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Abstract Cell migration, a hallmark of cancer malignancy, plays a critical role in cancers. Improperly initiated or misdirected cell migration can lead to invasive metastatic cancer. Migrasomes are newly discovered vesicular cellular organelles produced by migrating cells and depending on cell migration. Four marker proteins [NDST1 (bifunctionalheparan sulfate N-deacetylase/N-sulfotransferase 1), EOGT (Epidermal growth factor domains pecific O-linked N-acetylglucosaminetransferase), CPQ (carboxypeptidase Q), and PIGK (phosphatidylinositol glycan anchor biosynthesis, class K)] of migrasomes were successfully identified. There are three marker proteins (NDST1, PIGK, and EOGT) of migrasome expressed in cancer. In this review, we will discuss the process of migrasome discovery, the formation of migrasome, the possible functions of migrasome, and the differences between migrasomes and exosomes, especially, the biological functions of migrasome marker proteins in cancer, and discuss some possible roles of migrasomes in cancer. We speculate that migrasomes and migracytosis can play key roles in regulating the development of cancer.

Abstract Breast cancer (BC) ranks first among female malignant tumors and involves hormonal changes and genetic as well as environmental risk factors. In recent years, with the improvement of medical treatment, a variety of therapeutic approaches for breast cancer have emerged and have strengthened to accommodate molecular diversity. However, the primary way to improve the effective treatment of breast cancer patients is to overcome treatment resistance. Recent studies have provided insights into the mechanisms of resistance to exosome effects in BC. Exosomes are membrane-bound vesicles secreted by both healthy and malignant cells that facilitate intercellular communication. Specifically, exosomes released by tumor cells transport their contents to recipient cells, altering their properties and promoting oncogenic components, ultimately resulting in drug resistance. As important coordinators, non-coding RNAs (ncRNAs) are involved in this process and are aberrantly expressed in various human cancers. Exosome-derived ncRNAs, including microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as crucial components in understanding drug resistance in breast cancer. This review provides insights into the mechanism of exosome-derived ncRNAs in breast cancer drug resistance, thereby suggesting new strategies for the treatment of BC.

Abstract Background Malaria-associated acute lung injury (MA-ALI) is a well-recognized clinical complication of severe, complicated malaria that is partly driven by sequestrations of infected red blood cells (iRBCs) on lung postcapillary induced impaired blood flow. In earlier studies the mechanosensitive Piezo1 channel emerged as a regulator of mechanical stimuli, but the function and underlying mechanism of Piezo1 impacting MA-ALI severity via sensing the impaired pulmonary blood flow are still not fully elucidated. Thus, the present study aimed to explore the role of Piezo1 in the severity of murine MA-ALI. Methods Here, we utilized a widely accepted murine model of MA-ALI using C57BL/6 mice with Plasmodium berghei ANKA infection and then added a Piezo1 inhibitor (GsMTx4) to the model. The iRBC-stimulated Raw264.7 macrophages in vitro were also targeted with GsMTx4 to further explore the potential mechanism. Results Our data showed an elevation in the expression of Piezo1 and number of Piezo1+-CD68+ macrophages in lung tissues of the experimental MA-ALI mice. Compared to the infected control mice, the blockage of Piezo1 with GsMTx4 dramatically improved the survival rate but decreased body weight loss, peripheral blood parasitemia/lung parasite burden, experimental cerebral malaria incidence, total protein concentrations in bronchoalveolar lavage fluid, lung wet/dry weight ratio, vascular leakage, pathological damage, apoptosis and number of CD68+ and CD86+ macrophages in lung tissues. This was accompanied by a dramatic increase in the number of CD206+ macrophages (M2-like subtype), upregulation of anti-inflammatory cytokines (e.g. IL-4 and IL-10) and downregulation of pro-inflammatory cytokines (e.g. TNF-α and IL-1β). In addition, GsMTx4 treatment remarkably decreased pulmonary intracellular iron accumulation, protein level of 4-HNE (an activator of ferroptosis) and the number of CD68+-Piezo1+ and CD68+-4-HNE+ macrophages but significantly increased protein levels of GPX4 (an inhibitor of ferroptosis) in experimental MA-ALI mice. Similarly, in vitro study showed that the administration of GsMTx4 led to a remarkable elevation in the mRNA levels of CD206, IL-4, IL-10 and GPX-4 but to a substantial decline in CD86, TNF-α, IL-1β and 4-HNE in the iRBC-stimulated Raw264.7 cells. Conclusions Our findings indicated that blockage of Piezo1 with GsMTx4 alleviated the severity of experimental MA-ALI in mice partly by triggering pulmonary macrophage M2 polarization and subsequent anti-inflammatory responses but inhibited apoptosis and ferroptosis in lung tissue. Our data suggested that targeting Piezo1 in macrophages could be a promising therapeutic strategy for treating MA-ALI. Graphical Abstract

Abstract Objective To assess lung deformation in patients with idiopathic pulmonary fibrosis (IPF) using with elastic registration algorithm applied to three-dimensional ultrashort echo time (3D-UTE) MRI and analyze relationship of lung deformation with the severity of IPF. Methods Seventy-six patients with IPF (mean age: 62 ± 6 years) and 62 age- and gender-matched healthy controls (mean age: 58 ± 4 years) were prospectively enrolled. End-inspiration and end-expiration images acquired with a single breath-hold 3D-UTE sequence were registered using elastic registration algorithm. Jacobian determinants were calculated from deformation fields and represented on color maps. Jac-mean (absolute value of the log means of Jacobian determinants) and the Dice similarity coefficient (Dice) were compared between different groups. Results Compared with healthy controls, the Jac-mean of IPF patients significantly decreased (0.21 ± 0.08 vs. 0.27 ± 0. 07, p < 0.001). Furthermore, the Jac-mean and Dice correlated with the metrics of pulmonary function tests and the composite physiological index. The lung deformation in IPF patients with dyspnea Medical Research Council (MRC) ≥ 3 (Jac-mean: 0.16 ± 0.03; Dice: 0.06 ± 0.02) was significantly lower than MRC1 (Jac-mean: 0. 25 ± 0.03, p < 0.001; Dice: 0.10 ± 0.01, p < 0.001) and MRC 2 (Jac-mean: 0.22 ± 0.11, p = 0.001; Dice: 0.08 ± 0.03, p = 0.006). Meanwhile, Jac-mean and Dice correlated with health-related quality of life, 6 min-walk distance, and the extent of pulmonary fibrosis. Jac-mean correlated with pulmonary vascular-related indexes on high-resolution CT. Conclusion The decreased lung deformation in IPF patients correlated with the clinical severity of IPF patients. Elastic registration of inspiratory-to-expiratory 3D UTE MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. Critical relevance statement This prospective study demonstrated that lung deformation decreased in idiopathic pulmonary fibrosis (IPF) patients and correlated with the severity of IPF. Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. Key points • Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI could evaluate lung deformation. • Lung deformation significantly decreased in idiopathic pulmonary fibrosis (IPF) patients, compared with the healthy controls. • Reduced lung deformation of IPF patients correlated with worsened pulmonary function and the composite physiological index (CPI). Graphical Abstract

