bluuebunny/crossref_metadata_2025 huggingface dataset:
The development and improvement of immunodeficient mice and humanized immune system mouse models
Authors: Chen Jiaxuan , Liao Shuzhen , Xiao Zengzhi , Pan Quanren , Wang Xi , Shen Kangyuan , Wang Shuting , Yang Lawei , Guo Fengbiao , Liu Hua-feng , Pan Qingjun
Published: October 2022

Animal models play an indispensable role in the study of human diseases. However, animal models of different diseases do not fully mimic the complex internal environment of humans. Immunodeficient mice are deficient in certain genes and do not express these or show reduced expression in some of their cells, facilitating the establishment of humanized mice and simulation of the human environmentin vivo. Here, we summarize the developments in immunodeficient mice, from the initial nude mice lacking T lymphocytes to NOD/SCID rgnullmice lacking T, B, and NK cell populations. We describe existing humanized immune system mouse models based on immunodeficient mice in which human cells or tissues have been transplanted to establish a human immune system, including humanized-peripheral blood mononuclear cells (Hu-PBMCs), humanized hematopoietic stem cells (Hu-HSCs), and humanized bone marrow, liver, thymus (Hu-BLT) mouse models. The different methods for their development involve varying levels of complexity and humanization. Humanized mice are widely used in the study of various diseases to provide a transitional stage for clinical research. However, several challenges persist, including improving the efficiency of reconstructing the human B cell immune response, extending lifespan, improving the survival rate of mice to extend the observation period, and improving the development of standardized commercialized models and as well as their use. Overall, there are many opportunities and challenges in the development of humanized immune system mouse models which can provide novel strategies for understanding the mechanisms and treatments of human disease.
Feasibility of avian antibodies as prophylaxis against enterotoxigenic escherichia coli colonization
Authors: Brumfield Kyle , Seo Hyesuk , Idegwu Nnebuefe , Artman Chad , Gonyar Laura , Nataro James , Zhang Weiping , Sack David , Geyer James , Goepp Julius
Published: October 2022

Background

This research aims to evaluate the feasibility of using avian immunoglobulins (IgY) raised against adhesion factors of enterotoxigenic Escherichia coli (ETEC) as prophylaxis of diarrheal illness caused by these pathogens. ETEC requires adhesion to human intestinal epithelial cells as a primary step in establishing enteric infection. Therefore, inhibition of adhesion may prevent such infections and reduce clinical burdens of diarrheal illness.

Methods

IgY samples were prepared from eggs of hens immunized with an adhesin-tip multiepitope fusion antigen (MEFA), developed against nine adhesin tip epitopes derived from clinically relevant ETEC strains. The resulting IgY was evaluated for its ability to inhibit adhesion of ETEC to cell-surface targets. Potential impacts of anti-MEFA IgY on growth of both pathogenic and commensal E. coli isolates were also evaluated.

Results

Enzyme linked immunosorbent assay (ELISA) titers were achieved for IgY targeting each of the nine individual epitopes included in the adhesin-tip MEFA. Furthermore, anti-MEFA titers exceeding 1:219 were sustained for at least 23 weeks. All ETEC strains used in design of the adhesin-tip MEFA, and five of five clinical ETEC strains were significantly (P < 0.05) inhibited from adhesion to mammalian cells in culture.

Conclusions

These findings demonstrate that IgY targeting ETEC adhesin-tip MEFA have the potential to disrupt in vitro adherence of ETEC. A formulation containing adhesin-tip MEFA IgY can be considered a potential candidate for in vivo evaluation as prophylaxis of diarrheal diseases. Animal studies of this formulation are planned.
Evaluation of nanobody-based biologics targeting purinergic checkpoints in tumor models in vivo
Authors: Demeules Mélanie , Scarpitta Allan , Hardet Romain , Gondé Henri , Abad Catalina , Blandin Marine , Menzel Stephan , Duan Yinghui , Rissiek Björn , Magnus Tim , Mann Anna Marei , Koch-Nolte Friedrich , Adriouch Sahil
Published: October 2022

