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Thoughts on the relationship between Buddhism and Tibetans permeate Pema Tseden’s films. His early films focused on whether the Buddhist spirit, such as feelings, dedication, and self-sacrifice, was recognized in modern Tibet. Identity is a problem that Tibetans have always faced in the process of modernization. People in economically disadvantaged positions often face difficult choices between self-survival and maintaining moral and cultural traditions. Pema Tseden’s films, however, focus more on the philosophy of Buddhism and use an ethnic internal perspective to examine the problems in ethnic modernization, which provides his stories with a strong allegorical color.

Powered Activated Carbon – Membrane Bioreactors (PAC-MBRs) have been used with good results for slightly polluted water treatment. Our batch experiments showed that the transmembrane pressure of a PAC-MBR was 25% less than that of a MBR in one period of test, which indicated that PAC did help control the fouling in MBRs. Based on this observation, several mechanisms of membrane fouling of MBRs and PAC-MBRs were investigated to have some insight into how PAC brought a positive impact. The total resistances decreased by 60% and different resistances were redistributed after adding PAC. The dominant one changed from filtration resistance to cake resistance. These smaller cake resistances resulted from the PAC because, showing in the scanning electron microscopy pictures, it made the cake layer looser and rougher than that on a normal membrane. Meanwhile, the analysis of the membrane eluent showed that the addition of PAC changed the microbial species and its metabolites on the membrane and effectively reduced the adsorption of hydrophilic organic molecules on the membrane surface. Additionally, PAC prevented polypeptide compounds from being trapped inside the pores of membranes, so the cake on the PAC-MBR contaminated membrane surface was easier to scrape off. In the test of cleaning methods, alkaline cleaning removed the most organics from contaminated membranes to restore membrane performance.

Crop growth modeling is an important aspect of facility horticulture. Due to the imperfect structural and poor environmental control capabilities of most solar greenhouses, tomato growth in solar greenhouses in the winter half-year often occurs under unsuitable environmental conditions that do not facilitate tomato growth. However, existing crop growth models are difficult to apply to crop growth in solar greenhouses in China because suitable environmental factors are used as the main parameters in these models. The real-time tomato measurement system developed was used to measure the real-time growth of tomato plants. Combined with environmental data. A tomato growth model, an aboveground organ allocation model and conversion coefficient model between fresh weight and dry weight of tomato plants based on real-time tomato weight that are able to overcome the influence of environmental stress were established. The results of this study lay the foundation for appropriate management and fertilization in solar greenhouses.

Polyethylene terephthalate (PET), one of the most widely used plastics in the world, causes serious environmental pollution. Recently, researchers have focused their efforts on enzymatic degradation of PET, which is an attractive way of degrading and recycling PET. In this work, PET hydrolase SbPETase from Schlegelella brevitalea sp. nov. was biochemically characterized, and rational design was performed based on its sequence similarity with the previously reported IsPETase from Ideonella sakaiensis, resulting in a triple mutant with increased activity. Furthermore, using a sec-dependent signal peptide PeIB and colicin release protein Kil, we set up a high-efficiency secretion system of PETase in Escherichia coli BL21(DE3), enabling higher PETase secretion. Utilizing this secretion system, we established a high-throughput screening method named SecHTS (secretion-based high-throughput screening) and performed directed evolution of IsPETase and SbPETase through DNA shuffling. Finally, we generated a mutant IsPETaseS139T with increased activity from the mutant library.

Arsenic, an identified environmental toxicant, poses threats to the health of human beings through contaminated water and food. Recently, increasing reports focused on arsenic-induced nerve damage, however, the underlying mechanism remains elusive. Microglia are important immune cells in the nervous system, which produce a large number of inflammatory factors including TNF-α when activated. Recent reports indicated that TNF-α is involved in the process of necroptosis, a new type of programmed cell death discovered recently. Although there were evidences suggested that arsenic could induce both microglia activation and TNF-α production in the nervous system, the mechanism of arsenic-induced neurotoxicity due to microglia activation is rarely studied. In addition, the role of microglia-derived TNF-α in response to arsenic exposure in necroptosis has not been documented before. In this study, we found that arsenite induced microglial activation through p38 MAPK signaling pathway, leading to the production of TNF-α. Microglia-derived TNF-α further induced necroptosis in the neuronal cells. Our findings suggested that necroptosis induced by microglia-derived TNF-α upon arsenite exposure partially played a role in arsenic-induced cell death which underlie the fundamental event of arsenic-related neurotoxicity.

Abstract Background Bone defects can be seen everywhere in the clinic, but it is still a challenge for clinicians. Bibliometrics tool CiteSpace is based on the principle of “co-citation analysis theory” to reveal new technologies, hotspots, and trends in the medical field. In this study, CiteSpace was used to perform co-citation analysis on authors, countries (regions) and institutions, journals and cited journals, authors and cited literature, as well as keywords to reveal leaders, cooperative institutions, and research hotspots of bone defects and predict development trends. Method Data related to bone defect from 1994 to 2019 were retrieved from the Web of Science core collection; then, we use Excel to construct an exponential function to predict the number of annual publications; conduct a descriptive analysis on the top 10 journals with the largest number of publications; and perform co-citation analysis on authors, countries (regions) and institutions, journals and cited journals, authors and cited reference, and keywords using CiteSpace V5.5 and use the Burst Detection Algorithm to perform analysis on the countries (regions) and institutions and keywords, as well as cluster the keywords using log-likelihood ratio. Results A total of 5193 studies were retrieved, and the number of annual publications of bone defects showed an exponential function Y = 1×10− 70e0.0829x (R 2 = 0.9778). The high-yield author was Choi Seong-Ho at Yonsei University in South Korea. The high-yielding countries were the USA and Germany, and the high-yielding institutions were the Sao Paulo University and China and the Chinese Academy of Sciences which were the emerging research countries and institutions. The research results were mainly published in the fields of dentistry, bone, and metabolism. Among them, the Journal of Dental Research and Journal of Bone and Mineral Research were high-quality journals that report bone defect research, but the most cited journal was the Clinical Orthopaedics and Related Research. Hot keywords were regeneration, repair, in vitro, bone regeneration, reconstruction, and graft. The keywords that were strongly cited in 2010–2019 were transportation, osteogenic differentiation, proliferation, and biomaterials. After 2018, proliferation, osteogenic differentiation, stromal cells, transmission, and mechanical properties have become new vocabulary. The drug delivery, vascularization, osteogenic differentiation and biomaterial properties of bone defects were expected to be further studied. Conclusion The application of CiteSpace can reveal the leaders, cooperating institutions and research hotspots of bone defects and provide references for new technologies and further research directions.

Du meridian moxibustion is a special external therapy which combines the meridian theory of traditional Chinese medicine and traditional moxibustion. This therapy are given"spreading moxibustion with ginger mud"on the spinal segment of the dorsal Du meridian with moxa and ginger, and can be combined with Du meridian moxibustion powder. It can concentrate the comprehensive effect on the lesion to maximize the effect in a short time such as meridian, acupoint, moxibustion, medicine and so on, which has the effects of reinforcing kidney and unblocking Du meridian, warming yang and dispelling cold, unblocking Du meridian and relieve pain, regulating yin and yang, etc.. It has been widely used to treat various diseases and health care. The operation standard of traditional Chinese medicine rehabilitation technology of moxibustion is mainly to standardize the management and guide the professional and technical personnel of Chinese medicine to correctly use moxibustion therapy. The standard introduces the technical scope, normative references, terms and definitions, operation steps and requirements, precautions, taboos, appendices. In particular, it focuses on the three parts of the operation steps and requirements of the standard. For example, preparation before moxibustion (preparation of wormwood and ginger mud, acupoint selection and positioning, body position selection, moxibustion supervision device and its auxiliary supplies, preparation of the subject, environmental requirements, etc.); moxibustion process (body position, acupoint selection, scraping, disinfection, moxibustion supervision powder, ginger mud paving, preparation and placement of moxibustion device, moxibustion, cleaning moxibustion place, etc.); operation steps and requirements after moxibustion. In addition, the selection of moxa and Du meridian moxibustion apparatus, the preparation of Du meridian moxibustion powder, the main role and indications of Du meridian moxibustion rehabilitation technology were also explained. It is suitable to guide the professional and technical personnel of TCM with standard rehabilitation technology operation of moxibustion. This standard is good in applicability and effectiveness.