Abstract. Background:. The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. Methods:. In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. Results:. A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age,

Abstract Introduction The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient‐reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient‐reported outcomes. Methods This is a single‐center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient‐reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load

Abstract Introduction Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) are well tolerated and effective in clinical trials. This study aimed to evaluate the safety and efficacy of these two schemes in a real-world setting and to obtain the first dataset for switching to BIC/FTC/TAF and DTG + 3TC in a Chinese population. Methods This retrospective single-center cohort study in China included participants who switched to DTG + 3TC or BIC/FTC/TAF between January 2020 and February 2023. The main endpoint was the proportion of participants with HIV-1 RNA levels of ≥ 50 copies/mL. Safety, tolerance, and the incidence of low-level viremia (LLV) were evaluated. Results A total of 525 participants were included, 454 of whom were included in the PP analysis. At week 48, the proportions of participants with HIV-1 RNA ≥ 50 copies/mL were 4.4% (10/225) for DTG + 3TC and 6.1% (14/229) for BIC/FTC/TAF; virological efficacy did not differ significantly between the two groups. Consistent results were obtained in an intent-to-treat (ITT) analysis. The incidences of LLV were 3.6% (7/193) and 4.9% (10/206), respectively. During the study, none of the participants stopped taking drugs because of a lack of efficacy or adverse reactions. Conclusions Both regimens are well tolerated and effective for switching HIV-1 infection therapy. However, the detection of genotypic drug resistance should be considered when baseline virological non-suppression is observed.

ObjectiveTo evaluate the causal relationship between childhood body-mass index (BMI) at different ages and adult cardiometabolic traits.MethodsWe retrieved genetic instrument variables (IVs) for exposures (standardized BMI at newborn, infant, toddler and late childhood), cardiometabolic traits and potential confounders or mediators (adult BMI, SHBG, testosterone and age at menarche) from the corresponding genome-wide association analysis. We performed univariate and multivariable Mendelian randomization (MR) to dissect associations between age-specific childhood BMI and adult cardiometabolic outcomes. Odds ratio was used to present the direction of the causal association.ResultsIn univariate MR, higher newborn BMI was causally associated with reduced risk for type 2 diabetes in women. Late childhood BMI was associated with increased risk for female diabetes and coronary artery disease (CAD), myocardial infarction (MI), and chronic kidney disease (CKD) in general population. Among these associations, only association between late childhood BMI with MI remained significant after adjusting for adult male BMI and sex hormones, (OR = 1.120, 95% CI 1.023-1.226, p = 0.014). Besides, in multivariable MR, we found evidence for causal association between newborn BMI with reduced risk for CAD (OR = 0.862, 95% CI 0.751-0.989, p = 0.034) and MI (OR = 0.864, 95% CI 0.752-0.991, p = 0.037) in men. No obvious impact of infant or toddler BMI was identified on the above-mentioned diseases. For continuous cardiometabolic traits, in all age epochs except infant, higher BMI was associated with increased level of fasting glucose in women.ConclusionBMI at birth and late childhood exerts different impact on adult cardiometabolic diseases, while BMI at infant and toddler ages is not causally associated with these outcomes. The effect of childhood BMI may be influenced by sex disparities.

PurposeThe current study designed a unique type of corneal topography evaluation method based on deep learning and traditional image processing algorithms. The type of corneal topography of patients was evaluated through the segmentation of important medical zones and the calculation of relevant medical indicators of orthokeratology (OK) lenses.MethodsThe clinical data of 1,302 myopic subjects was collected retrospectively. A series of neural network-based U-Net was used to segment the pupil and the treatment zone in the corneal topography, and the decentration, effective defocusing contact range, and other indicators were calculated according to the image processing algorithm. The type of corneal topography was evaluated according to the evaluation criteria given by the optometrist. Finally, the method described in this article was used to evaluate the type of corneal topography and compare it with the type classified by the optometrist.ResultsWhen the important medical zones in the corneal topography were segmented, the precision and recall of the treatment zone reached 0.9587 and 0.9459, respectively, and the precision and recall of the pupil reached 0.9771 and 0.9712. Finally, the method described in this article was used to evaluate the type of corneal topography. When the reviewed findings based on deep learning and image processing algorithms were compared to the type of corneal topography marked by the professional optometrist, they demonstrated high accuracy with more than 98%.ConclusionThe current study provided an effective and accurate deep learning algorithm to evaluate the type of corneal topography. The deep learning algorithm played an auxiliary role in the OK lens fitting, which could help optometrists select the parameters of OK lenses effectively.

Venetoclax (VCX) is a BCL2 inhibitor approved for treating B cell-derived leukemia, including chronic lymphocytic leukemia (CLL). VCX’s role in apoptosis induction is well-defined, whereas its other mechanistic roles need to be clarified. Autophagy is an intracellular degradation process involving the lysosome, playing a fundamental role in cancer cell survival and death. In this study, we aim to investigate VCX’s function in autophagy. Following the measurement of autophagic flux by western blot and fluorescent microscopy, we demonstrate that VCX is a novel autophagy inhibitor and reduces the level of the essential autophagy pathway protein ATG12 (autophagy-related 12). VCX sensitizes B cell lines and primary CLL cells to cell death induced by amino acid starvation or ibrutinib. These findings provide a rationale for VCX treatment in combination therapies that inhibit the pro-cell survival function of autophagy in B cell-derived malignancies. Abbreviations: ATG12, autophagy-related 12; BCL2, BCL2 apoptosis regulator; CLL, chronic lymphocytic leukemia; CQ, chloroquine; IBR, ibrutinib; BTK, Bruton’s tyrosine kinase; LC3B, MAP1LC3B (microtubule-associated protein 1 light chain 3 beta); VCX, venetoclax; BECN1, beclin 1

Evapotranspiration (ET) is an important process of the regional hydrothermal cycle. However, it is unclear how the mitigation of urban ET in urban thermal environments occurs in a spatial context. Landsat 8 satellite images from 2014 to 2018 of Xuzhou and corresponding meteorological observations were selected, and the improved mono-window algorithm (IMW) and urban RS-PM model were applied to invert land surface temperature (LST) and ET, respectively. In addition, spatial analysis methods (a profile analysis, standard deviation ellipse (SDE) analysis, and bivariate Moran's I) were employed to quantify and simulate the spatial characteristics of the ET effect on LST. The results indicated the following: (1) There was a significant linear negative correlation between ET and LST, which confirms that ET has a negative effect on LST; (2) the SDE overlap ratios between patches with higher ET and lower LST imply that higher ET patches have a significant impact on the spatial distribution of LST; and (3) bivariate Moran's I between ET and LST and their linear mixture spectral analysis (LISA) maps reveal a significant negative spatial correlation between ET and LST. In addition, the landscape pattern of higher ET parches is also an important factor affecting the environmental temperature. HIGHLIGHTS A significant negative spatial correlation between ET and LST was found.; Areas with various ET intensities have different regulatory effects on LST.; Higher ET intensity is not an absolute factor in mitigating the urban thermal environment.; Landscape pattern of the patches with higher ET also has a significant impact on LST regulation.;

Abstract Studies have found that RNA encoding proteins only account for a small part of the total number, most RNA is non-coding RNA, and non-coding RNA may affect the occurrence and development of human cancers by affecting gene expression, therefore play an important role in human pathology. At present, ncRNAs studied include miRNA, circRNA, lncRNA, piRNA, and snoRNA, etc. After decades of research, the basic role of these ncRNAs in many cancers has been clear. As far as we know, the role of miRNAs in cancer is one of the hottest research directions, however, it is also found that the imbalance of ncRNAs will affect the occurrence of gastric cancer, breast cancer, lung cancer, meanwhile, it may also affect the prognosis of these cancers. Therefore, the study of ncRNAs in cancers may help to find new cancer diagnostic and treatment methods. Here, we reviewed the biosynthesis and characteristics of miRNA, cricRNA, and lncRNA etc., their roles in human cancers, as well as the mechanism through which these ncRNAs affect human cancers.