Adenosine triphosphate (ATP) represents a danger signal that accumulates in injured tissues, in inflammatory sites, and in the tumor microenvironment. ATP promotes tumor growth but also anti-tumor immune responses notably via the P2X7 receptor. ATP can also be catabolized by CD39 and CD73 ecto-enzymes into immunosuppressive adenosine. P2X7, CD39 and CD73 have attracted much interest in cancer as targets offering the potential to unleash anti-tumor immune responses. These membrane proteins represent novel purinergic checkpoints that can be targeted by small drugs or biologics. Here, we investigated nanobody-based biologics targeting mainly P2X7, but also CD73, alone or in combination therapies. Blocking P2X7 inhibited tumor growth and improved survival of mice in cancer models that express P2X7. P2X7-potentiation by a nanobody-based biologic was not effective alone to control tumor growth but enhanced tumor control and immune responses when used in combination with oxaliplatin chemotherapy. We also evaluated a bi-specific nanobody-based biologic that targets PD-L1 and CD73. This novel nanobody-based biologic exerted a potent anti-tumor effect, promoting tumor rejection and improving survival of mice in two tumor models. Hence, this study highlights the importance of purinergic checkpoints in tumor control and open new avenues for nanobody-based biologics that may be further exploited in the treatment of cancer.
Transcriptome analysis identifies LGP2 as an MDA5-mediated signaling activator following spring viremia of carp virus infection in common carp (Cyprinus carpio L.)
Authors: Liu Rongrong , Niu Yan , Qi Yue , Li Hua , Yang Guiwen , Shan Shijuan
Published: October 2022

The common carp (Cyprinus carpio L.) is an important farmed species worldwide. Mucosal-associated lymphoid tissues play an essential role in the fight against pathogen infection. Spring viremia of carp virus (SVCV) poses a serious threat to the common carp aquaculture industry. Understanding the molecular mechanisms driving mucosal immune responses to SVCV infection is critical. In this study, the mucosal tissues (gills, foregut and hindgut) were collected from normal and infected fishes for transcriptome analysis. A total of 932,378,600 clean reads were obtained, of which approximately 80% were successfully mapped to the common carp genome. 577, 1,054 and 1,014 differential expressed genes (DEGs) were identified in the gills, foregut and hindgut, respectively. A quantitative polymerase chain reaction assay indicated that the DEGs expression in the foregut following SVCV infection was consistent with the transcriptome results. Among them, two key genes of the retinoic acid-inducible gene I (RIG-I)-like receptor family, melanoma-differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) (i.e., CcMDA5 and CcLGP2), underwent further analysis. Overexpression of CcMDA5 or CcLGP2 increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3 and the expression of interferon-1 (ifn-1), myxovirus resistance (mx), viperin and interferon-stimulated gene 15 (isg15), and inhibited SVCV replication in epithelioma papulosum cyprini cells. Furthermore, CcLGP2 significantly upregulated the CcMDA5-induced ifn-1 mRNA expression and the activation of the ifn-1 promoter. Finally, confocal microscopy and coimmunoprecipitation experiments revealed that CcLGP2 colocalizes and interacts with CcMDA5 via the C-terminal regulatory domain. This study provides essential gene resources for understanding the fish immune response to SVCV infection and sheds light on the potential role of fish LGP2 in the MDA5 regulation.
Conservative oxygen therapy in critically ill and perioperative period of patients with sepsis-associated encephalopathy
Authors: Li Yun , Zhao Lina , Yu Yang , Zhang Kai , Jiang Yi , Wang Zhiwei , Xie Keliang , Yu Yonghao
Published: October 2022

Objectives

Sepsis-associated encephalopathy (SAE) patients in the intensive care unit (ICU) and perioperative period are administrated supplemental oxygen. However, the correlation between oxygenation status with SAE and the target for oxygen therapy remains unclear. This study aimed to examine the relationship between oxygen therapy and SAE patients.

