infections in humans. Tsukamurella pneumonia has often been misdiagnosed as pulmonary tuberculosis due to its clinical presentation resembling tuberculosis-like syndromes. Tsukamurella species have also been confused in the laboratory with other phylogenetic bacteria, such as Gordonia. This study aimed to investigate the clinical, microbiological, and molecular characteristics; species distribution; and antimicrobial susceptibility of Tsukamurella species. Immunodeficiency and chronic pulmonary disease appeared to be risk factors for Tsukamurella pneumonia, and the presence of bronchiectasis and pulmonary nodules on imaging was highly correlated with this infection. The study confirmed that groEL (heat shock protein 60) and secA (the secretion ATPase) genes are reliable for identifying Tsukamurella species. Additionally, the ssrA (stable small RNA) gene showed promise as a tool for discriminating between different Tsukamurella species with the shortest sequence length. In terms of antimicrobial susceptibility, quinolones, trimethoprim/sulfamethoxazole, amikacin, minocycline, linezolid, and tigecycline demonstrated potent in vitro activity against Tsukamurella isolates in our study. The study also proposed a resistance mechanism involving a substitution (S91R) within the quinolone-resistance-determining region of the gyrA gene, which confers resistance to levofloxacin and ciprofloxacin. Furthermore, we found that disk diffusion testing is not suitable for testing the susceptibilities of Tsukamurella isolates to ciprofloxacin, imipenem, and minocycline. In conclusion, our systematic investigation may contribute to a better understanding of this rare pathogen. Tsukamurella species are rare but emerging human pathogens that share remarkable similarities with other mycolic acid–containing genera of the order Actinomycetales, especially Mycobacterium tuberculosis. Consequently, misdiagnosis and therapeutic failures can occur in clinical settings. Despite the significance of accurate identification, antimicrobial susceptibility, and understanding the resistance mechanism of this important genus, our knowledge in these areas remains fragmentary and incomplete. In this study, we aimed to address these gaps by investigating promising identification methods, the antimicrobial susceptibility patterns, and a novel quinolone resistance mechanism in Tsukamurella species, utilizing a collection of clinical isolates. The findings of our study will contribute to improve diagnosis and successful management of infections caused by Tsukamurella species, as well as establishing well-defined performance and interpretive criteria for antimicrobial susceptibility testing.

ABSTRACTHaemophilus parasuis (H. parasuis) causes exudative inflammation, implying endothelial dysfunction during pathogen infection. However, so far, the molecular mechanism of endothelial dysfunction caused by H. parasuis has not been clarified. By using the transwell-based cell co-culture system, we demonstrate that knocking out resistin in porcine alveolar macrophages (PAMs) dramatically attenuated endothelial monolayer damage caused by H. parasuis. The resistin secreted by PAMs inhibited the expression of the tight junction proteins claudin-5 and occludin rather than the adherens junction protein VE-cadherin in co-cultured porcine aortic endothelial cells (PAECs). Furthermore, we demonstrate that resistin regulated claudin-5 and occludin expression and monolayer PAEC permeability in an LKB1/AMPK/mTOR pathway-dependent manner. Additionally, we reveal that the outer membrane lipoprotein gene lppA in H. parasuis induced resistin expression in PAMs, as deleting lppA reduced resistin expression in H. parasuis-infected PAMs, causing a significant change in LKB1/AMPK/mTOR pathway activity in co-cultured PAECs, thereby restoring tight junction protein levels and endothelial monolayer permeability. Thus, we postulate that the H. parasuis lppA gene enhances resistin production in PAMs, disrupting tight junctions in PAECs and causing endothelial barrier dysfunction. These findings elucidate the pathogenic mechanism of exudative inflammation caused by H. parasuis for the first time and provide a more profound angle of acute exudative inflammation caused by bacteria.

ABSTRACT Identification of microbial functional association networks allows interpretation of biological phenomena and a greater understanding of the molecular basis of pathogenicity and also underpins the formulation of control measures. Here, we describe PPNet, a tool that uses genome information and analysis of phylogenetic profiles with binary similarity and distance measures to derive large-scale bacterial gene association networks of a single species. As an exemplar, we have derived a functional association network in the pig pathogen Streptococcus suis using 81 binary similarity and dissimilarity measures which demonstrates excellent performance based on the area under the receiver operating characteristic (AUROC), the area under the precision-recall (AUPR), and a derived overall scoring method. Selected network associations were validated experimentally by using bacterial two-hybrid experiments. We conclude that PPNet, a publicly available (https://github.com/liyangjie/PPNet), can be used to construct microbial association networks from easily acquired genome-scale data. IMPORTANCE This study developed PPNet, the first tool that can be used to infer large-scale bacterial functional association networks of a single species. PPNet includes a method for assigning the uniqueness of a bacterial strain using the average nucleotide identity and the average nucleotide coverage. PPNet collected 81 binary similarity and distance measures for phylogenetic profiling and then evaluated and divided them into four groups. PPNet can effectively capture gene networks that are functionally related to phenotype from publicly prokaryotic genomes, as well as provide valuable results for downstream analysis and experiment testing.