Highlights The gelation of hole transport layer generates a dense and uniform hole transport layer film and significantly inhibits the aggregation of lithium bis(trifluoromethane sulfonyl)imide in spiro-OMeTAD. The gelated hole transport layer confers enhanced charge carrier transport and better humidity and operational stability of perovskite solar cells.

Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria, and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of ischemic injury and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion of Sirt2 (Sirt2-/-) display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress. Similar results were obtained in mice with cardiomyocyte-specific Sirt2 deletion. Mechanistic studies suggest that SIRT2 modulates cellular levels and activity of nuclear factor (erythroid-derived 2)-like 2 (NRF2), which results in reduced expression of antioxidant proteins. Deletion of Nrf2 in the hearts of Sirt2-/- mice reversed protection after PO. Finally, treatment of mouse hearts with a specific SIRT2 inhibitor reduced cardiac size and attenuates cardiac hypertrophy in response to PO. These data indicate that SIRT2 has detrimental effects in the heart and plays a role in cardiac response to injury and the progression of cardiac hypertrophy, which makes this protein a unique member of the SIRT family. Additionally, our studies provide a novel approach for treatment of cardiac hypertrophy and injury by targeting SIRT2 pharmacologically, providing a novel avenue for the treatment of these disorders.

Abstract Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated anticancer and hypoglycemic effects, but their mechanisms of action are not yet fully understood. We used the GeneCards and PharmMapper databases to identify therapeutic targets for diabetes, breast cancer and PPIs. We identified common targets and constructed a regulatory network of diseases and drugs using the STRING database and Cytoscape software. We also explored the binding between small molecule ligands and protein receptors using Discovery Studio software. We identified 33 shared targets for breast cancer, diabetes, and PPIs including lansoprazole, omeprazole, and pantoprazole, which play a critical role in fatty acid transport, insulin resistance, apoptosis, and cancer-related signaling pathways. Our findings demonstrated that PPIs had a strong affinity for AKT1 and MMP9. This study provides insights into the mechanisms of action of PPIs in breast cancer and diabetes and identifies AKT1 and MMP9 as critical targets for future drug development. Our findings highlight the potential of PPIs as a novel therapeutic approach for these challenging diseases.

ABSTRACT Importance Infantile spasm (IS) is a kind of refractory epilepsy. The first‐line treatments for IS are adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin. Objective This study aimed to evaluate the efficacy of magnesium sulfate and ACTH (MgSO4+ACTH) combination therapy in patients with IS who failed first‐line treatments. Methods In this retrospective study, the clinical data of patients with IS who failed first‐line treatments were collected in the Chinese PLA General Hospital. Patients received MgSO4+ACTH combination therapy after first‐line treatments failed. The course of treatments was 2 weeks. The therapeutic dose of ACTH and MgSO4 was 2.5 U·kg−1·d−1 and 0.25 g·kg−1·d−1, respectively. Results A total of 229 patients with IS who failed the first‐line treatments were collected. At the end of the MgSO4+ACTH combination treatment, the seizure‐free rate was 48.5% (111/229), and the resolution of hypsarrhythmia on electroencephalogram (EEG) was 72.1% (165/229). About 21.4% (49/229) of patients showed side effects, including infectious diseases, hypokalemia, and diarrhea. Interpretation For patients with IS who failed first‐line treatments, in terms of the seizure‐free rate and resolution of hypsarrhythmia on EEG, MgSO4+ACTH combination therapy can be considered.

Objective: To investigate the effects of cell passage number on the establishment of an oxidative stress model in human colon adenocarcinoma cells (Caco-2) caused by tert-butyl hydroperoxide (t-BHP). Methods: First, by applying various t-BHP concentrations (1, 2 and 3 mmol/L) to the F15 generation of Caco-2 cells for 1, 2, 3, 4, 5 and 6 hours, the content of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) in different treatment groups were measured to determine the basic conditions for constructing the oxidative stress model of Caco-2 cells. Then, based on the fundamental parameters, the effect of cell passage number (F14, F15, F18, F19 and F20) on the development of oxidative stress model was investigated using the content of 8-OHdG as an index. Results: When exposed to 1, 2 and 3 mmol/L of t-BHP for 3 to 6 hours, the oxidative stress model of Caco-2 cells from the F15 generation could be established steadily. The content of 8-OHdG in Caco-2 cells of the F14, F15 and F18 generations was significantly higher than that in control group (which had not been treated with t-BHP) after being exposed to 2.0 mmol/L t-BHP for 5 hours (P

Abstract Background Studies on the incidence of venous thromboembolism (VTE) events in patients with interstitial lung disease (ILD) are limited and the results are inconsistent. The aim of this research was to investigate the incidence and risk factors of VTE in ILD during hospitalization. Materials and methods In this retrospective, cross-sectional, observational study, a total of 5009 patients diagnosed with ILD from January 2016 to March 2022 in our hospital were retrospectively included. In ILD patients, VTE including pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT) were screened from the electronic medical record system. Diagnosis of PTE and DVT were performed by CT pulmonary angiography (CTPA), CTV or ultrasound. And then the incidence and risk factors of VTE in different types of ILD were assessed. Results Among 5009 patients with ILD, VTE was detected in 129 (2.6%) patients, including 15(0.3%) patients with both PTE and DVT, 34 (0.7%) patients with PTE and 80 (1.6%) patients with DVT. 85.1% of patients with APE were in the intermediate-low risk group. The incidence of VTE in Anti-Neutrophil Cytoplasmic Antibodies -associated vasculitis related ILD (ANCA-AV-ILD), hypersensitivity pneumonitis and idiopathic pulmonary fibrosis (IPF) respectively was 7.9% and 3.6% and 3.5%. In patients with connective tissue disease-associated ILD (CTD-ILD), the incidence of VTE, DVT, PTE, combined PTE and DVT respectively was 3.0%, 2.3%, 0.4% and 0.3%. Among the various risk factors, different ILD categories, age ≥ 80 years (OR 4.178, 95% CI 2.097–8.321, P 21 days). Conclusion The incidence of VTE during hospitalization in ILD patients was 2.6%, with a 1.6% incidence of DVT, higher than the 0.7% incidence of PTE. Advanced age, ILD categories, respiratory failure and varicose veins as independent risk factors for the development of VTE should be closely monitored.

