bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive Outcomes of In Vitro Fertilization and Fresh Embryo Transfer in Infertile Women With Adenomyosis: A Retrospective Cohort Study
Authors: Liang Tingting , Zhang Wen , Pan Ningning , Han Bing , Li Rong , Ma Caihong
Published: July 2022

Background

Adenomyosis is commonly encountered in infertile women; however, it is still unclear whether adenomyosis has a detrimental effect on in vitro fertilization and embryo transfer (IVF-ET) outcomes.

Method

We enrolled 1146 patients with adenomyosis and 1146 frequency-matched control women in a 1:1 ratio based on age, BMI, and basal follicle-stimulating hormone (FSH) level. After controlling for other factors, the rates of clinical pregnancy, miscarriage, live birth, and obstetric complications were compared between two groups.

Results

There was no significant difference in clinical pregnancy rate between the two groups (38.1% vs. 41.6%; P=0.088). The implantation rate (25.6% versus 28.6%, P=0.027) and live birth rate (26% versus 31.5%, P=0.004) were significantly lower in the women with adenomyosis than in the controls. The miscarriage rate in the adenomyosis group was higher than that in the control group (29.1% versus 17.2%, P=0.001). After adjusting for confounding factors, multivariate analysis showed the clinical pregnancy rate was not statistically different between the two groups (OR: 0.852, P=0.070). In the adenomyosis group, the rate of miscarriage(OR: 1.877, P=0.000), placenta previa (OR: 2.996, P=0.042)and preeclampsia (OR: 2.287, P=0.042)were increased significantly, while live birth rate (OR: 0.541, P=0.000) was reduced significantly than control group.

Conclusion

Adenomyosis has negative effect on IVF-ET outcomes in which miscarriage risk increased, live birth rate reduced and obstetric complications increased.
Chronic constant light exposure aggravates high fat diet-induced renal injury in rats
Authors: Xing Lin , Wu Shanyu , Shi Ying , Yue Fangzhi , Wei Lin , Russell Ryan , Zhang Dongmei
Published: July 2022

Obesity-related kidney disease is now recognized as a global health issue, with a substantial number of patients developing progressive renal failure and end-stage renal disease. Interestingly, recent studies indicate light pollution is a novel environmental risk factor for chronic kidney disease. However, the impact of light pollution on obesity-related kidney disease remains largely unknown, with its underlying mechanism insufficiently explained. Renal hypoxia induced factor 1α (HIF1α) is critical in the development of glomerulosclerosis and renal fibrosis. The present study explored effects of constant light exposure on high fat diet (HFD) -induced renal injury and its association with HIF1α signal pathway. Thirty-two male Sprague Dawley rats were divided into four groups according to diet (HFD or normal chow diet) and light cycles (light/dark or constant light). After 16 weeks treatment, rats were sacrificed and pathophysiological assessments were performed. In normal chow fed rats, constant light exposure led to glucose abnormalities and dyslipidemia. In HFD fed rats, constant light exposure exacerbated obesity, glucose abnormalities, insulin resistance, dyslipidemia, renal functional decline, proteinuria, glomerulomegaly, renal inflammation and fibrosis. And, constant light exposure caused an increase in HIF1α and a decrease in prolyl hydroxylase domain 1 (PHD1) and PHD2 expression in kidneys of HFD-fed rats. Then, we demonstrated that BMAL1 bound directly to the promoters of PHD1 in mouse podocyte clone 5 cell line (MPC5) by ChIP assays. In conclusion, chronic constant light exposure aggravates HFD-induced renal injuries in rats, and it is associated with activation of HIF1α signal pathway.
5-Hydroxymethylcytosine profiles in plasma cell-free DNA reflect molecular characteristics of diabetic kidney disease
Authors: Chu Jin-Lin , Bi Shu-Hong , He Yao , Ma Rui-Yao , Wan Xing-Yu , Wang Zi-Hao , Zhang Lei , Zheng Meng-Zhu , Yang Zhan-Qun , Du Ling-Wei , Maimaiti Yiminiguli , Biekedawulaiti Gulinazi , Duolikun Maimaitiyasen , Chen Hang-Yu , Chen Long , Li Lin-Lin , Tie Lu , Lin Jian
Published: July 2022

Background

Diabetic kidney disease (DKD), one of the main complications of diabetes mellitus (DM), has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions.

Methods

We utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially hydroxymethylated genes and differentially expressed genes from the GSE30528 and GSE30529. Then, a protein interaction network was constructed for the candidate genes, and the hub genes were identified by the MCODE and cytoHubba algorithm. The correlation analysis between the hydroxymethylation level of the hub genes and estimated glomerular filtration rate (eGFR) was carried out. Finally, we demonstrated differences in expression levels of the protein was verified by constructing a mouse model of DKD. In addition, we constructed a network of interactions between drugs and hub genes using the Comparative Toxicogenomics Database.

Results

This study found that there were significant differences in the overall distribution of 5hmC in plasma of patients with DKD, and an alteration of hydroxymethylation levels in genomic regions involved in inflammatory pathways which participate in the immune response. The final 5 hub genes, including (CTNNB1, MYD88, CD28, VCAM1, CD44) were confirmed. Further analysis indicated that this 5-gene signature showed a good capacity to distinguish between DKD and DM, and was found that protein levels were increased in renal tissue of DKD mice. Correlation analysis indicated that the hydroxymethylation level of 5 hub genes were nagatively correlated with eGFR. Toxicogenomics analysis showed that a variety of drugs for the treatment of DKD can reduce the expression levels of 4 hub genes (CD44, MYD88, VCAM1, CTNNB1).

