bluuebunny/crossref_metadata_2025 huggingface dataset:
On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
Authors: Meneghini Maria , Perona Anna , Crespo Elena , Bemelman Frederike , Reinke Petra , Viklicky Ondrej , Giral Magali , Palou Eduard , Torija Alba , Donadeu Laura , Melilli Edoardo , Zuñiga Jose , Sefrin Anett , Lachmann Nils , Hu Liu , Hruba Petra , Guillot-Gueguen Cécile , Brouard Sophie , Grinyo Josep , Bestard Oriol
Published: September 2022

Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor–recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA−). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA− and LR_dnDSA+/HR_dnDSA− (logRank < 0.001), and higher risk of death-censored graft loss (logRank = 0.001). Both LR_dnDSA+ (HR: 3.51, 95% CI = 1.25–9.85) and LR_dnDSA+/HR_dnDSA+ (HR: 4.09, 95% CI = 1.45–11.54), but not LR_dnDSA+/HR_dnDSA− independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes.
Cannabidiol modulates expression of type I IFN response genes and HIV infection in macrophages
Authors: Tomer Shallu , Mu Wenli , Suryawanshi Gajendra , Ng Hwee , Wang Li , Wennerberg Wally , Rezek Valerie , Martin Heather , Chen Irvin , Kitchen Scott , Zhen Anjie
Published: September 2022

Cannabis (Cannabis sativa) is a widely used drug in the United States and the frequency of cannabis use is particularly high among people living with HIV (PLWH). One key component of cannabis, the non-psychotropic (−)-cannabidiol (CBD) exerts a wide variety of biological actions, including anticonvulsive, analgesic, and anti-inflammatory effects. However, the exact mechanism of action through which CBD affects the immune cell signaling remains poorly understood. Here we report that CBD modulates type I interferon responses in human macrophages. Transcriptomics analysis shows that CBD treatment significantly attenuates cGAS-STING-mediated activation of type I Interferon response genes (ISGs) in monocytic THP-1 cells. We further showed that CBD treatment effectively attenuates 2’3-cGAMP stimulation of ISGs in both THP-1 cells and primary human macrophages. Interestingly, CBD significantly upregulates expression of autophagy receptor p62/SQSTM1. p62 is critical for autophagy-mediated degradation of stimulated STING. We observed that CBD treated THP-1 cells have elevated autophagy activity. Upon 2’3’-cGAMP stimulation, CBD treated cells have rapid downregulation of phosphorylated-STING, leading to attenuated expression of ISGs. The CBD attenuation of ISGs is reduced in autophagy deficient THP-1 cells, suggesting that the effects of CBD on ISGs is partially mediated by autophagy induction. Lastly, CBD decreases ISGs expression upon HIV infection in THP-1 cells and human primary macrophages, leading to increased HIV RNA expression 24 hours after infection. However, long term culture with CBD in infected primary macrophages reduced HIV viral spread, suggesting potential dichotomous roles of CBD in HIV replication. Our study highlights the immune modulatory effects of CBD and the needs for additional studies on its effect on viral infection and inflammation.
Explainable artificial intelligence for precision medicine in acute myeloid leukemia
Authors: Gimeno Marian , San José-Enériz Edurne , Villar Sara , Agirre Xabier , Prosper Felipe , Rubio Angel , Carazo Fernando
Published: September 2022

Artificial intelligence (AI) can unveil novel personalized treatments based on drug screening and whole-exome sequencing experiments (WES). However, the concept of “black box” in AI limits the potential of this approach to be translated into the clinical practice. In contrast, explainable AI (XAI) focuses on making AI results understandable to humans. Here, we present a novel XAI method -called multi-dimensional module optimization (MOM)- that associates drug screening with genetic events, while guaranteeing that predictions are interpretable and robust. We applied MOM to an acute myeloid leukemia (AML) cohort of 319 ex-vivo tumor samples with 122 screened drugs and WES. MOM returned a therapeutic strategy based on the FLT3, CBFβ-MYH11, and NRAS status, which predicted AML patient response to Quizartinib, Trametinib, Selumetinib, and Crizotinib. We successfully validated the results in three different large-scale screening experiments. We believe that XAI will help healthcare providers and drug regulators better understand AI medical decisions.
Identification and validation of ferroptosis-related lncRNA signature as a prognostic model for skin cutaneous melanoma
Authors: Guo Sen , Chen Jianru , Yi Xiuli , Lu Zifan , Guo Weinan
Published: September 2022

Background

Melanoma is a type of skin cancer, which originates from the malignant transformation of epidermal melanocytes, with extremely high lethality. Ferroptosis has been documented to be highly related to cancer pathogenesis and the effect of immunotherapy. In addition, the dysregulation of lncRNAs is greatly implicated in melanoma progression and ferroptosis regulation. However, the significance of ferroptosis-related lncRNA in melanoma treatment and the prognosis of melanoma patients remains elusive.