Methods

Patients diagnosed with sepsis 3.0 in the intensive care unit (ICU) were enrolled. The data were collected from the Medical Information Mart for Intensive Care IV (MIMIC IV) database and the eICU Collaborative Research Database (eICU-CRD) database. The generalized additive models were adopted to estimate the oxygen therapy targets in SAE patients. The results were confirmed by multivariate Logistic, propensity score analysis, inversion probability-weighting, doubly robust model, and multivariate COX analyses. Survival was analyzed by the Kaplan-Meier method.

Results

A total of 10055 patients from eICU-CRD and 1685 from MIMIC IV were included. The incidence of SAE patients was 58.43%. The range of PaO2 (97-339) mmHg, PaO2/FiO2 (189-619), and SPO2≥93% may reduce the incidence of SAE, which were verified by multivariable Logistic regression, propensity score analysis, inversion probability-weighting, and doubly robust model estimation in MIMIC IV database and eICU database. The range of PaO2/FiO2 (189-619) and SPO2≥93% may reduce the hospital mortality of SAE were verified by multivariable COX regression.

Conclusions

SAE patients in ICU, including perioperative period, require conservative oxygen therapy. We should maintain SPO2≥93%, PaO2 (97-339) mmHg and PaO2/FiO2 (189-619) in SAE patients.
Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia
Authors: Wang Dandan , Wang Yewei , Chen Yan , Yu Lingfang , Wu Zenan , Liu Ruimei , Ren Juanjuan , Fang Xinyu , Zhang Chen
Published: October 2022

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1β, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1β, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1β, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.
Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis
Authors: Yan Jipeng , Zhao Jin , Ning Xiaoxuan , Qin Yunlong , Xing Yan , Wang Yuwei , Jia Qing , Huang Boyong , Ma Rui , Lei Changhui , Zhou Meilan , Yu Zixian , Zhang Yumeng , Guo Wei-Feng , Sun Shiren
Published: October 2022

Background

Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis.

Methods

To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis.

Results

There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis.

Conclusions

For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.
T-cell receptor signaling in Schimke immuno-osseous dysplasia is SMARCAL1-independent
Authors: Marin Ana V. , Jiménez-Reinoso Anaïs , Mazariegos Marina S. , Román-Ortiz Elena , Regueiro José R.
Published: October 2022

Schimke immuno-osseous dysplasia (SIOD) caused by mutations in SMARCAL1 is an ultra-rare disease characterized by specific facial features, skeletal dysplasia, and steroid-resistant nephrotic syndrome, which often leads to kidney failure and requires transplantation. Cellular (T-cell) deficiency, lymphopenia, and infections have been frequently reported, but whether they are due to T-cell-intrinsic defects in T-cell receptor (TCR) signaling associated with SMARCAL1 deficiency or to T-cell-extrinsic effects such as the impaired proliferation of hematopoietic precursors or T-cell-specific immunosuppression after renal transplantation remains unknown. We have explored the effects of SMARCAL1 deficiency on T-cell receptor signaling in primary and immortalized T cells from a 9-year-old SIOD patient under immunosuppression treatment when compared to healthy donors. Immortalized T cells recapitulated the SMARCAL1 deficiency of the patient, as judged by their impaired response to gamma irradiation. The results indicated that TCR-mediated signaling was normal in SIOD-derived immortalized T cells but strongly impaired in the primary T cells of the patient, although rescued with TCR-independent stimuli such as PMA + ionomycin, suggesting that SIOD-associated T-cell signaling is not intrinsically defective but rather the result of the impaired proliferation of hematopoietic precursors or of T-cell-specific immunosuppression. The lack of early thymic emigrants in our patients may support the former hypothesis.
Microglia morphophysiological diversity and its implications for the CNS
Authors: Vidal-Itriago Andrés , Radford Rowan A. W. , Aramideh Jason A. , Maurel Cindy , Scherer Natalie M. , Don Emily K. , Lee Albert , Chung Roger S. , Graeber Manuel B. , Morsch Marco
Published: October 2022

