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Wind energy development in Central Asia can help alleviate drought and fragile ecosystems. Nevertheless, current studies mainly used the global climate models (GCMs) to project wind speed and energy. The simulated biases in GCMs remain prominent, which induce a large uncertainty in the projected results. To reduce the uncertainties of projected near-surface wind speed (NSW) and better serve the wind energy development in Central Asia, the Weather Research and Forecasting (WRF) model with bias-corrected GCMs was employed. Compared with the outputs of GCMs, dynamical downscaling acquired using the WRF model can better capture the high- and low-value centres of NSWS, especially those of Central Asia's mountains. Meanwhile, the simulated NSWS bias was also reduced. For future changes in wind speed and wind energy, under the Representative Concentration Pathway 4.5 (RCP4.5) scenario, NSWS during 2031–2050 is projected to decrease compared with that in 1986–2005. The magnitude of NSWS reduction during 2031–2050 will reach 0.1 m s−1, and the maximum reduction is projected to occur over the central and western regions (>0.2 m s−1). Furthermore, future wind power density (WPD) can reveal nonstationarity and strong volatility, although a downward trend is expected during 2031–2050. In addition, the higher frequency of wind speeds at the turbine hub height exceeding 3.0 m s−1 can render the plain regions more suitable for wind energy development than the mountains from 2031 to 2050. This study can serve as a guide in gaining insights into future changes in wind energy across Central Asia and provide a scientific basis for decision makers in the formulation of policies for addressing climate change.

Abstract Objectives To investigate the effect of neutral 10-methacryloyloxydecyl dihydrogen phosphate salt (MDP-Na) on the dentin bond strength and remineralization potential of etch-&-rinse adhesive. Methods Two experimental etch-&-rinse adhesives were formulated by incorporating 0 wt% (E0) or 20 wt% (E20) neutral MDP-Na into a basic primer. A commercial adhesive, Adper Single Bond 2 (SB, 3 M ESPE), served as the control. Sixty prepared teeth were randomly allocated into three groups (n = 20) and bonded using either one of the experimental adhesives or SB. Following 24 h of water storage, the bonded specimens were sectioned into resin-dentin sticks, with four resin-dentin sticks obtained from each tooth for microtensile bond strength (MTBS) test. Half of the sticks from each group were immediately subjected to tensile loading using a microtensile tester at a crosshead speed of 1 mm/min, while the other half underwent tensile loading after 6-month incubation in artificial saliva (AS). The degree of conversion (DC) of both the control and experimental adhesives (n = 6 in each group) and the adsorption properties of MDP-Na on the dentin organic matrix (n = 5 in each group) were determined using Fourier-transform infrared spectrometry. Furthermore, the effectiveness of neutral MDP-Na in promoting the mineralization of two-dimensional collagen fibrils and the adhesive-dentin interface was explored using transmission electron microscopy and selected-area electron diffraction. Two- and one-way ANOVA was employed to assess the impact of adhesive type and water storage on dentin bond strength and the DC (α = 0.05). Results The addition of MDP-Na into the primer increased both the short- and long-term MTBS of the experimental adhesives (p = 0.00). No difference was noted in the DC between the control, E0 and E20 groups (p = 0.366). The MDP-Na remained absorbed on the demineralized dentin even after thorough rinsing. The intra- and extra-fibrillar mineralization of the two-dimensional collagen fibril and dentin bond hybrid layer was confirmed by transmission electron microscopy and selected-area electron diffraction when the primer was added with MDP-Na. Conclusions The use of neutral MDP-Na results in high-quality hybrid layer that increase the dentin bond strength of etch-&-rinse adhesive and provides the adhesive with remineralizing capability. This approach may represent a suitable bonding strategy for improving the dentin bond strength and durability of etch-&-rinse adhesive.

Objective: To identify distinct trajectories of psychological resilience among Chinese patients with maintenance hemodialysis, explore influencing factors and inform the formulation of corresponding interventions. Methods: This was a multi-center longitudinal study with a 6-month follow-up. With convenience sampling, a total of 231 patients with maintenance hemodialysis were recruited between September 2020 and July 2021. Patients’ characteristics, including sociodemographic information, social support and family resilience was collected through structured questionnaires as potential baseline influencing factors of psychological resilience trajectories. Psychological resilience was evaluated using the 25-item Chinese version of the Conner and Davidson resilience scale. Latent class growth modeling was conducted to identify homogeneous subgroups with distinct trajectories of psychological resilience. Univariable and multinomial logistic regression analysis were used to examine whether baseline influencing factors were associated with trajectories in patients with maintenance hemodialysis. Results: Five distinct psychological resilience trajectory groups were identified: declining group (n = 20, 8.7 %), rising group (n = 17, 7.4 %), moderate-stable group (n = 128, 55.4 %), high-stable group (n = 7, 3.0 %) and low-stable group (n = 59, 25.5 %). High-stable group and moderate-stable group were combined into the well-psychological resilience group for multinomial logistic regression analysis. The multinomial logistic regression analysis showed that influencing factors associated with trajectories of psychological resilience were age, religion, monthly household income per capita, and baseline family resilience. Conclusions: The results highlight the heterogeneity in the development of psychological resilience among Chinese patients with maintenance hemodialysis. There is a need for healthcare professionals to screen for trajectories of psychological resilience in Chinese maintenance hemodialysis patients and prepare individual mental healthcare interventions.