There lacks a method to measure the rapid changes of vehicle emissions. Here the authors proposed a big data approach ‘TrackATruck’, and their estimates using the new approach show that the heavy-duty trucks (HDT) emissions of primary cargo routes/terminals were underestimated by 2–10 times in proxy-based emission inventories.

Abstract Background Acute coronary syndrome (ACS) is a group of clinical syndromes associated with substantial morbidity and mortality rate. SYNTAX and SYNTAX II score used to be a reference for surgical selection of coronary revascularization and prognosis evaluation in patients with 3-vessel or left main artery disease. In addition, apoB/apoA1 is an important predictor of ACS risk. This study aims to assess the prognosis value of different kinds of SYNTAX score together with apoB/apoA1 in universal ACS patients (Regardless of ACS type, lesion location and vessel numbers). Method Three hundred ninety-six patients with ACS undergoing percutaneous coronary intervention(PCI)and coronary stenting from 2013 to 2014 were chosen and recorded the major adverse cardiovascular and cerebrovascular events (MACCE) and quality of life during the next 5 years. According to SYNTAX and SYNTAX II score, the patients were divided into low-risk, medium-risk and high-risk groups, and the clinical features, MACCE incidence and EQ-5D score at each time points were compared. And the predictive factors of MACCE incidence were analyzed. Results ① Compared with SYNTAX low-risk group, MACCE incidence in 1 year significantly increased in medium/high risk group (p = 0.011). Compared with SYNTAX II low-risk group, MACCE incidence in 5 years significantly increased in medium and high-risk group (p = 0.032). ② Compared with SYNTAX II low-risk group, cardiovascular mortality in 3 and 5 years significantly elevated in high-risk group (p = 0.001, p

Abstract Background Evidence has demonstrated conditioned medium (CM) from periodontal ligament stem cells (PDLSCs) improved periodontal regeneration. Gingival mesenchymal stem cells (GMSCs) have been considered an alternative strategy for regenerative medicine. To determine whether GMSC-CM could promote periodontal wound healing, we compared the effects of GMSC-CM and PDLSC-CM on periodontal regeneration and the underlying mechanisms in rat periodontal defects. Methods Cell-free CMs were collected from PDLSCs, GMSCs, and gingival fibroblasts (GFs) using ultracentrifugation (100-fold concentration). Periodontal defects were created on the buccal side of the first molar in the left mandible of 90 rats by a surgical method. Collagen membranes loaded with concentrated CMs (α-MEM, GF-CM, GMSC-CM, PDLSC-CM) were transplanted into periodontal defects. After 1, 2, and 4 weeks, the animals were sacrificed and specimens including the first molar and the surrounding tissues were separated and decalcified. Hematoxylin-eosin and Masson’s trichrome staining were performed to evaluate periodontal regeneration. Immunohistochemical staining for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 was conducted to analyze inflammation. Immunohistochemistry of BSP-II and Runx2 was performed to analyze osteoblast differentiation. Results Histological analysis showed the amount of newly formed periodontal tissue was significantly higher in both the GMSC-CM and PDLSC-CM groups than in the other groups, with no significant difference between these two groups. At 1 and 2 weeks, the expression levels of TNF-α and IL-1β were significantly lower in the GMSC-CM and PDLSC-CM groups than in the other three groups, while there was no significant difference between these two groups. IL-10 expression was significantly higher in the GMSC-CM group than in the PDLSC-CM group and the other three groups. At 1, 2, and 4 weeks, BSP-II and Runx2 expressions were significantly higher in the GMSC-CM and PDLSC-CM groups than in the other three groups, with no significant difference between the two groups. Conclusions Our results demonstrate that GMSC-CM transplantation can significantly promote periodontal regeneration in rats and achieve the same effect as PDLSC-CM. The mechanism of periodontal regeneration may involve the regulation of inflammatory factors and the promotion of osteogenic differentiation of bone progenitor cells in the wound region by CMs from MSCs.

Abstract Background Growth hormone inducible transmembrane protein (GHITM) is a highly conserved transmembrane protein. This study was conducted to investigate the role of GHITM gene in the apoptosis and growth of the golden apple snail Pomacea canaliculate. Results The complete cDNA of this gene was cloned using the rapid amplification of cDNA ends (RACE) method and subjected to bioinformatics analysis. The full-length cDNA was 2242 bp, including an open reading frame of 1021 bp that encoded a protein of 342 amino acid residues. The mRNA expression profiles of GHITM gene in different tissues (liver, kidney, gonad and foot) and different growth phases (6-months old and 2-years old) showed that it was expressed in various tissues and different growth phases. Silencing of the GHITM gene by RNAi (RNA interference) experiments revealed that the GHITM gene possibly plays a role in inhibiting apoptosis through detecting the Caspase (Cysteine-requiring Aspartate Protease)-3 activity. In addition, the aperture width and body whorl length of the snail was significantly affected by RNAi, suggesting that this gene plays a significant role in promoting the growth of the organism. Conclusions These results demonstrated that the GHITM gene was involved in apoptosis and growth in golden apple snail.

Mycoplasma pneumoniae (MP) is a one of most common pathogen in causing respiratory infection in children and adolescents. Rapid and efficient diagnostic methods are crucial for control and treatment of MP infections. Herein, we present an operationally simple, rapid and efficient molecular method for MP identification, which eliminates expensive instruments and specialized personnel. The method combines recombinase polymerase amplification (RPA) with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins (Cas) 12a-based detection, with an optimal procedure less than 1 h from sample to result including DNA extraction (25 min), RPA reaction (39°C for 15-20 min), CRISPR/Cas12a detection (37°C for 10 min) and visual detection by naked eyes (2 min). This diagnostic method shows high sensitivity (two copies per reaction) and no cross-reactivity against other common pathogenic bacteria. Preliminary evaluation using 201 clinical samples shows sensitivity of 99.1% (107/108), specificity of 100% (93/93) and consistency of 99.5% (200/201), compared with real-time PCR method. The above data demonstrate that our developed method is reliable for rapid diagnosis of MP. In conclusion, the RPA-CRISPR/Cas12a has a great potential to be as a useful tool for reliable and quick diagnosis of MP infection, especially in primary hospitals with limited conditions.

The Pacific oyster, Crassostrea gigas, is widely distributed and is substantially important to shellfish cultivation. Oysters with melanin-colored shells and soft parts are increasingly popular and are of high economic value. However, the distribution and synthesis of melanin in C. gigas remains unclear and there have been only few relevant studies on it. In this study, transmission electron microscopy (TEM) was used to observe melanin in the epidermis of dark mantle tissue. Melanocytes containing melanosomes were observed below the epidermis, suggesting the possibility of a gradual transfer of melanin from the mantle tissue to the epithelium. The frozen section technique and three melanin staining methods were used to confirm the presence of melanin. The results suggest that enzyme identification (DOPA) is a suitable method of melanin staining in the mantle tissues of C. gigas. This study preliminarily identified the existence of melanin in the mantle tissues of C. gigas and is a foundation for the study of melanin synthesis. Furthermore, it provides new insights into the mechanism of shell color formation.