Glaesserella parasuis is well-known for causing Glässer’s disease, which costs the worldwide swine industry millions of dollars each year. It has been reported the symptom of pleural thickening during Glässer’s disease but this symptom has received little attention. And there is no research on the elements which promote pleural thickening. In this study, pleural thickening was discovered to be associated with increased collagen fibers and elastic fibers. Furthermore, collagen-I and elastin were found to be up-regulated and concentrated in the pleura at the mRNA and protein levels following infection. To summarize, our findings add to the theoretical understanding of Glässer’s disease and provide strong support for further research into the pathogenic mechanism of Glaesserella parasuis and the program’s target treatment.

Bacterial infections activate autophagy and autophagy restricts pathogens such as Haemophilus parasuis through specific mechanisms. Autophagy is associated with the pathogenesis of H. parasuis. However, the mechanisms have not been clarified. Here, we monitored autophagy processes using confocal microscopy, western blot, and transmission electron microscopy (TEM) and found that H. parasuis SH0165 (high-virulent strain) but not HN0001 (non-virulent strain) infection enhanced autophagy flux. The AMPK/mTOR autophagy pathway was required for autophagy initiation and ATG5, Beclin-1, ATG7, and ATG16L1 emerged as important components in the generation of the autophagosome during H. parasuis infection. Moreover, autophagy induced by H. parasuis SH0165 turned to fight against invaded bacteria and inhibit inflammation. Then we further demonstrated that autophagy blocked the production of the cytokines IL-8, CCL4, and CCL5 induced by SH0165 infection through the inhibition of NF-κB, p38, and JNK MAPK signaling pathway. Therefore, our findings suggest that autophagy may act as a cellular defense mechanism in response to H. parasuis and provide a new way that autophagy protects the host against H. parasuis infection.

In this study, animal experimentation verified that the canonical Wnt/β-catenin signaling pathway was activated under a reduced activity of p-β-catenin (Ser33/37/Thr41) and an increased accumulation of β-catenin in the lungs and kidneys of pigs infected with a highly virulent strain of H. parasuis. In PK-15 and NPTr cells, it was also confirmed that infection with a high-virulence strain of H. parasuis induced cytoplasmic accumulation and nuclear translocation of β-catenin. H. parasuis infection caused a sharp degradation of E-cadherin and an increase of the epithelial cell monolayer permeability, as well as a broken interaction between β-catenin and E-cadherin dependent on Wnt/β-catenin signaling pathway. Moreover, Wnt/β-catenin signaling pathway also contributed to the initiation of epithelial-mesenchymal transition (EMT) during high-virulence strain of H. parasuis infection with expression changes of epithelial/mesenchymal markers, increased migratory capabilities as well as the morphologically spindle-like switch in PK-15 and NPTr cells. Therefore, we originally speculated that H. parasuis infection activates the canonical Wnt/β-catenin signaling pathway leading to a disruption of the epithelial barrier, altering cell structure and increasing cell migration, which results in severe acute systemic infection characterized by fibrinous polyserositis during H. parasuis infection.

BackgroundSubthreshold depression (StD) is a condition that significantly influences the mental health and quality of life of college students and increases the risk of developing major depressive disorder (MDD). Exercise therapy has been found to be effective, but may not be enjoyable for everyone. exergames, as a form of exercise therapy, address the limitations of traditional exercise by incorporating gaming elements to make physical activity more entertaining and interactive. Currently, the Nintendo Switch is one of the most widely used exergame devices.AimsTo explore the effectiveness of a Nintendo Switch-based exergame intervention on college students with StD compared to a control group, and to analyze their perceptions of the program.MethodsThis study will employ an explanatory sequential design, starting with a quantitative evaluation using a randomized controlled trial (RCT), followed by a supplementary qualitative study. College students identified as having StD will be randomly allocated in a 1:1 ratio into the exergame intervention group (EIG) or the control group (CG). College students in the EIG will participate in a Nintendo Switch-based exergame program for 8 weeks, with 2–3 sessions per week, lasting 50–60 min each. Participant outcomes in both conditions will be assessed at pre-intervention (T0, week 0), post-intervention (T1, week 8), 1 month after the intervention (T2, week 12), and 2 months after the intervention (T3, week 16), and a generalized linear mixed model will be used for analysis. In the qualitative part of this study, interviews will be conducted with college students with StD from the EIG at T1 to explore their experiences of receiving the intervention, and content analysis will be applied to the data collected.DiscussionNintendo provides a user-friendly platform for college students with StD to engage in electronic gaming. Limited research has explored the mental health outcomes of interventions using this type of technology in young people with StD. If the exergame program proves to be effective, it could offer a convenient and feasible intervention for further enhancing the psychological well-being of college students.Clinical trial registrationThis study was registered in the Chinese Clinical Trial Registry (number: ChiCTR2300068970) on 2nd March 2023.

Background and objectivesTo develop a nomogram for mild cognitive impairment (MCI) in patients with subjective cognitive decline (SCD) undergoing physical examinations in China.MethodsWe enrolled 370 patients undergoing physical examinations at the Medical Center of the First Hospital of Jilin University, Jilin Province, China, from October 2022 to March 2023. Of the participants, 256 were placed in the SCD group, and 74 were placed in the MCI group. The population was randomly divided into a training set and a validation set at a 7:3 ratio. A least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. The performance and clinical utility of the nomogram were determined using Harrell’s concordance index, calibration curves, and decision curve analysis (DCA).ResultsCognitive reserve (CR), age, and a family history of hypertension were associated with the occurrence of MCI. The predictive nomogram showed satisfactory performance, with a concordance index of 0.755 (95% CI: 0.681–0.830) in internal verification. The Hosmer–Lemeshow test results suggested that the model exhibited good fit (p = 0.824). In addition, DCA demonstrated that the predictive nomogram had a good clinical net benefit.DiscussionWe developed a simple nomogram that could help secondary preventive health care workers to identify elderly individuals with SCD at high risk of MCI during physical examinations to enable early intervention.