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon’s optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3–5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders’ cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways.

A rapid high-performance liquid chromatography (HPLC) protocol for the determination of amino acids with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatization was successfully developed for assessing amino acid levels in six species of representative commercial bee pollen. Based on a poroshell column, a favorable chromatographic separation of seventeen amino acids was achieved in approximately 10 min with satisfactory resolution. The LOD and LOQ of this method were less than 0.034 μg/mL and 0.232 μg/mL, and the intra- and inter-day RSDs ranged between 0.86–5.28 % and 3.21–6.50 %, respectively. The matrix effect (ME) ranged from −8 to 3, implying that the matrix effect was not significant. Under the optimum conditions, the established method was adopted to determine amino acids in six types of bee pollens. The results showed that the total amino acid content ranged from 151.94 mg/g (Rosa rugosa) to 214.52 mg/g (Leonurus artemisia) in the six bee pollen species. Notably, proline (Pro), valine (Val), leucine (Leu), and phenylalanine (Phe) were abundant in the majority of samples. To identify the suspicious samples, principal component analysis (PCA) was performed, and each type of bee pollen was differentiated. Results showed that, in the market, the qualification rate of RR was 100 %, but that of NN was merely 62.5 %, revealing that a few of them were counterfeit. This method offers advantages such as high speed, low cost, and outstanding performance.

Abstract Adaptive metabolic responses and innate metabolites hold promising therapeutic potential for stroke, while targeted interventions require a thorough understanding of underlying mechanisms. Adiposity is a noted modifiable metabolic risk factor for stroke, and recent research suggests that it benefits neurological rehabilitation. During the early phase of experimental stroke, the lipidomic results showed that fat depots underwent pronounced lipolysis and released fatty acids (FAs) that feed into consequent hepatic FA oxidation and ketogenesis. Systemic supplementation with the predominant ketone beta‐hydroxybutyrate (BHB) is found to exert discernible effects on preserving blood‐brain barrier (BBB) integrity and facilitating neuroinflammation resolution. Meanwhile, blocking FAO‐ketogenesis processes by administration of CPT1α antagonist or shRNA targeting HMGCS2 exacerbated endothelial damage and aggravated stroke severity, whereas BHB supplementation blunted these injuries. Mechanistically, it is unveiled that BHB infusion is taken up by monocarboxylic acid transporter 1 (MCT1) specifically expressed in cerebral endothelium and upregulated the expression of tight junction protein ZO‐1 by enhancing local β‐hydroxybutyrylation of H3K9 at the promoter of TJP1 gene. Conclusively, an adaptive metabolic mechanism is elucidated by which acute lipolysis stimulates FAO‐ketogenesis processes to restore BBB integrity after stroke. Ketogenesis functions as an early metabolic responder to restrain stroke progression, providing novel prospectives for clinical translation.

Abstract Background Previous studies have found that frailty and sarcopenia are commonly diagnosed in inflammatory bowel disease (IBD) patients, indicating an association between these conditions. Nonetheless, the cause‒effect connection between IBD, frailty, and sarcopenia remains unclear. Methods We sourced the genetic variants for the exposures and outcomes from publicly accessible, extensive genome-wide association studies (GWAS). Specifically, we obtained IBD data from the International IBD Genetics Consortium, frailty index (FI) data from the United Kingdom Biobank and Swedish TwinGene, and sarcopenia data from a recent GWAS meta-analysis. Five methods, including inverse variance weighted (IVW), simple mode, MR-Egger, weighted mode, and the weighted median, were used to proceed with MR estimates. We also performed heterogeneity and horizontal pleiotropy tests. Results Our results indicated a positive causal relationship between ulcerative colitis (UC) (IVW: β = 0.014, 95% CI, 0.006 to 0.021, p = 0.001) and Crohn's disease (CD) (IVW: β = 0.012; 95% CI, 0.006 to 0.018, p = 2e−04) with the FI. However, we uncovered no proof of a cause-and-effect relationship between UC (IVW: β = 0.001, 95% CI, −0.015 to 0.017, p = 0.344) or CD (IVW: β = 0.003, 95% CI, −0.009 to 0.015, p = 0.214) and sarcopenia. Additionally, in the inverse order, we also discovered no cause-and-effect connection between FI or sarcopenia on UC or CD in this study. Conclusion The MR analysis showed a positive causal association between IBD and FI, indicating that IBD patients may exhibit aging-related characteristics. Therefore, frailty assessments should be conducted as early as possible in IBD patients.

Abstract The experimental observation of quantum phase transitions predicted by the quantum Rabi model in quantum critical systems is usually challenging due to the lack of signature experimental observables associated with them. Here, we describe a method to identify the dynamical critical phenomenon in the quantum Rabi model consisting of a three-level atom and a cavity at the quantum phase transition. Such a critical phenomenon manifests itself as a sudden change of steady-state output photons in the system driven by two classical fields, when both the atom and the cavity are initially unexcited. The process occurs as the high-frequency pump field is converted into the low-frequency Stokes field and multiple cavity photons in the normal phase, while this conversion cannot occur in the superradiant phase. The sudden change of steady-state output photons is an experimentally accessible measure to probe quantum phase transitions, as it does not require preparing the equilibrium state.