IKK proteins are key signaling molecules in the innate immune system of animals, and act downstream of pattern recognition receptors. However, research on IKKs in invertebrates, especially marine mollusks, remains scarce. In this study, we cloned CfIKK1 gene from the Zhikong scallop (Chlamys farreri) and studied its function and the signaling it mediates. The open reading frame of CfIKK1 was 2190 bp and encoded 729 amino acids. Phylogenetic analysis showed that CfIKK1 belonged to the invertebrate IKKα/IKKβ family. Quantitative real-time PCR analysis revealed the ubiquitous expression of CfIKK1 mRNA in all scallop tissues and challenge with lipopolysaccharide, peptidoglycan, or poly(I:C) significantly upregulated the expression of CfIKK1. Co-immunoprecipitation assays confirmed the interaction of CfIKK1 with scallop MyD88 (Myeloid differentiation actor 88, the key adaptor of the TLR signaling pathway) via its N-terminal kinase domain. Additionally, CfIKK1 protein could form homodimers and even oligomers, with N-terminal kinase domain and C-terminal scaffold dimerization domain playing key roles in this process. Finally, the results of RNAi experiments showed that when the scallop IKK1 gene was suppressed, the expression of IRF genes also decreased significantly. In conclusion, CfIKK1 could respond to PAMPs challenge and interact with MyD88 protein of scallop TLR signaling, with the formation of CfIKK1 dimers or oligomers. At the same time, the results of RNAi experiments revealed the close regulatory relationship between IKK1 and IRF genes of scallop. Therefore, as a key signal transduction molecule and immune activity regulator, CfIKK1 plays important roles in the innate immune system of scallops.

The allocation of exogenously cued spatial attention is governed by a saliency map. Yet, how salience is mapped when multiple salient stimuli are present simultaneously, and how this mapping interacts with awareness remains unclear. These questions were addressed here using either visible or invisible displays presenting two foreground stimuli (whose bars were oriented differently from the bars in the otherwise uniform background): a high salience target and a distractor of varied, lesser salience. Interference, or not, by the distractor with the effective salience of the target served to index a graded or non-graded nature of salience mapping, respectively. The invisible and visible displays were empirically validated by a two-alternative forced choice test (detecting the quadrant of the target) demonstrating subjects’ performance at or above chance level, respectively. By combining psychophysics, fMRI, and effective connectivity analysis, we found a graded distribution of salience with awareness, changing to a non-graded distribution without awareness. Crucially, we further revealed that the graded distribution was contingent upon feedback from the posterior intraparietal sulcus (pIPS, especially from the right pIPS), whereas the non-graded distribution was innate to V1. Together, this awareness-dependent mapping of saliency reconciles several previous, seemingly contradictory findings regarding the nature of the saliency map.

The study aims to examine the predictive value of arterial blood lactic acid concentration for in-hospital all-cause mortality in the intensive care unit (ICU) for patients with acute heart failure (AHF). We retrospectively analyzed the clinical data of 7558 AHF patients in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The exposure variable of the present study was arterial blood lactic acid concentration and the outcome variable was in-hospital all-cause death. The patients were divided into those who survived (n = 6792) and those who died (n = 766). The multivariate logistic regression model, restricted cubic spline (RCS) plot, and subgroup analysis were used to evaluate the association between lactic acid and in-hospital all-cause mortality. In addition, receiver operating curve (ROC) analysis also was performed. Finally, we further explore the association between NT-proBNP and lactic acid and in-hospital all-cause mortality. Compared with the lowest quartiles, the odds ratios with 95% confidence intervals for in-hospital all-cause mortality across the quartiles were 1.46 (1.07–2.00), 1.48 (1.09–2.00), and 2.36 (1.73–3.22) for lactic acid, and in-hospital all-cause mortality was gradually increased with lactic acid levels increasing (P for trend

The aim of the study was to investigate the factors influencing contrast-induced acute kidney injury (CI-AKI) after percutaneous intervention (PCI) in patients with acute coronary syndrome (ACS) with diabetes mellitus (DM). A total of 1073 patients with ACS combined with DM who underwent PCI at the Affiliated Hospital of Xuzhou Medical University were included in this study. We divided the patients into the CI-AKI and non-CI-AKI groups according to whether CI-AKI occurred or not. The patients were then randomly assigned to the training and validation sets at a proportion of 7 : 3. Based on the results of the LASSO regression and multivariate analyses, we determined that the subtypes of ACS, age, multivessel coronary artery disease, hyperuricemia, low-density lipoprotein cholesterol, triglyceride-glucose index, and estimated glomerular filtration rate were independent predictors on CI-AKI after PCI in patients with ACS combined with DM. Using the above indicators to develop the nomogram, the AUC-ROC of the training and validation sets were calculated to be 0.811 (95% confidence interval (CI): 0.766-0.844) and 0.773 (95% CI: 0.712-0.829), respectively, indicating high prediction efficiency. After verification by the Bootstrap internal verification, we found that the calibration curves showed good agreement between the nomogram predicted and observed values. And the DCA results showed that the nomogram had a high clinical application. In conclusion, we constructed and validated the nomogram to predict CI-AKI risk after PCI in patients with ACS and DM. The model can provide a scientific reference for predicting the occurrence of CI-AKI and improving the prognosis of patients.

The relationship between standardized serum 25-hydroxyvitamin D (25(OH)D) concentration and incident anemia in the United States (U.S.) is unclear. The purpose of our study was to examine the association between serum 25(OH)D and anemia risk. We performed a cross-sectional analysis of the U.S. population participating in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. A generalized linear model and restricted cubic spline (RCS) plot curve were constructed to assess the relationship between serum 25(OH)D concentration and anemia incidence. Additionally, the association between serum 25(OH)D concentration and red blood cell (RBC) count and hemoglobin (HB) levels was investigated using generalized additive models with smooth functions. Subgroup analysis also was performed. A total of 29933 individuals were included in our research. After adjusting for known confounding variables, compared with the lowest quartile, the odds ratios (ORs) with 95% confidence intervals (CIs) for association of serum 25(OH)D with anemia across the second, third, and fourth quartiles were 0.735 (0.651, 0.829), 0.527 (0.461, 0.602), and 0.696 (0.611, 0.792), respectively. Serum 25(OH)D concentration was associated with anemia risk in a U-shaped pattern, as shown by an RCS plot (P for nonlinearity

The high incidence of readmission for patients with reduced ejection fraction heart failure (HFrEF) can seriously affect the prognosis. In this study, we aimed to build a simple predictive model to predict the risk of heart failure (HF) readmission in patients with HFrEF within one year of discharge from the hospital. This retrospective study enrolled patients with HFrEF evaluated in the Heart Failure Center of the Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2020. The patients were allocated into the readmission or nonreadmission group, according to whether HF readmission occurred within 1 year of hospital discharge. Subsequently, all patients were randomly divided into training and validation sets in a 7 : 3 ratio. A nomogram was established according to the results of univariate and multivariate logistic regression analysis. Finally, the area under the receiver operating characteristic curve (AUC-ROC), calibration plot, and decision curve analysis (DCA) were used to validate the nomogram. Independent risk factors for HF readmission of patients with HFrEF within 1 year of hospital discharge were as follows: age, body mass index, systolic blood pressure, diabetes mellitus, left ventricular ejection fraction, and angiotensin receptor-neprilysin inhibitors. The AUC-ROC of the training and validation sets were 0.833 (95% confidence interval (CI): 0.793-0.866) and 0.794 (95% CI: 0.727-0.852), respectively, which have an excellent distinguishing ability. The predicted and observed values of the calibration curve also showed good consistency. DCA also confirmed that the nomogram had good clinical value. In conclusion, we constructed an accurate and straightforward nomogram model for predicting the 1-year HF readmission risk in patients with HFrEF. This nomogram can guide early clinical intervention and improve patient prognosis.