Methods

Via Least Absolute Shrinkage Selection Operator (LASSO) regression analysis in the TCGA SKCM database, a cutaneous melanoma risk model was established based on differentially-expressed ferroptosis-related lncRNAs (DEfrlncRNAs). The nomogram, receiver operating characteristic (ROC) curves, and calibration plots were conducted to examine the predictive performance of this model. Sequentially, we continued to analyze the differences between the high- and low-risk groups, in terms of clinical characteristics, immune cell infiltration, immune-related functions, and chemotherapy drug sensitivity. Moreover, the expressions of DEfrlncRNAs, PD-L1, and CD8 were also examined by qRT-PCR and immunohistochemical staining in melanoma tissues to further confirm the potential clinical implication of DEfrlncRNAs in melanoma immunotherapy.

Results

16 DEfrlncRNAs were identified, and a representative risk score for patient survival was constructed based on these 16 genes. The risk score was found to be an independent prognostic factor for the survival of melanoma patients. In addition, the low-risk group of patients had higher immune cell infiltration in the melanoma lesions, higher sensitivity to chemotherapeutic agents, and a better survival prognosis. Besides, the high expression of the identified 5 DEfrlncRNA in the low-risk group might suggest a higher possibility to benefit from immune checkpoint blockade therapy in the treatment of melanoma.

Conclusion

The DEfrlncRNA risk prediction model related to ferroptosis genes can independently predict the prognosis of patients with melanoma and provide a basis for evaluating the response of clinical treatment in melanoma.
Assessment of plasma Catestatin in COVID-19 reveals a hitherto unknown inflammatory activity with impact on morbidity-mortality
Authors: Schneider Francis , Le Borgne Pierrick , Herbrecht Jean-Etienne , Danion François , Solis Morgane , Hellé Sophie , Betscha Cosette , Clere-Jehl Raphaël , Lefebvre François , Castelain Vincent , Goumon Yannick , Metz-Boutigue Marie-Hélène
Published: September 2022

Introduction

Neuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity.

Patients & Methods

Admission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves).

Results

Among COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or (COVID-ICU+, patients n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p<0.03), with no difference between COVID+ and COVID-ICU+. There was no difference between groups in either CgA or CST/CgA ratios, but these parameters were lower in healthy controls (p<0.01). CST did not correlate with either hypoxia- or usual inflammation-related parameters. In-hospital mortality was similar whether COVID+ or not, but COVID+ had longer oxygen support and more complications (p<0.03). CST concentrations and the CST/CgA ratio were associated with in-hospital mortality (p<0.01) in COVID+, whereas CgA was not. CgA correlated with care-related infections (p<0.001).

Conclusion

Respiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections.
Independent value of serum β-human chorionic gonadotropin in predicting early pregnancy loss risks in IVF/ICSI cycles
Authors: Wang Liyan , Jiang Yanbiao , Shen Haofei , Ma Xiaoling , Gao Mingxia , Jin Panpan , Zhang Rui , Zhao Lihui , Zhang Xuehong
Published: September 2022

Background

Early pregnancy loss (EPL) is the most prevalent complication, particularly in couples undergoing assisted reproductive technology treatment. The present study aimed to determine whether the serum β-human chorionic gonadotropin (β-hCG) level after 14 days of embryo transfer, either alone or in conjunction with other parameters in IVF/ICSI cycles, could be used to predict subsequent EPL.

Methods

This was a retrospective cohort study of all couples who received clinical pregnancy and underwent fresh IVF/ICSI cycles at a single large reproductive medical center between January 2013 and June 2020. The research involved a total of 6600 cycles. For risk variables, we conducted the least absolute shrinkage and selection operator (LASSO) analysis, and for risk scoring, we used logistic regression coefficients. To analyze relevant risk factors for EPL, univariate and multivariate logistic regression analyses were employed. Areas under the curve (AUC) were determined and compared between β-hCG and other factors using receiver operating characteristic (ROC) curves.

Results

β-hCG level was considerably lower in women who had EPL than in those who were ongoing pregnancy (564.03 ± 838.16 vs 1139.04 ± 1048.72 IU/L, p< 0.001). Univariable and multivariable logistic regression revealed that β-hCG levels were significantly correlated with the probability of EPL, independent of other risk factors. More importantly, the β-hCG level could independently predict the occurrence of EPL and was comparable to the model that combined other risk factors. The optimal serum β-hCG cut-off value for predicting EPL was 542.45 IU/L.

