Beyond Immune Balance: The Pivotal Role of Decidual Regulatory T Cells in Unexplained Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive pregnancy failures, which brings tremendous stress to women of childbearing age and seriously affects family well-being. However, the reason in about 50% of cases remains unknown and is defined as unexplained recurrent spontaneous abortion (URSA). The immunological perspective in URSA has attracted widespread attention in recent years. The embryo is regarded as a semi-allogeneic graft to the mother. A successful pregnancy requires transition to an immune environment conducive to embryo survival at the maternal-fetal interface. As an important member of regulatory immunity, regulatory T (Treg) cells play a key role in regulating immune tolerance at the maternal-fetal interface. This review will focus on the phenotypic plasticity and lineage stability of Treg cells to illustrate its relationship with URSA.

18F-DGPET/CT Imaging of Ovarian Yolk Sac Tumor in a Woman after Induction of Labor: A Case Report.

Introduction: Ovarian yolk sac tumor (OYST) during pregnancy is rare and usually missed. There are few PET/CT studies on OYST in the literature. We reported a case of OYST detected by 18F-FDG PET/CT in a woman after induction of labor. Case Presentation: A 19-year-old woman after induction of labor because of severe malformation presented with abdominopelvic mass, laboratory tests revealed significantly elevated serum alpha-fetoprotein (AFP) level and elevated carbohydrate antigen 125 level. Abdomino-pelvic CT showed a cysticsolid mass of 82×152×167mm arising from the right ovary with abundant intratumoral vessels and intense enhancement in the solid part. Further evaluation of 18F-FDG PET/CT imaging showed significantly increased 18FDG uptake (SUVmax7.7) by the solid component of the ovarian mass and slight 18FDG-avid perihepatic effusion. The mass was resected and was confirmed to be the right OYST, After four courses of chemotherapy, the patient was followed up by PET/CT and had a complete metabolic response. Discussion: 18F-FDG PET/CT is a useful imaging modality for diagnosis and evaluation of OYST.

Notoginsenoside R1 promotes Lgr5+ stem cell and epithelium renovation in colitis mice via activating Wnt/ß-Catenin signaling.

Inflammatory bowel disease (IBD) is characterized by persistent damage to the intestinal barrier and excessive inflammation, leading to increased intestinal permeability. Current treatments of IBD primarily address inflammation, neglecting epithelial repair. Our previous study has reported the therapeutic potential of notoginsenoside R1 (NGR1), a characteristic saponin from the root of Panax notoginseng, in alleviating acute colitis by reducing mucosal inflammation. In this study we investigated the reparative effects of NGR1 on mucosal barrier damage after the acute injury stage of DSS exposure. DSS-induced colitis mice were orally treated with NGR1 (25, 50, 125 mg·kg-1·d-1) for 10 days. Body weight and rectal bleeding were daily monitored throughout the experiment, then mice were euthanized, and the colon was collected for analysis. We showed that NGR1 administration dose-dependently ameliorated mucosal inflammation and enhanced epithelial repair evidenced by increased tight junction proteins, mucus production and reduced permeability in colitis mice. We then performed transcriptomic analysis on rectal tissue using RNA-sequencing, and found NGR1 administration stimulated the proliferation of intestinal crypt cells and facilitated the repair of epithelial injury; NGR1 upregulated ISC marker Lgr5, the genes for differentiation of intestinal stem cells (ISCs), as well as BrdU incorporation in crypts of colitis mice. In NCM460 human intestinal epithelial cells in vitro, treatment with NGR1 (100 µM) promoted wound healing and reduced cell apoptosis. NGR1 (100 µM) also increased Lgr5+ cells and budding rates in a 3D intestinal organoid model. We demonstrated that NGR1 promoted ISC proliferation and differentiation through activation of the Wnt signaling pathway. Co-treatment with Wnt inhibitor ICG-001 partially counteracted the effects of NGR1 on crypt Lgr5+ ISCs, organoid budding rates, and overall mice colitis improvement. These results suggest that NGR1 alleviates DSS-induced colitis in mice by promoting the regeneration of Lgr5+ stem cells and intestinal reconstruction, at least partially via activation of the Wnt/ß-Catenin signaling pathway. Schematic diagram of the mechanism of NGR1 in alleviating colitis. DSS caused widespread mucosal inflammation epithelial injury. This was manifested by the decreased expression of tight junction proteins, reduced mucus production in goblet cells, and increased intestinal permeability in colitis mice. Additionally, Lgr5+ ISCs were in obviously deficiency in colitis mice, with aberrant down-regulation of the Wnt/ß-Catenin signaling. However, NGR1 amplified the expression of the ISC marker Lgr5, elevated the expression of genes associated with ISC differentiation, enhanced the incorporation of BrdU in the crypt and promoted epithelial restoration to alleviate DSS-induced colitis in mice, at least partially, by activating the Wnt/ß-Catenin signaling pathway.

