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BackgroundChicken meat is one of the most consumed meats worldwide and poultry production is increasing at an exponential rate. Reducing antibiotic usage has resulted in the recurrence of subclinical necrotic enteritis again and influenced global poultry production. Probiotics are potential antibiotic substitutes that can be used to prevent subclinical necrotic enteriti. However, the precise mechanism of action of probiotics and information on which gut microbes confer this efficacy remain elusive.Methods and resultsThe subclinical necrotic enteritis animal model was used to reveal the mechanism underlying the effect of probiotics on intestinal health through RNA sequencing and 16S rDNA amplicon sequencing. Bacillus licheniformis H2 feeding significantly reduced the relative abundance of Clostridium perfringens in the ileum and markedly ameliorated the pathological damage in the ileum and liver. In addition, oral administration of B. licheniformis H2 contributed to the enhancement of the intestinal barrier function and epithelial renewal, reducing energy consumption, and improving enteral nutrition absorption. Probiotic B. licheniformis H2 also ameliorated the inflammatory response and increased the immunity of subclinical necrotic enteritis infected broilers. Finally, B. licheniformis H2 feeding regulated liver gene expression to suppress immune response and promoted growth and metabolism depending on the gut microbiota.ConclusionsThese results indicated the mechanism of probiotic action of B. licheniformis H2 in maintaining intestinal health and thus promoting growth and B. licheniformis H2 may serve as an antibiotic substitute to prevent subclinical necrotic enteritis in poultry farming.

Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that tumor cells exhibit considerable plasticity based on fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of fatty acid metabolism in breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of tumor immune microenvironment, and the predictive significance in therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of fatty acid metabolism in breast cancer, supporting novel insights into breast cancer patients’ prognosis and administrating effective immunotherapy.

Dental caries, an ecological dysbiosis of oral microflora, initiates from the virulent biofilms formed on tooth surfaces where cariogenic microorganisms metabolize dietary carbohydrates, producing acid that demineralizes tooth enamel. Forming cariogenic biofilms, Streptococcus mutans and Candida albicans are well-recognized and emerging pathogens for dental caries. Recently, probiotics have demonstrated their potential in treating biofilm-related diseases, including caries. However, limited studies have assessed their effect on cariogenic bacteria–fungi cross-kingdom biofilm formation and their underlying interactions. Here, we assessed the effect of four probiotic Lactobacillus strains (Lactobacillus rhamnosus ATCC 2836, Lactobacillus plantarum ATCC 8014, Lactobacillus plantarum ATCC 14917, and Lactobacillus salivarius ATCC 11741) on S. mutans and C. albicans using a comprehensive multispecies biofilm model that mimicked high caries risk clinical conditions. Among the tested probiotic species, L. plantarum demonstrated superior inhibition on the growth of C. albicans and S. mutans, disruption of virulent biofilm formation with reduced bacteria and exopolysaccharide (EPS) components, and formation of virulent microcolonies structures. Transcriptome analysis (RNA sequencing) further revealed disruption of S. mutans and C. albicans cross-kingdom interactions with added L. plantarum. Genes of S. mutans and C. albicans involved in metabolic pathways (e.g., EPS formation, carbohydrate metabolism, glycan biosynthesis, and metabolism) were significantly downregulated. More significantly, genes related to C. albicans resistance to antifungal medication (ERG4), fungal cell wall chitin remodeling (CHT2), and resistance to oxidative stress (CAT1) were also significantly downregulated. In contrast, Lactobacillus genes plnD, plnG, and plnN that contribute to antimicrobial peptide plantaricin production were significantly upregulated. Our novel study findings support further assessment of the potential role of probiotic L. plantarum for cariogenic biofilm control.

Objective: To study the influence of pathological factors of glomerular, tubulointerstitial, and arteriosclerotic lesions on the blood pressure of lupus nephritis. Methods: The pathological data and clinical characteristics of 69 lupus nephritis patients who underwent their first renal biopsy in Chengdu Second People’s Hospital from 2012 to 2018 were retrospectively analyzed. The revised 2018 ISN/RPS classification criteria of lupus nephritis were used to assess the glomerular and tubulointerstitial lesions. The lesion index of interlobar/arcuate artery and arteriolar was calculated. Multiple linear regressions were used to analyze the effects of glomerular lesion (GL), tubulointerstitial lesion (TIL), and vascular lesion (VL) on estimated glomerular filtration rate (eGFR), systolic blood pressure, and proteinuria. Results: TIL and VL scores were different between the various grades of blood pressure (p = 0.009, 0.019). After adjusting for gender and age, multiple linear regression showed that only TIL was linearly correlated with systolic blood pressure (p = 0.022). Conclusion: After adjusting for gender and age, TIL is related to systolic blood pressure, and has a linear relationship with them.

Leucine-rich-repeat-containing G protein-coupled receptor 6 (LGR6) has been identified as the stem cell marker in multiple normal tissues and malignancies. Previous studies implicated paradoxical functions of LGR6 as a tumor-suppressor gene or oncogene given to the specific context. To explore the exact role of LGR6 in triple-negative breast cancer (TNBC) that never has been studied before, in this study, we assessed LGR6 expression levels by RT-PCR and immunohistochemistry. LGR6 stable expressing/silenced cells were established, and functional assays on tumor proliferation, as well as metastasis, were conducted both in vitro and in vivo. Here, we found that LGR6 was overexpressed in TNBC, which correlated with poor disease-free and overall survivals. Functional assays both in vitro and in vivo showed that LGR6 promotes tumor proliferation and metastasis. LGR6 also increased the ability of tumor spheroid formation. Underlying mechanism exploration further revealed that the oncogenic role of LGR6 might be associated with the Wnt/β-catenin pathway. In conclusion, our findings first proved that LGR6 acts as an oncogene in (TNBC), indicating that LGR6 might be a potential therapeutic target for TNBC treatment.

Abstract Background Thoracic spinal stenosis (TSS) is a rare but intractable disease that fails to respond to conservative treatment. Thoracic spinal decompression, which is traditionally performed using high-speed drills and Kerrison rongeurs, is a time-consuming and technically challenging task. Unfavorable outcomes and high incidence of complications are the major concerns. The development and adaptation of ultrasonic bone scalpel (UBS) have promoted its application in various spinal operations, but its application and standard operating procedure in thoracic decompression have not been fully clarified. Therefore, the purpose of this study is to describe our experience and technique note of using UBS and come up with a standard surgical procedure for thoracic spinal decompression. Methods A consecutive of 28 patients with TSS who underwent posterior thoracic spinal decompression surgery with UBS between December 2014 and May 2015 was enrolled in this study. The demographic data, perioperative complications, operation time, estimated blood loss, and pre- and postoperative neurological statuses were recorded and analyzed. Neurological status was evaluated with a modified Japanese Orthopaedic Association (JOA) scale, and the neurological recovery rate was calculated using the Hirabayashi’s Method. Results Thoracic spinal decompression surgery was successfully carried out in all cases via a single posterior approach. The average age at surgery was 49.7 ± 8.5 years. The mean operative time of single-segment laminectomy was 3.0 ± 1.4 min, and the blood loss was 108.3 ± 47.3 ml. In circumferential decompression, the average blood loss was 513.8 ± 217.0 ml. Two cases of instrument-related nerve root injury occurred during operation and were cured by conservative treatment. Six patients experienced cerebrospinal fluid (CSF) leakage postoperatively, but no related complications were observed. The mean follow-up period was 39.7 ± 8.9 months, the average JOA score increased from 4.7 before surgery to 10.1 postoperatively, and the average recovery rate was 85.8%. Conclusions The UBS is an optimal instrument for thoracic spinal decompression, and its application enables surgeons to decompress the thoracic spinal cord safely and effectively. This standard operating procedure is expected to help achieve favorable outcomes and can be used to treat various pathologies leading to TSS.