Abstract Molecular ions are relatively cold in the E region ionosphere; however, they can upwell to the magnetosphere during geomagnetically active times. Resonance between electrostatic ion cyclotron (EIC) waves is a potential pathway to energize molecular ions. In this work, the E region ionospheric plasma was modeled in the laboratory, and EIC waves were excited by a nonuniform field‐aligned current. The EIC wave was excited even when the ion neutral collision frequency is much higher than the ion cyclotron frequency, and the fundamental frequency was observed to be below the ion cyclotron frequency. In addition, the wave dispersion of the collisional EIC wave was calculated, which shows a consistent trend with experimental results as the collisions increasing. Therefore, this work suggests that EIC waves can be excited in the E region ionospheric‐like plasma, which can support the explanation of the energization of molecular ions in the E region ionosphere.

Abstract Surface coal mining procedures include piercing—blasting—mining and loading—transportation—discharging, blasting link exists due to the poor blasting effect leads to low loading efficiency, blasting dust caused by environmental pollution and other problems. In this paper, from the mechanical characteristics of the water medium, we analyze in detail the transferring effect, transducing effect and bubble pulsation phenomenon of the water medium in the blasting process. The results show that when the blasting medium is water medium, the maximum principal stress is 1.53 times that of air medium; the peak energy transfer can be up to 2.73 times that of air medium. With the help of TrueGrid/LS-DYNA finite element analysis software to simulate the dynamic process of blasting, the study of the maximum principal stresses around the hole, the top of the slope, the foot of the slope on the maximum principal stress changes, the results show that the maximum principal stresses around the hole, the top of the slope, the foot of the slope unit with the increase in the water content is gradually increasing trend. Finally, combined with the actual mine production conditions for blasting field test, water-mediated blasting dust reduction rate of 75%, the use of AHP—fuzzy comprehensive evaluation method of two groups of traditional dry hole blasting and three groups of water-mediated blasting comprehensive evaluation, the results show that the water-mediated blasting scores are higher than the traditional dry hole blasting, proving that the water-mediated blasting has a certain prospect of engineering applications.

Disrupted alternative polyadenylation (APA) is frequently involved in tumorigenesis and cancer progression by regulating the gene expression of oncogenes and tumor suppressors. However, limited knowledge of tumor-type- and cell-type-specific APA events may lead to novel APA events and their functions being overlooked. Here, we compared APA events across different cell types in non-small cell lung cancer (NSCLC) and normal tissues and identified functionally related APA events in NSCLC. We found several cell-specific 3′-UTR alterations that regulate gene expression changes showed prognostic value in NSCLC. We further investigated the function of APA-mediated 3′-UTR shortening through loss of microRNA (miRNA)-binding sites, and we identified and experimentally validated several oncogene-miRNA-tumor suppressor axes. According to our analyses, we found SPARC as an APA-regulated oncogene in cancer-associated fibroblasts in NSCLC. Knockdown of SPARC attenuates lung cancer cell invasion and metastasis. Moreover, we found high SPARC expression associated with resistance to several drugs except cisplatin. NSCLC patients with high SPARC expression could benefit more compared to low-SPARC-expression patients with cisplatin treatment. Overall, our comprehensive analysis of cell-specific APA events shed light on the regulatory mechanism of cell-specific oncogenes and provided opportunities for combination of APA-regulated therapeutic target and cell-specific therapy development.

An electrochemical/I– dual-catalyzed access to sulfonated pyrazoles from pyrazolones and sodium sulfites under external oxidant-free conditions has been developed. This established electrochemical reaction works smoothly under external oxidant-free conditions and has the advantages of good functional group tolerance, easy to gram-scale synthesis, delivering up to 95% yield for 35 examples.

Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo.

Abstract The explosive growth of biomedical Big Data presents both significant opportunities and challenges in the realm of knowledge discovery and translational applications within precision medicine. Efficient management, analysis, and interpretation of big data can pave the way for groundbreaking advancements in precision medicine. However, the unprecedented strides in the automated collection of large‐scale molecular and clinical data have also introduced formidable challenges in terms of data analysis and interpretation, necessitating the development of novel computational approaches. Some potential challenges include the curse of dimensionality, data heterogeneity, missing data, class imbalance, and scalability issues. This overview article focuses on the recent progress and breakthroughs in the application of big data within precision medicine. Key aspects are summarized, including content, data sources, technologies, tools, challenges, and existing gaps. Nine fields—Datawarehouse and data management, electronic medical record, biomedical imaging informatics, Artificial intelligence‐aided surgical design and surgery optimization, omics data, health monitoring data, knowledge graph, public health informatics, and security and privacy—are discussed.