Conclusions

The 5hmC-Seal assay was successfully applied to the plasma cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and it provides new insight for the future molecularly targeted anti-inflammation therapeutic strategies of DKD.
Identification of neurohypophysial hormones and the role of VT in the parturition of pregnant seahorses (Hippocampus erectus)
Authors: Zhang Huixian , Liu Yali , Qin Geng , Lin Qiang
Published: July 2022

Neurohypophysial hormones regulate the reproductive behavior of teleosts; however, their role in the gestation and parturition of ovoviviparous fishes with male pregnancy (syngnathids) remains to be demonstrated. In the present study, the complementary DNA (cDNA) sequences of arginine vasotocin (VT) and isotocin (IT) from the lined seahorse (Hippocampus erectus) were cloned and identified. We observed that the mature core peptides of seahorse VT and IT were conserved among teleosts. In the phylogenic tree, seahorse VT and IT were clustered independently with teleost VT and IT. The tissue distribution patterns of VT and IT were similar, and both were highly expressed in the brain, gills, and gonads. Interestingly, they were also expressed to some extent in the brood pouch. In situ hybridization revealed that VT and IT messenger RNA (mRNA) signals in the brain were mainly located in the preoptic area region of the hypothalamus. Intraperitoneal administration of the VT core peptide to pregnant seahorses induced premature parturition, stimulated gonadotropin release, increased serum estrogen levels, and decreased prolactin secretion. Moreover, VT injection upregulated the mRNA expression of the membrane estrogen receptor in the brood pouch. In summary, neurohypophysial hormones promote premature parturition by regulating estrogen synthesis through the hypothalamus–pituitary–gonad axis.
Dynamic in vitro culture of cryopreserved-thawed human ovarian cortical tissue using a microfluidics platform does not improve early folliculogenesis
Authors: Del Valle Julieta S. , Mancini Vanessa , Laverde Garay Maitane , Asseler Joyce D. , Fan Xueying , Metzemaekers Jeroen , Louwe Leoni A. , Pilgram Gonneke S. K. , Westerlaken Lucette A. J. van der , van Mello Norah M. , Chuva de Sousa Lopes Susana M.
Published: July 2022

Current strategies for fertility preservation include the cryopreservation of embryos, mature oocytes or ovarian cortical tissue for autologous transplantation. However, not all patients that could benefit from fertility preservation can use the currently available technology. In this regard, obtaining functional mature oocytes from ovarian cortical tissue in vitro would represent a major breakthrough in fertility preservation as well as in human medically assisted reproduction. In this study, we have used a microfluidics platform to culture cryopreserved-thawed human cortical tissue for a period of 8 days and evaluated the effect of two different flow rates in follicular activation and growth. The results showed that this dynamic system supported follicular development up to the secondary stage within 8 days, albeit with low efficiency. Surprisingly, the stromal cells in the ovarian cortical tissue were highly sensitive to flow and showed high levels of apoptosis when cultured under high flow rate. Moreover, after 8 days in culture, the stromal compartment showed increase levels of collagen deposition, in particular in static culture. Although microfluidics dynamic platforms have great potential to simulate tissue-level physiology, this system still needs optimization to meet the requirements for an efficient in vitro early follicular growth.
Thyroid Function, Inflammatory Response, and Glucocorticoids in COVID-19
Authors: Świątkowska-Stodulska Renata , Berlińska Agata , Puchalska-Reglińska Ewelina
Published: July 2022

The ongoing COVID-19 pandemic calls for extensive research on various medical topics. Since the beginning of the pandemic, multiple studies investigated the impact of SARS CoV-2 on thyroid function. However, crucial data, such as trend progression over time or influence of commonly used drugs, might still be missing. We checked the thyroid function in 174 patients with PCR-confirmed COVID-19. Our research covered three separate time points of hospitalization (days 1, 4, and 10). We did not exclude patients treated with glucocorticoids but, instead, compared them with patients not treated with steroids. We correlated the results of thyroid function tests with markers of systemic inflammation. We checked if abnormal thyroid function can predict unfavorable outcomes defined as combined primary endpoint and/or secondary endpoints; the combined primary endpoint was the occurrence of death, mechanical ventilation, non-invasive ventilation, vasopressor infusion, or prolonged hospital stay, and the secondary endpoint was any of the listed events. In general, 80.46% of evaluated patients displayed abnormalities in thyroid function tests over at least one time point throughout the observation. We noticed a high prevalence of features typical for thyroid dysfunction in non-thyroidal illness (NTI). Free triiodothyronine (fT3) concentration was significantly lower in the group requiring glucocorticoids. Patients displaying abnormal thyroid function were statistically more likely to meet the predefined combined primary endpoint. We found that fT3 measured at admission could be perceived as an independent predictor of endpoint completion for all analyzed groups. Thyroid involvement is common in COVID-19. Our study supports the idea of thyroid function abnormalities being important clinical tools and allowing early recognition of possible detrimental outcomes of the disease.
Monocyte biology conserved across species: Functional insights from cattle
Authors: Talker Stephanie C. , Barut G. Tuba , Lischer Heidi E.L. , Rufener Reto , von Münchow Lilly , Bruggmann Rémy , Summerfield Artur
Published: July 2022