Abstract Background Probiotics are being considered as valuable microorganisms related to human health. Hu sheep is referred as one of the important sheep breeds in China. Goat milk produced by Hu sheep is characterized with high nutritional value and hypoallergenic in nature. Particularly, this milk contains plenty of milk prebiotic and probiotic bacteria. This study was aimed to scrutinize more bacterial strains from Hu sheep milk with potential probiotic activity. Results Based on 16S rRNA sequence analysis, pool of forty bacterial strains were identified and evaluated their antimicrobial activities against Staphylococcus aureus, enterohemorrhagic Escherichia coli (EHEC), Salmonella typhimurium, Listeria monocytogenes enterotoxigenic E. coli (ETEC) and Aeromonas caviae. Four out of these isolated strains demonstrated their efficient bacteriostatic ability and potential healthy properties. We also examined the safety aspects of these bacterial candidates including three Lactococcus lactis strains (named as HSM-1, HSM-10, and HSM-18) and one Leuconostoc lactis strain (HSM-14), and were further evaluated via in vitro tests, including antimicrobial activity, cell surface characteristics (hydrophobicity, co-aggregation, and self-aggregation), heat treatment, antibiotic susceptibility, simulated transport tolerance in the gastrointestinal tract, and acid/bile tolerance. The obtained results revealed that HSM-1, HSM-10, HSM-14, and HSM-18 showed high survival rate at different conditions for example low pH, presence of bovine bile and demonstrated high hydrophobicity. Moreover, HSM-14 had an advantage over other strains in terms of gastrointestinal tract tolerance, antimicrobial activities against pathogens, and these results were significantly better than other bacterial candidates. Conclusion Hu sheep milk as a source of exploration of potential lactic acid bacteria (LAB) probiotics open the new horizon of probiotics usage from unconventional milk sources. The selected LAB strains are excellent probiotic candidates which can be used for animal husbandry in the future. Rationale of the study was to utilize Hu sheep milk as a source of potential probiotic LABs. The study has contributed to the establishment of a complete bacterial resource pool by exploring the Hu sheep milk microflora.

Abstract Background Although pelvic and related parameters have been well stated in lumbar developmental spondylolisthesis, cervical sagittal alignment in these patients is poorly studied, especially in high dysplastic developmental spondylolisthesis (HDDS). The purpose of this study is to investigate the sagittal alignment of the cervical spine in HDDS and how the cervical spine responds to reduction of spondylolisthesis. Methods Thirty-three adolescent patients with lumbar developmental spondylolisthesis who received preoperative and postoperative whole-spine x-rays were reviewed. They were divided into the HDDS group (n = 24, 13.0 ± 2.2 years old) and the low dysplastic developmental spondylolisthesis (LDDS) group (n = 9, 15.6 ± 1.9 years old). Spinal and pelvic sagittal parameters, including cervical lordosis (CL), were measured and compared between groups. In the HDDS group, the postoperative parameters were measured and compared with those before surgery. Results HDDS group had a higher proportion of cervical kyphosis (70.8% vs. 22.2%, P = 0.019), and there was a significant difference in CL between the two groups (− 8.5° ± 16.1° vs. 10.5° ± 11.8°, P = 0.003). CL was correlated with the Dubousset’s lumbosacral angle (Dub-LSA), pelvic tilt (PT), and thoracic kyphosis (TK). In the HDDS group, CL in patients with a kyphotic cervical spine was significantly improved after reduction of spondylolisthesis (− 16.4° ± 5.9° vs. − 3.6° ± 9.9°, P < 0.001). In the HDDS group, 46% (6/13) of the patients with postoperative Dub-LSA < 90° still had sagittal imbalance (sagittal vertical axis, [SVA] > 5 cm), while no sagittal imbalance was observed in patients with postoperative Dub-LSA > 90° (46% [6/13] vs. 0% [0/11], P = 0.016). Conclusions HDDS can lead to cervical kyphosis through a series of compensatory mechanisms. Reduction of spondylolisthesis and correction of lumbosacral kyphosis may correct the cervical kyphosis and normalize the overall spinal sagittal profile. Correction of Dub-LSA to above 90° might be used as an objective to better improve the sagittal alignment of the spine.

Significantly increasing crop yield is a major and worldwide challenge for food supply and security. It is well-known that rice cultivated at Taoyuan in Yunnan of China can produce the highest yield worldwide. Yet, the gene regulatory mechanism underpinning this ultrahigh yield has been a mystery. Here, we systematically collected the transcriptome data for seven key tissues at different developmental stages using rice cultivated both at Taoyuan as the case group and at another regular rice planting place Jinghong as the control group. We identified the top 24 candidate high-yield genes with their network modules from these well-designed datasets by developing a novel computational systems biology method, i.e., dynamic cross-tissue (DCT) network analysis. We used one of the candidate genes, OsSPL4, whose function was previously unknown, for gene editing experimental validation of the high yield, and confirmed that OsSPL4 significantly affects panicle branching and increases the rice yield. This study, which included extensive field phenotyping, cross-tissue systems biology analyses, and functional validation, uncovered the key genes and gene regulatory networks underpinning the ultrahigh yield of rice. The DCT method could be applied to other plant or animal systems if different phenotypes under various environments with the common genome sequences of the examined sample. DCT can be downloaded from https://github.com/ztpub/DCT.

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.

Abstract Background The human myxovirus resistance 2 (Mx2/MxB) protein was originally found to regulate cytoplasmic-nuclear transport but was recently reported to restrict HIV-1 replication by binding to HIV-1 capsid (CA), preventing uncoating, the nuclear import of pre-integration complex (PIC) and viral DNA integration. This work explores the mechanisms of MxB-mediated HIV-1 inhibition. Results We demonstrated that MxB represses NUP358-mediated PIC nuclear import and HIV-1 replication. Moreover, MxB’s effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding to PIC. More intriguingly, CPSF6’s role in nuclear import depends on MxB, being a facilitator of HIV-1 nuclear import on its own, but becoming an inhibitor when MxB is present. Conclusions Our work establishes that MxB impedes the NUP358-mediated HIV-1 nuclear import and viral replication cooperatively with CPSF6.

Abstract Background The localization of lumbar fourth spinous process (L4-SP) is an important anatomical landmark, and identifying its accurate position is essential for the diagnosis and treatment of waist diseases. Methods Five hundred participants were scanned with positive and lateral computed tomography (CT), which aimed to clarify anatomic characteristics of L4-SP. Anatomical parameters of the surface localization of L4-SP were measured and recorded through a three-dimensional (3D) reconstruction. Results Five hundred participants were classified into three types according to the position of BC with the iliac spine. There are just 266 that the line between the highest point of the iliac spine on both sides located on L4-SP (type I, 53.20%), 16 above L4-SP (type II, 3.20%), and 218 below L4-SP (type III, 43.60%). BC in type I (15.92 ± 1.30 mm) is longer than type III (15.56 ± 1.32 mm). While the angle combined with AB and BC is different in the three groups, the angle in type I (173.00 ± 4.83°) is larger than that in type II (164.69 ± 5.50°) and type III (159.45 ± 8.39°). Other measurements were not found any significant differences between above. Conclusion The traditional palpation for L4-SP is not absolutely exact. The accuracy rate is only 53.20%, and the errors may cause serious consequences.

Alfalfa is an important forage crop, but genetic improvement is challenging due to the lack of a reference genome and an efficient genome editing protocol. Here, the authors report the chromosome-level assembly of the autotetraploid genome and a CRISPR/Cas9-based transgene-free genome editing protocol.