Measurement(s) knowledge graph • Relation Code • textual entity Technology Type(s) machine learning • computational modeling technique

Lung adenocarcinoma (LUAD) is a deadly tumor with dynamic evolutionary process. Although much endeavors have been made in identifying the temporal patterns of cancer progression, it remains challenging to infer and interpret the molecular alterations associated with cancer development and progression. To this end, we developed a computational approach to infer the progression trajectory based on cross-sectional transcriptomic data. Analysis of the LUAD data using our approach revealed a linear trajectory with three different branches for malignant progression, and the results showed consistency in three independent cohorts. We used the progression model to elucidate the potential molecular events in LUAD progression. Further analysis showed that overexpression of BUB1B, BUB1 and BUB3 promoted tumor cell proliferation and metastases by disturbing the spindle assembly checkpoint (SAC) in the mitosis. Aberrant mitotic spindle checkpoint signaling appeared to be one of the key factors promoting LUAD progression. We found the inferred cancer trajectory allows to identify LUAD susceptibility genetic variations using genome-wide association analysis. This result shows the opportunity for combining analysis of candidate genetic factors with disease progression. Furthermore, the trajectory showed clear evident mutation accumulation and clonal expansion along with the LUAD progression. Understanding how tumors evolve and identifying mutated genes will help guide cancer management. We investigated the clonal architectures and identified distinct clones and subclones in different LUAD branches. Validation of the model in multiple independent data sets and correlation analysis with clinical results demonstrate that our method is effective and unbiased.

Background: Recently, various combination therapies for tumors have garnered popularity because of their synergistic effects in improving therapeutic efficacy and reducing side effects. However, incomplete intracellular drug release and a single method of combining drugs are inadequate to achieve the desired therapeutic effect.Methods: A reactive oxygen species (ROS)-sensitive co-delivery micelle (Ce6@PTP/DP). It was a photosensitizer and a ROS-sensitive paclitaxel (PTX) prodrug for synergistic chemo-photodynamic therapy. Micelles size and surface potential were measured. In vitro drug release, cytotoxicity and apoptosis were investigated.Results: Ce6@PTP/DP prodrug micelles exhibited good colloidal stability and biocompatibility, high PTX and Ce6 loading contents of 21.7% and 7.38%, respectively. Upon light irradiation, Ce6@PTP/DP micelles endocytosed by tumor cells can generate sufficient ROS, not only leading to photodynamic therapy and the inhibition of tumor cell proliferation, but also triggering locoregional PTX release by cleaving the thioketal (TK) bridged bond between PTX and methoxyl poly (ethylene glycol). Furthermore, compared with single drug-loaded micelles, the light-triggered Ce6@PTP/DP micelles exhibited self-amplified drug release and significantly greater inhibition of HeLa cell growth.Conclusion: The results support that PTX and Ce6 in Ce6@PTP/DP micelles exhibited synergistic effects on cell-growth inhibition. Thus, Ce6@PTP/DP micelles represent an alternative for realizing synergistic chemo-photodynamic therapy.

As a typical human pathogenic fungus, Cryptococcus neoformans is a life-threatening invasive fungal pathogen with a worldwide distribution causing ∼700,000 deaths annually. Cryptococcosis is not just an infection with multi-organ involvement, intracellular survival and extracellular multiplication of the fungus also play important roles in the pathogenesis of C. neoformans infections. Because adequate accumulation of drugs at target organs and cells is still difficult to achieve, an effective delivery strategy is desperately required to treat these infections. Here, we report a bioresponsive micro-to-nano (MTN) system that effectively clears the C. neoformans in vivo. This strategy is based on our in-depth study of the overexpression of matrix metalloproteinase 3 (MMP-3) in infectious microenvironments (IMEs) and secreted protein acidic and rich in cysteine (SPARC) in several associated target cells. In this MTN system, bovine serum albumin (BSA, a natural ligand of SPARC) was used for the preparation of nanoparticles (NPs), and then microspheres were constructed by conjugation with a special linker, which mainly consisted of a BSA-binding peptide and an MMP-3-responsive peptide. This MTN system was mechanically captured by the smallest capillaries of the lungs after intravenous injection, and then hydrolyzed into BSA NPs by MMP-3 in the IMEs. The NPs further targeted the lung tissue, brain and infected macrophages based on the overexpression of SPARC, reaching multiple targets and achieving efficient treatment. We have developed a size-tunable strategy where microspheres “shrink” to NPs in IMEs, which effectively combines active and passive targeting and may be especially powerful in the fight against complex fungal infections.

In forest ecosystems, elevation gradient is one of the most influential factors on soil characteristics, vegetation types, and soil microorganisms. However, it remains unclear how the elevation gradient and the soil environment under its influence affect soil microbial communities under two distinct vegetation types. In this study, high-throughput sequencing technology from Illumina was utilized to examine the response of soil microbial communities to elevation and their driving factors in forests of Pinus taiwanensis and Pinus massoniana in various Jiangxi Province locales. The results demonstrated that the elevation gradients of the two pines had significant effects on soil organic carbon (SOC) and total nitrogen (TN), both in unimodal mode as well as on the alpha diversity of soil microbes. The community structure of soil bacteria is more sensitive to elevation than that of soil fungus. At different elevations in the two pine forests, Acidobacteria, Proteobacteria, Chloroflexi, Verrucomicrobia, Bacteroidetes, Patescibacteria, and Thaumarchaeota are the dominant bacterial phyla, and Ascomycota, Basidiomycota, and Mucoromycota are the dominant fungal phyla. This investigation revealed that SOC and TN were the two most influential factors on the alteration of the soil microbial community in two pine forests. In summary, there were substantial changes in soil microbial diversity and community composition across the two different pine forests, with elevation and soil characteristics (SOC and TN) serving as the primary drivers.