Three-dimensional object detection has been substantially improved with the use of expensive LiDAR and stereo vision systems in intelligent driving. The less-expensive and more scalable solution of monocular 3D object detection, however, remains a key challenge. This study primarily explores real-time pseudo 3D object detection with monocular vision and designs a single-shot RPN model, VKP-P3D, which relies purely on visual feature extraction. Through a multiscale feature fusion and an attention mechanism module, this model obtains high-dimensional feature representations during the feature extraction phase. In the detection head of the VKP-P3D model, the pseudo 3D object detection is obtained by regressing 2D bounding box and the visible key points within the image coordinate of the 3D box from the camera’s perspective. Finally, assuming flat ground and considering geometric parameters of the camera, the object’s 3D information can be extracted. To verify the effectiveness of the proposed algorithm, we constructed two pseudo 3D object detection datasets based on visible key points and compared with current state-of-the-art real-time object detector. Results showed that the proposed model has high detection accuracy and speed.

Abstract Background Psychological distress is common in maintenance hemodialysis patients, and high psychological resilience can promote psychological well-being. The current research focuses on psychological resilience protective factors such as family resilience and social support. However, the trajectories of psychological resilience, family resilience, and social support over time and their longitudinal relationships in maintenance hemodialysis patients have not been fully explored yet. Therefore, this study aims to explore the longitudinal relationship between these factors. Methods Patients who received regular hemodialysis treatment for more than three months at dialysis centers of three tertiary hospitals in Zhejiang, China, were recruited from September to December 2020. A total of 252 patients who met the inclusion and exclusion criteria completed three follow-up surveys, including social support, family resilience, and psychological resilience assessments. A repeated measures ANOVA was used to explore differences in their respective scores at different time points. The cross-lagged analysis was performed in AMOS using the maximum likelihood method to examine the the reciprocal predictive relationships between these factors. Results Social support and psychological resilience remained relatively stable over time, whereas family resilience indicated a little increasing trend. According to the cross-lagged analysis, higher T1 social support predicted higher family resilience at T2 [β = 0.123, 95% CI (0.026–0.244)]. Further, the effects of T2 social support to T3 family resilience [β = 0.194, 95%CI (0.039–0.335)] and psychological resilience [β = 0.205, 95%CI (0.049–0.354)] were significant. Finally, the effects of T2 family resilience to T3 social support [β = 0.122, 95%CI (0.010–0.225)] and psychological resilience [β = 0.244, 95%CI (0.119–0.359)] were also significant. Conclusions The study showed that the directionality of the relationship appears to be from social support or family resilience to patients’ psychological resilience but not vice versa. This finding reminds healthcare professionals to emphasize the vital role of social and family resources in providing appropriate support and interventions for maintenance hemodialysis patients to promote psychological resilience and mental health development.

Mitral valve repair is the ideal approach in managing mitral valve infective endocarditis for patients requiring surgery. However, viable repair is influenced by the extent of valve destruction and there can be technical challenges in reconstruction following debridement. Overall, data describing long-term outcomes following mitral repair of infective endocarditis are scarce. We, therefore, assessed the late outcomes of 101 consecutive patients who underwent mitral valve repair for IE at the University of Ottawa Heart Institute from 2001 to 2021. The 5- and 10-year survival rate was 80.8 ± 4.7% and 61.2 ± 9.2%, respectively. Among these 101 patients, 7 ultimately required mitral valve reoperation at a median of 5 years after their initial operation. These patients were of a mean age of 35.9 ± 7.3 years (range 22–44 years) at the time of their initial operation. The 5- and 10-year freedom from mitral valve reoperation was 93.6 ± 3.4% and 87.7 ± 5.2%, respectively. Overall, mitral valve repair can be an effective method for treating infective endocarditis with a favourable freedom from reoperation and mortality over the long term.

Background: Persistent cough is one of the most common complications following pulmonary resection, that impairs patients’ quality of life and prolongs recovery time. However, a comprehensive review of persistent cough after pulmonary resection (CAP) has not been performed. Methods: A literature search of PubMed/MEDLINE, Web of Science, and Embase database was conducted for persistent-CAP up to June 2023. Subsequent qualitative systematic review focused on definition, risk factors, prevention, and treatment of persistent-CAP. Results: Persistent-CAP stands as a prevalent postoperative complication subsequent to pulmonary resection procedures. with an incidence of 24.4–55.0 %. Although persistent-CAP has a minor impact on survival, this condition is of critical importance because it presents a major hurdle in recovery after surgery. In this review, we proposed a systemic definition for persistent-CAP based on available evidence and our own data. Several assessment tools used to assess severity of persistent-CAP are also introduced. Risk factors associated with persistent-CAP are explored, including surgical approaches, resection extent, surgical site, lymph node dissection, postoperative gastroesophageal acid reflux, tracheal intubation anesthesia, preoperative comorbidity, and sex among others. Surgical and anesthesia preventions targeting risk factors to prevent persistent-CAP are elaborated. A number of studies have shown that a multidisciplinary approach can effectively relieve persistent-CAP. Conclusions: Although the mechanisms underlying persistent-CAP are still unclear, existing studies demonstrated that persistent-CAP is related to surgical and anesthesia factors. Therefore, in the future, prevention and treatment should be developed based on risk factors to overcome the hurdle of persistent-CAP.