Conclusions

Our results suggest that the serum β-hCG level has a strong independent predictive value for EPL occurrence in fresh IVF/ICSI cycles.
Rebirth of a reef: As-built description and rapid returns from the Palos Verdes Reef Restoration Project
Authors: Williams Jonathan P. , Williams Chelsea M. , Pondella Daniel J. , Scholz Zoe M.
Published: September 2022

Palos Verdes Reef (PVR) is an artificial reef designed to restore rocky-reef associated marine species by directly restoring rocky-reef habitat that has been impacted by scour, sedimentation, and burial in the shallow subtidal portion of the Palos Verdes Peninsula in Los Angeles County, California, USA. The restoration reef provides high-quality habitat that is contiguous with the natural reef and allows for rapid succession. This project is a unique endeavor as restoring lost habitat in situ and has not been attempted in a temperate rocky reef and kelp forest community. While the primary design criteria for PVR is fish production in an area where already-limited hard substrate had been lost, it is also designed to be resilient to ongoing sedimentation and turbidity challenges on the peninsula. Following over a decade of design, planning, outreach, site surveying, and permitting, PVR was built in 2020 as 18 discrete modules using 52,729 tons of quarry rock placed approximately 8–80 m from existing, unburied rocky-reef habitat. There was no significant accumulation or scouring of sediment due to the placement of the reef and temperature data shows that internal tides regularly inundate the reef with cool, nutrient rich water. Rocky-reef associated taxa rapidly recruited to the restoration site, with visible changes occurring within just a few months post-construction. PVR modules showed rapid, significantly positive responses in fish density, fish biomass, kelp density, and biotic benthic cover less than 18 months after reef placement with a general pattern of succession in giant kelp growth from nearshore to offshore resulting in an established, thick canopy, in the nearshore, shallow modules. The newly available, high-quality habitat was quickly colonized and already shows late successional patterns with respect to fish and benthic communities. This restoration reef will produce large amounts of biomass over the long-term, though future surveys of multiple restored, adjacent, and reference sites will determine if high biomass at PVR is a result of new secondary production or attraction from nearby reefs.
Origin of dissolved organic carbon under phosphorus-limited coastal-bay conditions revealed by fluorescent dissolved organic matter
Authors: Kim Jeonghyun , Song Byung-Chan , Kim Tae-Hoon
Published: September 2022

To determine the origins of dissolved organic carbon (DOC) in a bay of volcanic Jeju Island, where the discharge of fresh groundwater (FGW) is dominant, we measured fluorescent dissolved organic matter (FDOM) and implemented a parallel factor analysis (PARAFAC). The PARAFAC model identified three humic-like components (FDOMH) and one protein-like component (FDOMP). DOC was extremely deficient in the FGW (35 ± 13 μM) and positively correlated with salinity in the coastal environment, indicating oceanic DOC contribution. The FDOMP pattern was similar to that of DOC, suggesting that marine biological production is a primary DOC source in this region. Particularly, significant FDOMP correlations in the coastal waters with the fluxes of dissolved inorganic phosphorus (DIP; R2 = 0.31) and dissolved silicon (R2 = 0.46) from the FGW demonstrated that in situ biological production is facilitated by FGW-borne nutrient addition. However, the absence of a correlation between the fluxes of dissolved inorganic nitrogen (DIN) and FDOMP (R2 <0.01) indicated that anthropogenic DIN is not essential for DOC production under the P-limited nutrient conditions and diatom-dominant conditions prevailing on the coastal Jeju Island. Here, we calculated the potential capacity of carbon fixation by marine biological activity based on the Redfield ratio of carbon and phosphorus with DIP fluxes. The flux accounts for approximately 2% of the terrestrial carbon uptake in South Korea. Therefore, optical properties of FDOM may be good indicators of coastal DOC origin, and nutrient speciation may be linked to the carbon cycle.
Identification of diagnostic gene biomarkers and immune infiltration in patients with diabetic kidney disease using machine learning strategies and bioinformatic analysis
Authors: Fu Shaojie , Cheng Yanli , Wang Xueyao , Huang Jingda , Su Sensen , Wu Hao , Yu Jinyu , Xu Zhonggao
Published: September 2022

Objective

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early diagnosis is critical to prevent its progression. The aim of this study was to identify potential diagnostic biomarkers for DKD, illustrate the biological processes related to the biomarkers and investigate the relationship between them and immune cell infiltration.

Materials and methods

Gene expression profiles (GSE30528, GSE96804, and GSE99339) for samples obtained from DKD and controls were downloaded from the Gene Expression Omnibus database as a training set, and the gene expression profiles (GSE47185 and GSE30122) were downloaded as a validation set. Differentially expressed genes (DEGs) were identified using the training set, and functional correlation analyses were performed. The least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forests (RF) were performed to identify potential diagnostic biomarkers. To evaluate the diagnostic efficacy of these potential biomarkers, receiver operating characteristic (ROC) curves were plotted separately for the training and validation sets, and immunohistochemical (IHC) staining for biomarkers was performed in the DKD and control kidney tissues. In addition, the CIBERSORT, XCELL and TIMER algorithms were employed to assess the infiltration of immune cells in DKD, and the relationships between the biomarkers and infiltrating immune cells were also investigated.