The main peach-producing area in Shandong is an important peach fruit-producing area in China. Understanding the nutritional properties of the soil in peach orchards helps us to understand the evolution of soil properties and adjust management methods in a timely manner. This study focuses on 52 peach orchards in the main peach-producing area in Shandong as the research object. The spatiotemporal changes in soil traits and their influential factors were studied in depth, and the changes in soil fertility were effectively evaluated. The results showed that the input of nitrogen, phosphorus and potassium from organic fertilizer in 2021 was significantly higher than that in 2011, while the input of fertilizer in 2011 was significantly higher than that in 2021. Compared with traditional parks, both organic fertilizer inputs and chemical fertilizer inputs in demonstration parks showed a significant downwards trend. There was no significant change in pH values between 2011 and 2021. In 2021, the soil organic matter (SOM) contents of the 0–20 cm and 20–40 cm layers were 24.17 g·kg−1 and 23.38 g·kg−1, respectively, an increase of 29.3% and 78.47% over the values measured in 2011. Compared with 2011, the content of soil alkaloid nitrogen (AN) decreased significantly in 2021, and the contents of available phosphorus (AP) and available potassium (AK) in the soil increased significantly. According to the calculation results of the comprehensive fertility index (IFI) value, we found that in 2021, compared with 2011, the quality of soil fertility improved, most of which was at the medium and high levels. The research results show that the fertilizer-saving and synergistic approach in peach orchards in China significantly improved the soil nutrition. In the future, research on suitable comprehensive technologies should be strengthened in the management of peach orchards.

Because of implementation of ecological projects, the restoration of vegetation not only changes the typological composition and spatial structure of the landscape, but also improves the regional ecosystem function. The present study considered the effects of natural-anthropogenic factors and landscape connectivity on vegetation restoration. It also explored the impact and underlying mechanisms by which structural changes in landscape connectivity affect vegetation coverage in the karst region of Guizhou Province and provided a novel perspective for the maintenance of regional ecological security. We used morphological spatial pattern analysis (MSPA) and integrated valuation of ecosystem services and tradeoffs (InVEST) and circuit theory to identify ecological networks and explore the changes in landscape structure. We performed a Theil-Sen Median trend analysis and a Mann-Kendall (MK) trend test to determine spatiotemporal variations in vegetation coverage. We conducted a coupling analysis to discover correlations between the average cumulative current density (CCD) and the normalized difference vegetation index (NDVI) in various karst landform counties. We also implemented a geographical detector to detect the factors affecting the NDVI trend and disclose interactions among factors. The results showed that (1) Though the total area of forests and core areas was reduced, the ecological networks and landscape connectivity steadily improved. (2) Areas with improved vegetation coverage accounted for 77.77% of the total. By contrast, the degraded areas covered 14.28% while the remaining 7.95% was stable. (3) The relationships between the average CCD and the NDVI were inconsistent among various geomorphological counties. The counties with the highest proportions of karst landforms presented with negative correlations between the average CCD and the NDVI in 2005 and positive correlations between these parameters in 2018. (4) The NDVI trend was influenced by several factors. Of these, anthropogenic activity played a dominant role. Nevertheless, changes in landscape connectivity was also implicated. Attention should be paid to the impact of landscape connectivity on ecological restoration. The foregoing results indicated that the rocky desertification projects effectively improved landscape connectivity and vegetation coverage and provided a reference for developing policies establishing and maintaining ecological security of the karst ecosystem and coordinating sustainable development in this region.

Partially ionized plasma is a common occurrence in astrophysical and space environments. The emergence and development of plasma instabilities are significantly impacted by the inelastic collisions between the ions and neutrals in the partially ionized plasma, such as the charge exchange. In this study, the effect of the ion–neutral collisions on the sheared E × B flow was experimentally investigated. In the weak collision range, the shear-driven plasma instability, such as Kelvin–Helmholtz instability, was excited by the velocity-sheared flow. However, increasing ion–neutral collisions resulted in a decrease in the magnitude of the sheared E × B flow due to charge exchange–induced drag forces. Consequently, the Kelvin–Helmholtz instability is suppressed, and the Rayleigh–Taylor instability is triggered. The underlying mechanism was elucidated through experimental findings and numerical analysis. The result of this study proposes that a transition between the two modes occurred with increasing ion–neutral collision strength. It could be applied to the study of the solar chromosphere and prominence and planetary ionospheres, where plasma is partially ionized and the sheared E × B flow is often encountered.

Calcium and magnesium are major nutrient elements of plants, and both play an important role in plant growth and development. Pinus massoniana and P. hwangshanensis are important afforestation tree species in barren mountains in China. However, observation and research on calcium and magnesium nutrition of dominant forest species in China are still limited. This study determined the concentration of calcium and magnesium in needles for two species from five sites in East China by inductively coupled plasma optical emission spectrometry (ICP-OES). We then explored the inter- and intra-population variation pattern of calcium and magnesium and their relationship with environmental factors. There were significant differences in traits among populations. The strongest factors, which impacted the variation of calcium and magnesium concentration, were elevation and individual differences, respectively. Element concentration was correlated to environmental factors such as longitude, latitude, elevation, and mean annual temperature. The results of this study can be helpful for a better understanding of tree growth, population survival, and forest succession.