[Hydrochemical Characteristics and Genesis Mechanism of Groundwater in the Dry Period in the Zhangjiakou Area].

In order to better support the construction of the capital water conservation functional area and ecological environment support area， research on the chemical characteristics of groundwater and its formation mechanism in the dry period in the Zhangjiakou area can provide a great reference for the rational development and utilization of groundwater resources. A total of 41 groups of groundwater samples were collected， and the hydrochemical types， composition characteristics， and control factors of groundwater in the study area were analyzed by using the combined method of descriptive statistical analysis， Piper triplot， correlation analysis， Gibbs plot， and ion ratio. The results showed that the groundwater in the study area was weakly alkaline， with the total hardness and ρ（TDS） ranging from 105.00 mg·L-1 to 1 433.00 mg·L-1 and 137.00 mg·L-1 to 2 286.00 mg·L-1， respectively. The total hardness and TDS mass concentrations of groundwater in the Bashang area were higher than those in the Baxia area. HCO3- and Na+ were the main dominant anions and cations in the groundwater in the study area. The highest overstandard rate of the main components in groundwater was that of total hardness （36.59%）. The overstandard rate and maximum excess multiple of each component in groundwater in the Bashang area were greater than those in the Baxia area. HCO3-Ca·Mg·Na was the main type of groundwater hydrochemistry in the study area， and there was little difference between the Bashang area and the Baxia area. SO42-， Cl-， HCO3-， Na+， and Mg2+ contributed the most to TDS. The chemical characteristics of groundwater were affected by weathering and filtration of rock minerals such as salt rock， albite， and dolomite； cation exchange； and human activities. Evaporative crystallization and atmospheric precipitation contributed to a small part of the main ion source of groundwater in the area. The effect of human activities on groundwater in the Bashang area was greater than that in the Baxia area， and NO3- mainly originated from agricultural activities.

Molecular epidemiological characteristics of carbapenem-resistant Pseudomonas aeruginosa clinical isolates in southeast Shanxi, China.

OBJECTIVES: Infection by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious clinical problem worldwide. However, the molecular epidemiology of the clinical isolates varies depending on the region. This study was conducted to analyse the resistance phenotype and clarify the genetic and epidemiological properties of CRPA clinical isolates from southeast Shanxi, China. METHODS: Fifty-seven isolates of CRPA were collected from a hospital in this region. These isolates were reidentified by MALDI-TOF and subjected to whole-genome sequencing by next-generation sequencing. Phylogenetic trees were constructed based on single nucleotide polymorphisms (SNPs), after which multilocus sequence typing (MLST) was performed and antimicrobial resistance genes were identified. RESULTS: All the 57 CRPA isolates carried at least one kind of gene encoding carbapenemase, such as blaIMP-1, blaIMP-10, blaOXA-10, blaOXA-395, blaOXA-396, blaOXA-485, blaOXA-486, blaOXA-488, blaOXA-494, and blaOXA-50. The isolates harboured AIM-1, CMY-51, mecD, and NmcR genes and carried one kind of Pseudomonas-derived cephalosporinase (PDC) ß-lactamase-encoding gene, such as blaPCD-1 to blaPCD-3, blaPCD-5, or blaPCD-7 to blaPCD-10. Two isolates were found to harbour the aminoglycoside-modifying enzyme genes aadA1 and aadA7; however, no isolates were found to harbour genes encoding 16S rRNA methylase or quinolone resistance-related genes. These CRPA isolates belonged to various sequence types (STs), two of which, namely, ST235 and ST277, were high-risk types. CONCLUSIONS: Our findings indicate that CRPA isolates carrying resistance genes with unique regional characteristics are spreading in this region, with a high diversity of STs, especially in high-risk clones. These findings highlight the necessity for further measures to prevent CRPA spread in Shanxi.