Similar to human monocytes, bovine monocytes can be split into CD14highCD16- classical, CD14highCD16high intermediate and CD14-/dimCD16high nonclassical monocytes (cM, intM, and ncM, respectively). Here, we present an in-depth analysis of their steady-state bulk- and single-cell transcriptomes, highlighting both pronounced functional specializations and transcriptomic relatedness. Bulk gene transcription indicates pro-inflammatory and antibacterial roles of cM, while ncM and intM appear to be specialized in regulatory/anti-inflammatory functions and tissue repair, as well as antiviral responses and T-cell immunomodulation. Notably, intM stood out by high expression of several genes associated with antigen presentation. Anti-inflammatory and antiviral functions of ncM are further supported by dominant oxidative phosphorylation and selective strong responses to TLR7/8 ligands, respectively. Moreover, single-cell RNA-seq revealed previously unappreciated heterogeneity within cM and proposes intM as a transient differentiation intermediate between cM and ncM.
A robust experimental and computational analysis framework at multiple resolutions, modalities and coverages
Authors: Tran M. , Yoon S. , Teoh M. , Andersen S. , Lam PY. , Purdue B. W. , Raghubar A. , Hanson SJ. , Devitt K. , Jones K. , Walters S. , Monkman J. , Kulasinghe A. , Tuong ZK. , Soyer HP. , Frazer I. H. , Nguyen Q.
Published: July 2022

The ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is needed, especially for cancer immunotherapy development, which requires understanding of molecular mechanisms and discovery of more druggable targets. In this work, we assembled and evaluated an integrated experimental framework and analytical process to enable genome-wide scale discovery of ligand-receptors potentially used for cellular crosstalks, followed by targeted validation. We assessed the complementarity of four different technologies: single-cell RNA sequencing and Spatial transcriptomic (measuring over >20,000 genes), RNA In Situ Hybridization (RNAscope, measuring 4-12 genes) and Opal Polaris multiplex protein staining (4-9 proteins). To utilize the multimodal data, we implemented existing methods and also developed STRISH (Spatial TRanscriptomic In Situ Hybridization), a computational method that can automatically scan across the whole tissue section for local expression of gene (e.g. RNAscope data) and/or protein markers (e.g. Polaris data) to recapitulate an interaction landscape across the whole tissue. We evaluated the approach to discover and validate cell-cell interaction in situ through in-depth analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma, which account for over 70% of cancer cases. We showed that inference of cell-cell interactions using scRNA-seq data can misdetect or detect false positive interactions. Spatial transcriptomics still suffers from misdetecting lowly expressed ligand-receptor interactions, but reduces false discovery. RNAscope and Polaris are sensitive methods for defining the location of potential ligand receptor interactions, and the STRISH program can determine the probability that local gene co-expression reflects true cell-cell interaction. We expect that the approach described here will be widely applied to discover and validate ligand receptor interaction in different types of solid cancer tumors.
Aspirin eugenol ester alleviates lipopolysaccharide-induced acute lung injury in rats while stabilizing serum metabolites levels
Authors: Tao Qi , Zhang Zhen-Dong , Qin Zhe , Liu Xi-Wang , Li Shi-Hong , Bai Li-Xia , Ge Wen-Bo , Li Jian-Yong , Yang Ya-Jun
Published: July 2022

Aspirin eugenol ester (AEE) was a novel drug compound with aspirin and eugenol esterified. AEE had various pharmacological activities, such as anti-inflammatory, antipyretic, analgesic, anti-oxidative stress and so on. In this study, it was aimed to investigate the effect of AEE on the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. In vitro experiments evaluated the protective effect of AEE on the LPS-induced A549 cells. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured in the cell supernatant. The Wistar rats were randomly divided into five groups (n = 8): control group, model group (LPS group), LPS + AEE group (AEE, 54 mg·kg−1), LPS + AEE group (AEE, 108 mg·kg−1), LPS + AEE group (AEE, 216 mg·kg−1). The lung wet-to-dry weight (W/D) ratio and immune organ index were calculated. WBCs were counted in bronchoalveolar lavage fluid (BALF) and total protein concentration was measured. Hematoxylin-Eosin (HE) staining of lung tissue was performed. Glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), antioxidant superoxide dismutase (SOD), total antioxidant capacity (T-AOC), lactate dehydrogenase (LDH), C-reactive protein (CRP), myeloperoxidase (MPO), malondialdehyde (MDA), macrophage mobility inhibitory factor (MIF), TNF-α, IL-6, and IL-1β activity were measured. The metabolomic analysis of rat serum was performed by UPLC-QTOF-MS/MS. From the results, compared with LPS group, AEE improved histopathological changes, reduced MDA, CRP, MPO, MDA, and MIF production, decreased WBC count and total protein content in BALF, pro-inflammatory cytokine levels, immune organ index and lung wet-dry weight (W/D), increased antioxidant enzyme activity, in a dose-dependent manner. The results of serum metabolomic analysis showed that the LPS-induced ALI caused metabolic disorders and oxidative stress in rats, while AEE could ameliorate it to some extent. Therefore, AEE could alleviate LPS-induced ALI in rats by regulating abnormal inflammatory responses, slowing down oxidative stress, and modulating energy metabolism.
Inhibition of human macrophage activation via pregnane neurosteroid interactions with toll-like receptors: Sex differences and structural requirements
Authors: Balan Irina , Aurelian Laure , Williams Kimberly S. , Campbell Brian , Meeker Rick B. , Morrow A. Leslie
Published: July 2022