N, S co-doped bio-carbons with a hierarchical porous structure and high surface area were prepared using a molten salt method and by adopting Entermorpha prolifera (EP) as a precursor. The structure and composition of the bio-carbons could be manipulated by the salt types adopted in the molten salt assisted pyrolysis. When the carbons were used as an activating agent for peroxydisulfate (PDS) in SMX degradation in the advanced oxidation process (AOP), the removal performance in the case of KCl derived bio-carbon (EPB-K) was significantly enhanced compared with that derived from NaCl (EPB-Na). In addition, the optimized EPB-K also demonstrated a high removal rate of 99.6% in the system that used local running water in the background, which proved its excellent application potential in real water treatment. The degradation mechanism study indicated that the N, S doping sites could enhance the surface affinity with the PDS, which could then facilitate 1O2 generation and the oxidation of the SMX. Moreover, a detailed techno-economic assessment suggested that the price of the salt reaction medium was of great significance as it influenced the cost of the bio-carbons. In addition, although the cost of EPB-K was higher (USD 2.34 kg−1) compared with that of EPB-Na (USD 1.72 kg−1), it was still economically competitive with the commercial active carbons for AOP water treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.

Mild cognitive impairment (MCI) is a transition between normal cognition (NC) and Alzheimer’s disease (AD). Differences in cortical thickness (ΔCT) have been reported in cases that degenerate from MCI to AD. The aspects of genetic and transcriptional variation related to ΔCT are vague. In this study, using an 8-year longitudinal follow-up outcome, we investigated the genetic correlates of ΔCT in MCI subjects with degeneration from MCI to AD (MCI_AD). We employed partial least squares regression (PLSR) on brain T1-weighted magnetic resonance imaging (MRI) images of 180 participants [143 stable MCI (MCI_S) participants and 37 MCI_AD participants] and brain gene expression data from the Allen Institute for Brain Science (AIBS) database to investigate genes associated with ΔCT. We found that upregulated PLS component 1 ΔCT-related genes were enriched in chemical synaptic transmission. To verify the robustness and specificity of the results, we conducted PLSR analysis invalidation and specificity datasets and performed weighted gene co-expression network analysis instead of PLSR for the above three datasets. We also used gene expression data in the brain prefrontal cortex from the Gene Expression Omnibus (GEO) database to indirectly validate the robustness and specificity of our results. We conclude that transcriptionally upregulated genes involved in chemical synaptic transmission are strongly related to global ΔCT in MCI patients who experience degeneration from MCI to AD.

Nitrogen is an important nutrient element that limits plant growth and yield formation, but excessive nitrogen has negative effects on plants and the environment. It is important to reveal the molecular mechanism of high NUE (nitrogen use efficiency) for breeding peach rootstock and variety with high NUE. In this study, two peach rootstocks, Shannong–1 (S) and Maotao (M), with different NUE were used as materials and treated with 0.1 mM KNO3 for transcriptome sequencing together with the control group. From the results of comparison between groups, we found that the two rootstocks had different responses to KNO3, and 2151 (KCL_S vs. KCL_M), 327 (KNO3_S vs. KCL_S), 2200 (KNO3_S vs. KNO3_M) and 146 (KNO3_M vs. KCL_M) differentially expressed genes (DEGs) were identified, respectively, which included multiple transcription factor families. These DEGs were enriched in many biological processes and signal transduction pathways, including nitrogen metabolism and plant hormone signal transduction. The function of PpNRT2.1, which showed up-regulated expression under KNO3 treatment, was verified by heterologous expression in Arabidopsis. The plant height, SPAD (soil and plant analyzer development) of leaf and primary root length of the transgenic plants were increased compared with those of WT, indicating the roles of PpNRT2.1 in nitrogen metabolism. The study uncovered for the first time the different molecular regulatory pathways involved in nitrogen metabolism between two peach rootstocks and provided gene reserve for studying the molecular mechanism of nitrogen metabolism and theoretical basis for screening peach rootstock or variety with high NUE.

Ecosystem services (ESs) are an essential link between ecosystems and human well-being, and trade-offs/synergies happen in ESs at different temporal and spatial scales. It is crucial to explore patterns of trade-offs/synergies among ESs, and their nonlinear relationships with changes in ESs. The primary objective of this study was to evaluate five ESs in 2000 and 2018: namely, water yield, food production, carbon sequestration, soil conservation, and habitat quality in mountainous regions of Southwest China. The mean values of the five ESs increased by 365.8 m3/ha, 13.92 t/hm2, 497.09 TgC/yr2, 138.48 t/km2, and 0.002, respectively. Using spatial statistics and analysis, an ES trade-off synergy model (ESTD) was constructed for the five ESs change values. Overall, soil conservation has a trade-off with all five ESs, except habitat quality; this trade-off is increasing slightly. Water yield is in synergy with all ESs except soil conservation, with decreasing synergy; habitat quality is in synergy with all ESs except food production, with increasing synergy. Finally, the nonlinear relationship between the value of the change in the ES and ESTD was analyzed using a generalized additive model. Changes in water yield showed the greatest impact on ESTD except for food production, wherein changes in all three ESs had minimal impacts on ESTD. Food production dominates its trade-offs/synergies relationship with soil conservation; carbon sequestration is the dominant player in its trade-offs/synergies relationship with soil conservation. Habitat quality has a secondary position of influence, except in the trade-offs/synergies involving food production. By exploring the drivers of trade-offs/synergies among ESs, this study can provide guidance for the effective implementation of policies related to ecological protection and restoration.