The ectonucleotidase CD39 has been regarded as a promising immune checkpoint in solid tumors. However, the expression of CD39 by tumor-infiltrating CD8+ T cells as well as their potential roles and clinical implications in human gastric cancer (GC) remain largely unknown. Here, we found that GC-infiltrating CD8+ T cells contained a fraction of CD39hi cells that constituted about 6.6% of total CD8+ T cells in tumors. These CD39hi cells enriched for GC-infiltrating CD8+ T cells with features of exhaustion in transcriptional, phenotypic, metabolic and functional profiles. Additionally, GC-infiltrating CD39hiCD8+ T cells were also identified for tumor-reactive T cells, as these cells expanded in vitro were able to recognize autologous tumor organoids and induced more tumor cell apoptosis than those of expanded their CD39int and CD39-CD8+ counterparts. Furthermore, CD39 enzymatic activity controlled GC-infiltrating CD39hiCD8+ T cell effector function, and blockade of CD39 efficiently enhanced their production of cytokines IFN-γ and TNF-α. Finally, high percentages of GC-infiltrating CD39hiCD8+ T cells correlated with tumor progression and independently predicted patients’ poor overall survival. These findings provide novel insights into the association of CD39 expression level on CD8+ T cells with their features and potential clinical implications in GC, and empowering those exhausted tumor-reactive CD39hiCD8+ T cells through CD39 inhibition to circumvent the suppressor program may be an attractive therapeutic strategy against GC.

Abstract Major depressive disorder (MDD) is one of the most common and disabling mental disorders, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of depression, underlying mechanisms remain elusive. Here, using murine depression models, we demonstrated that MSCs could alleviate depressive and anxiety-like behaviors not due to a reduction in proinflammatory cytokines, but rather activation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons. Mechanistically, peripheral delivery of MSCs activated pulmonary innervating vagal sensory neurons, which projected to the nucleus tractus solitarius, inducing the release of 5-HT in DRN. Furthermore, MSC-secreted brain-derived neurotrophic factor activated lung sensory neurons through tropomyosin receptor kinase B (TrkB), and inhalation of a TrkB agonist also achieved significant therapeutic effects in male mice. This study reveals a role of peripheral MSCs in regulating central nervous system function and demonstrates a potential “lung vagal-to-brain axis” strategy for MDD.

Abstract Stevia rebaudiana Bertoni is a valuable medicinal plant and an essential source of natural sweetener, steviol glycosides (SGs), with rebaudioside A (RA) being one of the main components of SGs. bHLH transcription factors play a crucial role in plant development and secondary metabolism. In this study, 159 SrbHLH genes were identified from the S. rebaudiana genome, and each gene was named based on its chromosome location. The SrbHLH proteins were then clustered into 18 subfamilies through phylogenetic analysis. The analysis of conserved motifs and gene structure further supported the classification of the SrbHLH family. Chromosomal location and gene duplication events of SrbHLH genes were also studied. Moreover, based on the RNA-Seq data of different tissues of S. rebaudiana, 28 SrbHLHs were co-expressed with structural genes involved in RA biosynthesis. The expression pattern of candidate SrbHLH genes were confirmed by qPCR. Finally, dual luciferase reporter assays (DLAs) and subcellular localization analysis verified SrbHLH22, SrbHLH111, SrbHLH126, SrbHLH142, and SrbHLH152 are critical regulators of RA biosynthesis. This study provides new insights into the function of SrbHLHs in regulating SGs biosynthesis and lays the foundation for future applications of SrbHLH genes in molecular breeding of S. rebaudiana.

Abstract Objectives CD4+ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor‐infiltrating CD4+ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown. Methods A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD‐1 on CD4+ T cells in the different samples was analysed by flow cytometry. GC‐infiltrating CD4+ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC‐infiltrating T cells was investigated by inhibiting CD39 enzymatic activity. Results In comparison with CD4+ T cells from the non‐tumor tissues, significantly more GC‐infiltrating CD4+ T cells expressed CD39. Most GC‐infiltrating CD39+CD4+ T cells exhibited CD45RA−CCR7− effector–memory phenotype expressing more exhaustion‐associated inhibitory molecules and transcription factors and produced less TNF‐α, IFN‐γ and cytolytic molecules than their CD39−CD4+ counterparts. Moreover, ex vivo inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF‐α and IFN‐γ production. Finally, increased percentages of GC‐infiltrating CD39+CD4+ T cells were positively associated with disease progression and patients' poorer overall survival. Conclusion Our study demonstrates that CD39 expression defines GC‐infiltrating CD4+ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.

Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders.

Abstract Background Although ileal faecal diversion is commonly used in clinical settings, complications accompany it. Elucidating the intestinal changes caused by ileal faecal diversion will help resolve postoperative complications and elucidate the pathogenic mechanisms of associated intestinal disorders, such as Crohn's disease (CD). Therefore, our study aimed to provide new insights into the effects of ileal faecal diversion on the intestine and the potential mechanisms. Methods Single‐cell RNA sequencing was performed on proximal functional and paired distal defunctioned intestinal mucosae from three patients with ileal faecal diversion. We also performed in vitro cellular and animal experiments, tissue staining and analysed public datasets to validate our findings. Results We found that the epithelium in the defunctioned intestine tended to be immature, with defective mechanical and mucous barriers. However, the innate immune barrier in the defunctioned intestine was enhanced. Focusing on the changes in goblet cells, we demonstrated that mechanical stimulation promotes the differentiation and maturation of goblet cells through the TRPA1‐ERK pathway, indicating that the absence of mechanical stimulation may be the main cause of defects in the goblet cells of the defunctioned intestine. Furthermore, we found obvious fibrosis with a pro‐fibrotic microenvironment in the defunctioned intestine and identified that monocytes may be important targets for faecal diversion to alleviate CD. Conclusions This study revealed the different transcription landscapes of various cell subsets and the potential underlying mechanisms within the defunctioned intestine, when compared to the functional intestine, based on the background of ileal faecal diversion. These findings provide novel insights for understanding the physiological and pathological roles of the faecal stream in the intestine.