Hepatocellular carcinoma (HCC) arises from several different etiologies and carries a poor prognosis. Extrahepatic metastases of HCC are most frequently found in the lungs, lymph nodes, and bones, with adrenal metastases reported in less than 15% of metastatic cases. Herein, we report a case of a 71-year-old man without prior liver disease who presented with a 9-cm right adrenal mass extending into the IVC consistent with HCC on subsequent surgical pathology and immunohistochemical staining. Etiological possibilities for an adrenal tumor as the first presentation of HCC include metastasis from occult primary liver HCC, intra-adrenal hepatic heterotopia, and adrenohepatic fusion.

Dental pulp necrosis are serious pathologic entities that causes tooth nutrition deficiency and abnormal root development, while regeneration of functional pulp tissue is of paramount importance to regain tooth vitality. However, existing clinical treatments, which focus on replacing the necrotic pulp tissue with inactive filling materials, fail to restore pulp vitality and functions, thus resulting in a devitalized and weakened tooth. Currently, dental pulp regeneration via stem cell-based therapy for pulpless teeth has raised enormous attention to restore the functional pulp. Here, a novel design of injectable simvastatin (SIM) functionalized gelatin methacrylate (GelMA) cryogel microspheres (SMS) loaded with stem cells from human exfoliated deciduous teeth (SHEDs) was established to refine SHEDs biological behaviors and promote in vivo vascularized pulp-like tissue regeneration. In this system, SIM encapsulated poly (lactide-co-glycolide) (PLGA) nanoparticles were incorporated into GelMA cryogel microspheres via cryogelation and O1/W/O2 emulsion method. SMS with sustained release of SIM promoted SHEDs adhesion, proliferation and exhibited cell protection properties during the injection process. Furthermore, SMS enhanced SHEDs odontogenic differentiation and angiogenic potential, and SHEDs loaded SMS (SHEDs/SMS) are beneficial for human umbilical vein endothelial cells (HUVECs) migration and angiogenesis, demonstrating their potential for use in promoting vascularized tissue regeneration. SHEDs/SMS complexes were injected into cleaned human tooth root segments for subcutaneous implantation in nude mice. Our results demonstrated that SHEDs/SMS could induce vessel-rich pulp-like tissue regeneration in vivo and that such an injectable nano-in-micro multistage system for the controlled delivery of bioactive reagents would be suitable for clinical application in endodontic regenerative dentistry.

Light not only conveys image-forming vision but also has an impact on various physiological functions. In particular, ultraviolet B (UVB) radiation has the closest relationship with living organisms. For Pacific oysters (Crassostrea gigas), alteration of valve behavior is one of the most important ways responding to ambient UVB. In the present study, the response of adult C. gigas to sunlight (especially UVB) was evaluated by monitoring valve activity and further elucidated at the physiological and metabolomic levels. After exposure, the valve activity of C. gigas demonstrated flexible acclimation to the ambient conditions. The potential adjustment of osmoregulation and oxidative stress might be related to ambient UVB radiation. Mycosporine-like amino acids might contribute to the protection of C. gigas against UVB, while precursors of β-alanine and degradation products of 5-hydroxytryptamine might adjust the contraction of the adductor muscles. The different responses of the adductor muscles (smooth and striated) were manifested in signal transduction and metabolisms of energy and nucleotide. This study not only indicated the correlation between the valve behavioral changes in oysters and light radiation, especially UVB, but illustrated the acclimation strategies of oysters to ambient light (UVB) environment.

Background: Subthreshold depression (SD) is considered to be the precursor stage of major depression, which is correlated with functional impairment and increased suicide rate. Although there are multiple therapies for the treatment of SD, the comparison and efficacy of various methods has yet to be evaluated. This study aimed to evaluate the efficacy of different therapies by performing a Bayesian network meta-analysis.Methods: We searched eight databases on April 3, 2021. Center for Epidemiologic Studies Depression Scale (CES-D), Beck Depression Inventory scale (BDI), the Patient Health Questionnaire-9 (PHQ-9), and the Kessler Screening Scale for Psychological Distress (K-6) were used as efficacy outcomes. This Bayesian network meta-analysis used a fixed-effects model.Findings: Twenty-one randomized controlled trials involving 5,048 participants were included in this study. The results suggested that electroacupuncture (MD −12.00, 95% CrI −15.00, −10.00), conventional acupuncture plus wheat-grain moxibustion (MD −9.70, 95% CrI −14.00, −5.30), and the Chinese traditional peripateticism pill plus group counseling (MD −9.00, 95% CrI −11.00, −6.70) had better efficacy than the control group (CG) in improving CES-D. For BDI outcome, bright light therapy (MD −9.70, 95% CrI −13.00, −6.00), behavioral activation program (MD −5.70, 95% CrI −6.10, −5.40), and dim light therapy (MD −6.30, 95% CrI −10.00, −2.20) were better than the CG. Tai chi (MD −3.00, 95% CrI −4.00, −2.00) was better than CG for PHQ-9 outcomes. Telephone-based cognitive behavioral treatment (MD −2.50 95% CrI −2.70, −2.30) was better than the CG for K-6 scores.Conclusion: Our results suggest that electroacupuncture or bright light therapy appear to be the better choices in the treatment of SD. This study provide new insights into clinical treatment selection and may aid the development of guidelines for the management of SD.

Antipsychotic-related constipation (APRC) is one of the most common side effects of taking antipsychotic medication. APRC can seriously impact patient quality of life and is potentially fatal, though the efficacy of current APRC treatments is low for most patients. In this study, we conducted a controlled, pilot randomized, sham-electroacupuncture (SEA) study to assess the efficacy of electroacupuncture (EA) in patients with APRC. We used 16S rRNA gene sequencing to assess the microbial profiles of these patients and analyze how EA treatments affected their bacteria.Methods: We treated 133 APRC patients with randomly assigned EA treatments or SEA treatments for 4 consecutive weeks, fully evaluating the patients 8 weeks after treatment. The participants, outcome assessors, and statistics were all blind to the EA and SEA treatments. Outcomes assessed included changes in spontaneous bowel movements (SBMs) and the frequency of rescue measures. We detected assessed the microbial diversity of stool specimens both before and after EA treatment using 16S rRNA gene sequencing.Results: Both EA and SEA treatments reduced the need for constipation rescue measures and did not have serious side effects. EA treatments were better than SEA treatments at increasing SBMs and reducing rescue measures. The diversity of gut microbiota changed after EA treatment. LEfSe analysis indicated changes in the genus (belonging to phylum Proteobacteria) of gut microbiota in patients following EA treatment.Conclusions: This study found that EA treatment is effective and safe for patients with APRC, and could be associated with changes in their microbial profiles. Further study, with larger sample sizes, is needed to explore the efficacy of EA intervention as a clinical treatment for APRC.Trial Registration: ChiCTR, ChiCTR-ONC-17010842, http://www.chictr.org.cn/showproj.aspx?proj=18420.