Microglia are mononuclear phagocytes of mesodermal origin that migrate to the central nervous system (CNS) during the early stages of embryonic development. After colonizing the CNS, they proliferate and remain able to self-renew throughout life, maintaining the number of microglia around 5-12% of the cells in the CNS parenchyma. They are considered to play key roles in development, homeostasis and innate immunity of the CNS. Microglia are exceptionally diverse in their morphological characteristics, actively modifying the shape of their processes and soma in response to different stimuli. This broad morphological spectrum of microglia responses is considered to be closely correlated to their diverse range of functions in health and disease. However, the morphophysiological attributes of microglia, and the structural and functional features of microglia-neuron interactions, remain largely unknown. Here, we assess the current knowledge of the diverse microglial morphologies, with a focus on the correlation between microglial shape and function. We also outline some of the current challenges, opportunities, and future directions that will help us to tackle unanswered questions about microglia, and to continue unravelling the mysteries of microglia, in all its shapes.
Spatio-temporal nonconvex penalty adaptive chirp mode decomposition for signal decomposition of cross-frequency coupled sources in seafloor dynamic engineering
Authors: Li Qing
Published: October 2022

Electromagnetic field noise and clutter generated from the motion of ocean waves are the main obstacles in the research of magnetotelluric dynamic analysis, and it is difficult to extract the crossed instantaneous frequencies (IFs) of underwater electromagnetic detected (UEMD) data due to the limited resolution of the current time-frequency techniques. To alleviate this bottleneck issue, a new spatio-temporal nonconvex penalty adaptive chirp mode decomposition (STNP-ACMD) is originally proposed for separating each mono-component individually from a complicated multi-component with severely crossed IFs or overlapped components, in this paper. Specifically, the idea of a nonconvex penalty greedy strategy is incorporated into the vanilla ACMD method by using a recursive mode extraction scheme, and the fractional-order characteristic of the observation signal is also considered. Meanwhile, the spatio-temporal matrices were constructed elaborately and then applied to capture coupling characteristics and spatio-temporal relationships among all estimated mono-components. Eventually, a high-resolution adaptive time-frequency spectrum is obtained according to the IFs and instantaneous amplitudes (IAs) of each estimated mono-component. The effectiveness and practicability of the proposed algorithm were verified via simulated scenarios and velocity dynamic data of the seafloor from the South China Sea, compared with four state-of-the-art benchmarks.
Preparation of PCU/PPy composites with self-healing and UV shielding properties
Authors: Xiong Zhengrong , Zhang Hang , Zhou Yan , Yang Yuming
Published: October 2022

Polycarbonate-based polyurethanes (PCU) are frequently used in airship envelope materials because of its outstanding mechanical performances and aging resistance. However, the surface of PCU is likely damaged during processing and operating and the emerged minuscule cracks will lead to deterioration of perfomances for airship’s envelope materials. Herein, self-healing PCU/polypyrrole nanoparticles (PPy) composites were prepared by solution blending and quick healing of specific area for PCU was realized due to the high photo-thermal conversion merit of PPy. The results show that, the mechanical properties of PCU/PPy composites can be restored to more than 80% and the gas barrier properties can also be basically repaired when irradiating the destroyed surface using near-infrared light for only 60s. In addition, the ultraviolet visible (UV-vis) shielding performance of the PCU/PPy composites was enhanced significantly and the UV-vis transmittance was less than 14% and 2% with 0.25wt% and 0.5wt% PPy, respectively. Meanwhile when 0.25wt% PPy was added, the tensile strength increased from 17.9MPa to 21.7 MPa and the elongation at break increased from 647% to 829%. Besides, the thermal decomposition temperature at 5wt% loss increased from 277.8°C to 300.7°C and 304.88°C with 0.25 wt% and 0.5 wt% PPy, respectively. The prepared composites show promising application in aerospace domain.
Stereopsis and visual acuity: Bilateral trifocal versus blended extended depth of focus and diffractive bifocal intraocular lenses
Authors: Zhu Meiyi , Fan Wei , Zhang Guangbin
Published: October 2022

Purpose

To compare stereopsis and visual acuity (VA) between bilateral implantation of trifocal intraocular lenses (IOL) and blended implantation of an extended depth of focus (EDOF) IOL with a bifocal IOL.