Abstract Background SHR2554, a novel oral Enhancer of Zeste Homolog 2 inhibitor, shows broad‐spectrum anti‐tumor efficacy in preclinical studies. As SHR2554 is mainly metabolized by CYP3A4, it is helpful to conduct research on the effects of itraconazole, a strong inhibitor of CYP3A4‐metabolizing enzymes, on the pharmacokinetic characteristics and safety of SHR2554. Methods We conducted a single‐center, open‐label pharmacokinetic study of itraconazole on SHR2554 in 18 healthy Chinese subjects. Subjects were orally administrated SHR2554 50 mg on Day 1, itraconazole 200 mg Quaque Die (QD) from Days 4 to 7, SHR2554 50 mg co‐administrated with itraconazole 200 mg on Day 8, and itraconazole 200 mg QD from Days 9 to 12. Then, 4 ml of venous blood was collected at predetermined time points. Plasma SHR2554 concentrations were analyzed using a validated high‐performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters were calculated using Phoenix WinNonlin v8.1. Results The Cmax of SHR2554 alone and in combination was 10.197 ± 7.0262 ng·ml−1 versus 70.538 ± 25.0219 ng·ml−1, AUC0–∞ was 50.99 ± 19.358 h·ng·ml−1 versus 641.53 ± 319.538 h·ng·ml−1, and AUC0–t was 28.70 ± 18.913 h·ng·ml−1 versus 612.13 ± 315.720 h·ng·ml−1. Co‐administration of SHR2554 and itraconazole caused 7.73‐, 12.47‐, and 23.75‐fold adjusted geometric mean ratios increases in SHR2554 Cmax, AUC0−∞ and AUC0−t respectively. The co‐administration regimen was well tolerated and had a good safety profile. Conclusions Compared with a single dose of SHR2554 50 mg, the exposure of SHR2554 in vivo was significantly affected by the combined administration of itraconazole.

Abstract Background Many data suggest that the sucrose non-fermenting 1-related kinases 2 (SnRK2s) are very important to abiotic stress for plants. In rice, these kinases are known as osmotic stress/ABA–activated protein kinases (SAPKs). Osmotic stress/ABA–activated protein kinase 3 (OsSAPK3) is a member of SnRK2II in rice, but its function is still unclear. Results The expression of OsSAPK3 was up regulated by drought, NaCl, PEG and ABA. OsSAPK3 mutated seedings (sapk3-1 and sapk3-2) showed reduced hypersensitivity to exogenous ABA. In addition, under drought conditions, sapk3-1 and sapk3-2 showed more intolerance to drought, including decreased survival rate, increased water loss rate, increased stomatal conductance and significantly decreased expression levels of SLAC1 and SLAC7. Physiological and metabolic analyses showed that OsSAPK3 might play an important role in drought stress signaling pathway by affecting osmotic adjustment and osmolytes, ROS detoxification and expression of ABA dependent and independent dehydration-responsive genes. All gronomic traits analyses demonstrated that OsSAPK3 could improve rice yield by affecting the regulation of tiller numbers and grain size. Conclusion OsSAPK3 plays an important role in both ABA-dependent and ABA-independent drought stress responses. More interestingly, OsSAPK3 could improve rice yield by indirectly regulating tiller number and grain size. These findings provide new insight for the development of drought-resistant rice.

Abstract Background Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. Methods We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan–Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. Results Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p

Abstract Background An increasing prevalence of mental disorders (MDs) has been reported among children and adolescents. However, only few studies have conducted ocular examinations, including those on refractive status, in these groups of patients. Thus, the purpose of this study was to evaluate the refractive status and ocular findings in children and adolescents with MDs compared with matched controls with similar socioeconomic backgrounds. Methods A total of 178 participants with MDs and 200 controls were recruited between April 2021 and May 2022. All the children and adolescents underwent cycloplegic or noncycloplegic autorefraction and retinoscopy, slit-lamp biomicroscopy, and dilated fundus examinations. Ocular alignment was assessed using Hirschberg, Krimsky, or prism cover tests. The prevalence of refractive errors and ocular findings was the main outcome. Results Twenty-seven percent of patients with MDs and 8% of controls had ocular findings, the most common of which were conjunctivitis, keratitis, and trichiasis. For refractive status, 70% (124/178) of patients with MDs had myopia ≤-1.00 DS, and 2% (4/178) had hyperopia ≥+2.00 DS. In the control group, 70% (140/200) of patients had myopia ≤-1.00 DS, and 1% (2/200) had hyperopia ≥+2.00 DS. No differences were observed between the MD and control groups. However, the patients in the MD group (14.25±2.69 years) were significantly more susceptible to strabismus (P

Abstract Background The evaluation of refraction is indispensable in ophthalmic clinics, generally requiring a refractor or retinoscopy under cycloplegia. Retinal fundus photographs (RFPs) supply a wealth of information related to the human eye and might provide a promising approach that is more convenient and objective. Here, we aimed to develop and validate a fusion model-based deep learning system (FMDLS) to identify ocular refraction via RFPs and compare with the cycloplegic refraction. In this population-based comparative study, we retrospectively collected 11,973 RFPs from May 1, 2020 to November 20, 2021. The performance of the regression models for sphere and cylinder was evaluated using mean absolute error (MAE). The accuracy, sensitivity, specificity, area under the receiver operating characteristic curve, and F1-score were used to evaluate the classification model of the cylinder axis. Results Overall, 7873 RFPs were retained for analysis. For sphere and cylinder, the MAE values between the FMDLS and cycloplegic refraction were 0.50 D and 0.31 D, representing an increase of 29.41% and 26.67%, respectively, when compared with the single models. The correlation coefficients (r) were 0.949 and 0.807, respectively. For axis analysis, the accuracy, specificity, sensitivity, and area under the curve value of the classification model were 0.89, 0.941, 0.882, and 0.814, respectively, and the F1-score was 0.88. Conclusions The FMDLS successfully identified the ocular refraction in sphere, cylinder, and axis, and showed good agreement with the cycloplegic refraction. The RFPs can provide not only comprehensive fundus information but also the refractive state of the eye, highlighting their potential clinical value.