The Fujian oyster (Crassostrea angulate) is an important marine bivalve mollusk with high economic value. Gene function research and gene editing techniques have broad application prospects in oyster. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been widely used for genome engineering in many species. CRISPR-mediated gene editing has also been used successfully in the Pacific oyster through direct delivery of the CRISPR/Cas9 components into oyster embryos by microinjection. However, the low throughput and operational difficulties associated with microinjection is one of the factors limiting the widespread application of CRISPR/Cas9 in oysters. In this study, we attempted to deliver the CRISPR/Cas9-system into the embryos of C. angulate by electroporation. An all-in-one CRISPR/Cas9 vector plasmid was used as CRISPR/Cas9 system in this study. Electroporation was carried out using both eggs and blastula larvae. A large number of larvae became malformed or die after electroporation. A single base substitution mutation was detected in the D-larvae developed from electroporated eggs. Our results demonstrate that the CRISPR/Cas9 system can be delivered into embryos of C. angulate for gene editing by electroporation, which provides a reference and will further contribute to the future application of electroporation in mollusks.

Nitrous acid (HONO) plays a key role in atmospheric chemistry. Nevertheless, the HONO formation mechanism in the atmosphere, especially in the marine boundary layer, remains to be fully understood. Here, Born–Oppenheimer molecular dynamic and metadynamics simulations were performed to study the formation mechanism of HONO from the oxidation reactions of ClO radical and NO with the addition of (H2O)1–2, considering a monohydrated system ((ClO)(NO)(H2O)1) and dihydrated system ((ClO)(NO)(H2O)2), as well as at the air-water interface. This study shows that HONO formation follows a single-water mechanism in gas-phase and air-water interface systems. The free-energy barrier of the (ClO)(NO)(H2O)1 system was 9.66 kJ mol−1, whereas the (ClO)(NO)(H2O)2 system was a barrierless reaction. HONO formation at the air-water interface was faster than that in monohydrated and dihydrated systems. Although the concentration of ClO radical in the marine boundary layer is two orders higher than that of Cl radical, the production rates of HONO from the (ClO)(NO)(H2O)1 system are six orders lower than that from the (Cl)(NO)(H2O)1 system, which means that Cl radical dominates HONO formation rather than ClO radical in the marine boundary layer. These results can deepen our understanding of the HONO formation mechanism and be used to reduce HONO emissions and establish HONO-control strategies.

Particulate matter PM2.5 pollution affects the Chinese population, particularly in cities such as Shenyang in northeastern China, which occupies a number of traditional heavy industries. This paper proposes a semi-supervised learning model used for predicting PM2.5 concentrations. The model incorporates rich data from the real world, including 11 air quality monitoring stations in Shenyang and nearby cities. There are three types of data: air monitoring, meteorological data, and spatiotemporal information (such as the spatiotemporal effects of PM2.5 emissions and diffusion across different geographical regions). The model consists of two classifiers: genetic programming (GP) to forecast PM2.5 concentrations and support vector classification (SVC) to predict trends. The experimental results show that the proposed model performs better than baseline models in accuracy, including 3% to 18% over a classic multivariate linear regression (MLR), 1% to 11% over a multi-layer perceptron neural network (MLP-ANN), and 21% to 68% over a support vector regression (SVR). Furthermore, the proposed GP approach provides an intuitive contribution analysis of factors for PM2.5 concentrations. The data of backtracking points adjacent to other monitoring stations are critical in forecasting shorter time intervals (1 h). Wind speeds are more important in longer intervals (6 and 24 h).

Light-driven synthetic biology refers to an autotrophic microorganisms-based research platform that remodels microbial metabolism through synthetic biology and directly converts light energy into bio-based chemicals. This technology can help achieve the goal of carbon neutrality while promoting green production. Cyanobacteria are photosynthetic microorganisms that use light and CO2 for growth and production. They thus possess unique advantages as “autotrophic cell factories”. Various fuels and chemicals have been synthesized by cyanobacteria, indicating their important roles in research and industrial application. This review summarized the progresses and remaining challenges in light-driven cyanobacterial cell factory. The choice of chassis cells, strategies used in metabolic engineering, and the methods for high-value CO2 utilization will be discussed.

Abstract Background By 2030, diabetes mellitus (DM) will be the 7th leading cause of death worldwide. Type 2 DM (T2DM) is the most common type of DM and is characterized by insulin resistance and defective β-cell secretory function. Stem cells from human exfoliated deciduous teeth (SHED) are favorable seed cells for mesenchymal stem cells (MSCs)-based therapy due to their higher proliferation rates and easier access to retrieval. Currently, no study has revealed the therapeutic efficiency of MSCs for T2DM in Goto-Kakizaki (GK) rats. Hence, we aimed to explore the effect of SHED on T2DM in GK rats. Materials and methods We investigated the effects of SHED on the progression of T2DM in GK rats. SHED and bone marrow mesenchymal stem cells (BMSCs) were injected via the tail vein. Body weight, fasting blood glucose and non-fasting blood glucose were measured before and after administration. At 8 weeks after injection, intraperitoneal insulin tolerance tests (IPITTs) and insulin release tests (IRTs) were performed. Additionally, hematoxylin–eosin (HE) staining, periodic acid-Schiff (PAS) staining and double-label immunofluorescence staining were used to explore the pathological changes in pancreatic islets and the liver. Immunohistochemistry (IHC) was employed to detect SHED engraftment in the liver. Additionally, real-time PCR and western blotting were used to explore glycogen synthesis, glycolysis and gluconeogenesis in the liver. Results At 8 weeks after SHED injection, T2DM was dramatically attenuated, including hyperglycemia, IPGTT and IRT. Additionally, histological analysis showed that SHED injection improved pancreatic islet and liver damage. Real-time PCR analysis showed that SHED significantly reversed the diabetic-induced increase of G-6-Pase, Pck1 and PK; and significantly reversed the diabetic-induced decrease of GSK3β, GLUT2, and PFKL. In addition, western blotting demonstrated that SHED significantly reversed the diabetic-induced increase of G-6-Pase and reversed the diabetic-induced decrease of GLUT2, GSK3β and PFKM. Conclusion Stem cells from human exfoliated deciduous teeth offers a potentially effective therapeutic modality for ameliorating T2DM, including hyperglycemia, insulin resistance, pancreatic islets and liver damage, and decreased glycogen synthesis, inhibited glycolysis and increased gluconeogenesis in the liver.

Owing to its pH-sensitive property and chelating Cu2+ effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC50 value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application.