We recently discovered that (3α,5α)3-hydroxypregnan-20-one (allopregnanolone) inhibits pro-inflammatory toll-like receptor (TLR) activation and cytokine/chemokine production in mouse macrophage RAW264.7 cells. The present studies evaluate neurosteroid actions upon TLR activation in human macrophages from male and female healthy donors. Buffy coat leukocytes were obtained from donors at the New York Blood Center (http://nybloodcenter.org/), and peripheral blood mononuclear cells were isolated and cultured to achieve macrophage differentiation. TLR4 and TLR7 were activated by lipopolysaccharide (LPS) or imiquimod in the presence/absence of allopregnanolone or related neurosteroids and pro-inflammatory markers were detected by ELISA or western blotting. Cultured human monocyte-derived-macrophages exhibited typical morphology, a mixed immune profile of both inflammatory and anti-inflammatory markers, with no sex difference at baseline. Allopregnanolone inhibited TLR4 activation in male and female donors, preventing LPS-induced elevations of TNF-α, MCP-1, pCREB and pSTAT1. In contrast, 3α,5α-THDOC and SGE-516 inhibited the TLR4 pathway activation in female, but not male donors. Allopregnanolone completely inhibited TLR7 activation by imiquimod, blocking IL-1-β, IL-6, pSTAT1 and pIRF7 elevations in females only. 3α,5α-THDOC and SGE-516 partially inhibited TLR7 activation, only in female donors. The results indicate that allopregnanolone inhibits TLR4 and TLR7 activation in cultured human macrophages resulting in diminished cytokine/chemokine production. Allopregnanolone inhibition of TLR4 activation was found in males and females, but inhibition of TLR7 signals exhibited specificity for female donors. 3α,5α-THDOC and SGE-516 inhibited TLR4 and TLR7 pathways only in females. These studies demonstrate anti-inflammatory effects of allopregnanolone in human macrophages for the first time and suggest that inhibition of pro-inflammatory cytokines/chemokines may contribute to its therapeutic actions.
Extracellular vesicles from A23187-treated neutrophils cause cGAS-STING-dependent IL-6 production by macrophages
Authors: Allen Edwina R. , Whitefoot-Keliin Kaitlyn M. , Palmatier Ellen M. , Mahon Andrew R. , Greenlee-Wacker Mallary C.
Published: July 2022

In response to several types of bacteria, as well as pharmacological agents, neutrophils produce extracellular vesicles (EVs) and release DNA in the form of neutrophil extracellular traps (NETs). However, it is unknown whether these two neutrophil products cooperate to modulate inflammation. Consistent with vital NETosis, neutrophils challenged with S. aureus, as well as those treated with A23187, released significantly more DNA relative to untreated or fMLF-treated neutrophils, with no lysis occurring for any condition. To test the hypothesis that EVs generated during NETosis caused macrophage inflammation, we isolated and characterized EVs from A23187-treated neutrophils (A23187-EVs). A23187-EVs associated with neutrophil granule proteins, histone H3, transcription factor A, mitochondrial (TFAM), and nuclear and mitochondrial DNA (mtDNA). We showed that DNA from A23187-EVs, when transfected into macrophages, led to production of IL-6 and IFN-α2, and this response was blunted by pre-treatment with the STING inhibitor H151. Next, we confirmed that A23187-EVs were engulfed by macrophages, and showed that they induced cGAS-STING-dependent IL-6 production. In contrast, neither EVs from untreated or fMLF-treated cells exhibited pro-inflammatory activity. Although detergent-mediated lysis of A23187-EVs diminished IL-6 production, removal of surface-associated DNA with DNase I treatment had no effect, and A23187-EVs did not induce IFN-α2 production. Given these unexpected results, we investigated whether macrophage mtDNA activated the cGAS-STING signaling axis. Consistent with mitochondrial outer membrane permeabilization (MOMP), a defined mechanism of mtDNA release, we observed macrophage mitochondrial membrane depolarization, a decrease in cytosolic Bax, and a decrease in mitochondrial cytochrome c, suggesting that macrophage mtDNA may initiate this EV-dependent signaling cascade. All together, these data demonstrate that A23187-EVs behave differently than transfected NET- or EV-DNA, and that neutrophil-derived EVs could be used as a model to study NF-κB-dependent STING activation.
Interaction between microbiota and immunity and its implication in colorectal cancer
Authors: Xing Changsheng , Du Yang , Duan Tianhao , Nim Kelly , Chu Junjun , Wang Helen Y. , Wang Rong-Fu
Published: July 2022

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Besides genetic causes, colonic inflammation is one of the major risk factors for CRC development, which is synergistically regulated by multiple components, including innate and adaptive immune cells, cytokine signaling, and microbiota. The complex interaction between CRC and the gut microbiome has emerged as an important area of current CRC research. Metagenomic profiling has identified a number of prominent CRC-associated bacteria that are enriched in CRC patients, linking the microbiota composition to colitis and cancer development. Some microbiota species have been reported to promote colitis and CRC development in preclinical models, while a few others are identified as immune modulators to induce potent protective immunity against colitis and CRC. Mechanistically, microbiota regulates the activation of different immune cell populations, inflammation, and CRC via crosstalk between innate and adaptive immune signaling pathways, including nuclear factor kappa B (NF-κB), type I interferon, and inflammasome. In this review, we provide an overview of the potential interactions between gut microbiota and host immunity and how their crosstalk could synergistically regulate inflammation and CRC, thus highlighting the potential roles and mechanisms of gut microbiota in the development of microbiota-based therapies to prevent or alleviate colitis and CRC.
Three-dimensional smoothed particle hydrodynamics modeling of near-shore current flows over rough topographic surface
Authors: Gabreil Eslam , Wu Haitao , Chen Chen , Li Jiaye , Rubinato Matteo , Zheng Xing , Shao Songdong
Published: July 2022