Iron tailing powder (ITP) is considered to have the potential to replace cement to manufacture ultra-high-performance concrete (UHPC). However, the performance of UHPC with the addition of ITP after exposure to high temperatures is more complex. This investigation prepares seven UHPC formulations by introducing different contents of ITP and investigates the mechanical behavior (residual strength), bound water content, and microstructural properties (crystalline and amorphous phases, chemical structure, and morphology) of UHPC subjected to elevated temperatures. The experimental results show that the addition of ITP postpones the spalling of concrete when exposed to high temperatures. The concrete incorporating 15% ITP maintains 53.8% of its original strength at 800°C, unlike the concrete without ITP that maintains 31.6% of its original strength. The addition of ITP increases the number of micropores/cracks in concrete and helps release the vapor pressure caused by water evaporation. The findings of this investigation highlight the potential application of ITP for future UHPC design and manufacture.

BackgroundAmong patients with acute respiratory failure requiring prolonged mechanical ventilation, tracheostomies are typically placed after approximately 7 to 10 days. Yet half of patients admitted to the intensive care unit receiving tracheostomy will die within a year, often within three months. Existing mortality prediction models for prolonged mechanical ventilation, such as the ProVent Score, have poor sensitivity and are not applied until after 14 days of mechanical ventilation. We developed a model to predict 3-month mortality in patients requiring more than 7 days of mechanical ventilation using deep learning techniques and compared this to existing mortality models.MethodsRetrospective cohort study. Setting: The Medical Information Mart for Intensive Care III Database. Patients: All adults requiring ≥ 7 days of mechanical ventilation. Measurements: A neural network model for 3-month mortality was created using process-of-care variables, including demographic, physiologic and clinical data. The area under the receiver operator curve (AUROC) was compared to the ProVent model at predicting 3 and 12-month mortality. Shapley values were used to identify the variables with the greatest contributions to the model.ResultsThere were 4,334 encounters divided into a development cohort (n = 3467) and a testing cohort (n = 867). The final deep learning model included 250 variables and had an AUROC of 0.74 for predicting 3-month mortality at day 7 of mechanical ventilation versus 0.59 for the ProVent model. Older age and elevated Simplified Acute Physiology Score II (SAPS II) Score on intensive care unit admission had the largest contribution to predicting mortality.DiscussionWe developed a deep learning prediction model for 3-month mortality among patients requiring ≥ 7 days of mechanical ventilation using a neural network approach utilizing readily available clinical variables. The model outperforms the ProVent model for predicting mortality among patients requiring ≥ 7 days of mechanical ventilation. This model requires external validation.

Cement emulsified asphalt (CEA) mortars achieve insufficient bond strength with substrate cement concrete slab. To ameliorate problems emerging from this, the emulsified asphalt (EA) in CEA mortars was partly replaced by epoxy emulsion (EE) at contents of 0%, 10%, 20%, and 30%, yielding CEA mortars with enhanced properties. The bond strength, mechanical strength, toughness, and durability (including drying shrinkage and erosion resistance) of modified CEA mortars were assessed. The results showed that partial replacement of EA with EE improved the bond strength, mechanical strength, drying shrinkage, and erosion resistance of CEA mortars. A good correlation was found between the proportions of the EE replacement and the bond strength of CEA mortars. Partial replacement of EA with a small amount of EE exerted no significant effect on the toughness of CEA mortar. The stronger network structure of CEA mortars containing EE improved the compactness, thus improving the performance of CEA mortars. Based on these findings, EE is suggested as partial replacement of EA for enhancing the properties of CEA mortars.

Objective: This work is to study the effect of Rhizopus nigrum polysaccharide EPS1-1 on hepatocellular carcinoma (HCC) in vitro and in vivo.Methods: HepG2 and Huh-7 cells and nude mice models of liver cancers were used in this study. The cells and nude mice were treated with EPS1-1 at different concentrations. The CCK8 assays were used to measure the proliferation activities of cells, apoptosis was determined with flow cytometry, cell migration was measured by wound-healing assays, cell invasion was evaluated by Transwell assay, and the survival periods of different groups of tumor-bearing mice were compared. Real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins of the genes related to proliferation, apoptosis, migration, and invasion.Results:In vitro experiments revealed that when treated with EPS1-1, HepG2 and Huh-7 cell proliferation activities decreased, while there was an increase for the apoptosis rate, and the migration and invasion capabilities were significantly reduced. In vivo experiments showed that EPS1-1 could significantly reduce the tumor growth and lung metastasis of HCC, and prolong the survival periods of tumor-bearing nude mice. Furthermore, EPS1-1 has no apparent damage to the heart, liver, and kidney. Further studies showed that EPS1-1 could affect the expression of proliferation-related genes CCND1 and c-Myc, apoptosis-related genes BAX and Bcl-2, and migration and invasion related genes Vimentin and Slug, thereby affecting the biological process of HCC.Conclusion: EPS1-1 can inhibit the malignant process of HCC in vitro and in vivo, which indicates that EPS1-1 has the potential value of clinical application as chemotherapy or adjuvant in the treatment of liver cancer.