Objectives To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with H. pylori infection. Methods A total of 971 H. pylori positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether H. pylori was eradicated. Results There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of H. pylori between dual therapy and quadruple therapy were 88.31% and 85.26% (p=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (p=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (p=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (p

Abstract Background Prospective studies examining long‐term therapeutic outcomes of the Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) regimen in human immunodeficiency virus (HIV) infection remain limited. This study assessed the actual efficacy and safety of BIC/FTC/TAF in HIV‐infected individuals in southwest China. Methods This was a single‐center, prospective study enrolling ART‐naïve (n = 32) and ART‐experienced (n = 177) HIV‐infected patients administered BIC/FTC/TAF treatment between March 2022 and August 2022. The data were collected until February 28, 2023. Virological reactions and adverse events to the treatment were recorded, and patient subjective feelings in the form of Electronic Patient Reporting Outcome (ePRO) were collected. The primary endpoint was the rate of patients with HIV viral load

ABSTRACT Yersinia pestis is the etiological agent of plague. Marmota himalayana of the Qinghai-Tibetan plateau is the primary host of flea-borne Y. pestis. This study is the report of isolation of Mu-like bacteriophages of Y. pestis from M. himalayana. The isolation and characterization of four Mu-like phages of Y. pestis were reported, which were named as vB_YpM_3, vB_YpM_5, vB_YpM_6, and vB_YpM_23 according to their morphology. Comparative genome analysis revealed that vB_YpM_3, vB_YpM_5, vB_YpM_6, and vB_YpM_23 are phylogenetically closest to Escherichia coli phages Mu, D108 and Shigella flexneri phage SfMu. The role of LPS core structure of Y. pestis in the phages’ receptor was pinpointed. All the phages exhibit “temperature dependent infection,” which is independent of the growth temperature of the host bacteria and dependent of the temperature of phage infection. The phages lyse the host bacteria at 37°C, but enter the lysogenic cycle and become prophages in the chromosome of the host bacteria at 26°C. IMPORTANCE Mu-like bacteriophages of Y. pestis were isolated from M. himalayana of the Qinghai-Tibetan plateau in China. These bacteriophages have a unique temperature dependent life cycle, follow a lytic cycle at the temperature of warm-blooded mammals (37°С), and enter the lysogenic cycle at the temperature of its flea-vector (26°С). A switch from the lysogenic to the lytic cycle occurred when lysogenic bacteria were incubated from lower temperature to higher temperature (initially incubating at 26°C and shifting to 37°C). It is speculated that the temperature dependent lifestyle of bacteriophages may affect the population dynamics and pathogenicity of Y. pestis.

Abstract Background The deficiency of serine/threonine protein kinase 11 (STK11), one of the most common tumor suppressor genes in non‐small‐cell lung cancer, is a crucial player in tumor immune microenvironment regulation. This study attempted to unveil how mutated STK11 impact the differentiation of macrophages in lung adenocarcinoma (LUAD). Methods STK11 and CD1E expression levels in different cell models were assessed by quantitative reverse transcription polymerase chain reaction. Western blot was utilized to detect the protein expression levels of STK11, CD1E, apoptosis markers, and AMPK signaling pathway markers after transfection treatment. Cell viability and macrophage differentiation were detected by CCK‐8 and flow cytometry. Immunohistochemistry and immunofluorescence were employed to detect the expression of related genes and macrophage markers, respectively. Results This study found that STK11 mutations promoted the proliferation of LUAD cells and inhibited the differentiation of M1 macrophages, apoptosis, and the AMPK signaling pathway. Mutated STK11 led to CD1E downregulation, which curbed the differentiation of M1 macrophages and hence promoted LUAD progression. It was further validated by the in vivo experimental results that STK11 mutation significantly decreased the immune infiltration of M1 macrophages and promoted LUAD progression. Conclusion It was revealed that STK11 mutation affected CD1E expression to regulate macrophage differentiation in LUAD and then promote tumor progression. In this way, CD1E could be a potential biological target for the therapeutic interventions of STK11‐mutant LUAD patients. These findings also threw new light on a new therapeutic strategy for STK11‐mutant tumor patients that assisted the macrophage polarization pathway.

Bacteria are the key group of micro-organisms during the fermentation of Paocai. This study applied the high-throughput sequencing technology to trace the dynamics of Paocai brine bacterial community structures at constant temperature (25 ℃) under airtight microcosm condition. The results showed that there were 10 phyla and 205 genera had been detected within 30 days after the experiment setup. Among them, there were 12 dominant genera which accounted for 94.7%~97.8% of the total OTUs. The sub-dominant were 13 genera and accounted for 2.1%~3.3%. The rare genera were 180 genera and accounted for 0.08%~2.7%. During the 1~7 days after the experiment setup, the community was relatively stable (phase A). From the 8~20 days, the sub-dominant and rare genera were continuously changing (phase B), and on the 8th day, the communities of sub-dominant and rare genera were acutely fluctuated. From 22~30 days, all of the genera changed obviously (phase C). Meanwhile, the Chao1, Ace indices were increasing during 1~30 days, in addition, the Shannon and Simpson indices reached the thresholds during phase C. Therefore, phase A and B, phase B and C had the similar communities, but not the phase A and C, while the pH during the three phases changed correspondingly. The results also showed that at 25 ℃, the dynamics of sub-dominant and rare genera were the key factor which caused the dynamic of the bacterial communities in Paocai brine during the 30 days experiment. In addition, the accumulated effect had been detected, the pH and the bacterial communities havd mutual influences. The optimal preservation time for the Paocai brine was one week under airtight condition at 25 ℃. The functional effects of rare genera from Paocai brine need pay more attentions on.

Helical piles are a new type of pile that has good application prospects, and researchers have carried out an in-depth investigation into their vertical uplift and compressive bearing capacity. However, there is relatively little research on the dynamic bearing characteristics of helical piles. Therefore, the lateral vibration of a helical pile embedded in the viscoelastic foundation is systematically studied in this article. Utilizing the equivalent stiffness method to transform a helical pile into a cylindrical pile of special diameter, the lateral vibration model of the helical pile considering shear deformation is established based on the Winkler foundation model and the Timoshenko beam theory. The analytical solutions for the lateral dynamic displacement, bending moment, and shear force of the helical pile are strictly derived, and the rationality of the present solutions is also verified by comparing them with existing solutions. Based on the present solutions, a parametric study is carried out to investigate the influence of the pile and soil properties on the lateral dynamic response of the helical pile. It is found that the load excitation frequency and pile–soil stiffness ratio have a significant influence on the lateral dynamic displacement, bending moment, and shear force of the helical pile with space and time response.

Abstract Background Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. Methods In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. Results As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p

【Objective】The study was conducted to explore the phyllosphere bacterial community structure and diversity of landscaping plants in the niche, and to understand the effects of similar environmental conditions and plant characteristics on microbial community in the niche, with a view to provide references for the health management of garden plants and the exploitation of phyllosphere bacterial resources.【Method】High-throughput sequencing technology was applied to explore the bacterial community structure and diversity of Eriobotyra japonica, Magnolia grandiflora and Ficus altissima leaves facing east within 50 m radius circle of Dali University campus.【Result】Among the three garden plants, E. japonica had the highest phyllosphere bacterial diversity, followed by M. grandiflora and F. altissima. The dominant bacterial phylum of phyllosphere bacteria in different plants was Proteobacteria, and the first dominant bacterial genus was different. However, the top five dominant genera were Sphingopyxis, Methylobacterium, Spirosoma, Hymenobacter and Achromobacter. There were significant differences in phyllosphere bacterial community structure among the three plants, but the bacterial communities were similar among the leaves with different sizes of the same plant. Only E. japonica and M. grandiflora leaves had the largest phylum and genus distribution, indicating that the phyllosphere bacterial communities of evergreen broad-leaved plants was more diverse and complex than those of deciduous broad-leaved plants.【Conclusion】There were differences in the composition and diversity of phyllosphere bacterial communities among different plants, and the primary reasons for these differences were the characteristics of the plants themselves. Therefore, it is urgent to strengthen the researches on the utilization of phyllosphere bacterial resources of plants.