In this study, a three-dimensional (3D) numerical model based on the smoothed particle hydrodynamics (SPH) approach was developed to simulate the near-shore current flows over a rough topographic surface in the coastal area, where the flows are shallow and demonstrate strong turbulent characteristics. The numerical program is based on the open-source code SPHysics (http://www.sphysics.org), and two major improvements are made to treat the turbulence and rough boundary effects: A modified sub-particle-scale (SPS) eddy viscosity model is developed to address the turbulence transfer of flows, and a drag force equation is included in the momentum equations to account for the influence of roughness element on the bed and lateral boundaries. The computed results of flow velocity, shear stress, and free surface characteristics are compared with the laboratory measurements for a variety of test conditions. It has shown that the present SPH model can accurately simulate 3D-free surface near-shore current flows over a realistic topography with roughness.
Liver fibrosis progression in a cohort of young HIV and HIV/ HBV co-infected patients: A longitudinal study using non-invasive APRI and Fib-4 scores
Authors: Iacob Diana Gabriela , Luminos Monica , Benea Otilia Elisabeta , Tudor Ana-Maria , Olariu Cristina Mihaela , Iacob Simona Alexandra , Ruta Simona
Published: July 2022

Background

The risk of liver fibrosis increases over time in HIV and HIV-HBV individuals even under antiretroviral treatment (ART), warranting a rigorous and periodic monitorization. Given the lower availability of transient elastography, we aimed to assess the longitudinal variation of two non-invasive liver fibrosis scores, APRI and Fib-4, in cases with HIV monoinfection, HIV-HBV co-infection and individuals with HBsAg-seroclearance.

Methods

We performed an observational retrospective study between 2013 and 2019 on 212 HIV patients including 111 individuals with HIV mono-infection, 62 individuals with HIV-HBV co-infection and positive HBsAg and 39 cases with HIV-HBV infection and HBsAg-loss. The groups were followed at 36, 48, and 60 months. Liver fibrosis was indicated by an APRI >0.5 or Fib-4≥1.45 score and advanced fibrosis by an APRI score >1.5 or Fib-4 >3.25. Logistic regression with generalized estimating equations (GEE) was used to assess the predictors for the presence of liver fibrosis over time.

Results

During a median follow-up of 58.5 months the prevalence of liver fibrosis in all patients increased with 0.5% reaching 11.3% using an APRI score and with 0.9% reaching 10.8% using the Fib-4 score. At the visit corresponding to 60 months the prevalence of liver fibrosis was higher in all HIV-HBV patients compared with individuals with HIV mono-infection, namely: 16.1% on APRI and 12.9% on the Fib-4 score in HIV-HBV/HBsAg-positive individuals, 12.8% on both APRI and Fib-4 scores in HIV-HBV/HBsAg-negative individuals vs. 8.1 and 9%, respectively in HIV mono-infection. The presence of liver fibrosis over the study period was independently associated with plasma HIV RNA, CD4+T cell counts, HIV-HBV co-infection (for APRI >0.5) and ART non-adherence (for Fib-4 >1.45). At the final visit, non-adherence to ART and CD4+T cell counts remained associated with liver fibrosis.

Conclusions

The study found a slow progression of APRI and Fib-4 scores over time in young PLWH with extensive ART. Liver fibrosis scores continued to increase in patients with HIV mono-infection yet remained lower than in HIV-HBV patients irrespective on the presence of HBsAg. The periodic follow-up using non-invasive scores on the long-term could help improve the surveillance in low-income settings and high scores should be followed by additional diagnostic methods.
Reliability, repeatability, and accordance between three different corneal diagnostic imaging devices for evaluating the ocular surface
Authors: Garcia-Terraza Abril L. , Jimenez-Collado David , Sanchez-Sanoja Francisco , Arteaga-Rivera José Y. , Morales Flores Norma , Pérez-Solórzano Sofía , Garfias Yonathan , Graue-Hernández Enrique O. , Navas Alejandro
Published: July 2022

Purpose

To evaluate repeatability, reproducibility, and accordance between ocular surface measurements within three different imaging devices.

Methods

We performed an observational study on 66 healthy eyes. Tear meniscus height, non-invasive tear break-up time (NITBUT) and meibography were measured using three corneal imaging devices: Keratograph 5M (Oculus, Wetzlar, Germany), Antares (Lumenis, Sidney, Australia), and LacryDiag (Quantel Medical, Cournon d’Auvergne, France). One-way ANOVAs with post hoc analyses were used to calculate accordance between the tear meniscus and NITBUT. Reproducibility was assessed through coefficients of variation and repeatability with intraclass correlation coefficients (ICC). Reliability of meibography classification was analyzed by calculating Fleiss’ Kappa Index and presented in Venn diagrams.

Results

Coefficients of variation were high and differed greatly depending on the device and measurement. ICCs showed moderate reliability of NITBUT and tear meniscus height measurements. We observed discordance between measurements of tear meniscus height between the three devices, F2, 195 = 15.24, p < 0.01. Measurements performed with Antares were higher; 0.365 ± 0.0851, than those with Keratograph 5M and LacryDiag; 0.293 ± 0.0790 and 0.306 ± 0.0731. NITBUT also showed discordance between devices, F2, 111 = 13.152, p < 0.01. Measurements performed with LacryDiag were lower (10.4 ± 1.82) compared to those of Keratograph 5M (12.6 ± 4.01) and Antares (12.6 ± 4.21). Fleiss’ Kappa showed a value of -0.00487 for upper lid and 0.128 for inferior lid Meibography classification, suggesting discrete to poor agreement between measurements.