Vitamin D receptor induces oxidative stress to promote esophageal squamous cell carcinoma proliferation via the p53 signaling pathway.

Background: Esophageal squamous cell carcinoma (ESCC) is a common pathological esophageal cancer with poor prognosis. Vitamin D deficiency reportedly occurs in ESCC patients, and this is related to single nucleotide polymorphism of vitamin D receptor (VDR). Objective: We investigated the effect of VDR on ESCC proliferation, invasion, and metastasis and its potential mechanism. Methods: ESCC and normal tissues were collected from 20 ESCC patients. The ESCC tissue microarray contained 116 pairs of ESCC and normal tissues and 73 single ESCC tissues. VDR expression and its clinicopathological role were determined by real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry staining. sh-VDR and VDR overexpression were used to validate the effect of VDR on ESCC cell phenotype, and tandem mass tag-based quantitative proteomics and bioinformatics methods identified differential VDR-related proteins. The downstream pathway and regulatory effect were analyzed using ingenuity pathway analysis (IPA). Differentially expressed proteins were verified through parallel reaction monitoring and Western blot. In vivo imaging visualized subcutaneous tumor growth following tail vein injection of VDR-deficient ESCC cells. Results: High VDR expression was observed in ESCC tissues and cells. Gender, T stage, and TNM stage were related to VDR expression, which was the independent prognostic factor related to ESCC. VDR downregulation repressed ESCC cell proliferation, invasion, and migration in vitro and subcutaneous tumor growth and lung metastases in vivo. The cell phenotype changes were reversed upon VDR upregulation, and differential proteins were mainly enriched in the p53 signaling pathway. TP53 cooperated with ABCG2, APOE, FTH1, GCLM, GPX1, HMOX1, JUN, PRDX5, and SOD2 and may activate apoptosis and inhibit oxidative stress, cell metastasis, and proliferation. TP53 was upregulated after VDR knockdown, and TP53 downregulation reversed VDR knockdown-induced cell phenotype changes. Conclusions: VDR may inhibit p53 signaling pathway activation and induce ESCC proliferation, invasion, and metastasis by activating oxidative stress.

Pre-procedure 18F-FDG PET/CT imaging improves the performance of CT-guided transthoracic biopsy.

PURPOSE: To compare computed tomography (CT)-guided transthoracic lung biopsies (CTLB) with and without pre-procedure 18F-fluorodeoxgyglucose positron emission tomography (18F-FDG PET)/CT images in the diagnosis of pulmonary nodules/masses. METHODS: This is a case-control study in a single center. The data of patients with a transthoracic lung biopsy guided by CT and pre-procedure 18F-FDG PET/CT (group 2, here called the "PETCTLB" group), including demographics, clinical characteristics, and biopsy-related parameters, were collected. The PET/CT scan was performed within 15 days before the biopsy. The data from patients with CTLB were used as controls (group 1). Biopsies for all patients were performed by the same physician between January 2019 and December 2021. The final diagnosis was based on surgical outcomes, or imaging findings, and the results of at least one 6-month follow-up. The demographics and clinical characteristics of patients, lesions and biopsy-related variables, diagnostic yields, and incidence of complications were compared between the two groups. Two-tailed t-tests were used to compare the mean values in the two independent groups, while categorical variables were compared using the Pearson chi-squared test, and P values < 0.05 were considered to be significant. RESULTS: A total of 84 patients were included, and 84 biopsies of 84 lung nodules/masses were analyzed. The demographics and clinical characteristics of group 2 (n = 39; 21 men; mean age, 63.2 ± 9.29 years) and group 1 (n = 45; 30 men; mean age, 61.2 ± 12.3 years) had no significant difference (P = 0.230 and 0.397, respectively). The procedure duration (11.1 ± 3.0 vs. 12.9 ± 3.3 minutes, P = 0.008), the number of samples (2.6 ± 0.5 vs. 3.1 ± 0.4, P < 0.001), diagnostic accuracy (97.4% vs. 82.2%, P = 0.033), and bleeding complication (25.6% vs. 42.2%, P = 0.034) of group 2 and group 1 were statistically different. CONCLUSION: A biopsy guided by CT plus pre-procedure 18F-FDG PET/CT (PETCTLB) is a safe procedure that can provide a precise diagnosis in the majority of lung nodules/masses. It has better diagnostic performance than CTLB.