Abstract Background Metastatic non‐small cell lung cancer (NSCLC) is mostly seen in older patients and is associated with poor prognosis. There is no reliable method to predict the prognosis of elderly patients (≥60 years old) with metastatic NSCLC. The aim of our study was to develop and validate nomograms which accurately predict survival in this group of patients. Methods NSCLC patients diagnosed between 2010 and 2015 were all identified from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed by significant clinicopathological variables (p

A T/C variant in miR-27a is associated with bipolar disorder, potentially by reducing the ability of this microRNA to target important neurodevelopmental genes like NCAM1.

Indole compounds with their unique properties of mimicking peptide structures and reversible binding to enzymes are of great exploitative value in the regulation of plant growth. They stimulate root and fruit formation and activate the plant’s immune system against biotic and abiotic factors harmful to the plant. Analysis of target recognition, receptor recognition, key activation sites and activation mechanisms of indoles in plant to enhance crop growth or disease resistance is a crucial step for further developing compounds as plant growth regulators and immune inducers. Therefore, this review focused on the mechanism of action of indoles in regulating plant growth and enhancing plant resistance to biotic and abiotic stresses.

BackgroundThe prognosis of colorectal cancer with atypical metastasis is poor. However, atypical metastasis was less common and under-appreciated.MethodsIn this study we attempted to present the first machine learning models to predict the risk of atypical metastasis in colorectal cancer patients. We evaluated the differences between metastasis and non-metastasis groups, assessed factors associated with atypical metastasis using univariate and multivariate logistic regression analyses, and preliminarily developed the multiple machine learning models to predict atypical metastasis.Results168 patients were included. Prognostic Nutritional Index (PNI) [OR = 0.998; P = 0.030], Cancer antigen 19–9 (CA19-9) [OR = 1.011; P = 0.043] and MR-Distance [-mid OR = 0.289; P = 0.009] [-high OR = 0.248; P = 0.021] were shown to be independent risk factors for the atypical metastasis via multivariate analysis. Furthermore, the machine learning model based on AdaBoost algorithm (AUC: 0736) has better predictive performance comparing to Logistic Regression (AUC: 0.671) and KNeighbors Classifier (AUC: 0.618) by area under the curve (AUC) in the validation cohorts. The accuracy, sensitivity, and specificity of the model trained using the Adaboost method in the validation set are 0.786, 0.776 and 0.700, while 0.601, 0.933, 0.508 using Logistic Regression and 0.743, 0.390, 0.831 using KNeighbors Classifier.ConclusionMachine-learning approaches containing PNI, CA19-9 and MR-Distance show great potentials in atypical metastasis prediction.

Plant-specific TCP transcription factors play an essential role in plant growth and development. They can regulate leaf curvature, flower symmetry and the synthesis of secondary metabolites. The flavonoids in Ginkgo biloba leaf are one of the main medicinally bioactivate compounds, which have pharmacological and beneficial health effects for humans. In this study, a total of 13 TCP genes were identified in G. biloba, and 5 of them belonged to PCF subclades (GbTCP03, GbTCP07, GbTCP05, GbTCP13, GbTCP02) while others belonged to CIN (GbTCP01, GbTCP04, GbTCP06, GbTCP08, GbTCP09, GbTCP10, GbTCP11, GbTCP12) subclades according to phylogenetic analysis. Numerous cis-acting elements related to various biotic and abiotic signals were predicted on the promoters by cis-element analysis, suggesting that the expression of GbTCPs might be co-regulated by multiple signals. Transcript abundance analysis exhibited that most of GbTCPs responded to multiple phytohormones. Among them, the relative expression levels of GbTCP06, GbTCP11, and GbTCP13 were found to be significantly influenced by exogenous ABA, SA and MeJA application. In addition, a total of 126 miRNAs were predicted to target 9 TCPs (including GbTCP01, GbTCP02, GbTCP04, GbTCP05, GbTCP06, GbTCP08, GbTCP11, GbTCP12, GbTCP13). The correlation analysis between the expression level of GbTCPs and the flavonoid contents showed that GbTCP03, GbTCP04, GbTCP07 might involve in flavonoid biosynthesis in G. biloba. In short, this study mainly provided a theoretical foundation for better understanding the potential function of TCPs in G. biloba.

A three-dimensional (3D) ZnO-supported carbon fiber aerogel (ZnO/CFA) was successfully prepared by using natural cotton with hydrophilicity as the precursor. The facile synthetic strategy includes two steps: Zn2+ exchange on the surface of cotton and thermal treatment at high temperatures. Particularly, the calcination temperature was found to greatly affect the content, dispersity, and size of supported ZnO nanoparticles, and the product obtained at 600 °C (ZnO/CFA-600) exhibited both high ZnO loading and well-dispersed ZnO nanoparticles. Therefore, ZnO/CFA-600 has superior photocatalytic activity for tetracycline (TC) degradation under UV light irradiation compared with others. Additionally, the unique 3D crosslinking network inside the ZnO/CFA generates an open channel for the rapid migration and diffusion of reactants and products. In a dynamical water-treated system, the 3D porous ZnO/CFA-600 continuously works for TC removal without any separation operation and maintains high synergistic performance of adsorption and photocatalysis for at least 8 h. Consequently, the 3D porous ZnO/CFA product, with its large adsorbability and high photoactivity, shows a lot of industrial potential in wastewater treatments.

Cells with various structures and proteins naturally come together to cooperate in vivo. This study used cell spheroids cultured in agarose micro-wells as a 3D model to study the movement of cells or spheroids toward other spheroids. The formation dynamics of tumor spheroids and the interactions of two batches of cells in the agarose micro-wells were studied. The results showed that a concave bottom micro-well (diameter: 2 mm, depth: 2 mm) prepared from 3% agarose could be used to study the interaction of two batches of cells. The initial tumor cell numbers from 5 × 103 cells/well to 6 × 104 cells/well all could form 3D spheroids after 3 days of incubation. Adding the second batch of DU 145 cells to the existing DU 145 spheroid resulted in the formation of satellite cell spheroids around the existing parental tumor spheroid. Complete fusion of two generation cell spheroids was observed when the parental spheroids were formed from 1 × 104 and 2 × 104 cells, and the second batch of cells was 5 × 103 per well. A higher amount of the second batch of cells (1 × 104 cell/well) led to the formation of independent satellite spheroids after 48 h of co-culture, suggesting the behavior of the second batch of cells towards existing parental spheroids depended on various factors, such as the volume of the parental spheroids and the number of the second batch cells. The interactions between the tumor spheroids and Human Umbilical Vein Endothelial Cells (HUVECs) were modeled on concave agarose micro-wells. The HUVECs (3 × 103 cell/well) were observed to gather around the parental tumor spheroids formed from 1 × 104, 2 × 104, and 3 × 104 cells per well rather than aggregate on their own to form HUVEC spheroids. This study highlights the importance of analyzing the biological properties of cells before designing experimental procedures for the sequential fusion of cell spheroids. The study further emphasizes the significant roles that cell density and the volume of the spheroids play in determining the location and movement of cells.