Methods

This is a non-randomized, prospective comparative study included 74 eyes of 37 patients who underwent phacoemulsification and bilateral implantation of AT LISA tri 839MP IOL (bilateral group; 21 patients) or blended implantation of Tecnis Symfony ZXR00 and Tecnis ZLB00 IOL (blended group; 16 patients). The primary outcomes were stereoacuity and binocular VA. The secondary outcomes were visual defocus curve, quality of life, and patient satisfaction. Follow-up was performed 3 months after the surgery.

Results

The mean near stereoacuity was 49.76 ± 22.67 and 120.63 ± 90.94 seconds of arc (arcsec) in the bilateral and blended groups, respectively (P < 0.001). Near stereoacuity was positively correlated with VA difference of two eyes (r = 0.896, P < 0.001). The mean binocular uncorrected visual acuity at 40 cm, 80 cm, 5 m, and corrected distance visual acuity at 5 m of the bilateral and blended groups was not statistically significant different. The bilateral group had better VA at a vergence from −2.5 to −4.0 D. Both groups obtained high quality of life and patient satisfaction scores.

Conclusion

The bilateral and blended groups achieved good binocular VA, quality of life, and high patient satisfaction. However, the near stereoacuity of the blended group was worse.
Effect of keratometric astigmatism on visual outcomes following small incision lenticule extraction
Authors: Liu Shengtao , Yu Lanhui , Lu Zhiyuan , Cheng Chiwen , Gu Xuejun , Liu Jingying , Zhou Xingtao
Published: October 2022

Purpose

To investigate the influence of keratometric astigmatism on visual outcomes following small incision lenticule extraction (SMILE).

Methods

Eighty eyes undergoing SMILE for myopia correction were classified into two groups based on preoperative keratometric astigmatism: low keratometric astigmatism (LA) and high keratometric astigmatism (HA) groups. Refractive outcomes, vector components, and changes in higher order aberrations (HOAs) were evaluated preoperatively and 6 months postoperatively.

Results

At the postoperative 6-month visit, no significant difference was observed in the decentered distance between the HA and LA groups (HA: 0.17 ± 0.08 mm, LA: 0.16 ± 0.08 mm, P = 0.189). No significant differences in the correction index (P = 0.481), absolute angle of error (P = 0.104), or index of success (P = 0.147) were observed between the two groups. There was no significant difference in the induction of corneal aberrations between the two groups. Furthermore, there were no significant associations between the decentered distance and the vector components of astigmatic correction or induction of higher-order aberration in the HA group (P ≥ 0.294, P ≥ 0.112) or the LA group (P ≥ 0.323, P ≥ 0.080).

Conclusions

SMILE for high keratometric astigmatism could achieve comparable treatment centration and visual quality to that of low keratometric astigmatism
Effects of nitrogen addition and root fungal inoculation on the seedling growth and rhizosphere soil microbial community of Pinus tabulaeformis
Authors: Xu Lingjie , Niu Xiaoyun , Li Xia , Zheng Yanyan , Feng Hualei , Fu Qiang , Zhou Yong
Published: October 2022