Abstract Background Pituicytoma is a rare pituitary non-neuroendocrine tumour. The awareness of pituitary non-neuroendocrine tumours has gradually increased over the past several decades, but the knowledge of some histological variants of the tumours is limited, particularly in clinicopathological significance. Here, we report a rare case of pituicytoma variant. Case presentation A 71-year-old man presented with sudden symptoms of stroke including urinary incontinence, weakness in right lower limb, and trouble speaking. Physical examinations showed a right facial paralysis. The radiological examinations eventually found a 1.7 × 1.4 × 1.3 cm sellar occupied lesion. After symptomatic treatment improved the symptoms, the patient underwent transsphenoidal resection of the pituitary mass. Histologically, the tumour contained hypocellular area and hypercellular area. The hypocellular area showed elongated spindle cells arranged in a fascicular pattern around small vessels and scattered Herring bodies; the hypercellular area showed a large number of pseudorosettes. Immunohistochemistrically, the tumour cells were positive for thyroid transcription factor-1, S100, and neuron-specific enolase. Neurofilament only showed a little positive in the hypocellular area, and silver impregnation was only noted in a perivascular distribution. The patient had no recurrence 4 months after the surgery. Conclusions The rare variant of pituicytoma has a favourable prognosis. Moreover, it needs to be distinguished pituicytomas with pseudorosettes from ependymomas because of different prognosis. Lastly, Herring bodies may occasionally be seen in the pituicytoma, which could be a potential diagnostic pitfall.

A transposon insertion in the regulatory region of maize Tb1 gene leads to increased apical dominance and a reduction of tillering. Here, the authors showed that a duplicated rice Tb1 orthologue, OsTb2, has gained a regulatory effect on tillering opposite that of OsTb1 during artificial selection only in upland japonica rice.

ABSTRACTProlonged presence of viral nucleic acid was reported in certain patients with coronavirus disease 2019 (COVID-19), with unclear clinical and epidemiological significance. We here described the clinical and epidemiological characteristics of 37 recovered COVID-19 patients with prolonged presence of viral RNA in Wuhan, China. For those who had been discharged and re-admitted, their close contacts outside the hospital were traced and evaluated. The median age of the 37 patients was 62 years (IQR 50, 68), and 24 (64.9%) were men. They had common or severe COVID-19. With prolonged positive RT-PCR, most patients were clinically stable, 29 (78.4%) denied any symptoms. A total of 431 PCR tests were carried out, with each patient at a median of 8 time points. The median time of PCR positivity to April 18 was 78 days (IQR 67.7, 84.5), and the longest 120 days. 22 of 37 patients had been discharged at a median of 44 days (IQR 22.3, 50) from disease onset, and 9 had lived with their families without personal protections for a total of 258 person-days and no secondary infection was identified through epidemiological investigation, nucleic acid and antibody screening. Infectiousness in COVID-19 patients with prolonged presence of viral nucleic acid should not solely be evaluated by RT–PCR. Those patients who have clinically recovered and whose disease course has exceeded four weeks were associated with very limited infectiousness. Reconsideration of disease control in such patients is needed.

Tuberculous bronchoesophageal fistula is a rare complication of tuberculosis. Herein, we report the case of a woman in her late 60s with a choking cough for more than 1 month. Iohexol esophagography revealed a fistulous communication between the esophagus and the right principal bronchus, and gastroscopy documented a fistulous orifice in the esophagus. Endoscopic closure with metal clips failed, and other treatment options, such as extended conservative treatment, covered self-expandable metal stents, and over-the-scope clips were rejected by the patient. Therefore, a combined therapy, endoscopic submucosal dissection-based suture combined with medical adhesive, was performed. Follow-up iohexol esophagography and gastroscopy confirmed fistula closure. During 1 year of follow-up after discharge, the bronchoesophageal fistula did not recur. Endoscopic submucosal dissection-based suture combined with medical adhesive appears to be a practical and feasible solution to complicated tuberculous bronchoesophageal fistula.

Sepsis represents a syndrome of systemic inflammatory response, which is mostly a result of infection with various pathogenic microorganisms, characterized by an uncontrolled infection response of the organism leading to life-threatening organ dysfunction. Long noncoding RNA (lncRNA), as competing endogenous RNA, can affect the binding of microRNA (miRNA) to mRNA, thus influencing the development of sepsis. In this study, based on transcriptome data from GEO database, we screened differentially expressed lncRNAs and constructed lncRNA-miRNA-mRNA network. And pathway IL-17RA-1/miR-7847-3p/protein kinase C gamma (PRKCG) coexpression network was successfully sorted out. The effect of this network on LPS-induced sepsis model in THP-1 cells was also verified by CCK-8, scratch, ELISA, Western blot, and qRT-PCR assays. Corresponding binding sites of miR-7847-3p to IL-17RA-1 and miR-7847-3p to PRKCG were verified using dual luciferase gene reporter assays, respectively. Compared with control, si-IL-17RA-1 significantly inhibited the cell viability and migration ability of THP-1, and levels of proinflammatory factors IL-6, IL-1β, and TNF-α secreted were markedly decreased, and the expression of IL-17RA-1, PRKCG, p-MEKK1, and p-JNK were markedly reduced. In addition, IL-17RA-1 could target binding to miR-7847-3p and inhibit its expression, and miR-7847-3p could also bind to PRKCG. Our experiments demonstrate that IL17-RA-1 attenuates the sepsis response through the miR-7847-3p/MAPK pathway, and this competing endogenous RNA (ceRNA) network may be a potential approach to predict and combat sepsis.

In complex biochemical systems, an enzyme, protein, or RNA, symbolized as E, has hundreds or thousands of substrates or interacting partners. The relative specificity hypothesis proposes that such an E would differentially interact with and influence its many distinct, downstream substrates, thereby regulating the underlying biological process (es). The importance of relative specificity has been underappreciated, and evidence of its physiological consequences particularly lacking. Previously we showed that human Drosha and Dicer ribonucleases (RNases) both discriminate their respective microRNA (miRNA) substrates, and that differential cleavage by Drosha contributes to global differential miRNA expression. If relative specificity is an important biological mechanism, it should be evolutionarily conserved. To test this hypothesis, we hereby examined the cleavage of hundreds of zebrafish and fruitfly miRNA intermediates by Drosha and Dicer and the impact on miRNA biogenesis in these organisms. We showed that Drosha action regulates differential miRNA expression in zebrafish and fruitflies and identified the conserved secondary structure features and sequences in miRNA transcripts that control Drosha activity and miRNA expression. Our results established the conservation of miRNA processing mechanisms and regulatory functions by Drosha and Dicer, greatly strengthened the evidence for the physiological consequences of relative specificity as well as demonstrated its evolutionary significance.

BackgroundConstipation and dementia have similar epidemiological characteristics. Changes in intestinal flora and characteristics of the brain-gut axis play roles in the pathogeneses of the two diseases, suggesting that there may be a close connection between the two. Most of the studies on constipation in dementia patients have focused on the population with α-synucleinopathies [Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB)]. Few studies have reported the prevalence of constipation in all-cause dementia and mild cognitive impairment (MCI) populations.ObjectiveTo assess the prevalence of constipation in patients with all-cause dementia and MCI subtypes and to explore the association between constipation with dementia and MCI subtypes.MethodsFrom May 2019 to December 2019, we conducted a population-based cross-sectional survey. A total of 11,743 participants aged 65 or older from nine cities in China were surveyed. Participants underwent a series of clinical examinations and neuropsychological measurements. Constipation, dementia, MCI and MCI subtype were diagnosed according to established criteria through standard diagnostic procedures.ResultsThe overall age- and sex-adjusted prevalence of constipation in individuals aged 65 years and older was 14.8% (95% CI, 14.6–15.0). The prevalence rates of constipation were19.2% (95% CI, 17.3–21.0), 19.1% (95% CI, 16.8–21.5), 14.4% (95% CI, 12.8–15.9), and 13.8% (95% CI, 13.0–14.6) in the dementia, non-amnestic (na)-MCI, amnestic (a)-MCI and normal cognition populations, respectively. Multivariate logistic regression analysis showed that higher prevalence of constipation was associated with dementia (p = 0.0.032, OR = 1.18, 95% CI: 1.02–1.38) and na-MCI (p = 0.003, OR = 1.30, 95% CI: 1.09–1.54).ConclusionThe present study found a high prevalence of constipation in elderly individuals in China, and higher in patients with dementia and na-MCI.