Results

A total of 95 DEGs were identified. Using three machine learning algorithms, DUSP1 and PRKAR2B were identified as potential biomarker genes for the diagnosis of DKD. The diagnostic efficacy of DUSP1 and PRKAR2B was assessed using the areas under the curves in the ROC analysis of the training set (0.945 and 0.932, respectively) and validation set (0.789 and 0.709, respectively). IHC staining suggested that the expression levels of DUSP1 and PRKAR2B were significantly lower in DKD patients compared to normal. Immune cell infiltration analysis showed that B memory cells, gamma delta T cells, macrophages, and neutrophils may be involved in the development of DKD. Furthermore, both of the candidate genes are associated with these immune cell subtypes to varying extents.

Conclusion

DUSP1 and PRKAR2B are potential diagnostic markers of DKD, and they are closely associated with immune cell infiltration.
Dropout from a maternal and newborn continuum of care after antenatal care booking and its associated factors in Debre Berhan town, northeast Ethiopia
Authors: Tadese Mesfin , Tessema Saba Desta , Aklilu Dawit , Wake Getu Engida , Mulu Getaneh Baye
Published: September 2022

Background

Continuum of care (CoC) is the continuity of care from the beginning of pregnancy to the postnatal period to improve maternal, neonatal, and child health. Dropout from the maternal CoC remains a public health challenge in Ethiopia. There are limited studies on women who dropped out of the CoC. The available studies have focused on the time dimension of the CoC, and there is a paucity of data on the place dimension of the CoC. Thus, this study aimed to determine the prevalence of dropout from the maternal CoC and its associated factors in Debre Berhan town, northeast Ethiopia.

Methods

A community-based cross-sectional study design was conducted among 842 mothers from September to October 2020. A cluster sampling technique was applied, and data were collected through face-to-face interviews using a structured and pre-tested questionnaire. Data were cleaned and entered into EpiData version 4.6 and exported to SPSS version 25 for analysis. Descriptive statistics, and bivariable and multivariable logistic regression analyses were performed to summarize the findings, and a p-value of <0.05 was considered statistically significant.

Result

The overall prevalence of dropout from the maternity continuum of care was 69.1% [95% CI (66.0–72.3)]. The prevalence of dropout from ANC, skilled birth attendant, and PNC visits was 45.4, 0.5, and 48.7%, respectively. Rural residents, partners' level of education, monthly income, the timing of the first ANC visit, antenatal counseling about a continuum of care, and the level of satisfaction with the service delivery were significantly associated with ANC dropout. Maternal age and occupation, partners' age, media exposure, parity, the timing of the first ANC visit, the place of ANC visit, and the time spent for an ANC visit were significantly associated with dropout from PNC visits. Husbands' occupation, monthly income, number of alive children, the timing of the first ANC visit, and the time spent for an ANC visit had a statistically significant association with dropout from the maternity CoC.

Conclusion

Dropout from the CoC in the study area was high. Socioeconomic development, partner involvement, antenatal counseling, efficient service delivery, and media exposure are vital to improving the high dropout rate from the maternal continuum of care.
Timing of glaucoma treatment in patients with MICOF: A retrospective clinical study
Authors: Li Zhao , Wang Qun , Zhang Shi-Feng , Huang Yi-Fei , Wang Li-Qiang
Published: September 2022

Purpose

To summarize and discuss the treatment and timing of glaucoma in patients with MICOF keratoprosthesis implantation to guide follow-up clinical treatment.

Methods

The data of 39 eyes (39 patients) with the Moscow Eye Microsurgery Complex in Russia (MICOF) keratoprosthesis implantation in our hospital from 1 January 2002 to 31 December 2017 were collected, including patients with preexisting glaucoma and those who developed glaucoma de novo after MICOF. The sex, age, preoperative diagnosis, glaucoma surgery, keratoplasty, times of keratoplasty, best corrected visual acuity (BCVA) and final follow-up corrected visual acuity, visual field (VF) defect, and cup-to-disk ratio (CDR) were statistically analyzed.