ObjectivesThe frontal-striatum-thalamus pathway is important in the glutamic neural circuit. The hypofunction of GRIN1 and GRIA2 subunits from glutamic receptors has been hypothesized as the primary process in the etiology of schizophrenia. Identified gene polymorphism involved in the pathogenesis of schizophrenia may uncover relevant mechanism pathways.MethodsWe selected two loci of rs11146020 and rs3813296 distributed in GRIN1 and GRIA2 genes and tested their main and interaction effects on causality connections and structural characteristics in the frontal-striatum-thalamus pathway in 55 Han Chinese first-episode negative schizophrenia patients.ResultsWe found that: (1) rs11146020 has a significant main effect on the causality connections between the bilateral dorsolateral prefrontal cortex, and rs3813296 mainly influences those of the descending pathway from the prefrontal cortex to the striatum; (2) interaction effect of rs11146020 and rs3813296 on causality connections are located in the ascending pathway from the pallidum to the dorsolateral prefrontal cortex; and (3) the two loci have effects on the volumes of several regions of this pathway.ConclusionOur results suggested there is modulation on glutamic frontal-striatum-thalamus pathway by rs11146020 and rs3813296 gene polymorphism. Patients with different genotypes have different neuroimaging characteristics, which indirectly reminded clinicians those patients should receive different clinical interventions.

Humulus scandens was first adopted as a biomass precursor to prepare biochars by means of a facile molten salt method. The optimized biochar exhibits a high specific surface area of ~450 m2/g, a rich porous structure and abundant oxygen functional groups, which demonstrate excellent adsorption performance for heavy metal ions. The isotherm curves fit well with the Langmuir models, indicating that the process is governed by the chemical adsorption, and that the maximum adsorption capacity can reach 748 and 221 mg/g for Pb2+ and Cu2+, respectively. In addition, the optimized biochar demonstrates good anti-interference ability and outstanding removal efficiency for Cu2+ and Pb2+ in simulated wastewater. The mechanism investigation and DFT calculation suggest that the oxygen functional groups play dominant roles in the adsorption process by enhancing the binding energy towards the heavy metal ions. Meanwhile, ion exchange also serves as the main reason for the effective removal.

Herein, a composite structure, consisting of Cu nanoparticles (NPs) deposited onto carbon nanotubes and modified with ferrocene-branched chitosan, was prepared in order to develop a nonenzymatic electrochemical glucose biosensor ferrocene-chitosan/carbon nanotube@ Cu (Fc-CHIT/CNT@Cu). The elemental composition of the carbon nanohybrids, morphology and structure were characterized by various techniques. Electrochemical impedance spectroscopy (EIS) was used to study the interfacial properties of the electrodes. Cyclic voltammetry (CV) and chronoamperometry methods in alkaline solution were used to determine glucose biosensing properties. The synergy effect of Cu NPs and Fc on current responses of the developed electrode resulted in good glucose sensitivity, including broad linear detection between 0.2 mM and 22 mM, a low detection limit of 13.52 μM and sensitivity of 1.256 μA mM−1cm−2. Moreover, the modified electrode possessed long-term stability and good selectivity in the presence of ascorbic acid, dopamine and uric acid. The results indicated that this inexpensive electrode had potential application for non-enzymatic electrochemical glucose detection.

Chemical examination of a South China Sea soft coral Lobophytum sp. led to the isolation of three new α-methylene-γ-lactone-containing cembranoids, (1R*,3R*, 4R*,14R*,7E,11E)-3,4-epoxycembra-7,11,15(17)-trien-16,14-olide (1), (1R*,7S*,14S*,3E, 11E)-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide (2), and (1R*,7S*,14S*, 3E,11E)-18-acetoxy-7-hydroperoxycembra-3,8(19),11,15(17)-tetraen-16,14-olide (3), along with eleven known analogues 4–14. The structures of the new compounds were elucidated through extensive spectroscopic analysis, including 1D and 2D NMR data. Compounds 1–3 exhibited moderate cytotoxic activity against the selected tumor cell lines. Moreover, 2 and 3 were found to be moderate inhibitors against the bacteria S. aureus and S. pneumoniae.

Six new casbane diterpenoids, named as sinularcasbanes A–F (1–6), along with six known analogues 7–12, were isolated from a South China Sea soft coral, Sinularia sp. The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with data reported in the literature. All compounds were evaluated for their cytotoxicity against selected cancer cell lines and the inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages.

Ten new cembrane-based diterpenes, locrassumins A–G (1–7), (–)-laevigatol B (8), (–)-isosarcophine (9), and (–)-7R,8S-dihydroxydeepoxysarcophytoxide (10), were isolated from a South China Sea collection of the soft coral Lobophytum crassum, together with eight known analogues (11–18). The structures of the new compounds were determined by extensive spectroscopic analysis and by comparison with previously reported data. Locrassumin C (3) possesses an unprecedented tetradecahydrobenzo[3,4]cyclobuta[1,2][8]annulene ring system. Compounds 1, 7, 12, 13, and 17 exhibited moderate inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC50 values of 8–24 μM.