The sensitivity and specificity of 18F-FDG PET/CT in spinal leptomeningeal metastases: the synergistic effect of the 18F-FDG PET-CT to gadolinium-enhanced MRI.

Background: Magnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center. Methods: Patients with SLM who had undergone 18F-FDG PET/CT and MRI were enrolled. 18F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM. Results: A total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively. Conclusions: 18F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role.

Parallel detection of multiple zoonotic parasites using a real-time fluorogenic loop-mediated isothermal amplification-based quadruple-sample microfluidic chip.

Zoonotic parasites pose significant health risks globally. In the present study, we combined a microfluidic chip with loop-mediated isothermal amplification (on-chip LAMP) to detect five zoonotic parasites: Toxoplasma gondii, Cryptosporidium parvum, Cryptosporidium hominis, Clonorchis sinensis, and Taenia solium. This method enabled the simultaneous parallel analysis of five genetic markers from a maximum of four samples per chip. The on-chip LAMP assay was conducted in a highly automated format via the addition (by pipetting) of each sample in a single operation. The reaction was performed in volumes as low as 5 µL at a temperature of 65°C for 60 min, achieving limits of detection ranging from 10-2 to 10-3 pg./µL of recombinant plasmid DNA. All the time-to-positive values were less than 40 min, and almost all the coefficients of variation were less than 10%, even when using limit of detection concentrations for multiple pathogens, indicating robust reproducibility among replicates. The clinical sensitivity and specificity for detecting 135 field samples were 98.08 and 97.59%, respectively, compared with traditional biological methods, indicating good applicability in the detection of field samples. This on-chip LAMP assay allows for low reagent consumption, ease of operation, and multiple analyses of samples and genetic targets, and is applicable for on-site detection and the routine monitoring of multiple zoonotic parasites.

A comprehensive and systematic review of the potential neuroprotective effect of quercetin in rat models of spinal cord injury.

CONTEXT: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid. OBJECTIVE: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research. DATA SOURCES: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI. STUDY SELECTION: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality. RESULTS: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (p < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females (p = 0.008). Quercetin was also associated with improved inclined plane test score (p = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA (p < 0.0001) and MPO (p = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased (p = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI. CONCLUSIONS: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

[Hemophagocytic Syndrome Secondary to Human Parvovirus B19 Infection in an Acquired Immunodeficiency Syndrome Patient:Report of One Case].

The acquired immunodeficiency syndrome patients with compromised immunity are prone to hemophagocytic syndrome secondary to opportunistic infections.This paper reports a rare case of hemophagocytic syndrome secondary to human parvovirus B19 infection in an acquired immunodeficiency syndrome patient,and analyzes the clinical characteristics,aiming to improve the diagnosis and treatment of the disease and prevent missed diagnosis and misdiagnosis.

Asymmetric Intramolecular Hydroalkylation of Internal Olefin with Cycloalkanone to Directly Access Polycyclic Systems.

An asymmetric intramolecular hydroalkylation of unactivated internal olefins with tethered cyclic ketones was realized by the cooperative catalysis of a newly designed chiral amine (SPD-NH2 ) and PdII complex, providing straightforward access to either bridged or fused bicyclic systems containing three stereogenic centers with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (up to >20 : 1 dr). Notably, the bicyclic products could be conveniently transformed into a diverse range of key structures frequently found in bioactive terpenes, such as Δ6 -protoilludene, cracroson D, and vulgarisins. The steric hindrance between the Ar group of the SPD-NH2 catalyst and the branched chain of the substrate, hydrogen-bonding interactions between the N-H of the enamine motif and the C=O of the directing group MQ, and the counterion of the PdII complex were identified as key factors for excellent stereoinduction in this dual catalytic process by density functional theory calculations.