The optimum ultrasound-assisted extraction parameters of Vitamin C from Capsella bursa-pastoris was studied by Response Surface Methodology. The main factors of the extraction were selected by the Confounded Fractional Factorial test. The extraction process was optimized by Box-Behnken test. The results showed that the major influential factors of extraction were: ultrasonic time, ultrasonic temperature and material to solvent ratio. The optimum conditions were as follows: 1% oxalic acid, material to solvent ratio of 1∶10 (g/mL), ultrasonic time of 12 min, ultrasonic temperature of 32 ℃ and ultrasonic power of 100 W. In this condition, the extraction amount of Vitamin C from Capsella bursa-pastoris was (54.88±0.22) mg/100 g.

The regulatory mechanisms contributing to male reproductive ageing are unknown. Here, the authors show that Nestin-dependent mito-ER contacts (MERCs) regulate stem Leydig cell (SLC) senescence and provide insights into SLCs-targeting therapies.

ABSTRACT: Objectives: A specific and sensitive automated chemiluminescent immunoassay (CLIA) was developed to detect neutralizing antibody (NAb) levels. This assay can be used for the diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, treatment and vaccine evaluation. Methods: The SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike ectodomain as antigens were detected by CLIA. Sera NAb titers and concentrations from 860 SARS-CoV-2 vaccinees, 232 SARS-CoV-2 convalescent patients and 675 healthy individuals were tested by microneutralization test (MNT) and CLIA, respectively. Mathematical models were established to evaluate the relationship between two variables in different groups. Conclusions: With the RBD-based CLIA protocol, CLIA can be used to replace MNT to test SARS-CoV-2 NAb. Vaccine effectiveness, protectiveness and durability can be evaluated effectively by mathematical models. It is Results: Analysing the relationship between NAb titers and concentrations, R2 for the decision-making tree was 0.870 and that of progressive linear fitting was 0.821. The receiver operating characteristic curve indicated specificity of 78.1%, sensitivity of 87.4%, cut-off value of 6.43 AU/mL and borderline range of 5.79–7.07 AU/mL for CLIA. Three-quarters (75.4%) of vaccinees were found to be NAb positive, and 5.35% vaccinees had NAb protective capability. The half-life of NAb in vaccinees was 10–11 weeks.for vaccinees to take a NAb assay periodically.

Background: As a novel approach for people to directly communicate with an external device, the study of brain-computer interfaces (BCIs) has become well-rounded. However, similar to the real-world scenario, where individuals are expected to work in groups, the BCI systems should be able to replicate group attributes. Methods: We proposed a 4-order cumulants feature extraction method (CUM4-CSP) based on the common spatial patterns (CSP) algorithm. Simulation experiments conducted using motion visual evoked potentials (mVEP) EEG data verified the robustness of the proposed algorithm. In addition, to freely choose paradigms, we adopted the mVEP and steady-state visual evoked potential (SSVEP) paradigms and designed a multimodal collaborative BCI system based on the proposed CUM4-CSP algorithm. The feasibility of the proposed multimodal collaborative system framework was demonstrated using a multiplayer game controlling system that simultaneously facilitates the coordination and competitive control of two users on external devices. To verify the robustness of the proposed scheme, we recruited 30 subjects to conduct online game control experiments, and the results were statistically analyzed. Results: The simulation results prove that the proposed CUM4-CSP algorithm has good noise immunity. The online experimental results indicate that the subjects could reliably perform the game confrontation operation with the selected BCI paradigm. Conclusions: The proposed CUM4-CSP algorithm can effectively extract features from EEG data in a noisy environment. Additionally, the proposed scheme may provide a new solution for EEG-based group BCI research.

Time-varying directed electroencephalography (EEG) network is the potential tool for studying the dynamical causality among brain areas at a millisecond level; which conduces to understanding how our brain effectively adapts to information processing, giving inspiration to causality- and brain-inspired machine learning. Currently, its construction still mainly relies on the parametric approach such as multivariate adaptive autoregressive (MVAAR), represented by the most widely used adaptive directed transfer function (ADTF). Restricted by the model assumption, the corresponding performance largely depends on the MVAAR modeling which usually encounters difficulty in fitting complex spectral features. In this study, we proposed to construct EEG directed network with multivariate nonparametric dynamical Granger causality (mndGC) method that infers the causality of a network, instead, in a data-driven way directly and therefore avoids the trap in the model-dependent parametric approach. Comparisons between mndGC and ADTF were conducted both with simulation and real data application. Simulation study demonstrated the superiority of mndGC both in noise resistance and capturing the instantaneous directed network changes. When applying to the real motor imagery (MI) data set, distinguishable network characters between left- and right-hand MI during different MI stages were better revealed by mndGC. Our study extends the nonparametric causality exploration and provides practical suggestions for the time-varying directed EEG network analysis.