China is implementing increasing stringent command-and-control environmental regulations to achieve high-quality development. However, we have limited understanding about whether such policies are effective. This study selects the policy of China’s National Environmental Protection “Eleventh Five-Year Plan” as a quasi-natural experiment and uses the difference-in-differences (DID) method to analyze the effect of stricter command-controlled environmental regulations on total factor productivity from the enterprise level. Our results indicate that stricter command-and-control environmental regulation promotes TFP of enterprises throughout the country. This effect is even greater in long-established, large-scale, or low capital density enterprises. In addition, stricter command-and-control environmental regulation has a greater positive effect on the TFP of companies in industries with high pollution intensity and fierce competition. Furthermore, government transformation and market green preference will magnify the positive effect of stricter command-and-control environmental regulation on corporate TFP. Moreover, stricter command-and-control environmental regulation promotes the growth of enterprise TFP mainly by improving the efficiency of resource allocation within and between enterprises, rather than stimulating innovation. Local governments should refine pollution control policies, optimize the external environment, and enhance the innovation power of enterprises.

The specified finite element model is proposed for preload bolted flange connection structure widely used in aerospace and rocket design. A fine hexahedral mesh model of the bolt is used to predict the dynamic response of the structure accurately. The tightening process, which is ignored in the traditional I-shaped simplified model of bolted flange connection structure, can be simulated well based on the proposed model. After the vibration analysis and stress analysis of the bolted flange connection structure under impact load, it is found that the change of contact state of the flange surface results in a larger sticking contact area. And the reduction of the contact area at the thread causes slippage when the bolt is loose. As bolt loosening leads to changes in the time and frequency domain of response, a new loosening detection method for the preload bolted flange connection is provided. The index for identifying the loosening is designed using empirical mode decomposition and discrete integral in the high-frequency domain. The experiment of the preload bolted flange connection structure under impact load shows the efficiency of the proposed method which can identify loosening based on acceleration signal quickly and nondestructively.

Acid mine drainage (AMD) causes environmental pollution that affects many countries with historic or current mining industries. The eco-remediation system (RW) which combined surface floating wetlands and bottom anaerobic sediments (SFW-BAS) was selected for AMD-contaminated lakes (AMDW). Meanwhile, AMDW and nature aquatic ecosystems (NW) were set as the control groups, respectively. The parameters, including pH, Eh, Fe, Mn, SO42−, and the degradation rate of the native dominant plant litter were investigated to assess the effects of remediation. The results showed that the average of pH, Eh, and EC, was 2.73, 484.08 mv, and 2395.33 μs·cm−1, respectively. The average content of SO42−, Fe, Mn, Cu, Zn, and Pb was 2190 mg·L−1, 40.2 mg·L−1, 4.6 mg·L−1, 249.2 μg·L−1, 1563 μg·L−1, and 112.9 μg·L−1, respectively. The degradation rate of plant litters in AMDW ranged from 14.5% to 22.6%. However, RW ultimately improved the water quality and the degradation of litters. RW has a good effect on buffering the acidity, ranging from 3.96 to 7.41. The pH of RW (6.14) is close to that of NW (7.41). The average content of SO42−, Fe, Mn, Cu, Zn, and Pb was 2071 mg·L−1, 3.4 mg·L−1, 2.4 mg·L−1, 85.3 μg·L−1, 607.4 μg·L−1, and 47.8 μg·L−1, respectively, which showed good pollutant removal performance. The degradation rate of plant litters in RW ranged from 27.8% to 32.6%. Therefore, RW can be used to remediate AMDW.

Probiotics interfere with pathogenic microorganisms or reinstate the natural microbiome. Streptococcus mutans and Candida albicans are well-known emerging pathogenic bacteria/fungi for dental caries. In this study, three probiotic Lactobacilli strains (Lactobacillus plantarum 8014, L. plantarum 14917, and Lactobacillus salivarius 11741) were tested on S. mutans and C. albicans clinical isolates using a multispecies biofilm model simulating clinical cariogenic conditions. The ten pairs of clinical isolates of S. mutans and C. albicans were obtained from children with severe early childhood caries. Our study findings show a remarkable inhibitory effect of L. plantarum 14917 on S. mutans and C. albicans clinical isolates, resulting in significantly reduced growth of S. mutans and C. albicans, a compromised biofilm structure with a significantly smaller microbial and extracellular matrix and a less virulent microcolony structure. FurTre, plantaricin, an antimicrobial peptide produced by L. plantarum, inhibited the growth of S. mutans and C. albicans. The mechanistic assessment indicated that L. plantarum 14917 had a positive inhibitory impact on the expression of S. mutans and C. albicans virulence genes and virulent structure, such as C. albicans hypha formation. Future utilization of L. plantarum 14917 and/or its antimicrobial peptide plantaricin could lead to a new paradigm shift in dental caries prevention.

Organic iron is expected to replace inorganic iron used in diets as an iron source. Organic iron possesses high absorption efficiency and low fecal iron excretion. This study aims to study the effect of organic iron produced by Saccharomyces cerevisiae (yeast iron) on digestion, utilization, antioxidation and caecum microflora in weaned piglets. In total, 20 piglets that had been weaned after 28 days were divided into 4 groups, each of which followed a different basal diet. The basal diet of each of these 4 groups contained, respectively, 104 mg/kg iron (ferrous sulfate, CON), 84 mg/kg iron (yeast iron, LSC), 104 mg/kg iron (yeast iron, MSC) or 124 mg/kg iron (yeast iron, HSC). This experiment lasted 35 d. The apparent digestibility of iron in LSC, MSC and HMS was higher than that in CON (p < 0.01) and the fecal iron content in LSC, MSC and HMS was lower than that in CON (p < 0.01). Serum iron contents in LSC, MSC and HMS were higher than that in CON (p < 0.01). The iron contents of the heart, lungs, liver, kidney and left gluteus muscle in the MSC and HMS groups were higher than that in CON and LSC (p < 0.05). Serum catalase, glutathione peroxidase, superoxide dismutase activity, superoxide anion, glutathione, hydroxyl free radical scavenging rate, total antioxidant capacity, and liver superoxide anion clearance rate and peroxidase in MSC and HMS were higher than that in CON and LSC (p < 0.05). The contents of nitric oxide and peroxide of the weaned piglets in MSC and HMS were lower than that in CON and LSC (p < 0.05). The abundance of Firmicutes, Blautia and Peptococcus in LSC, HSC and MSC was higher than that in CON (p < 0.01). The abundance of Lactobacillus in CON and LSC was higher than that in MSC and HSC (p < 0.01). The abundance of Acinetobacter, Streptococcus and Prevotella in LSC, MSC and HSC was lower than that in CON (p < 0.01). The results suggested that a diet containing 84 mg/kg iron of yeast iron has the same effect as a diet containing 104 mg/kg iron of ferric sulfate, and that a diet containing 104 or 124 mg/kg iron of yeast iron is superior to a diet containing 104 mg/kg iron of ferric sulfate.

Glycyrrhetic acid 3-O-mono-β-d-glucuronide (GAMG), a rare and innovative compound in licorice, exhibits high-potency sweetness and improved physiological activities. However, low amounts of GAMG from plants cannot meet the demands of growing markets. In this study, an efficient one-pot multienzyme cascade reaction for GAMG biosynthesis was constructed using a coupled catalysis of glycosyltransferase and uridine 5′-diphosphate (UDP) glucuronic acid (GlcA) regeneration system. The Glycyrrhiza uralensis glycosyltransferase UGT73F15 was expressed in Escherichia coli BL21 (DE3). The optimal reaction conditions of UGT73F15 were found to be pH 7.5 and 35 °C. The catalytic efficiency (kcat/Km) for glycyrrhetic acid (GA) was 2.14 min−1 mM−1 when using UDP-GlcA as sugar donor. To regenerate costly UDP-GlcA, the one-pot multienzyme cascade reaction including UGT73F15, sucrose synthase, UDP-glucose dehydrogenase, and lactate dehydrogenase was adopted to synthesize GAMG from GA on the basis of the UDP-GlcA regeneration system. By optimizing the cascade reaction conditions, the GAMG production successfully achieved 226.38 mg/L. Our study developed an economical and efficient one-pot multienzyme cascade method for facile synthesis of GAMG and other bioactive glucuronosides.