Ship exhaust emissions have been considered as a significant source of air pollution that has an adverse impact on the global climate and human health. It is of vital importance to create an accurate ship emission inventory for the purpose of formulating effective control measures. A wide range of inventory compilation methods have been proposed around the globe, and there has long been a pressing need to analyze and compare these methods in depth. This study sorted out and categorized inventory compilation methods of ship emissions in recent decades. Five main methods were compared and analyzed by their applicability, complexity, time of calculation, accuracy of results, etc. In addition, a new method was proposed to develop an emission inventory based on a vessel energy consumption reporting system. This method is believed to have the potential advantages to produce results of higher accuracy and temporal and spatial resolutions. To perform the validation, three cases at different scales were selected in part of China and surrounding maritime waters (large-scale), the Yangtze River Delta region (medium-scale), and Tianjin Port (small-scale), respectively. The analysis results show that: each of methods have different technical characteristics. Computed results significantly between methods, with the maximum deviation of up to 87%. It is advisable that the optimal method should be chosen based on the actual needs in inventory compilation and the data available. In terms of accuracy of results, Methods 1 and 5 offer moderately high accuracy; Method 2 provides average accuracy; while Methods 3 and 4 produce low accuracy. In terms of resolution of results, Methods 1 and 5 provide high-resolution temporal and spatial distribution of ship emissions; Method 2 delivers low-resolution spatial distribution; while Methods 3 and 4 are incapable of spatial distribution. In terms of applicability, Method 1 applies to the calculation of inventories of varying scales; Method 2 is more applicable to small-scale calculations, such as a port; Methods 3, 4, and 5 are more desirable for large-scale calculations, such as a country. The author recommends Methods 5, 1, 3, and 2/4 in a descending order of preference for large-scale ship emissions inventory compilations; recommends Method 5 (if accuracy is the first priority) or Method 1 (if temporal and spatial resolutions are given first priority), followed by Methods 2, 3, and 4 in a descending order of preference for small/medium-scale ship emissions inventory compilations. These results may serve to help inventory compilers choose an applicable method and support improvements in inventory compilation methods.

Carbazole is one of the typical heterocyclic aromatic compounds (NSO-HETs) observed in polluted urban atmosphere, which has become a serious environmental concern. The most important atmospheric loss process of carbazole is the reaction with OH radical. The present work investigated the mechanism of OH-initiated atmospheric oxidation degradation of carbazole by using density functional theory (DFT) calculations at the M06-2X/6-311++G(3df,2p)//M06-2X/6-311+G(d,p) level. The rate constants were determined by the Rice–Ramsperger–Kassel–Marcus (RRKM) theory. The lifetime of carbazole determined by OH was compared with other typical NSO-HETs. The theoretical results show that the degradation of carbazole initiated by OH radical includes four types of reactions: OH additions to “bend” C atoms, OH additions to “benzene ring” C atoms, H abstractions from C-H bonds and the H abstraction from N-H bond. The OH addition to C1 atom and the H abstraction from N-H bond are energetically favorable. The main oxidation products are hydroxycarbazole, dialdehyde, carbazolequinone, carbazole-ol, hydroxy-carbazole-one and hydroperoxyl-carbazole-one. The calculated overall rate constant of carbazole oxidation by OH radical is 6.52 × 10−12 cm3 molecule−1 s−1 and the atmospheric lifetime is 37.70 h under the condition of 298 K and 1 atm. The rate constant of carbazole determined by OH radical is similar with that of dibenzothiophene oxidation but lower than those of pyrrole, indole, dibenzofuran and fluorene. This work provides a theoretical investigation of the oxygenated mechanism of NSO-HETs in the atmosphere and should help to clarify their potential health risk for determining the reaction pathways and environmental influence of carbazole.

Retinoic acid (RA) signaling pathways mediated by RA receptors (RARs) are essential for many physiological processes such as organ development, regeneration, and differentiation in animals. Recent studies reveal that RARs identified in several mollusks, including Pacific oyster Crassostrea gigas, have a different function mechanism compared with that in chordates. In this report, we identified the molecular characteristics of CgRAR to further explore the mechanism of RAR in mollusks. RT-qPCR analysis shows that CgRAR has a higher expression level in the hemocytes and gonads, indicating that CgRAR may play roles in the processes of development and metabolism. The mRNA expression level of both CgRAR and CgRXR was analyzed by RT-qPCR after injection with RA. The elevated expression of CgRAR and CgRXR was detected upon all-trans-RA (ATRA) exposure. Finally, according to the results of Yeast Two-Hybrid assay and co-immunoprecipitation analysis, CgRAR and CgRXR can interact with each other through the C-terminal region. Taken together, our results suggest that CgRAR shows a higher expression level in gonads and hemocytes. ATRA exposure up-regulates the expression of CgRAR and CgRXR. Besides, CgRAR can interact with CgRXR to form a heterodimer complex.

Background The age‐related decline in testosterone levels is thought to be of great importance for male aging and cardiovascular diseases. However, data are controversial on whether abnormal sex hormones are linked to the presence of cardiovascular diseases and it is also uncertain how blood pressure modifies the association between testosterone levels and major cardiovascular diseases. Methods and Results This is a multicenter, population‐based, cross‐sectional study of 6296 men conducted between 2013 and 2016. Basic information and clinical symptoms were obtained by questionnaires. Blood pressure and plasma levels of total testosterone, sex hormone–binding globulin, luteinizing hormone, and free testosterone were determined in men in a multistage random, cluster sampling in 6 provinces of China. There were 5786 Chinese men (mean [SD] age 55.0 [10.1] years) included after exclusion criteria were applied; 37.2% (2150) of them were diagnosed with hypertension. Total testosterone, free testosterone, and sex hormone–binding globulin were inversely associated with the prevalence of hypertension. Age >65 years or body mass index ≥24 negatively impacted the inverse correlation between testosterone levels and hypertension, whereas smoking and family history of hypertension strengthened the correlation. In participants with grade 2 hypertension, total testosterone was positively associated with the presence of stroke, and luteinizing hormone was also positively correlated with cardiovascular and cerebrovascular diseases. Conclusions Lower total testosterone could be a promising risk marker for prevalent hypertension. Both low and high levels of testosterone are associated with greater cardiovascular risk. Primary hypogonadism may be a risk marker for major cardiovascular diseases in men with severe hypertension.

Leukemia is a malignant disease of hematopoietic tissue characterized by the differentiation arrest and malignant proliferation of immature hematopoietic precursor cells in bone marrow. ERG (ETS-related gene) is an important member of the E26 transformation-specific (ETS) transcription factor family that plays a crucial role in physiological and pathological processes. However, the role of ERG and its modification in leukemia remains underexplored. In the present study, we stably knocked down or overexpressed ERG in leukemia cells and observed that ERG significantly promotes the proliferation and inhibits the differentiation of AML (acute myeloid leukemia) cells. Further experiments showed that ERG was primarily modified by SUMO2, which was deconjugated by SENP2. PML promotes the SUMOylation of ERG, enhancing its stability. Arsenic trioxide decreased the expression level of ERG, further promoting cell differentiation. Furthermore, the mutation of SUMO sites in ERG inhibited its ability to promote the proliferation and inhibit the differentiation of leukemia cells. Our results demonstrated the crucial role of ERG SUMOylation in the development of AML, providing powerful targeted therapeutic strategies for the clinical treatment of AML.

The purpose of this study was to summarize the clinical characteristics and risk factors of major adverse cardiovascular events (MACEs) in patients who had had acute myocardial infarction (AMI) within 1 year of percutaneous coronary intervention (PCI). A total of 421 AMI patients who were treated with PCI and experienced MACEs within 1 year of their admission were included in this retrospective study. In addition, patients were matched for age, sex, and presentation with 561 patients after AMI who had not had MACEs. The clinical characteristics and risk factors for MACEs within 1 year in AMI patients were investigated, to develop a nomogram for MACEs based on univariate and multivariate analyses. The C statistic was used to assess the discriminative performance of the nomogram. In addition, calibration curve and decision curve analyses were conducted to validate the calibration performance and utility, respectively, of the nomogram. After univariate and multivariate analyses, a nomogram was constructed based on age (odds ratio (OR): 1.030; 95% confidence interval (CI): 1.014–1.047), diabetes mellitus (OR: 1.667; 95% CI: 1.151–2.415), low-density lipoprotein cholesterol (OR: 1.332; 95% CI: 1.134–1.565), uric acid (OR: 1.003; 95% CI: 1.001–1.005), lipoprotein (a) (OR: 1.003; 95% CI: 1.002–1.003), left ventricular ejection fraction (OR: 0.929; 95% CI: 0.905–0.954), Syntax score (OR: 1.075; 95% CI: 1.053–1.097), and hypersensitive troponin T (OR: 1.002; 95% CI: 1.002–1.003). The C statistic was 0.814. The calibration curve showed good concordance of the nomogram, while decision curve analysis demonstrated satisfactory positive net benefits. We developed a convenient, practical, and effective prediction model for predicting MACEs in AMI patients within 1 year of PCI. To ensure generalizability, this model requires external validation.