Abstract The stone walls remaining in the highly urbanized Macao area provide a special habitat for plants, repair the fragmentation of the habitat caused by urbanization, and enhance the urban biodiversity. The main object of this survey are stone wall trees in Macao. The species composition, frequency of occurrence and distribution were ascertained, and the feasibility of establishing stone wall tree landscape trail systems was discussed. The results showed that there were 96 stone wall trees in Macao. Among them, 47.9% of the total in the historical center of Macao. In addition, research and analysis on the species composition, life form, frequency and similarity of the associated plants of stone wall trees were analyzed. The survey found that there were 101 species of companion plants, and herbaceous plants had the greatest growth advantage. Most of the companion species were selective and incidental to the stone wall habitat; the similarity of the companion plants in different habitats was less than 0.25, showing that the stone wall was conducive to species diversity. The results of this research aim to explore planning strategies for holistic conservation of stone wall landscape, and provide a theoretical basis for studying the biodiversity of special habitats in Macao.

Objective To systematically evaluate the disinfection efficacy of the two most frequently used disinfectants, sodium hypochlorite and glutaraldehyde, and their effects on the surface properties of four different dental impression materials. Methods A systematic literature search was performed in four databases until May 1st, 2022 to select the studies which evaluated disinfection efficacy of disinfectants or surface properties of dental impressions after chemical disinfection. Main results A total of 50 studies were included through electronic database searches. Of these studies, 13 studies evaluated disinfection efficacy of two disinfectants, and 39 studies evaluated their effects on the surface properties of dental impressions. A 10-minute disinfection with 0.5–1% sodium hypochlorite or 2% glutaraldehyde was effective to inactivate oral flora and common oral pathogenic bacteria. With regard to surface properties, chemical disinfection within 30 min could not alter the dimensional stability, detail reproduction and wettability of alginate and polyether impressions. However, the wettability of addition silicone impressions and the dimensional stability of condensation silicone impressions were adversely affected after chemical disinfection, while other surface properties of these two dental impressions were out of significant influence. Conclusions Alginate impressions are strongly recommended to be disinfected with 0.5% sodium hypochlorite using spray disinfection method for 10 min. Meanwhile, elastomeric impressions are strongly recommended to be disinfected with 0.5% sodium hypochlorite or 2% glutaraldehyde using immersion disinfection method for 10 min, however, polyether impression should be disinfected with 2% glutaraldehyde.

ObjectiveTo explore the relationship between family socio-economic status and learning engagement of college students majoring in preschool education, as well as the mediating role of parental autonomy support and the moderating role of psychological capital.MethodsA sample of 986 college students majoring in preschool education from Guangdong Province and Jiangxi Province were investigated by family socio-economic status questionnaire, learning engagement questionnaire, parental autonomy support questionnaire and psychological capital questionnaire.ResultsFirst, there was a significant positive correlation between family socio-economic status and learning engagement (β = 0.09, p

Mechanosensation is essential for normal gastrointestinal (GI) function, and abnormalities in mechanosensation are associated with GI disorders. There are several mechanosensitive ion channels in the GI tract, namely transient receptor potential (TRP) channels, Piezo channels, two-pore domain potassium (K2p) channels, voltage-gated ion channels, large-conductance Ca2+-activated K+ (BKCa) channels, and the cystic fibrosis transmembrane conductance regulator (CFTR). These channels are located in many mechanosensitive intestinal cell types, namely enterochromaffin (EC) cells, interstitial cells of Cajal (ICCs), smooth muscle cells (SMCs), and intrinsic and extrinsic enteric neurons. In these cells, mechanosensitive ion channels can alter transmembrane ion currents in response to mechanical forces, through a process known as mechanoelectrical coupling. Furthermore, mechanosensitive ion channels are often associated with a variety of GI tract disorders, including irritable bowel syndrome (IBS) and GI tumors. Mechanosensitive ion channels could therefore provide a new perspective for the treatment of GI diseases. This review aims to highlight recent research advances regarding the function of mechanosensitive ion channels in the GI tract. Moreover, it outlines the potential role of mechanosensitive ion channels in related diseases, while describing the current understanding of interactions between the GI tract and mechanosensitive ion channels.

BackgroundDifferentiating multiple pulmonary lesions as multiple primary lung cancer (MLC) or intra-pulmonary metastasis (IPM) is critical. Lung cancer also has a high genetic heterogeneity, which influenced the treatment strategy. Genetic information may aid in tracing lineage information on multiple lung lesions. This study applied comprehensive genomic profiling to decipher the intrinsic genetics of multiple lung lesions.MethodsSixty-six lung adenocarcinomas (LUAD) tumor lesions (FFEP) archived from 30 patients were included in this study. The 508 cancer-related genes were evaluated by targeted next-generation sequencing (MGI-seq 2000).ResultsThe study included a total of 30 LUADs (66 samples). The majority of tumors demonstrated intra-tumoral heterogeneity. Two hundred twenty-four mutations were detected by sequencing the 66 samples. We investigated the driver gene mutations of NSCLC patients with multiple lesions. EGFR was the most frequently (48/198) mutated driver gene. The codons in EGFR mainly affected by mutations were p.L858R (18/66 [27.3%]) and exon 19del (8/66 [12.1%]). In addition, additional driver genes were found, including TP53, BRAF, ERBB2, MET, and PIK3CA. We also found that the inter-component heterogeneity of different lesions and more than two different mutation types of EGFR were detected in seven patients with two lesions (P3, P10, P24, P25, P28, P29, and P30). The TMB values of different lesions in each patient were different in 26 patients (except P4, P5, P14, and P30).ConclusionsComprehensive genomic profiling should be applied to distinguishing the nature of multiple lung lesions irrespective of radiologic and histologic diagnoses.