Abstract Background Despite the well-documented associations between poor maternal oral health and increased risk for adverse birth outcomes and dental caries in children after birth, prenatal oral health care is under-utilized, especially among the underserved population. In addition, oral Candida has recently been suggested as a potential culprit for children’s dental caries, with evident maternal contributions. Therefore, this study aimed to obtain epidemiological data on the oral health and oral Candida carriage in a cohort of underserved US pregnant women, and reveal factors associated with their oral Candida carriage. Methods Demographic-medical-oral hygiene practice data were collected. Comprehensive oral examination was conducted. Caries status and plaque index were recorded. Oral samples (saliva, plaque and swab) were processed to identify Candida species and Streptococcus mutans by culturing-dependent and -independent methods. Multiple logistic regression analyses were used to identify factors associated with oral Candida carriage and caries severity. Results Eighty-two socioeconomically disadvantaged women (48 pregnant and 34 non-pregnant) were enrolled. More pregnant women (79.1%) had > = 1 untreated decayed tooth when compared to their non-pregnant counterparts (47.1%) (p = 0.01). The average number of decayed teeth in pregnant and non-pregnant women was 3.9 and 3.1 (p > 0.05). Caries severity was positively associated with race (African American vs. white), plaque index and salivary Candida albicans level. C. albicans was the most predominant/abundant Candida strain, with cheek and tonsil as the most common colonized sites. The detection of C. albicans was 56%/56% in saliva and 40%/47% in plaque of the pregnant and non-pregnant groups, respectively. Study women’s oral Candida carriage is positively associated with hypertension [p = 0.03, odds ratio = 14.47(1.28, 163.51)], decayed teeth number [p = 0.04, odds ratio = 1.31 (1.01,1.69)] and salivary S. mutans level [p = 0.03, odds ratio = 4.80 (1.18–19.43)]. Conclusions Socioeconomically disadvantaged US women are in need of improved prenatal oral health, a large proportion of them have untreated decayed teeth and high carriage of oral Candida. Due to the observed significant association between the decayed teeth number and oral Candida carriage, providing oral health care during pregnancy (including limiting decayed teeth) will not only improve women’s oral health, but also present as a promising approach to reduce oral Candida carriage in women.

Avian influenza viruses can be efficiently transmitted through mucous membranes, and conventional vaccines are not effective in protecting against mucosal infection by influenza viruses. To induce multiple immune responses in an organism, we constructed a recombinant Lactobacillus plantarum expressing the influenza virus antigen HA1 with the adjuvant dendritic cell-targeting peptide (DCpep). The recombinant L. plantarum strains NC8Δ-pWCF-HA1 and NC8Δ-pWCF-HA1-DCpep were used to immunize mice via oral administration, and the humoral, cellular and mucosal immune responses were evaluated. In addition, the serum levels of specific antibodies and hemagglutination inhibition (HI) levels were also measured. Our results showed that recombinant L. plantarum activated dendritic cells in Peyer’s patches (PPs), increased the numbers of CD4+IFN-γ+ and CD8+IFN-γ+ cells in the spleen and mesenteric lymph nodes (MLNs), and affected the ability of CD4+ and CD8+ cells to proliferate in the spleen and MLNs. Additionally, recombinant L. plantarum increased the number of B220+IgA+ cells in PPs and the level of IgA in the lungs and different intestinal segments. In addition, specific IgG, IgG1 and IgG2a antibodies were induced at high levels in the mice serum, specific IgA antibodies were induced at high levels in the mice feces, and HI potency was significantly increased. Thus, the recombinant L. plantarum strains NC8Δ-pWCF-HA1 and NC8Δ-pWCF-HA1-DCpep have potential as vaccine candidates for avian influenza virus.

Abstract −: A 3D transient incompressible gas flow with multi-components was investigated in the present study to understand the gas mixing in a rectangular cubic gas chamber. Computation Fluid Dynamics (CFD) simulation was carried out to predict the detailed flow and concentration fields in the chamber. Experiments were conducted to measure the concentration of carbon dioxide at some locations in the chamber. The concentration of carbon dioxide increases with time initially and then approaches to a constant value. As expected, higher flow velocity results in faster transport of carbon dioxide and shorter time for carbon dioxide to reach saturation in the chamber. Consistent trends of carbon dioxide concentration can be observed from simulation and experimental data, which confirms the reciprocal validation between simulations and experiments. The experiment data show good agreement with the simulation results, which also implies that the simulation model could be applicable for other dual-gas mixtures in predicting their mixing behaviours, especially for the cases in which it may be difficult to conduct the experiments of gas mixing with toxic and corrosive gases.

Intestinal diseases are one of the main causes of captive giant panda death. Their special dietary habits and gastrointestinal tract structure often lead to intestinal epithelium damage and secondary intestinal infection. The captive giant panda is predisposed to suffer from microbiota dysbiosis due to long-term artificial feeding and antibiotic misuse. However, there are few reported probiotics to treat giant panda enteritis and the associated dysbiosis. This study aims to elucidate the mechanism by which Lactobacillus plantarum G201683 (L. plantarum G83), a promising panda-derived probiotic, exerts a protective effect on intestinal inflammation in the dextran sulfate sodium- (DSS) induced panda microbiota-associated (DPMA) mouse model. The DPMA mouse was generated by antibiotic treatment and 5% DSS drinking water administration to assess the effect of L. plantarum G83 on intestinal inflammation and microbiota in vivo. Our results demonstrated the successful generation of a DPMA mouse model with Enterobacteriaceae enrichment, consistent with the giant panda intestinal microbiota. L. plantarum G83 decreased clinical and histological severity of intestinal inflammation, enhanced intestinal tight junction protein expression (ZO-1, Occludin) and alleviated inflammatory cytokine production (TNF-) in the colon of DPMA mice. The administration of L. plantarum G83 altered the microbiota composition by decreasing pathogen associated taxa such as E. coli and increasing abundance of beneficial bacteria including Bifidobacterium spp. These changes in microbiota composition were associated with an increased concentration of short chain fatty acids (SCFA), reduced NF-κB signaling, and an altered balance of T helper cell subsets. Our findings support L. plantarum G83 as a promising probiotic to treat intestinal inflammation in the giant panda.

In previous experiments, we identified the effect of deletion of the Zbtb1 gene on circRNAs and microRNAs. In this study, we examined the expression profiles of lncRNAs and mRNAs using the RNA-seq method for Zbtb1-deficient EL4 cells and performed a clustering analysis of differentially expressed lncRNAs and mRNAs. GO term histograms and KEGG scatter plots were drawn. For the experimental results, a joint analysis was performed, which predicted the regulatory relationships among lncRNAs, mRNAs, microRNAs and circRNAs. For the regulatory relationship between lncRNAs and target genes, the chromatin structure and the degree of openness were verified for the possible target gene locations regulated by lncRNA using experimental methods such as Hi-C and ATAC-seq. Ultimately, the possible differential regulation of the Brcal and Dennd5d genes by lncRNAs and the differential changes in transcription factor binding sites in the promoter region were identified. For neRNA-regulated target genes with significantly differentially expressed mRNAs, a combined screen was performed, and the final obtained candidate target genes were subjected to GO and KEGG term enrichment analyses. Our results illustrate that the Zbtb1 gene can not only function as a regulatory factor but also regulate EL4 cells from multiple perspectives based on ceRNA theory.