Objective. This study is aimed at exploring the underlying molecular mechanisms of ST-segment elevation myocardial infarction (STEMI) and provides potential clinical prognostic biomarkers for STEMI. Methods. The GSE60993 dataset was downloaded from the GEO database, and the differentially expressed genes (DEGs) between STEMI and control groups were screened. Enrichment analysis of the DEGs was subsequently performed using the DAVID database. A protein–protein interaction network was constructed, and hub genes were identified. The hub genes in patients were then validated by quantitative reverse transcription-PCR. Furthermore, hub gene-miRNA interactions were evaluated using the miRTarBase database. Finally, patient data on classical cardiovascular risk factors were collected, and plasma microRNA-146a (miR-146a) levels were detected. An individualized nomogram was constructed based on multivariate Cox regression analysis. Results. A total of 239 DEGs were identified between the STEMI and control groups. Expression of S100A12 and miR-146a was significantly upregulated in STEMI samples compared with controls. STEMI patients with high levels of miR-146a had a higher risk of major adverse cardiovascular events (MACEs) than those with low levels of miR-146a (log-rank P=0.034). Multivariate Cox regression analysis identified five statistically significant variables, including age, hypertension, diabetes mellitus, white blood cells, and miR-146a. A nomogram was constructed to estimate the likelihood of a MACE at one, two, and three years after STEMI. Conclusion. The incidence of MACEs in STEMI patients expressing high levels of miR-146a was significantly greater than in those expressing low levels. MicroRNA-146a can serve as a biomarker for adverse prognosis of STEMI and might function in its pathogenesis by targeting S100A12, which may exert its role via an inflammatory response. In addition, our study presents a valid and practical model to assess the probability of MACEs within three years of STEMI.

The terrestrial ecosystem carbon cycle is essential to the global carbon cycle. Mining activities have seriously damaged the terrestrial ecosystem and destroyed the carbon sequestration ability of vegetation, which is of great significance to studying the effect of coal mining on land structure change and carbon sink function in cities and mining areas. However, the existing research lacks the targeted analysis of the carbon sink level of the mining area combined with the mining data. Based on the coal-mining information, land-use data, and MODIS NPP data, this study analyzed the spatio-temporal change characteristics of land use and NPP in Huainan City and its mining areas from 2001 to 2020. The results showed that: (1) 22.5% of the land types in the mining area have changed, much higher than 3.2% in Huainan; 40.08 km2 of the cropland in the mining area has been transformed into waterbodies, seriously affecting regional food security. (2) NPP fluctuates with rainfall, has a weak correlation with temperature, and is restricted by coal-mining factors. The average NPP of most coal mines is significantly lower than that of non-mining areas. The NPP of Huainan City showed an overall growth trend of 2.20 g/(m2 × a), which was much higher than the average value of 0.43 g/(m2 × a) in the mining area. Especially in the Guqiao mine, the difference in NPPslope before and after mining was as high as 16.92 g/(m2 × a). (3) The probability integral method was used to estimate that 195.16 km2 of land in Huainan would be damaged by mining in 2020. The distribution of damage degree was negatively correlated with NPPslope, which meant the more serious the damage was, the less NPPslope was. This study revealed the characteristics of land-use change and NPP spatio-temporal response in resource-based cities and mining-disturbed areas. It quantitatively estimated the impact of mining activities on regional carbon sink function. It can provide theory and data support for mining areas to carry out ecological protection and restoration, improve the environmental service function of resource-based cities, and formulate sustainable development strategies.

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the serious infectious diseases that threatens the swine industry. Increasing evidence shows that gut microbiota plays an important role in regulating host immune responses to PRRS virus (PRRSV). The aim of this study was to investigate gut microbiota difference between PRRSV-resistant pigs and PRRSV-suspectable pigs derived from a Tongcheng pigs and Large White pigs crossed population. PRRSV infection induces an increase in the abundance and diversity of gut microbiota. Correlation analysis showed that 36 genera were correlated with viral loads or weight gain after PRRSV infection. Prevotellaceae-NK3B31-group, Christensenellaceae-R7-group, and Parabacteroides were highly correlated with both viral load and weight gain. Notably, the diversity and abundance of beneficial bacteria such as Prevotellaceae-NK3B31-group was high in resistant pigs, and the diversity and abundance of pathogenic bacteria such as Campylobacter and Desulfovibrio were high in susceptible pigs. Gut microbiota were significantly associated with immune function and growth performance, suggesting that these genera might be related to viremia, clinical symptoms, and disease resistance. Altogether, this study revealed the correlation of gut microbiota with PRRSV infection and gut microbiota interventions may provide an effective prevention against PRRSV infection.

Naringenin (NRG) is a natural compound with several biological activities; however, its bioavailability is limited owing to poor aqueous solubility. In this study, NRG nanoparticles (NPs) were prepared using the wet media milling method. To obtain NRG NPs with a small particle size and high drug-loading content, the preparation conditions, including stirring time, temperature, stirring speed, and milling media amount, were optimized. The NRG (30 mg) and D-α-tocopherol polyethylene glycol succinate (10 mg) were wet-milled in deionized water (2 mL) with 10 g of zirconia beads via stirring at 50 °C for 2 h at a stirring speed of 300 rpm. As a result, the NRG NPs, with sheet-like morphology and a diameter of approximately 182.2 nm, were successfully prepared. The NRG NPs were stable in the gastrointestinal system and were released effectively after entering the blood circulation. In vivo experiments indicated that the NRG NPs have good antitussive effects. The cough inhibition rate after the administration of the NRG NPs was 66.7%, cough frequency was three times lower, and the potential period was 1.8 times longer than that in the blank model group. In addition, the enzyme biomarkers and histological analysis results revealed that the NRG NPs can effectively regulate the inflammatory and oxidative stress response. In conclusion, the NRG NPs exhibited good oral bioavailability and promoted antitussive and anti-inflammatory effects.

Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. To overcome the problems mentioned above. DOP was extracted and purified with an 8000–12,000 Da dialysis bag. The molecular weight and monosaccharide composition were determined using HPGPC and GC. Gas chromatography was used to detect the content of SCFA. 16S rDNA sequencing was used to analyze the diversity of human microbiota. The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. DOP can increase the relative abundance of benign microbiota and decrease the harmful types. Propionic acid content in women was significantly increased after DOP treatment. Finally, the correlation analysis revealed that DOP was beneficial to the microbiota of both men and women. It can be concluded from the results that DOP is a health supplement suitable for humans, and especially women.