Results

Among 16 eyes with preexisting glaucoma, eight eyes underwent glaucoma surgery before MICOF, 4 eyes underwent glaucoma surgery combined with MICOF, and four eyes were managed medically. Among 23 eyes with de novo glaucoma, seven eyes were treated with surgery and 16 eyes were treated with medication only. A total of 9 (56.3%) eyes had corneal transplants with preexisting glaucoma, which was a higher percentage than that in the patients with de novo glaucoma (n = 5, 21.7%, P = 0.043). In both the preexisting glaucoma group and the de novo glaucoma group, the most common causes were alkali burns (56.3% of preexisting glaucoma and 43.5% of de novo glaucoma). There was no significant difference between the operation and initial visual acuity, postoperative visual acuity, BCVA, CDR, or VF defect. In the de novo glaucoma group, the final follow-up visual acuity of the glaucoma surgery group (1.56 ± 1.07) was worse than that of the mediation group (0.44 ± 0.53) (P < 0.017). Among the complications, the incidence of cornea melting in the patients treated with medications only (n=10) was significantly higher than that in the patients treated with glaucoma surgery (n = 0, P = 0.007), but there was no significant difference in the other complications.

Conclusion

Among patients with MICOF, those patients who have undergone keratoplasty are more likely to develop glaucoma before surgery and glaucoma needs to be prevented. Surgical treatment can be selected according to the ocular surface condition in the patients with de novo glaucoma to reduce the occurrence of complications.
Comparison of assembly process and co-occurrence pattern between planktonic and benthic microbial communities in the Bohai Sea
Authors: Liu Jinmei , Wang Xiaolei , Liu Jiao , Liu Xiaoyue , Zhang Xiao-Hua , Liu Jiwen
Published: September 2022

Unraveling the mechanisms structuring microbial community is a central goal in microbial ecology, but a detailed understanding of how community assembly processes relate to living habitats is still lacking. Here, via 16S rRNA gene amplicon sequencing, we investigated the assembly process of microbial communities in different habitats [water verse sediment, free-living (FL) verse particle-associated (PA)] and their impacts on the inter-taxa association patterns in the coastal Bohai Sea, China. The results showed clear differences in the composition and diversity of microbial communities among habitats, with greater dissimilarities between water column and sediment than between FL and PA communities. The microbial community assembly was dominated by dispersal limitation, ecological drift, and homogeneous selection, but their relative importance varied in different habitats. The planktonic communities were mainly shaped by dispersal limitation and ecological drift, whereas homogeneous selection played a more important role in structuring the benthic communities. Furthermore, the assembly mechanisms differed between FL and PA communities, especially in the bottom water with a greater effect of ecological drift and dispersal limitation on the FL and PA fractions, respectively. Linking assembly process to co-occurrence pattern showed that the relative contribution of deterministic processes (mainly homogeneous selection) increased under closer co-occurrence relationships. By contrast, stochastic processes exerted a higher effect when there were less inter-taxa connections. Overall, our findings demonstrate contrasting ecological processes underpinning microbial community distribution in different habitats including different lifestyles, which indicate complex microbial dynamic patterns in coastal systems with high anthropogenic perturbations.
Hydrophobic cell surface display system of PETase as a sustainable biocatalyst for PET degradation
Authors: Jia Yunpu , Samak Nadia A. , Hao Xuemi , Chen Zheng , Wen Qifeng , Xing Jianmin
Published: September 2022

Remarkably, a hydrolase from Ideonella sakaiensis 201-F6, termed PETase, exhibits great potential in polyethylene terephthalate (PET) waste management due to it can efficiently degrade PET under moderate conditions. However, its low yield and poor accessibility to bulky substrates hamper its further industrial application. Herein a multigene fusion strategy is introduced for constructing a hydrophobic cell surface display (HCSD) system in Escherichia coli as a robust, recyclable, and sustainable whole-cell catalyst. The truncated outer membrane hybrid protein FadL exposed the PETase and hydrophobic protein HFBII on the surface of E. coli with efficient PET accessibility and degradation performance. E. coli containing the HCSD system changed the surface tension of the bacterial solution, resulting in a smaller contact angle (83.9 ± 2° vs. 58.5 ± 1°) of the system on the PET surface, thus giving a better opportunity for PETase to interact with PET. Furthermore, pretreatment of PET with HCSD showed rougher surfaces with greater hydrophilicity (water contact angle of 68.4 ± 1° vs. 106.1 ± 2°) than the non-pretreated ones. Moreover, the HCSD system showed excellent sustainable degradation performance for PET bottles with a higher degradation rate than free PETase. The HCSD degradation system also had excellent stability, maintaining 73% of its initial activity after 7 days of incubation at 40°C and retaining 70% activity after seven cycles. This study indicates that the HCSD system could be used as a novel catalyst for efficiently accelerating PET biodegradation.
Concepts and conjectures concerning predatory performance of myxobacteria
Authors: Phillips Kayleigh E. , Akbar Shukria , Stevens D. Cole
Published: September 2022