Spotted fever group rickettsioses caused by Rickettsia (R) are devastating human infections, which mainly target microvascular endothelial cells (ECs) and can induce lethal EC barrier dysfunction in the brain and lungs. Our previous evidence reveals that exosomes (Exos) derived from rickettsial-infected ECs, namely R-ECExos, can induce disruption of the tight junctional (TJ) protein ZO-1 and barrier dysfunction of human normal recipient brain microvascular endothelial cells (BMECs). However, the underlying mechanism remains elusive. Given that we have observed that microRNA23a (miR23a), a negative regulator of endothelial ZO-1 mRNA, is selectively sorted into R-ECExos, the aim of the present study was to characterize the potential functional role of exosomal miR23a delivered by R-ECExos in normal recipient BMECs. We demonstrated that EC-derived Exos (ECExos) have the capacity to deliver oligonucleotide RNAs to normal recipient BMECs in an RNase-abundant environment. miR23a in ECExos impairs normal recipient BMEC barrier function, directly targeting TJ protein ZO-1 mRNAs. In separate studies using a traditional in vitro model and a novel single living-cell biomechanical assay, our group demonstrated that miR23a anti-sense oligonucleotide-enriched ECExos ameliorate R-ECExo-provoked recipient BMEC dysfunction in association with stabilization of ZO-1 in a dose-dependent manner. These results suggest that Exo-based therapy could potentially prove to be a promising strategy to improve vascular barrier function during bacterial infection and concomitant inflammation.

Growing crops in salt-affected soils has become increasingly important for sustainable development in arid and semi-arid regions. Knowledge on the responses of alfalfa root development, yield, and quality to soil salinity is critical for assessing the productivity and profitability of salt-affected soils. A field experiment with a total of six treatments combining three soil salinity levels and two biosolids fertilizer levels was conducted in 2018 and 2019 in northwest China. For salinity treatments, the salt addition rates were 2‰, 4‰, and 6‰ of 0–60 cm soil dry weight, while a commercial biosolids fertilizer was added at a rate of 0 and 1.5 Mg·ha−1 of 0–10 cm soil for biosolids treatment. Root parameters of root length (RL), surface area (RSA), diameter (RD), volume (RV), and dry matter (RDM) were obtained at the end of each year, while yield and quality parameters of crude protein (CP), acid detergent fiber (ADF), neutral detergent fiber (NDF) were measured for each cut of the two years. Most root parameters were significantly reduced by the highest soil salinity treatment in 2018, but not affected by salinity in 2019. Higher salinity treatments consistently led to lower plant height and yield, higher CP, and lower ADF and NDF in both years. The absolute slope value of the regression between yield of each cut with the respective soil salt content was smaller for the later cuts. The relationship between plant height and quality parameters varied depending on soil salinity levels and between the two years, and plant height was found to be a good predictor for alfalfa quality in 2019. Biosolids fertilizer had no significant effect on any alfalfa root, growth, or quality parameters. The results are expected to assist determining the proper soil salinity range, maximizing the productivity that takes both yield and quality into consideration.

An ileostomy is a surgery that is commonly performed to protect low pelvic anastomoses or prevent high-risk anastomotic leakages. However, various postoperative complications remain of major concern. After an ileostomy, the distal intestinal segment is left open for an extended period and is in a non-functional state. Consequently, the intestinal mucosa, smooth muscle, and microbiota undergo significant changes that are closely related to postoperative recovery and complications. A systematic description of these changes is necessary to understand the relationship among them and take more effective measures for postoperative intervention.

Background: Almost all lung adenocarcinoma (LUAD) patients with EGFR mutant will develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs.Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, Lactate Dehydrogenase (LDH), flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, apoptosis rate, and colony formation ratio. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cycloheximide (CHX), MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B.Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and colony formed ability were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth, and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib. When LUAD cells were treated with ubiquitin activating enzyme inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro.Conclusion: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.

BackgroundNeoadjuvant immunotherapy has preliminarily been effective in multiple resectable cancers. However, its safety is still largely unknown.MethodsA systematic literature search was conducted in PubMed, Embase, Web of Science, and Cochrane Library up to February 28th, 2021. Pooled incidence and risk ratio (RR) of adverse events were calculated using the R software.ResultsTwenty-eight studies involving 2863 patients were included. First, the incidence for all-grade treatment-related adverse events (trAEs) was 94% (95% CI, 81%-98%), with 43% (95% CI, 24%-64%) for high-grade trAEs. For different treatment groups, neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy was associated with a higher incidence of all-grade [99% (95% CI, 98%-99%) vs. 76% (95% CI 47%-92%); P < 0.001] and high-grade [80% (58%-92%) vs. 15% (9%-24%); P < 0.001] trAEs compared with neoadjuvant ICIs alone. The most common high-grade trAEs were lipase increased (5%; 95% CI, 2%-10%), colitis (3%; 95% CI, 0-7%) and transaminitis (3%; 95% CI, 0-7%) for neoadjuvant ICIs, and neutropenia (53%; 95% CI, 31%-74%), anemia (8%; 95% CI, 3%-15%) and AST increased (4%; 95% CI, 2%-7%) for neoadjuvant ICIs plus chemotherapy. Furthermore, the incidence rates of progressive disease while on treatment, treatment-related surgical delays and deaths were 6% (95% CI, 4%-10%), 3.2% (12 of 377 patients) and 0.47% (5 of 1075 patients), respectively.ConclusionCompared with neoadjuvant ICIs alone, neoadjuvant ICIs plus chemotherapy had a higher incidence of trAEs. In addition, neoadjuvant immunotherapy had a low rate of progressive diseases, surgical delays and deaths.