[Evaluation and Source Analysis of Soil Heavy Metal Pollution in a Planting Area in Wanquan District, Zhangjiakou City].

Taking the soil of a vegetable planting area in Wanquan District of Zhangjiakou City as the research object, 132 surface and 80 deep soil samples were collected to test and analyze the contents of eight heavy metals such as As, Cd, Cr, Hg, Cu, Ni, Pb, and Zn and the occurrence forms of Cr and Ni. By applying geostatistical analysis and the PMF receptor model and combining three heavy metal pollution evaluation methods, the spatial distribution characteristics of soil heavy metals in the study area, the degree of heavy metal pollution, and the distribution of Cr and Ni fugitive forms in the vertical layer were clarified, and the sources and contribution rates of soil heavy metal pollution were analyzed. The results showed that the average contents of Cd and Pb in surface soils were higher than the background values of soils in Hebei Province, and the spatial distribution characteristics of Cr, Ni, Cu, Cd, Pb, and Zn in surface soils were similar. The ground accumulation index method showed that the study area was mainly free of pollution, with a small number of lightly polluted sites, and most of them were polluted with Cd. The enrichment factor method showed that the study area was mainly free-weakly polluted, with medium pollution of all elements; the significantly polluted elements in the background area were As, Pb, and Hg, and the significantly polluted element in the key area was Cd. The potential ecological risk index method showed that the study area was mainly lightly polluted, with local distribution. The potential ecological risk index method showed that the study area was mainly lightly polluted, with a local distribution of "medium" and "strong" risk points, with "very strong" risk points for Hg in the background area and "very strong" risk points for Cd in the focus area. These three evaluation results indicated that the background area was dominated by Cd and Hg pollution, whereas the focus area was dominated by Cd pollution. The study on the fugitive morphology of vertical soil showed that Cr was dominated by the residue state (F4) and supplemented by the oxidizable state (F3), and the vertical direction was dominated by the surface aggregation type and supplemented by the weak migration type. Ni was dominated by the residue state (F4) and supplemented by the reducible state (F2), and the vertical direction was dominated by the strong migration type and supplemented by the weak migration type. The sources of heavy metals in the surface soil were divided into three categories; Cr, Cu, and Ni were mainly from natural geological background sources. The contributions of Cr, Cu, and Ni were 66.9%, 66.9%, and 76.1%, respectively. As, Cd, Pb, and Zn were mainly from anthropogenic sources, with contributions of 77.38%, 59.2%, 83.5%, and 59.5%, respectively. Hg was mainly from dry and wet atmospheric deposition, with a contribution of 87.8%.

Pregnancy and lactation-associated osteoporosis with pyogenic spondylitis: A case report.

BACKGROUND: This case report presents a patient with pyogenic spondylitis (PS) associated with lactation-related osteoporosis during pregnancy. The 34-year-old female patient experienced low back pain for one month, beginning one month postpartum, with no history of trauma or fever. Dual-energy X-ray absorptiometry of the lumbar spine revealed a Z-score of -2.45, leading to a diagnosis of pregnancy and lactation-associated osteoporosis (PLO). The patient was advised to cease breastfeeding and take oral calcium and active vitamin D. Despite these interventions, her symptoms worsened, and she had difficulty walking one week later, prompting her to revisit our hospital. CASE SUMMARY: Lumbar magnetic resonance imaging (MRI) scans showed abnormal signals in the L4 and L5 vertebral bodies and intervertebral space, while an enhancement scan displayed abnormal enhanced high signals around the L4/5 intervertebral disc, suggesting a lumbar infection. A needle biopsy was performed for bacterial culture and pathological examination, culminating in a final diagnosis of pregnancy and lactation-related osteoporosis with PS. Following treatment with anti-osteoporotic medications and antibiotics, the patient's pain gradually subsided, and she returned to normal life within five months. PLO is a rare condition that has garnered increasing attention in recent years. Spinal infections during lactation in pregnancy are also relatively uncommon. CONCLUSION: Both conditions primarily manifest as low back pain but require distinct treatments. In clinical practice, when diagnosing patients with pregnancy and lactation-associated osteoporosis, the possibility of spinal infection should be considered. A lumbar MRI should be conducted as needed to prevent delays in diagnosis and treatment.