Conclusion

Depending on the device used and parameter analyzed, measurements varied between each other, showing a difference in image processing.
Microbiomics for enhancing electron transfer in an electrochemical system
Authors: Roy Ayush Singha , Sharma Aparna , Thapa Bhim Sen , Pandit Soumya , Lahiri Dibyajit , Nag Moupriya , Sarkar Tanmay , Pati Siddhartha , Ray Rina Rani , Shariati Mohammad Ali , Wilairatana Polrat , Mubarak Mohammad S.
Published: July 2022

In microbial electrochemical systems, microorganisms catalyze chemical reactions converting chemical energy present in organic and inorganic molecules into electrical energy. The concept of microbial electrochemistry has been gaining tremendous attention for the past two decades, mainly due to its numerous applications. This technology offers a wide range of applications in areas such as the environment, industries, and sensors. The biocatalysts governing the reactions could be cell secretion, cell component, or a whole cell. The electroactive bacteria can interact with insoluble materials such as electrodes for exchanging electrons through colonization and biofilm formation. Though biofilm formation is one of the major modes for extracellular electron transfer with the electrode, there are other few mechanisms through which the process can occur. Apart from biofilm formation electron exchange can take place through flavins, cytochromes, cell surface appendages, and other metabolites. The present article targets the various mechanisms of electron exchange for microbiome-induced electron transfer activity, proteins, and secretory molecules involved in the electron transfer. This review also focuses on various proteomics and genetics strategies implemented and developed to enhance the exo-electron transfer process in electroactive bacteria. Recent progress and reports on synthetic biology and genetic engineering in exploring the direct and indirect electron transfer phenomenon have also been emphasized.
Folic acid and zinc improve hyperuricemia by altering the gut microbiota of rats with high-purine diet-induced hyperuricemia
Authors: Sun Xuewei , Wen Jie , Guan Baosheng , Li Jialin , Luo Jincheng , Li Jie , Wei Mingyu , Qiu Hongbin
Published: July 2022

A high-purine diet can cause hyperuricemia and destroy the microbial composition of the gut microbiota. Both folic acid and zinc significantly reduce uric acid levels and alleviate hyperuricemia. However, whether the underlying mechanisms are associated with the regulation of the gut microbiota remain unknown. To explore alterations of the gut microbiota related to folic acid and zinc treatment in rats with hyperuricemia in our study. A hyperuricemic rat model was established with a high-purine diet. The effects of folic acid and zinc on uric acid levels were evaluated. Alterations of the gut microbiota related to hyperuricemia and the treatments were evaluated by sequencing using the Illumina MiSeq system. The results demonstrated that uric acid levels dropped observably, and the activities of adenosine deaminase (ADA) and xanthine oxidase (XOD) were downregulated after folic acid or zinc intervention. 16S rRNA gene sequencing-based gut microbiota analysis revealed that folic acid and zinc enhanced the abundance of probiotic bacteria and reduced that of pathogenic bacteria, thus improving intestinal barrier function. PICRUST analysis indicated that folic acid and zinc restored gut microbiota metabolism. These findings indicate that folic acid and zinc ameliorate hyperuricemia by inhibiting uric acid biosynthesis and stimulating uric acid excretion by modulating the gut microbiota. Thus, folic acid and zinc may be new and safe therapeutic agents to improve hyperuricemia.
Gut microbiota dysbiosis: The potential mechanisms by which alcohol disrupts gut and brain functions
Authors: Chen Ganggang , Shi Fenglei , Yin Wei , Guo Yao , Liu Anru , Shuai Jiacheng , Sun Jinhao
Published: July 2022

Alcohol use disorder (AUD) is a high-risk psychiatric disorder and a key cause of death and disability in individuals. In the development of AUD, there is a connection known as the microbiota-gut-brain axis, where alcohol use disrupts the gut barrier, resulting in changes in intestinal permeability as well as the gut microbiota composition, which in turn impairs brain function and worsens the patient’s mental status and gut activity. Potential mechanisms are explored by which alcohol alters gut and brain function through the effects of the gut microbiota and their metabolites on immune and inflammatory pathways. Alcohol and microbiota dysregulation regulating neurotransmitter release, including DA, 5-HT, and GABA, are also discussed. Thus, based on the above discussion, it is possible to speculate on the gut microbiota as an underlying target for the treatment of diseases associated with alcohol addiction. This review will focus more on how alcohol and gut microbiota affect the structure and function of the gut and brain, specific changes in the composition of the gut microbiota, and some measures to mitigate the changes caused by alcohol exposure. This leads to a potential intervention for alcohol addiction through fecal microbiota transplantation, which could normalize the disruption of gut microbiota after AUD.
Degradation of switchgrass by Bacillus subtilis 1AJ3 and expression of a beta-glycoside hydrolase
Authors: Ma Lingling , Wang Xin , Zhou Jingwen , Lü Xin
Published: July 2022