Myxobacteria are excellent model organisms for investigation of predator–prey interactions and predatory shaping of microbial communities. This review covers interdisciplinary topics related to myxobacterial predation and provides current concepts and challenges for determining predatory performance. Discussed topics include the role of specialized metabolites during predation, genetic determinants for predatory performance, challenges associated with methodological differences, discrepancies between sequenced and environmental myxobacteria, and factors that influence predation.
Taxol and β-tubulins from endophytic fungi isolated from the Himalayan Yew, Taxus wallichiana Zucc.
Authors: Vélëz Heriberto , Gauchan Dhurva Prasad , García-Gil María del Rosario
Published: September 2022

Paclitaxel, better known as the anticancer drug Taxol®, has been isolated from several plant species and has been shown to be produced by fungi, actinomycetes, and even bacteria isolated from marine macroalgae. Given its cytostatic effect, studies conducted in the 1990's showed that paclitaxel was toxic to many pathogenic fungi and oomycetes. Further studies led to the idea that the differences in paclitaxel sensitivity exhibited by different fungi were due to differences in the β-tubulin protein sequence. With the recent isolation of endophytic fungi from the leaves and bark of the Himalayan Yew, Taxus wallichiana Zucc., and the availability of genomes from paclitaxel-producing fungi, we decided to further explore the idea that endophytic fungi isolated from Yews should be well-adapted to their environment by encoding β-tubulin proteins that are insensitive to paclitaxel. Our results found evidence of episodic positive/diversifying selection at 10 sites (default p-value threshold of 0.1) in the β-tubulin sequences, corresponding to codon positions 33, 55, 172, 218, 279, 335, 359, 362, 379, and 406. Four of these positions (i.e., 172, 279, 359, and 362) have been implicated in the binding of paclitaxel by β-tubulin or formed part of the binding pocket. As expected, all the fungal endophytes grew in different media regardless of the paclitaxel concentration tested. Furthermore, our results also showed that Taxomyces andreanae CBS 279.92, the first fungus shown to produce paclitaxel, is a Basidiomycete fungus as the two beta tubulins encoded by the fungus clustered together with other Basidiomycete fungi.
Potential of plant growth promoting bacterial consortium for improving the growth and yield of wheat under saline conditions
Authors: Khan Muhammad Yahya , Nadeem Sajid Mahmood , Sohaib Muhammad , Waqas Muhammad Rashid , Alotaibi Fahad , Ali Liaqat , Zahir Zahir Ahmad , Al-Barakah Fahad N. I.
Published: September 2022

Owing to inconsistent results of a single bacterial strain, co-inoculation of more than one strain under salinity stress could be a more effective strategy to induce salt tolerance. Co-inoculation of more than one bacterial strain could be more effective due to the presence of several growths promoting traits. This study was conducted to evaluate the effectiveness of multi-strains bacterial consortium to promote wheat growth under salinity stress. Several plant growth promoting rhizobacteria (PGPR) had been isolated and tested for their ability to grow in increasing concentrations of sodium chloride (NaCl). Those rhizobacterial strains having tolerance against salinity were screened to evaluate their ability to promote wheat growth in the presence of salinity by conducting jar trials under axenic conditions. The rhizobacteria with promising results were tested for their compatibility with each other before developing multi-strain inoculum of PGPR. The compatible PGPR strains were characterized, and multi-strain inoculum was then evaluated for promoting wheat growth under axenic conditions at different salinity levels, i.e., 2.1 (normal soil), 6, 12, and 18 dS m–1. The most promising combination was further evaluated by conducting a pot trial in the greenhouse. The results showed that compared to a single rhizobacterial strain, better growth-promoting effect was observed when rhizobacterial strains were co-inoculated. The multi-strain consortium of PGPR caused a significant positive impact on shoot length, root length, shoot fresh weight, and root fresh weight of wheat at the highest salinity level in the jar as well as in the pot trial. Results showed that the multi-strain consortium of PGPR caused significant positive effects on the biochemical traits of wheat by decreasing electrolyte leakage and increasing chlorophyll contents, relative water contents (RWC), and K/Na ratio. It can be concluded that a multi-strain consortium of PGPR (Ensifer adhaerens strain BK-30, Pseudomonas fluorescens strain SN5, and Bacillus megaterium strain SN15) could be more effective to combat the salinity stress owing to the presence of a variety of growth-promoting traits. However, further work is going on to evaluate the efficacy of multi-strain inoculum of PGPR under salt-affected field conditions.
Staphylococcus aureus is able to generate resistance to novel lipoglycopeptide antibiotic gausemycin A
Authors: Poshvina Darya V. , Dilbaryan Diana S. , Kasyanov Sergey P. , Sadykova Vera S. , Lapchinskaya Olda A. , Rogozhin Eugene A. , Vasilchenko Alexey S.
Published: September 2022