RHD variants in D¯ Chinese pregnant women arose difficulties in management during pregnancy. Therefore, this study aims to precisely manage D¯ pregnant women by evaluating the spectrum of RHD mutations in D¯ pregnant women and getting insight into the possible rare alleles of RHD. A total of 76 D¯ pregnant women were analyzed by performing polymerase chain reactions with sequence-specific primers (PCR-SSP), the 10 RHD exons Sanger sequencing, RHD zygosity detection, and mRNA sequencing (mRNA-seq). About 40% of alleles are variations of RHD, including RHD 1227A homozygous, RHD-CE(2-9)-D, et al. Therefore, we developed a molecular diagnostic strategy for Chinese women, and most D¯ pregnant women can be diagnosed with this simple decision tree. After RHD genotyping for D¯ pregnancy women, we eliminated at least 15% unnecessary ante- and postpartum injections of Rh immunoglobulin (RhIG). As the first pedigree study and the first functional analysis under physiological conditions, mRNA-seq revealed that c.336-1G>A mutation mainly led to the inclusion of the intron 2, which indirectly explained the D¯ phenotype in this family. We also developed a robust protocol for determining fetal RhD status from maternal plasma. All 31 fetuses were predicted as RhD positive and confirmed the RhD status after birth.

Lactic acid bacteria (LAB) are vital probiotics in the food processing industry, which are widely spread in food additives and products, such as meat, milk, and vegetables. Pediococcus pentosaceus (P. pentosaceus), as a kind of LAB, has numerous probiotic effects, mainly including antioxidant, cholesterol-lowering, and immune effects. Recently, the applications in the probiotic- fermentation products have attracted progressively more attentions. However, it is necessary to screen P. pentosaceus with abundant functions from diverse sources due to the limitation about the source and species of P. pentosaceus. This review summarized the screening methods of P. pentosaceus and the exploration methods of probiotic functions in combination with the case study. The screening methods included primary screening and rescreening including gastric acidity resistance, bile resistance, adhesion, antibacterial effects, etc. The application and development prospects of P. pentosaceus were described in detail, and the shortcomings in the practical application of P. pentosaceus were evaluated to make better application of P. pentosaceus in the future.

With the widespread use of automatic identification systems (AISs), some ships use deceptive information or intentionally close their AISs to conceal their illegal activities or evade the supervision of maritime departments. Although radar measurements can be effectively utilized to evaluate the credibility of received AIS data, the propagation of non-line-of-sight (NLOS) signal conditions is an important factor that affects location accuracy. This study addresses the NLOS problem in a special geometric dilution of precision (GDOP) scenario on a coast and several base stations. We employed data augmentation and a deep residual shrinkage network in order to alleviate the adverse effects of NLOS errors. The results of our simulations demonstrate that the proposed method outperforms other range-based localization algorithms in a mixed LOS/NLOS environment. For a special GDOP scenario with four radars, our algorithm’s root-mean-square error (RMSE) was lower than 180 m.

AI provides a new method for massive simulated data calculations in molecular dynamics, materials, and other scientific computing fields. However, the complex structures and large-scale parameters of neural network models make them difficult to develop and train. The automatic parallel technology based on graph algorithms is one of the most promising methods to solve this problem, despite the low efficiency in the design, implementation, and execution of distributed parallel policies for large-scale neural network models. In this paper, we propose an adaptive distributed parallel training method based on the dynamic generation of critical DAG (directed acyclic graph) paths, called FD-DPS, to solve this efficiency problem. Firstly, the proposed model splits operators with the dimension of the tensor, which can expand the space available for model parallelism. Secondly, a dynamic critical path generation method is employed to determine node priority changes in the DAG of the neural network models. Finally, the model implements the optimal scheduling of critical paths based on the priority of the nodes, thereby improving the performance of parallel strategies. Our experiments show that FD-DPS can achieve 12.76% and 11.78% faster training on PnasNet_mobile and ResNet_200 models, respectively, compared with the MP-DPS and Fast methods.

Tea is a special economic crop that is widely distributed in tropical and subtropical areas. Timely and accurate access to the distribution of tea plantation areas is crucial for effective tea plantation supervision and sustainable agricultural development. Traditional methods for tea plantation extraction are highly dependent on feature engineering, which requires expensive human and material resources, and it is sometimes even difficult to achieve the expected results in terms of accuracy and robustness. To alleviate such problems, we took Xinchang County as the study area and proposed a method to extract tea plantations based on deep learning networks. Convolutional neural network (CNN) and recurrent neural network (RNN) modules were combined to build an R-CNN model that can automatically obtain both spatial and temporal information from multitemporal Sentinel-2 remote sensing images of tea plantations, and then the spatial distribution of tea plantations was predicted. To confirm the effectiveness of our method, support vector machine (SVM), random forest (RF), CNN, and RNN methods were used for comparative experiments. The results show that the R-CNN method has great potential in the tea plantation extraction task, with an F1 score and IoU of 0.885 and 0.793 on the test dataset, respectively. The overall classification accuracy and kappa coefficient for the whole region are 0.953 and 0.904, respectively, indicating that this method possesses higher extraction accuracy than the other four methods. In addition, we found that the distribution index of tea plantations in mountainous areas with gentle slopes is the highest in Xinchang County. This study can provide a reference basis for the fine mapping of tea plantation distributions.

Rosa roxburghii Tratt. is widely applied in food, cosmetics, and traditional medicine, and has been demonstrated to possess diverse bioactivities. Plant endophytic fungi are important microbial resources with great potential for application in many fields. They not only establish mutualistic symbiosis with host plants but also produce a variety of bioactive compounds. Therefore, in the present study, endophytic fungi were isolated from R. roxburghii, the diversity and antimicrobial activities were evaluated. As a result, 242 strains of endophytic Sordariomycetes were successfully isolated. Multigene phylogenetic analyses showed that these isolates included eight orders, 19 families, 33 genera. The dominant genera were Diaporthe (31.4%), Fusarium (14.4%), Chaetomium (7.9%), Dactylonectria (7.0%), Graphium (4.5%), Colletotrichum (4.1%), and Clonostachys (4.1%). For different tissues of R. roxburghii, alpha diversity analysis revealed that the diversity of fungal communities decreased in the order of root, fruit, stem, flower, leaf, and seed, and Clonostachys and Dactylonectria exhibited obvious tissue specificity. Meanwhile, functional annotation of 33 genera indicated that some fungi have multitrophic lifestyles combining endophytic, pathogenic, and saprophytic behavior. Additionally, antimicrobial activities of endophytic Sordariomycetes against Lasiodiplodia theobromae, Botryosphaeria dothidea, Colletotrichum capsici, Pyricularia oryzae, Rhizoctonia solani, Fusarium oxysporum, Pseudomonas syringae, Pantoea agglomerans, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa were screened. Dual culture test assays showed that there were 40 different endophytic species with strong inhibition of at least one or moderate inhibition of two or more against the 12 tested strains. The results from the filter paper diffusion method suggested that extracellular metabolites may be more advantageous than intracellular metabolites in the development of antimicrobial agents. Eleven isolates with good activities were screened. In particular, Hypomontagnella monticulosa HGUP194009 and Nigrospora sphaerica HGUP191020 have shown promise in both broad-spectrum and intensity. Finally, some fungi that commonly cause disease have been observed to have beneficial biological activities as endophytic fungi. In conclusion, this study showed the species composition, alpha diversity, and lifestyle diversity of endophytic Sordariomycetes from R. roxburghii and demonstrated these isolates are potential sources for exploring antimicrobial agents.