Increasing demand for carbon neutrality has led to the development of new techniques and modes of low carbon production. The utilization of microbiology to convert low-cost renewable resources into more valuable chemicals is particularly important. Here, we investigated the ability of a cellulolytic bacterium, Bacillus subtilis 1AJ3, in switchgrass lignocellulose degradation. After 5 days of culture with the strain under 37°C, cellulose, xylan, and acid-insoluble lignin degradation rates were 16.13, 14.24, and 13.91%, respectively. Gas chromatography–mass spectrometry (GC-MS) analysis and field emission scanning electron microscopy (FE-SEM) indicated that the lignin and surface of switchgrass were degraded after incubation with the bacterial strain. Strain 1AJ3 can grow well below 60°C, which satisfies the optimum temperature (50°C) condition of most cellulases; subsequent results emphasize that acid-heat incubation conditions increase the reducing sugar content in a wide range of cellulosic biomass degraded by B. subtilis 1AJ3. To obtain more reducing sugars, we focused on β-glycoside hydrolase, which plays an important role in last steps of cellulose degradation to oligosaccharides. A β-glycoside hydrolase (Bgl-16A) was characterized by cloning and expression in Escherichia coli BL21 and further determined to belong to glycoside hydrolase (GH) 16 family. The Bgl-16A had an enzymatic activity of 365.29 ± 10.43 U/mg, and the enzyme’s mode of action was explained by molecular docking. Moreover, the critical influence on temperature (50°C) of Bgl-16A also explained the high-efficiency degradation of biomass by strain under acid-heat conditions. In terms of potential applications, both the strain and the recombinant enzyme showed that coffee grounds would be a suitable and valuable substrate. This study provides a new understanding of cellulose degradation by B. subtilis 1AJ3 that both the enzyme action mode and optimum temperature limitation by cellulases could impact the degradation. It also gave new sight to unique advantage utilization in the industrial production of green manufacturing.
Effects of inoculation of Lactiplantibacillus plantarum and Lentilactobacillus buchneri on fermentation quality, aerobic stability, and microbial community dynamics of wilted Leymus chinensis silage
Authors: Wu Baiyila , Hu Zongfu , Wei Manlin , Yong Mei , Niu Huaxin
Published: July 2022

Leymus chinensis is an important crop that can be fed to ruminants. The purpose of this study was to investigate the roles of Lactiplantibacillus plantarum and Lentilactobacillus buchneri in fermentation quality, aerobic stability, and dynamics of wilted L. chinensis silage microorganisms. Wilted L. chinensis silages were ensiled with/without L. plantarum and L. buchneri. After 14 and 56 days of ensiling, the silos were opened and subjected to a 7-day aerobic deterioration test. This study looked at the composition of fermentation products as well as the microbial communities in silage. Silage inoculated with L. plantarum and L. buchneri had an increased lactic acid content as well as lactic acid bacterial (LAB) quantity, but a decrease in pH and levels of butyric acid, 2,3-butanediol, and ethanol was observed during ensiling. Non-treated and L. plantarum-treated silages deteriorated in the 7-day spoilage test after opening day-14 silos, whereas L. buchneri-inoculated silage showed no signs of deterioration. Lactobacillus abundance increased in the 7-day spoilage test after opening day-56 silos, while undesirable microorganisms such as Acetobacter, Bacillus, and molds, namely, Aspergillus and Penicillium were inhibited within L. plantarum- and L. buchneri-inoculated silages. The composition of fermentation products was related to the bacterial community, particularly Lactobacillus, Enterococcus, and Acetobacter. To summarize, L. plantarum- and L. buchneri-inoculated silage enhanced fermentation quality during ensiling and inhibited aerobic spoilage in a 7-day spoilage test of 56 days ensiling within wilted L. chinensis silage.
A novel of new class II bacteriocin from Bacillus velezensis HN-Q-8 and its antibacterial activity on Streptomyces scabies
Authors: Zhao Jing , Zhou Zhijun , Bai Xuefei , Zhang Dai , Zhang Likui , Wang Jinhui , Wu Beibei , Zhu Jiehua , Yang Zhihui
Published: July 2022

Potato common scab is a main soil-borne disease of potato that can significantly reduce its quality. At present, it is still a challenge to control potato common scab in the field. To address this problem, the 972 family lactococcin (Lcn972) was screened from Bacillus velezensis HN-Q-8 in this study, and an Escherichia coli overexpression system was used to obtain Lcn972, which showed a significant inhibitory effect on Streptomyces scabies, with a minimum inhibitory concentration of 10.58 μg/mL. The stability test showed that Lcn972 is stable against UV radiation and high temperature. In addition, long-term storage at room temperature and 4°C had limited effects on its activity level. The antibacterial activity of Lcn972 was enhanced by Cu2+ and Ca2+, but decreased by protease K. The protein was completely inactivated by Fe2+. Cell membrane staining showed that Lcn972 damaged the cell membrane integrity of S. scabies. Scanning electron microscope (SEM) and transmission electron microscope (TEM) observations revealed that the hyphae of S. scabies treated with Lcn972 were deformed and adhered, the cell membrane was incomplete, the cytoplasm distribution was uneven, and the cell appeared hollow inside, which led to the death of S. scabies. In conclusion, we used bacteriocin for controlling potato common scab for the first time in this study, and it provides theoretical support for the further application of bacteriocin in the control of plant diseases.
Antibiofilm property and multiple action of peptide PEW300 against Pseudomonas aeruginosa
Authors: Wang Meng , Deng Zifeng , Li Yanmei , Xu Keyong , Ma Yi , Yang Shang-Tian , Wang Jufang
Published: July 2022