Gausemycin A is the first member of the novel lipoglycopeptides family produced by Streptomyces roseoflavus INA-Ac-5812. Gausemycin A has a pronounced bactericidal activity against methicillin-resistant Staphylococcus aureus. However, the ability of S. aureus to be resistant to gausemycin A has not been investigated yet. Using serial passaging, we have obtained the resistant variant S. aureus 5812R, which is 80 times more resistant compared to the parent strain. Susceptibility testing of S. aureus 5812R revealed the acquisition of cross-resistance to daptomycin, cefazolin, tetracycline, and gentamicin, while the resistance to vancomycin, nisin, and ramoplanin was absent. Whole genome sequencing revealed single nucleotide polymorphism (SNP) and deletions in S. aureus 5812R, among which are genes encoding efflux pump (sepA), the two-component Kdp system (kdpE), and the component of isoprenoid biosynthesis pathway (hepT). Phenotypically, S. aureus 5812R resembles a small-colony variant, as it is slow-growing, forms small colonies, and is deficient in pigments. Profiling of fatty acids (FA) composition constituting the cytoplasmic membrane of S. aureus 5812R revealed the prevalence of anteiso-branched FA, while straight FA was slightly less present. The evidence also showed that the gausemycin A-resistant strain has increased expression of the cls2 gene of the cardiolipin synthase. The performed checkerboard assay pointed out that the combination of gausemycin A and ciprofloxacin showed a synergistic effect against S. aureus 5812R.
PUP-IT2 as an alternative strategy for PUP-IT proximity labeling
Authors: Yue Suyu , Xu Peng , Cao Zhihe , Zhuang Min
Published: September 2022

PUP-IT is a proximity labeling method based on the prokaryotic enzyme PafA. PafA mediates the ligation of Pup, a small peptide, to the proximal proteins. It is different from other proximity labeling methods, such as BioID and APEX, in that both the enzyme and the labeling tag are proteins, which allows for potential in vivo applications. All proximity labeling involves the genetic fusion of the proximity labeling enzyme with the bait protein. However, PafA is a 55 kDa enzyme which sometimes interferes with the bait function. In this study, we tested an alternative proximity labeling strategy, PUP-IT2, in which only a small 7 kDa protein is fused to the bait protein. We examined the activity of PUP-IT2 in vitro and in cells. We also compared it with the original PUP-IT. Finally, we applied PUP-IT2 coupled mass spectrometry to map protein-protein interactions. Overall, we established a new way to use PUP-IT2 for proximity labeling, and this method may have a broad application.
Two novel bombesin-like neuropeptides from the skin secretion of Pelophylax kl. esculentus: Ex vivo pharmacological characterization on rat smooth muscle types
Authors: Zhang Luyao , Chen Chen , Zou Wanchen , Chen Xiaoling , Zhou Mei , Ma Chengbang , Xi Xinping , Chen Tianbao , Shaw Chris , Liu Mingchun , Wang Lei
Published: September 2022

Mammalian bombesin-like neuropeptides (BLPs) play an important role in regulation of physiological and pathophysiological processes. Frog skin-derived BLPs, of smaller size and diverse lengths and sequences at their N-terminus, have attracted the attention of many researchers. However, these N-terminal variants and the receptors modulating their pharmacological actions are poorly studied and less understood. In this study, two BLPs, namely, [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin with primary structures NLGKQWATGHFM and NLGKQWAVGHFM were isolated from the skin secretion of hybrid Pelophylax kl. esculentus. Both BLPs share a similar primary structure with only a single amino acid substitution at the eighth position (threonine to valine), while they have quite different myotropic potencies with EC50 values in the range of 22.64 ± 9.7 nM (N = 8) to 83.93 ± 46.9 nM (N = 8). The potency of [Asn3, Lys6, Thr10, Phe13]3–14-bombesin was approximately 3-fold higher than that of [Asn3, Lys6, Phe13]3–14-bombesin. Through the investigation of receptor selectivity using a canonical bombesin receptor antagonist, it was found that [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin had an affinity to both BB1 and BB2 receptors. Their contractile functions are mainly modulated by both BB1 and BB2 receptors on rat urinary bladder and BB2 alone on rat uterus smooth muscle preparations. These data may provide new insights into the design of potent and selective ligands for bombesin receptors. Moreover, [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin did not induce significant hemolysis and toxicity in normal human cells, suggesting that these two natural novel BLPs have great potential for development into new drug candidates.
Gender difference in association between H-type hypertension and subcortical ischemic vascular disease
Authors: Wang Juan , Xi Yuan-Xue , Li Jia-Qi , Zhu Wei-Wen
Published: September 2022

Background

Subcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.

Materials and methods

A total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.

Results

For males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.