N6-methyladenosine (m6A) is the most abundant mRNA modification in mammals and has been implicated in various biological processes. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we investigated the alterations of 19 main m6A regulatory genes in HCC and their association with clinicopathological features, including survival. The mutation, copy number variation (CNV) and clinical data of HCC patients were retrieved from The Cancer Genome Atlas (TCGA) database. We found that the m6A regulators had high frequent alterations in HCC. The alterations of m6A regulators were significantly associated with clinicopathological features as well as TP53 alteration. Patients with any mutation of the m6A regulatory genes had worse overall survival (OS) and disease free survival (DFS). Deletion of METTL16 or ALKBH5 predicted poor OS and DFS of HCC patients. Moreover, deletion of METTL16 was an independent risk factor for DFS. Low METT16 expression was association with activation of multiple metabolic pathways in HCC. Finally, by RT-PCR, we confirmed that METTL16 was downregulated in HCC, and that lower METTL16 expression was associated with poor OS. In conclusion, we reported a significant association between alterations of m6A regulators and clinicopathological features, and highlighted the importance of METTL16 among the 19 m6A regulators in HCC pathogenesis. These findings will provide new insights into the role of m6A modification in HCC.

BackgroundLiver cancer is a frequent malignancy with poor prognosis and high mortality all over the world. It has been reported many lncRNAs could modulate the tumorigenesis of liver cancer. To identify novel potential targets for liver cancer, the differential expressed lncRNAs between liver cancer and adjacent normal tissues was analyzed with bioinformatics tool.MethodsThe differential expressed lncRNAs between liver cancer and adjacent normal tissues were analyzed with bioinformatics tool. Cell viability and proliferation was tested by CCK8 and Ki67, respectively. Apoptosis of liver cancer cells was tested by flow cytometry. Gene and protein expressions in liver cancer cells were measured by qRT-PCR and western blot, respectively. In vivo model of liver cancer was established to detect the effect of LINC01234 on liver cancer in vivo.ResultsLINC01234 was found to be negatively correlated with the survival rate of patients with liver cancer. Moreover, knockdown of LINC01234 significantly suppressed the proliferation and invasion of liver cancer cells via inducing the apoptosis. Meanwhile, miR-513a-5p was sponged by LINC01234, and USP4 was found to be a direct target of miR-513a-5p. In addition, LINC01234 knockdown inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling. Furthermore, silencing of LINC01234 notably inhibited the tumor growth of liver cancer in vivo.ConclusionDownregulation of LINC01234 could inhibit the tumorigenesis of liver cancer via mediation of miR-513a-5p/USP4/TGF-β axis. Thus, LINC01234 might serve as a new target for the treatment of liver cancer.

BackgroundSub-threshold depression is common and could impair function, as well as increase the risk of developing major depression. Despite evidence of efficacy for electroacupuncture (EA) and counseling in the treatment of sub-threshold depression, the sample size is insufficient and the level of evidence remains low. This study aims to evaluate the effectiveness of sub-threshold depression treatments by comparing the treatment effects among EA, counseling, and combination therapy, as well as to further study their mechanism.MethodsThis study is a multicenter, randomized, single blind clinical trial that will be conducted in settings at four clinical centers in China. The randomized controlled trial (RCT) will examine the effectiveness of EA intervention, compared with counseling and combination therapy. A total of 138 sub-threshold depression patients (18 to 55 years of age with Beck Depression Inventory (BDI-II) score ≥ 14 points and Hamilton Depression Scale (HAMD-17) score: 7 points ≤ HAMD total score

Enterobacter cloacae is a well-characterized opportunistic pathogen that is closely associated with various nosocomial infections. The O-antigen, which is one of the most variable constituents on the cell surface, has been used widely and traditionally for serological classification of many gram-negative bacteria. E. cloacae is divided into 30 serotypes, based on its O-antigen diversity. In this study, by using genomic and comparative-genomic approaches, we analyzed the O-antigen gene clusters of 26 E. cloacae serotypes in depth. We also identified the sero-specific gene for each serotype and developed a multiplex polymerase chain reaction (PCR) method. The sensitivity of the assay was 0.1 ng for genomic DNA and 103 colony forming units for pure cultures. The assay reliability was evaluated by double-blinded testing with 81 clinical strains. Furthermore, we established a valid, genome-based tool for in silico serotyping of E. cloacae. By screening 431 E. cloacae genomes deposited in GenBank, 304 were classified into current antigenic scheme, and 112 were allocated into 55 putative novel serotypes. Our results represent the first genetic basis of the O-antigen diversity and variation of E. cloacae, providing a rationale for studying the O-antigen associated evolution and pathogenesis of this bacterium. In addition, we extended the current serotyping system for E. cloacae, which is important for detection and epidemiological surveillance purposes for this important pathogen.

Vehicle evaporation is an essential source of VOCs in cities but is not well understood in China. Reported emission factors from previous studies are not enough for understanding the atmospheric chemical process of vehicular evaporative VOCs. In this work, a serious of detailed VOCs speciation profiles are developed based on test processes and emission processes. A mass balance method was used to divide different emission processes during diurnal tests. The results show that headspace vapor of gasoline cannot represent the real-world vehicle evaporation because of the significant differences in VOCs speciation profiles, especially for aromatics. To further distinguish emissions from evaporation and exhaust, only the ratios of MTBE/benzene and MTBE/toluene can serve as indicators when considering species from all evaporative processes. Besides, emissions from different sources change significantly with the seasons. To solve these problems, we developed a monthly comprehensive evaporation speciation profile. The individual profiles at the emission processes are weighted by the emission of the in-use vehicle fleet in Beijing to derive the comprehensive speciation profile of evaporative VOCs. Ozone formation potential (OFP) and secondary organic aerosol potential (SOAP) were used to evaluate the environmental impact. For SOAP, 100 ​g evaporative emissions are equal to 6.05–12.71 ​g toluene in different months, much higher than that given using headspace vapors, especially in winter (7.2 times higher in December). These findings would improve our understanding of the evaporative VOCs emissions in China and their environmental impacts (e.g., O3 and SOA formation).

Clinically, the treatments against asthma like β2 agonist focus on controlling the symptoms rather than inhibiting recurrence radically. This study aims to evaluate the efficacy and mechanism of a potent Chinese prescription Yu-Ping-Feng-San (YPFS) against asthma recurrence. We here established an optimized house dust mite (HDM)-induced asthma recurrence mice model with typical asthmatic responses such as significantly augmented airway hyperresponsiveness (AHR), elevated serum IgE, pulmonary type 2 cytokines IL-5 and IL-13 levels, pathological changes including thickening bronchial wall, inflammatory infiltration of lung tissue, etc. Moreover, all typical asthmatic pathological features were prominently alleviated by YPFS applied during remission phase ahead of second elicitation, which was even more effective than three different types of medications dexamethasone, montelukast and salbutamol, which were commonly applied in clinical practice, administered during recurrence phase. Besides, we found that desmoglein 1 (DSG1) remained deficient when asthmatic responses regressed whereas tight junction (TJ) claudin 1 (CLDN1) or adherin junction (AJ) E-cadherin restored spontaneously. In vitro, DSG1 interference resulted in increased thymic stromal lymphopoietin (TSLP) secretion, and epithelial barrier compromise evidenced by significantly elevated transepithelial electrical resistance (TEER) and increased 4-kDa FITC-dextran influx. YPFS could downregulate TSLP production and restore HDM-induced DSG1 deficiency and barrier destruction, which was further reversed by shDSG1. Collectively, administration of YPFS in remission prominently alleviated HDM-induced asthma relapse by restoring DSG1 and decreasing TSLP overexpression, which might be the key factors contributing to chronic asthma relapse. Our data not only demonstrated the pivotal role of DSG1 in asthma pathogenesis, but also provided a novel and potent therapeutic strategy against chronic asthma.