Pseudomonas aeruginosa (P. aeruginosa), an opportunistic pathogen, is often associated with difficulties in treating hospital-acquired infections. Biofilms formed by P. aeruginosa significantly improve its resistance to antimicrobial agents, thereby, posing a great challenge to the combat of P. aeruginosa infection. Antimicrobial peptides (AMPs) have recently emerged as promising antibiofilm agents and increasingly attracting the attention of scientists worldwide. However, current knowledge of their antibiofilm behavior is limited and their underlying mechanism remains unclear. In this study, a novel AMP, named PEW300, with three-point mutations (E9H, D17K, and T33A) from Cecropin A was used to investigate its antibiofilm property and antibiofilm pathway against P. aeruginosa. PEW300 displayed strong antibacterial and antibiofilm activity against P. aeruginosa with no significant hemolysis or cytotoxicity to mouse erythrocyte and human embryonic kidney 293 cells. Besides, the antibiofilm pathway results showed that PEW300 preferentially dispersed the mature biofilm, leading to the biofilm-encapsulated bacteria exposure and death. Meanwhile, we also found that the extracellular DNA was a critical target of PEW300 against the mature biofilm of P. aeruginosa. In addition, multiple actions of PEW300 including destroying the cell membrane integrity, inducing high levels of intracellular reactive oxygen species, and interacting with genomic DNA were adopted to exert its antibacterial activity. Moreover, PEW300 could dramatically reduce the virulence of P. aeruginosa. Taken together, PEW300 might be served as a promising antibiofilm candidate to combat P. aeruginosa biofilms.
Visualizing and Quantifying Longitudinal Changes in Verbal Fluency Using Recurrence Plots
Authors: Maboudian Samira A. , Hsu Ming , Zhang Zhihao
Published: July 2022

The verbal fluency task, where participants name as many instances of a specific semantic or phonemic category as possible in a certain time limit, is widely used to probe language and memory retrieval functions in research and clinical settings. More recently, interests in using longitudinal observations in verbal fluency to examine changes over the lifespan have grown, in part due to the increasing availability of such datasets, yet quantitative methods for comparing repeated measures of verbal fluency responses remain scarce. As a result, existing studies tend to focus only on the number of unique words produced and how this metric changes over time, overlooking changes in other important features in the data, such as the identity of the words and the order in which they are produced. Here, we provide an example of how the literature of recurrence analysis, which aims to visualize and analyze non-linear time series, may present useful visualization and analytical approaches for this problem. Drawing on this literature, we introduce a novel metric (the “distance from diagonal,” or DfD) to quantify semantic fluency data that incorporates analysis of the sequence order and changes between two lists. As a demonstration, we apply these methods to a longitudinal dataset of semantic fluency in people with Alzheimer’s disease and age-matched controls. We show that DfD differs significantly between healthy controls and Alzheimer’s disease patients, and that it complements common existing metrics in diagnostic prediction. Our visualization method also allows incorporation of other less common metrics—including the order that words are recalled, repetitions of words within a list, and out-of-category intrusions. Additionally, we show that these plots can be used to visualize and compare aggregate recall data at the group level. These methods can improve understanding of verbal fluency deficits observed in various neuropsychiatric and neurological disorders.
Associations of multiple visual rating scales based on structural magnetic resonance imaging with disease severity and cerebrospinal fluid biomarkers in patients with Alzheimer’s disease
Authors: Wan Mei-dan , Liu Hui , Liu Xi-xi , Zhang Wei-wei , Xiao Xue-wen , Zhang Si-zhe , Jiang Ya-ling , Zhou Hui , Liao Xin-xin , Zhou Ya-fang , Tang Bei-sha , Wang Jun-Ling , Guo Ji-feng , Jiao Bin , Shen Lu
Published: July 2022

The relationships between multiple visual rating scales based on structural magnetic resonance imaging (sMRI) with disease severity and cerebrospinal fluid (CSF) biomarkers in patients with Alzheimer’s disease (AD) were ambiguous. In this study, a total of 438 patients with clinically diagnosed AD were recruited. All participants underwent brain sMRI scan, and medial temporal lobe atrophy (MTA), posterior atrophy (PA), global cerebral atrophy-frontal sub-scale (GCA-F), and Fazekas rating scores were visually evaluated. Meanwhile, disease severity was assessed by neuropsychological tests such as the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating (CDR). Among them, 95 patients were tested for CSF core biomarkers, including Aβ1–42, Aβ1–40, Aβ1–42/Aβ1–40, p-tau, and t-tau. As a result, the GCA-F and Fazekas scales showed positively significant correlations with onset age (r = 0.181, p < 0.001; r = 0.411, p < 0.001, respectively). Patients with late-onset AD (LOAD) showed higher GCA-F and Fazekas scores (p < 0.001, p < 0.001). With regard to the disease duration, the MTA and GCA-F were positively correlated (r = 0.137, p < 0.05; r = 0.106, p < 0.05, respectively). In terms of disease severity, a positively significant association emerged between disease severity and the MTA, PA GCA-F, and Fazekas scores (p < 0.001, p < 0.001, p < 0.001, p < 0.05, respectively). Moreover, after adjusting for age, gender, and APOE alleles, the MTA scale contributed to moderate to severe AD in statistical significance independently by multivariate logistic regression analysis (p < 0.05). The model combining visual rating scales, age, gender, and APOE alleles showed the best performance for the prediction of moderate to severe AD significantly (AUC = 0.712, sensitivity = 51.5%, specificity = 84.6%). In addition, we observed that the MTA and Fazekas scores were associated with a lower concentration of Aβ1–42 (p < 0.031, p < 0.022, respectively). In summary, we systematically analyzed the benefits of multiple visual rating scales in predicting the clinical status of AD. The visual rating scales combined with age, gender, and APOE alleles showed best performance in predicting the severity of AD. MRI biomarkers in combination with CSF biomarkers can be used in clinical practice.