Conidia fusion (CF) is a commonly observed structure in fungi. However, it has not been systematically studied. This study examined 2457 strains of nematode-trapping fungi (NTF) to explore the species specificity, physiological period, and physiological significance of CF. The results demonstrated that only six species of Arthrobotrys can form CF among the sixty-five tested NTF species. The studies on the model species Arthrobotrys oligospora (DL228) showed that CF occurred in both shed and unshed plus mature and immature conidia. Additionally, the conidia fusion rate (CFR) increased significantly with the decrease of nutrient concentration in habitats. The studies on the conidia fusion body (CFB) produced by A. oligospora (DL228) revealed that the more conidia contained in the CFB, the faster and denser the mycelia of the CFB germinated in weak nutrient medium and soil plates. On the one hand, rapid mycelial extension is beneficial for the CFB to quickly find new nutrient sources in habitats with uneven nutrient distribution. On the other hand, dense mycelium increases the contact area with the environment, improving the nutrient absorption efficiency, which is conducive to improving the survival rate of conidia in the weak nutrient environment. In addition, all species that form CF produce smaller conidia. Based on this observation, CF may be a strategy to balance the defects (nutrient deficiency) caused by conidia miniaturization.

Obesity is a serious public health problem. According to statistics, there are millions of obese people worldwide. Research studies have discovered a complex and intricate relationship between the gut microbiota and obesity. Probing and summarizing the relationship between intestinal microbes and obesity has important guiding significance for the accurate control of the research direction and expanding the choice of obesity treatment methods. We used bibliometric analysis to analyze the published literature with the intention to reveal the research hotspots and development trends on the effects of intestinal microbes on obesity from a visualization perspective, both qualitatively and quantitatively. The results showed that current research is focusing on related mechanisms of the effects of intestinal microbes on obesity and therapeutic methods for obesity. Several noteworthy hotspots within this field have garnered considerable attention and are expected to remain the focal points of future research. Of particular interest are the mechanisms by which intestinal microbes potentially regulate obesity through metabolite interactions, as well as the role of microbiomes as metabolic markers of obesity. These findings strongly suggest that gut microbes continue to be a key target in the quest for effective obesity treatments. Co-operation and communication between countries and institutions should be strengthened to promote development in this field to benefit more patients with obesity.

Ground deformation is one of the most common geological disasters arising in underground mining areas, and mining-induced environmental impacts have resulted in numerous concerns, especially the impacts on the surface vegetation. The evaluation of mining-induced impacts on vegetation is beneficial to revegetation in mining areas; however, the impacts of ground deformation have seldom been systematically evaluated and explained on long time scales despite the long-term existence of ground deformation in underground mining areas. To address this, in this study a vegetation-soil-climate (VSC) model was developed to evaluate the long-term impacts of ground deformation on vegetation, and to reveal its mechanism. The results revealed that the long-term impacts of ground deformation on vegetation result from the degradation of the vegetation and soil when ground deformation occurs, which thereby limits the growth and succession of plants after the ground deformation has occurred. The intensity of the long-term impacts is determined by the severity of the ground deformation, but the duration, climate factors, the substrate conditions of the vegetation and soil before the deformation, and the natural change coefficient of the vegetation and soil are also relevant. Furthermore, the characteristics of the long-term impacts on vegetation were analyzed, and a framework for implementing revegetation and suggestions for the supervision of revegetation in underground mining areas are presented based on the characteristics. The results of this study provide insights into the impacts of mining-induced ground deformation on vegetation on long time scales, considering the comprehensive interactions between the vegetation and other environmental factors, and provide theoretical support for revegetation in underground mining areas.

The development of digital economy affects environmental pollution emission and green sustainable development. However, the relationship between digital economy and industrial wastewater discharge has rarely been examined. This study establishes the urban digital economy evaluation index system, measures the digital economy indexes of 281 prefecture-level cities in China from 2011 to 2016, and examines the impact effect of digital economy development on industrial wastewater discharge using the system generalized method of moment method and the intermediary effects model. The empirical results indicate that the digital economy reduces the industrial wastewater discharge. As evidence shows, the digital economy significantly promotes the upgrading of industrial structure, which is an important factor affecting the industrial wastewater discharge. Additionally, the inhibiting effect of digital economy on industrial wastewater discharge is more significant in big cities. This study provides a scientific base and guidance for reducing environmental pollution emissions and promoting the development of digital economy. HIGHLIGHTS The effect of digital economy on industrial wastewater discharge is explored.; The digital economy reduces the discharge of industrial wastewater.; The mediating role of upgrading the industrial structure is established.; The inhibitory effect of digital economy on the discharge of industrial wastewater is significant in big cities.;

Abstract Ginkgo biloba L. is an ancient relict plant with rich pharmacological activity and nutritional value, and its main physiologically active components are flavonoids and terpene lactones. The bZIP gene family is one of the largest gene families in plants and regulates many processes including pathogen defense, secondary metabolism, stress response, seed maturation, and flower development. In this study, genome-wide distribution of the bZIP transcription factors was screened from G. biloba database in silico analysis. A total of 40 bZIP genes were identified in G. biloba and were divided into 10 subclasses. GbbZIP members in the same group share a similar gene structure, number of introns and exons, and motif distribution. Analysis of tissue expression pattern based on transcriptome indicated that GbbZIP08 and GbbZIP15 were most highly expressed in mature leaf. And the expression level of GbbZIP13 was high in all eight tissues. Correlation analysis and phylogenetic tree analysis suggested that GbbZIP08 and GbbZIP15 might be involved in the flavonoid biosynthesis. The transcriptional levels of 20 GbbZIP genes after SA, MeJA, and low temperature treatment were analyzed by qRT-PCR. The expression level of GbbZIP08 was significantly upregulated under 4°C. Protein–protein interaction network analysis indicated that GbbZIP09 might participate in seed germination by interacting with GbbZIP32. Based on transcriptome and degradome data, we found that 32 out of 117 miRNAs were annotated to 17 miRNA families. The results of this study may provide a theoretical foundation for the functional validation of GbbZIP genes in the future.

Research has generally outlined that the Neolithic East Asian farmers expanded into Southeast Asia, leading to substantial social and cultural transformations. However, the associated archaeobotanical evidence until now has been insufficient to clarify the exact timing, dispersal route, and farming package of the emergence of agriculture in Mainland Southeast Asia. To clarify these issues, the micro-plant remains of phytolith and starch from three Neolithic sites in Ha Long Bay were extracted and analyzed. This study validates the earliest evidence of co-cropping in northern Vietnam, involving the cultivation of rice together with foxtail millet at 4000 years BP or slightly earlier. Moreover, the results indicate that at least two patterns of subsistence strategy were practiced simultaneously during the initial farming phase in the region. The Trang Kenh people, a regional variant of the Phung Nguyen cultural group often have been seen as the first farmers in northern Vietnam, and they mainly practiced a cereal-based subsistence strategy with more vital cultural characteristics of southern China origin. Meanwhile, the Ha Long people, mainly composed of indigenous hunter-gatherer descendants, continued to utilize a wide range of their preferred plant resources such as taros, yams, and acorns, while they absorbed and incorporated new elements such as millet and rice into their food system. This study provides solid information to understand the diverse economic systems among different cultural groups in Vietnam.