Transformation of the shape and shrinking the size of acid-resistant metal-organic frameworks (MOFs) for use as the vehicle of oral proteins.

The oral delivery of protein-based drugs is of great significance, but faces various obstacles, including the deactivation of proteins by the low pH in the stomach and the high concentration of protease, poor transport through intestinal bio-barriers, etc. Herein, we present an acid-resistant metal-organic framework (MOF), NU-1000, in which insulin (Ins, a model protein) was loaded with high capacity (Ins@NU-1000) through the pseudo second-order kinetic model and Langmuir isotherm model. Ins@NU-1000 protects Ins from deactivation in the stomach acid environment and releases it in the intestine through the transformation of the micro-sized rod particles into spherical nanoparticles. Interestingly, the rod particles exhibit long-term retention in the intestine, and Ins is efficiently transported by the shrunk nanoparticles through intestinal bio-barriers and released into the blood, resulting in significant oral hypoglycemic effects (lasting more than 16 h after a single oral administration). Our findings demonstrate that switching the physical properties of the delivery vehicle, such as the shape and size, can contribute to the success of oral protein administration.

Occurrence and ecological risk assessment of 16 phthalates in surface water of the mainstream of the Yangtze River, China.

Phthalic acid esters (PAEs), a class of typical endocrine disruptors, have received considerable attention due to their widespread applications and adverse effects on biological health. In this study, 30 water samples, along the mainstream of the Yangtze River (YR), were collected from Chongqing (upper stream) to Shanghai (estuary) from May to June in 2019. The total concentrations of 16 targeted PAEs ranged from 0.437 to 20.5 µg/L, with an average of 1.93 µg/L, where dibutyl phthalate (DBP, 0.222-20.2 µg/L), bis (2-ethylhexyl) phthalate (DEHP, 0.254-7.03 µg/L), and diisobutyl phthalate (DIBP, 0.0645-0.621 µg/L) were the most abundant PAEs. According to the pollution level in the YR to assess the ecological risk posed by PAEs, the results showed medium risk level of PAEs in the YR, among which DBP and DEHP posed a high ecological risk to aquatic organisms. The optimal solution for DBP and DEHP is found in ten fitting curves. The PNECSSD of them is 2.50 µg/L and 0.34 µg/L, respectively.

Bacillus coagulans XY2 ameliorates copper-induced toxicity by bioadsorption, gut microbiota and lipid metabolism regulation.

Excessive copper pollutes the environment and endangers human health, attracting plenty of global attention. In this study, a novel strain named Bacillus coagulans XY2 was discovered to have a great copper tolerance and adsorption capacity. B. coagulans XY2 might maintain copper homeostasis through multisystem synergies of copper resistance, sulfur metabolism, Fe-S cluster assembly, and siderophore transport. In mice, by promoting the expression of SREBF-1 and SREBF-2 and their downstream genes, B. coagulans XY2 significantly inhibited the copper-induced decrease in weight growth rate, ameliorated dyslipidemia, restored total cholesterol and triglyceride contents both in serum and liver. Furthermore, B. coagulans XY2 recovered the diversity of gut microbiota and suppressed the copper-induced reduction in the ratio of Firmicutes to Bacteroidota. Serum metabolomics analysis showed that the alleviating effect of B. coagulans XY2 on copper toxicity was mainly related to lipid metabolism. For the first time, we demonstrated mechanisms of copper toxicity mitigation by B. coagulans XY2, which was related to self-adsorption, host copper excretion promotion, and lipid metabolism regulation. Moreover, working model of B. coagulans XY2 on copper homeostasis was predicted by whole-genome analysis. Our study provides a new solution for harmfulness caused by copper both in human health and the environment.