Degenerative mitral valve (MV) disease is the most common cause of organic mitral regurgitation (MR) in developed countries. Surgical mitral valve repair is the gold standard treatment for primary MR. Surgical mitral valve repair is associated with excellent outcomes in terms of survival and freedom from recurrent MR. As well, innovations in surgical repair techniques, including thoracoscopically and robotically assisted approaches, further reduce morbidity. Emerging catheter-based therapies may also provide advantages in select patient groups. Although the outcomes following surgical mitral valve repair are well described in the literature, longitudinal follow-up is heterogenous. Indeed, longitudinal follow-up and long-term data are vital to better advise treatment and counsel patients.

Although the land-use harmonization (LUH) datasets have been widely applied in regional climate model (RCM) projections for investigating the role of the land-use forcing in future climate changes, few studies have thoroughly assessed them on local scale, which may bring large uncertainties in the resultant climate information for designing adaption and mitigation measures of climate change. The authors use a local land-use dataset (referred to as Li-LU) as the benchmark to assess the latest version of the LUH datasets, LUH2, in Central Asia (CA) which has undergone extensive land-use changes (LUCs) and might undergo extensive LUCs in the future. The results show that LUH2 has large biases in depicting the historical land-use states in CA for 1995–2015. For instance, the area of grassland (cropland) in LUH2 is about 1.4–1.5 (0.4–0.5) times of that of Li-LU. Moreover, the future LUCs predicted by LUH2 for 2045 (relative to 2005) are much smaller than those of Li-LU and these two datasets generally have opposite signals in changes. In addition, the predicted LUCs of LUH2 do not follow the causal mechanisms [the causal connections between the key drivers (e.g. population, economy, and environment) and land use] behind the LUCs in the past. If the future scenario of LUH2 is used for RCM projection in CA with the historical land-use information from Li-LU, the simulation results could be misleading for understanding the impacts of LUCs on future climate changes there. This study suggests that the LUH datasets should be carefully assessed before using them for regional studies and provides practical notes for selecting the appropriate land-use dataset for RCM projections in other areas around the world.

In recent years, with the rapid increase in coverage and lines, security maintenance has become one of the top concerns with regard to railway transportation in China. As the key transportation infrastructure, the railway turnout system (RTS) plays a vital role in transportation, which will cause incalculable losses when accidents occur. The traditional fault-diagnosis and maintenance methods of the RTS are no longer applicable to the growing amount of data, so intelligent fault diagnosis has become a research hotspot. However, the key challenge of RTS intelligent fault diagnosis is to effectively extract the deep features in the signal and accurately identify failure modes in the face of unbalanced datasets. To solve the above two problems, this paper focuses on unbalanced data and proposes a fault-diagnosis method based on an improved autoencoder and data augmentation, which realizes deep feature extraction and fault identification of unbalanced data. An improved autoencoder is proposed to smooth the noise and extract the deep features to overcome the noise fluctuation caused by the physical characteristics of the data. Then, synthetic minority oversampling technology (SMOTE) is utilized to effectively expand the fault types and solve the problem of unbalanced datasets. Furthermore, the health state is identified by the Softmax regression model that is trained with the balanced characteristics data, which improves the diagnosis precision and generalization ability. Finally, different experiments are conducted on a real dataset based on a railway station in China, and the average diagnostic accuracy reaches 99.13% superior to other methods, which indicates the effectiveness and feasibility of the proposed method.

Space-air-ground integrated networks (SAGIN) provide seamless global coverage and cross-domain interconnection for the ubiquitous users in heterogeneous networks, which greatly promote the rapid development of intelligent mobile devices and applications. However, for mobile devices with limited computation capability and energy budgets, it is still a serious challenge to meet the stringent delay and energy requirements of computation-intensive ubiquitous mobile applications. Therefore, in view of the significant success in ground mobile networks, the introduction of mobile edge computing (MEC) in SAGIN has become a promising technology to solve the challenge. By deploying computing, cache, and communication resources in the edge of mobile networks, SAGIN MEC provides both low latency, high bandwidth, and wide coverage, substantially improving the quality of services for mobile applications. There are still many unprecedented challenges, due to its high dynamic, heterogeneous and complex time-varying topology. Therefore, efficient MEC deployment, resource management, and scheduling optimization in SAGIN are of great significance. However, most existing surveys only focus on either the network architecture and system model, or the analysis of specific technologies of computation offloading, without a complete description of the key MEC technologies for SAGIN. Motivated by this, this paper first presents a SAGIN network system architecture and service framework, followed by the descriptions of its characteristics and advantages. Then, the MEC deployment, network resources, edge intelligence, optimization objectives and key algorithms in SAGIN are discussed in detail. Finally, potential problems and challenges of MEC in SAGIN are discussed for future work.