In natural communities, microbes exchange a variety of metabolites (public goods) with each other, which drives the evolution of auxotroph and shapes interdependent patterns at community-level. However, factors that determine the strategy of public goods synthesis for a given community member still remains to be elucidated. In anaerobic methanogenic communities, energy availability of different community members is largely varied. We hypothesized that this uneven energy availability contributed to the heterogeneity of public goods synthesis ability among the members in these communities. We tested this hypothesis by analyzing the synthetic strategy of amino acids of the bacterial and archaeal members involved in four previously enriched anaerobic methanogenic communities residing in thermophilic chemostats. Our analyses indicate that most of the members in the communities did not possess ability to synthesize all the essential amino acids, suggesting they exchanged these essential public goods to establish interdependent patterns for survival. Importantly, we found that the amino acid synthesis ability of a functional group was largely determined by how much energy it could obtain from its metabolism in the given environmental condition. Moreover, members within a functional group also possessed different amino acid synthesis abilities, which are related to their features of energy metabolism. Our study reveals that energy availability is a key driver of microbial evolution in presence of metabolic specialization at community level and suggests the feasibility of managing anaerobic methanogenic communities for better performance through controlling the metabolic interactions involved.

This trial evaluated how dietary-accommodated pomelo peel powder (PPP) affected average daily feed intake (ADFI) and average daily gain (ADG), diarrhea, antioxidation, and colonic microbial in weaned piglets. Thirty piglets weaned at 28 d were divided into three groups: a basal diet (CON); a CON containing 75 mg/kg chlortetracycline (CTC); and a CON containing 8 g/kg (PPP). This trial had a period of 28 days. Piglets supplemented with PPP had higher ADFI and ADG than piglets in CTC and CON (p < 0.05). The diarrhea rate in PPP and CTC was lower than in CON in the 3rd and 4th weeks (p < 0.05). Serum superoxide dismutase and glutathione peroxidase enzyme activities, and total antioxidant capacity in PPP were higher than those in CON (p < 0.05). Serum interleukin (IL)-4, insulin-like growth factor-I, immunoglobulin (Ig)A, and IgG concentrations in the PPP and CTC groups were higher than those in the CON group (p < 0.05). Serum IL-1β, IL-8, IL-17, and interferon (IFN)-γ concentrations and the cecal pH in PPP were lower than those in CON (p < 0.05). Serum IL-1β, IFN-γ, and IgA concentrations of piglets in PPP were lower than in CTC (p < 0.05). The villus height and villus height/crypt depth of the ileum of piglets in PPP and CTC were higher than those in CON (p < 0.05), but there was no difference between PPP and CTC (p > 0.05). The Firmicutes and Cyanobacteria relative abundances in PPP and CTC (p < 0.05) were lower than those in CON, whereas the Bacteroidetes relative abundances in PPP and CTC were higher than those in CON. The Prevotellaceae relative abundance in CTC was higher than in CON (p < 0.05), whereas the Lactobacillaceae relative abundance in CTC was lower than in CON (p < 0.05). The Ruminococcaceae relative abundance in PPP was higher than in CON (p < 0.05), whereas the Veillonellaceae relative abundance in PPP was lower than in CON (p < 0.05). PPP can improve ADFI and ADG, relieve diarrhea, and enhance the colonic microflora of weaned piglets. Therefore, PPP is expected to replace CTC as a feed additive to alleviate weaning stress and ensure normal growth and development of piglets.

The early detection of hepatic fibrosis is of critical importance. Ultrasound backscattered radiofrequency signals from the liver contain abundant information about its microstructure. We proposed a method for characterizing human hepatic fibrosis using one-dimensional convolutional neural networks (CNNs) based on ultrasound backscattered signals. The proposed CNN model was composed of four one-dimensional convolutional layers, four one-dimensional max-pooling layers, and four fully connected layers. Ultrasound radiofrequency signals collected from 230 participants (F0: 23; F1: 46; F2: 51; F3: 49; F4: 61) with a 3-MHz transducer were analyzed. Liver regions of interest (ROIs) that contained most of the liver ultrasound backscattered signals were manually delineated using B-mode images reconstructed from the backscattered signals. ROI signals were normalized and augmented by using a sliding window technique. After data augmentation, the radiofrequency signal segments were divided into training sets, validation sets and test sets at a ratio of 80%:10%:10%. In the test sets, the proposed algorithm produced an area under the receive operating characteristic curve of 0.933 (accuracy: 91.30%; sensitivity: 92.00%; specificity: 90.48%), 0.997 (accuracy: 94.29%; sensitivity: 94.74%; specificity: 93.75%), 0.818 (accuracy: 75.00%; sensitivity: 69.23%; specificity: 81.82%), and 0.934 (accuracy: 91.67%; sensitivity: 88.89%; specificity: 94.44%) for diagnosis liver fibrosis stage ≥F1, ≥F2, ≥F3, and ≥F4, respectively. Experimental results indicated that the proposed deep learning algorithm based on ultrasound backscattered signals yields a satisfying performance when diagnosing hepatic fibrosis stages. The proposed method may be used as a new quantitative ultrasound approach to characterizing hepatic fibrosis.

In order to alleviate the pressure on environmental resources faced by meat and dairy production and to satisfy the increasing demands of consumers for food safety and health, alternative proteins have drawn considerable attention in the food industry. However, despite the successive reports of alternative protein food, the processing and application foundation of alternative proteins for meat and dairy is still weak. This paper summarizes the nutritional composition and physicochemical characteristics of meat and dairy alternative proteins from four sources: plant proteins, fungal proteins, algal proteins and insect proteins. The difference between these alternative proteins to animal proteins, the effects of their structural features and environmental conditions on their properties, as well as the corresponding mechanism are compared and discussed. Though fungal proteins, algal proteins and insect proteins have shown some advantages over traditional plant proteins, such as the comparable protein content of insect proteins to meat, the better digestibility of fungal proteins and the better foaming properties of algal proteins, there is still a big gap between alternative proteins and meat and dairy proteins. In addition to needing to provide amino acid composition and digestibility similar to animal proteins, alternative proteins also face challenges such as maintaining good solubility and emulsion properties. Their nutritional and physicochemical properties still need thorough investigation, and for commercial application, it is important to develop and optimize industrial technology in alternative protein separation and modification.

Multiphase flows are encountered in various industries, and the Coriolis flowmeter (CFM) is considered a high potential flowmeter for the metering of these flows. However, the decoupling effect and asymmetrical gas distribution in a CFM might decrease the accuracy of its multiphase flow metering The asymmetry of gas distribution in a CFM and its influence on the metering accuracy have only been qualitatively investigated in a few studies. The present paper quantitatively describes the gas distribution asymmetry in several CFMs under different flow conditions by numerical simulation. The simulation methodology is developed and validated by a results comparison with a conducted experiment and published data for bubbly, stratified and transitional flow regimes. U-shaped and triangle-shaped CFMs of different diameters are investigated at different gas volume fractions and flow rates. It is shown that the increase in the gas volume fraction and the reduction in the mixture flow rate lead to the increase in the gas distribution asymmetry. The strong correlation between the gas distribution asymmetry and the experimentally observed CFM error is demonstrated. The correction of the CFM error is proposed based on this correlation allowing the metering error to be decreased from 34% to 10% for the investigated conditions.

The southeast coastal areas in China have distributed lots of granite outcrops of different periods. Previous research has shown that granite geothermal reservoirs are also distributed under sedimentary basins in these areas, such as in Zhangzhou basin. Therefore, granites with fractures buried in deep can be used as a potential deep geothermal reservoir in these areas. In order to study geological conditions of the deep granite reservoir and discuss the genesis of the deep granite geothermal system, rock geochemistry and zircon U-Pb chronology from outcrop and parts of the drilling cores of granitic rocks have been analyzed, combined with the anatomy of the deep seismic data and electromagnetic detection data in selected area. Based on the results of geochemistry and zircon U-Pb chronology, most granites in this area are of Yanshanian periods. Based on the seismic data, the thickness of the overlying strata on granite in Huangshadong area of Huizhou City is up to 1.5 km. According to the regional geological survey, multi-stage joints are developed in the granite, and most of hot springs rise from intersection of fracture with different directions to the surface. The heat source in the study area mainly comes from the mantle carried up by the deep NNE-trending faults. There are a large number of thermal springs at the intersection of the surface and the NW-trending fault, and the NW-trending fault provides the drainage conditions for the upwelling of underground thermal springs. There is a huge amount of deep granite geothermal resources in the southeast coastal area. The analysis of deep granite geological conditions and genetic models can provide guidance for the evaluation of deep granite geothermal resources and the further optimization of favorable zones in these areas.