[Characteristics and Causes of Ge Enrichment in Vegetable Growing Areas of Beixintun Town, Zhangjiakou City].

The vegetable planting base in the Beixintun area of Zhangjiakou City was selected as the study area, divided into the focus area and regional range as well as the upstream area. A total of 132 surface soil samples, 16 vertical soil profiles, 3 groups of surface profiles, and 4 samples each of colored pepper fruit, purple kale fruit, and corn fruit were collected. From the soil, rock, and crop sample Sc, Cr, Mo, Cd, V, Zn, Sr, Pb, Co Ni, Cu, Ge, and REE on the basis of the referenced germanium (Ge) enrichment standards and enrichment factor levels, it was found that the regional Ge enrichment rate was not high (19.7%), whereas the key area had a high Ge enrichment rate (52%). The spatial distribution of Ge and rare earth elements in the soils of the regional scope and the focal area showed a more obvious consistency, and further comparison of the correlation characteristics of Ge and rare earth elements in soil and crops showed that the ranking of rare earth content was purple kale>colored pepper>maize, whereas the ranking of the Ge element uptake intensity was maize (weak uptake)>purple kale (very weak uptake)>colored pepper (very weak uptake), and there was no obvious synergy between the uptake of Ge and rare earth elements by crops. The PMF and RDA analysis of 28 elements and indicators of soil in the study area showed that the source of regional Ge was dominated by natural geological background factors (66.3%), supplemented by anthropogenic activity-influenced factors (27%) and river deposition factors (6.7%). The source of Ge in the focal area was dominated by natural geological background factors (33.8%) and anthropogenic activity-influenced factors (27.2%), with river sedimentation factors (18.5%) and atmospheric dry and wet deposition factors Ge (20.5%) being supplemented. Soil Ge was positively correlated with rare earth elements and trace elements such as Cd, Zn, Mn, Ni, V, Co, and Cr and negatively correlated with the main elements CNa2[KG-*2/5]O, SiO2, and K2[KG-*2/5]O and pH. Finally, by combining the analysis of soil lateral profiles with vertical profiles, it was found that the Ge migrating from the source area to the area was primarily in the main river pathway, supplemented by the secondary river and flood flow pathways.

Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota.

BACKGROUND: The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated. METHODS: The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group. RESULTS: A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis. CONCLUSIONS: We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis.

Relationship between the expression level of miRNA-4485 and the severity of depressive symptoms in major depressive disorder patients

Background and objectives: Despite the growing pieces of evidence on the relationship between the altered expression level of miRNAs and major depressive disorder (MDD), few studies have focused on the relationship between the altered expression of miRNAs and the severity of depressive symptoms. This study aimed to investigate the relationship between the expression level of miRNA-4485 and the severity of depressive symptoms in major depressive disorder (MDD) patients.MethodsEighty MDD patients without antidepressants and 45 healthy controls were placed and tested for the expression level of miRNA-4485 using quantitative RT‒PCR. At the same time, the Hamilton Depression Scale (HAMD) was used to assess depression symptoms for MDD patients. Twenty-nine out of 80 MDD patients were selected for miRNA expression level testing and symptomatology assessments before and after three weeks of treatment.ResultsThe expression level of miRNA-4485 in the MDD group was significantly overexpressed compared to that in healthy controls (P < 0.05), and the expression level of miRNA-4485 in the higher HAMD group was also much higher than that in the lower HAMD group and healthy controls (P < 0.05). The expression level of miRNA-4485 in MDD patients was negatively correlated with HAMD total score, anxiety/somatization, and bodyweight factor score (P < 0.05), accounting for 9.4%, 12.4% and 5.7%, respectively. MiRNA-4485 significantly predicted MDD and the severity of depressive symptoms (P < 0.05). Compared with that before treatment, the expression level of miRNA-4485 was significantly downregulated after treatment, while the patient's depressive symptoms were improved (p < 0.05). The improvement in depressive symptoms was positively correlated with the downregulation of miRNA-4485, which could significantly predict the effects of antidepressant treatment on MDD (P < 0.05). (AU)