Conclusion

H-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.
Association between descending pain modulatory system and cognitive impairment in fibromyalgia: A cross-sectional exploratory study
Authors: Serrano Paul Vicuña , Zortea Maxciel , Alves Rael Lopes , Beltran Gerardo , Deliberali Cibely Bavaresco , Maule Amanda , Torres Iraci L. S. , Fregni Felipe , Caumo Wolnei
Published: September 2022

Background

The successful regulation of sensory input to the central nervous system depends on the descending pain modulatory system (DPMS). For the effective regulation of sensory input to the central nervous system and behavioral responses to pain, the DPMS is required. Its connection to fibromyalgia (FM)-related cognitive dysfunction has not yet been investigated. Therefore, this study tested whether measures of verbal fluency, sustained attention, and short-term and working memory could distinguish FM patients from healthy controls (HC). Additionally, it investigated, using a standardized paradigm, the link between cognitive ability and the function of the DPMS in responders and non-responders to the conditioned pain modulation test (CPM-test).

Materials and methods

We enrolled 21 HC women and 69 FM patients, all of whom ranged in age from 30 to 65. We employed scores from the Trail Making Test (TMTB-A) (sustained and divided attention), the Controlled Oral Word Association Test (COWAT) (orthographic and semantic fluency), and the Digits subtest of the Wechsler Adult Intelligence Scale (WAIS-III) as dependent variables.

Results

A generalized linear model (GLM) adjusted by educational level revealed significantly lower scores in FM than HC on the Span digits forward, COWAT-orthographic, and TMTB-A. For FM patients, multilevel MANCOVA revealed that the cognitive performance of non-responders compared to responders to CPM-test showed lower adjusted scores in Span digits forward (Partial-η2 = 0.358, P = 0.001), Span digits backward (Partial-η2 = 0.358, P = 0.001), COWAT-orthographic (Partial-η2 = 0.551, P = 0.001), COWAR-semantic (Partial-η2 = 0.355, P = 0.001), and TMTB-A (Partial-η2 = 0.360, P = 0.001). The association between the cognitive tests and the DPMS is moderated by the serum level of brain-derived neurotrophic factor (BDNF). Additionally, these cognitive assessments had a positive correlation with antidepressant use and pain threshold. The cognitive assessments, on the other hand, were conversely associated with a life of quality.

Conclusion

Based on these findings, it can be shown that HC performed substantially better on cognitive exams than FM did. They demonstrated a link between clinical complaints about attention and memory and decreased DPMS effectiveness. Additionally, they demonstrated that the BDNF is a moderating element in a potential relationship between the severity of cognitive impairment and DPMS dysfunction.
Efficient recognition of dynamic user emotions based on deep neural networks
Authors: Zheng Qi
Published: September 2022

The key issue at this stage is how to mine the large amount of valuable user sentiment information from the massive amount of web text and create a suitable dynamic user text sentiment analysis technique. Hence, this study offers a writing feature abstraction process based on ON-LSTM and attention mechanism to address the problem that syntactic information is ignored in emotional text feature extraction. The study found that the Att-ON-LSTM improved the micro-average F1 value by 2.27% and the macro-average F value by 1.7% compared to the Bi-LSTM model with the added attentivity mechanisms. It is demonstrated that it can perform better extraction of semantic information and hierarchical structure information in emotional text and obtain more comprehensive emotional text features. In addition, the ON-LSTM-LS, a sentiment analysis model based on ON-LSTM and tag semantics, is planned to address the problem that tag semantics is ignored in the process of text sentiment analysis. The experimental consequences exposed that the accuracy of the ON-LSTM and labeled semantic sentiment analysis model on the test set is improved by 0.78% with the addition of labeled word directions compared to the model Att-ON-LSTM without the addition of labeled semantic information. The macro-averaged F1 value improved by 1.04%, which indicates that the sentiment analysis process based on ON-LSTM and tag semantics can effectively perform the text sentiment analysis task and improve the sentiment classification effect to some extent. In conclusion, deep learning models for dynamic user sentiment analysis possess high application capabilities.
Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries
Authors: Tian Mi , Mao Lei , Zhang Li
Published: September 2022

Central nervous system (CNS) injuries, including traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and ischemic stroke, are the most common cause of death and disability around the world. As the most common modification on ribonucleic acids (RNAs), N6-methyladenosine (m6A) modification has recently attracted great attentions due to its functions in determining the fate of RNAs through changes in splicing, translation, degradation and stability. A large number of studies have suggested that m6A modification played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that m6A modification could improve neurological impairment, inhibit apoptosis, suppress inflammation, reduce pyroptosis and attenuate ferroptosis in CNS injuries via different molecules including phosphatase and tensin homolog (PTEN), NLR family pyrin domain containing 3 (NLRP3), B-cell lymphoma 2 (Bcl-2), glutathione peroxidase 4 (GPX4), and long non-coding RNA (lncRNA). Therefore, m6A modification showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the role of m6A modification in CNS injuries. Hence, on the basis of these properties and effects, m6A modification may be developed as therapeutic agents for CNS injury patients.