Summary: Germline alterations of the NF2 gene cause neurofibromatosis type 2, a syndrome manifested with benign tumors, and Nf2 deletion in mice also results in slow tumorigenesis. As a regulator of the Hippo signaling pathway, NF2 induces LATS1/2 kinases and consequently represses YAP/TAZ. YAP/TAZ oncoproteins are also inhibited by motin family proteins (Motins). Here, we show that the Hippo signaling is fine-tuned by Motins in a NF2-dependent manner, in which NF2 recruits E3 ligase RNF146 to facilitate ubiquitination and subsequent degradation of Motins. In the absence of NF2, Motins robustly accumulate to restrict full activation of YAP/TAZ and prevent rapid tumorigenesis. Hence, NF2 deficiency not only activates YAP/TAZ by inhibiting LATS1/2 but also stabilizes Motins to keep YAP/TAZ activity in check. The upregulation of Motins upon NF2 deletion serves as a strategy for avoiding uncontrolled perturbation of the Hippo signaling and may contribute to the benign nature of most NF2-mutated tumors.

Objectives: To assess the oral health condition and oral microbial outcomes from receiving an innovative treatment regimen - Prenatal Total Oral Rehabilitation (PTOR). Methods: This prospective cohort study included 15 pregnant women in the PTOR group who had a baseline visit before PTOR and three follow-up visits (immediate after, 2 weeks and 2 months) after receiving PTOR. A historical control group of additional 15 pregnant women was matched from a separate study based on a propensity score. Along with demographic and medical background, oral health conditions and perinatal oral health literacy were assessed. Oral samples (saliva and plaque) were analyzed to identify and quantify Streptococcus mutans and Candida species by culturing-dependent and -independent methods. Results: Significant reductions of salivary S. mutans were observed following PTOR, the effect remained until 2-month follow-up (p < 0.05). The carriage of salivary and plaque S. mutans at the 2-month visit of the PTOR group was significantly lower than that of the control group (p < 0.05). Oral health conditions reflected by BOP and PI were significantly improved upon receiving PTOR (p < 0.05). Receiving PTOR significantly improved the perinatal oral health literacy score, and the knowledge retained until 2-month follow-up (p < 0.05). Conclusions: PTOR is associated with an improvement in oral health conditions and perinatal oral health literacy, and a reduction in S. mutans carriage, within a 2-month follow-up period. Future clinical trials are warranted to comprehensively assess the impact of PTOR on the maternal oral flora other than S. mutans and Candida, birth outcomes, and their offspring's oral health.

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson’s disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, g_Bifidobacterium, o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, g_Lactobacillus) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from Mycobacterium tuberculosis, triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from Mycobacterium tuberculosis and Mycobacterium leprae may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.

Zinc finger and BTB domain containing 1(Zbtb1) is a transcriptional suppressor protein, and a member of the mammalian Zbtb gene family. Previous studies have shown that Zbtb1 is essential for T-cell development. However, the role of Zbtb1 in T-cell lymphoma is undetermined. In this study, an EL4 cell line with Zbtb1 deletion was constructed using the CRISPR-Cas9 technique. The expression profiles of microRNA and circRNA produced by the control and gene deletion groups were determined by RNA-seq. In general, 24 differentially expressed microRNA and 16 differentially expressed circRNA were found between normal group and gene deletion group. Through further analysis of differentially expressed genes, GO term histogram and KEGG scatter plot were drawn, and three pairs of miRNA and circRNA regulatory relationships were found. This study describes the differentially expressed microRNA and circRNA in normal and Zbtb1-deficient EL4 cell lines, thus providing potential targets for drug development and clinical treatment of T-cell lymphoma.

Objective: Randomized clinical trials and published meta-analyses assessing the clinical effectiveness of Chinese herbal medicine (CHM) on the treatment of stable chronic obstructive pulmonary disease (COPD) yielded inconsistent results in terms of disease outcomes, in which the design of placebo-controlled studies can contribute to the heterogeneity. This study aimed to evaluate the efficacy and safety of CHM compared to placebo on the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. Methods: Nine electronic databases were searched from inception to October 1, 2019 to identify placebo controlled randomized trials of CHM for the treatment of stable COPD and studies in English or Chinese were included. The primary outcomes were symptom score (CAT score), quality of life (SGRQ) and frequency of acute exacerbations. The secondary outcomes included lung function, clinical total effective rate and adverse events. The selection of studies, data extraction and coding and assessment of risk of bias of the included studies were conducted by two reviewers independently. Mean difference (MD) was used to analyze continuous variable and relative risk ratio (RR) for dichotomous data. Results: A total of eleven studies involving 1223 patients were included. While maintaining routine western pharmacotherapies (WP), CHM had significant advantage over the treatment of placebo in improving CAT score (MD -3.93; 95 %CI -6.01 to -1.85) and SGRQ score (MD -6.20; 95 %CI -10.13 to -2.28), reducing the frequency of acute exacerbations (MD -0.78; 95 %CI -1.40 to -0.16) and improving clinical effective rate (RR 1.29; 95 %CI 1.14 to 1.45), but had no significant effect on improving FEV1%pred (MD 8.18; 95 %CI -4.22 to 20.58). High heterogeneity was found for the changes in exacerbation frequency and FEV1%pred. No serious adverse events related to CHM were reported. Conclusions: This meta-analysis of placebo-controlled RCTs demonstrated that the use of CHM in addition to WP could alleviate clinical symptoms, improve quality of life and clinical efficiency and reduce the frequency of exacerbations, which could be an alternative approach for treatment adjustment of COPD. CHM was a relatively safe treatment. These findings need to be verified in future with high-quality clinical trials.

Fluoride which is widespread in our environment and food due to its geological origin and industrial pollution has been identified as a developmental neurotoxicant. Gut-brain axis provides new insight into brain-derived injury. We previously found the psychoactive effects of a probiotic strain, Lactobacillus johnsonii BS15 against fluoride-induced memory dysfunction in mice by modulating the gut-brain axis. In this study, we aimed to detect the link between the reconstruction of gut microbiota and gut-brain axis through which probiotic alleviate fluoride-induced memory impairment. We also added an hour of water avoidance stress (WAS) before behavioral tests and sampling, aiming to demonstrate the preventive effects of the probiotic on fluoride-induced memory impairment after psychological stress. Mice were given fluoridated drinking water (sodium fluoride 100 ppm, corresponding to 37.8 ± 2.4 ppm F¯) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. Results showed that fluoride increases the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and reduces the exploration ratio in novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following WAS, which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant separation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the main targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate content and diamine oxidase (DAO) activity, two biomarkers of gut permeability were reduced in the serum of probiotic-inoculated mice. ZO-1, an intestinal tight junction protein was reduced by fluoride in mRNA, and its protein levels were increased by the probiotic treatment. Moreover, the hippocampus which is essential to learning and memory, down-regulated mRNA level of both the myelin-associated glycoprotein (MAG), and protein levels of brain-derived neurotrophic factor (BDNF), including the improvement of cAMP response element-binding protein (CREB) by BS15 in fluoride-exposed mice after WAS. Via spearman correlation analysis, Lactobacillus displayed significantly positive associations with the behavioral tests, levels of nerve development related factors, and intestinal tight junction proteins ZO-1, and negative association with TNF-α of the hippocampus, highlighting regulatory effects of gut bacteria on memory potential and gut barrier. These results suggested the psychoactive effects of BS15 on fluoride-induced memory dysfunction after psychological stress. In addition, there may be some correlations between fluoride-induced memory dysfunction and reconstruction of gut microbiota. Availability of data and materials: 16S rRNA sequencing reads have uploaded to NCBI. The accession code of 16S rRNA sequencing reads in the National Center for Biotechnology Information (NCBI) BioProject database: PRJNA660154.