Background Early diagnosis and treatment are imperative for improving survival in gastric cancer (GC). This work aimed to assess the ability of human serum amino acid and acylcarnitine profiles in distinguishing GC cases from atrophic gastritis (AG) and control superficial gastritis (SG) patients. Methods Sixty-nine GC, seventy-four AG and seventy-two SG control patients treated from May 2018 to May 2019 in Gansu Provincial Hospitalwere included. The levels of 42 serum metabolites in the GC, AG and SG groups were detected by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Then, orthogonal partial least squares discriminant analysis (OPLS-DA) and the Kruskal-Wallis H test were used to identify a metabolomic signature among the three groups. Metabolites with highest significance were examined for further validation. Receiver operating characteristic (ROC) curve analysis was carried out for evaluating diagnostic utility. Results The metabolomic analysis found adipylcarnitine (C6DC), 3-hydroxy-hexadecanoylcarnitine (C16OH), hexanoylcarnitine (C6), free carnitine (C0) and arginine (ARG) were differentially expressed (all VIP >1) and could distinguish GC patients from AG and SG cases. In comparison with the AG and SG groups, GC cases had significantly higher C6DC, C16OH, C6, C0 and ARG amounts. Jointly quantitating these five metabolites had specificity and sensitivity in GC diagnosis of 98.55% and 99.32%, respectively, with an area under the ROC curve (AUC) of 0.9977. Conclusion This study indicates C6DC, C16OH, C6, C0 and ARG could effectively differentiate GC cases from AG and SG patients, and may jointly serve as a valuable circulating multi-marker panel for GC detection.

ObjectiveTo study the effect of treatment zone (TZ) decentration on axial length growth (ALG) in adolescents after wearing the orthokeratology lenses (OK lenses).Materials and methodsThis retrospective clinical study selected 251 adolescents who were fitted OK lenses at the Clinical College of Ophthalmology, Tianjin Medical University (Tianjin, China) from January 2018–December 2018 and wore them continuously for >12 months. The age of the subjects was 8–15 years, spherical equivalent (SE): −1.00 to −5.00 diopter (D), and astigmatism ≤ 1.50 D. The corneal topography were recorded at baseline and 1-, 6-, and 12-month visits, and the axial length (AL) were recorded at baseline and 6-, 12-month visits. The data of the right eye were collected for statistical analysis.ResultsThe subjects were divided into three groups according to the decentration distance of the TZ after wearing lenses for 1 month: 56 cases in the mild (1.0 mm). A significant difference was detected in the ALG between the three groups after wearing lenses for 6 and 12 months (F = 10.223, P < 0.001; F = 13.380, P < 0.001, respectively). Among these, the 6- and 12-month ALG of the mild decentration group was significantly higher than that of the other two groups. Multivariable linear regression analysis showed that age, baseline SE, and 1-month decentration distance associated with the 12-month ALG (P < 0.001, P < 0.001, and P = 0.001, respectively).ConclusionThe decentration of the TZ of the OK lens affected the growth of the AL in adolescents, i.e., the greater the decentration, the slower the ALG.

ObjectiveObese or overweight is a risk factor for some chronic diseases, and oxidative stress and inflammation may be one of the molecular mechanisms leading to the persistence of these chronic diseases. Discovering interventions to alleviate oxidative stress and inflammation in the overweight/obese population, is very important for public health and health education.MethodsA two-week panel intervention study (Run 0-Run 1-Run 2) was conducted. The subjects were 77 overweight/obese undergraduates attending Dali University, with a BMI>24 kg/m2. The physical indices measured at the end of each run included BMI, waist circumference, serum ROS, TNF-α, IL-1β and urinary 8-OHdG. Students were allocated to one of four intervention groups: No intervention (control); walking; taking vitamin C; and walking + taking vitamin C.ResultsThe results demonstrated (1) Walking significantly alleviated ROS levels, and this was consistent in Run 1 and Run 2; (2) During Run1, all three intervention modes reduced levels of 8-OHdG, but there was a statistically insignificant increase during Run 2; (3) No alleviating effects of the three intervention modes on TNF-α levels during Run 1 and Run 2 were observed; (4) The alleviating effects of the three intervention modes on IL-1β levels during Run 1 and Run 2 were clear.ConclusionWalking and taking vitamin C can reduce levels of ROS, 8-OHdG and IL-1β, but not TNF-α, in overweight/obese participants. These interventions may become potential preventive measures for the overweight against obese-induced oxidative stress and inflammation.

Delphinium grandiflorum L. (family Ranunculaceae), one of the most important and widely distributed Delphinium species, has received considerable interest due to its extremely high medicinal value. The discovery of novel metabolites from D. grandiflorum supported and broadened its application as an herbal medicine. In this study, the whole herb of D. grandiflorum was phytochemically investigated to obtain fourteen C19-lycaconitine-type diterpenoid alkaloids (1–14), including six undescribed alkaloids, grandiflolines A–F (1–6). The structural elucidation of them was accomplished by detailed spectroscopic analyses, mainly including HR-MS, 1D and 2D NMR (1H–1H COSY, NOESY, HMBC and HSQC), and IR spectra. New alkaloids 1–3 and 5 possess a characteristic △2,3 functional group in the A ring, while compounds 5 and 6 feature a rare OH-16 substituent. In addition, known compounds 7–12 were isolated from D. grandiflorum for the first time. Moreover, according to its medicinal use, new alkaloids 1–6 were estimated for their potential in vitro anti-inflammatory effects, and some of them exhibited inhibitory effects on NO production in LPS-activated RAW 264.7 macrophages. Our work enriched the chemical diversity of D. grandiflorum and the genus Delphinium and presented beneficial information for further investigations.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system related to autoimmunity and is characterized by demyelination, neuroinflammation, and neurodegeneration. Cell therapies mediated by dendritic cells (DCs) and regulatory T cells (Tregs) have gradually become accumulating focusing in MS, and the protective crosstalk mechanisms between DCs and Tregs provide the basis for the efficacy of treatment regimens. In MS and its animal model experimental autoimmune encephalomyelitis, DCs communicate with Tregs to form immune synapses and complete a variety of complex interactions to counteract the unbalanced immune tolerance. Through different co-stimulatory/inhibitory molecules, cytokines, and metabolic enzymes, DCs regulate the proliferation, differentiation and function of Tregs. On the other hand, Tregs inhibit the mature state and antigen presentation ability of DCs, ultimately improving immune tolerance. In this review, we summarized the pivotal immune targets in the interaction between DCs and Tregs, and elucidated the protective mechanisms of DC-Treg cell crosstalk in MS, finally interpreted the complex cell interplay in the manner of inhibitory feedback loops to explore novel therapeutic directions for MS.