Nitrogen (N) availability is significant in different ecosystems, but the response of forest plant-microbial symbionts to global N deposition remains largely unexplored. In this study, the effects of different N concentration levels on four types of fungi, Suillus granulatus (Sg), Pisolithus tinctorius (Pt), Pleotrichocladium opacum (Po), and Pseudopyrenochaeta sp. (Ps), isolated from the roots of Pinus tabulaeformis were investigated in vitro. Then, the effects of the fungi on the growth performance, nutrient uptake, and rhizosphere soil microbial community structure of P. tabulaeformis under different N addition conditions (0, 40, and 80 kg hm−2 year−1) were examined. The biomass and phytohormone contents of the Sg, Pt and Po strains increased with increasing N concentration, while those of the Ps strain first increased and then decreased. All four fungal strains could effectively colonize the plant roots and form a strain-dependent symbiosis with P. tabulaeformis. Although the effects depended on the fungal species, the growth and root development of inoculated seedlings were higher than those of uninoculated seedlings under N deficiency and normal N supply conditions. However, these positive effects disappeared and even became negative under high N supply conditions. The inoculation of the four fungal strains also showed significant positive effects on the shoot and root nutrient contents of P. tabulaeformis. Fungal inoculation significantly increased different microbial groups and the total soil microorganisms but decreased the microbial diversity under N deficiency stress. In summary, exogenous symbiotic fungal inoculations could increase the growth performance of P. tabulaeformis under N deficiency and normal N supply conditions, but the effects were negative under excessive N addition.
Pigment production by a newly isolated strain Pycnoporus sanguineus SYBC-L7 in solid-state fermentation
Authors: Meng Di , Shao Xuan , Luo Shou-Peng , Tian Qiao-Peng , Liao Xiang-Ru
Published: October 2022

Natural pigments are playing important roles in our daily lives. They not only make products colorful but also provide various health benefits for humans. In addition, Pycnoporus genus, listed as food- and cosmetic-grade microorganism, is one of the promising organisms for developing natural pigments. In this study, a new fungal strain with high efficiency in producing intense orange pigments was isolated and identified as Pycnoporus sanguineus SYBC-L7. Different agro-industrial wastes were applied to evaluate the growth and pigment production of strain SYBC-L7. SYBC-L7 can grow rapidly and effectively produce pigments using wood chips as substrate in solid-state fermentation (SSF). Culture conditions were also optimized for value-added pigments production and the optimum production conditions were glucose as carbon source, ammonium tartrate as nitrogen source, initial pH 6.0, and relative humidity of 65%. Pigment components, cinnabarinic acid, tramesanguin, and 2-amino-9-formylphenoxazone-1-carbonic acid were confirmed by liquid chromatography–mass spectrometry. Meanwhile, an agar plate diffusion assay was performed to evaluate the antimicrobial activity of the pigment. These pigments showed more significant inhibition of Gram-positive than Gram-negative bacteria. The results showed that Pycnoporus sanguineus SYBC-L7 was able to cost-effectively produce intense natural orange pigments with antibacterial activity in SSF, which is the basis of their large-scale production and application.
The transcriptional characteristics of NADC34-like PRRSV in porcine alveolar macrophages
Authors: Wang Peixin , Ma Xin , Zhang Riteng , Zhao Yongxin , Hu Ruochen , Luo Chen , Zeshan Basit , Yang Zengqi , Qiu Li , Wang Juan , Liu Haijin , Zhou Yefei , Wang Xinglong
Published: October 2022

The widespread and endemic circulation of porcine reproductive and respiratory syndrome virus (PRRSV) cause persistent financial losses to the swine industry worldwide. In 2017, NADC34-like PRRSV-2 emerged in northeastern China and spread rapidly. The dynamics analysis of immune perturbations associated with novel PRRSV lineage is still incomplete. This study performed a time-course transcriptome sequencing of NADC34-like PRRSV strain YC-2020-infected porcine alveolar macrophages (PAMs) and compared them with JXA1-infected PAMs. The results illustrated dramatic changes in the host’s differentially expressed genes (DEGs) presented at different timepoints after PRRSV infection, and the expression profile of YC-2020 group is distinct from that of JXA1 group. Functional enrichment analysis showed that the expression of many inflammatory cytokines was up-regulated following YC-2020 infection but at a significantly lower magnitude than JXA1 group, in line with the trends for most interferon-stimulated genes (ISGs) and their regulators. Meanwhile, numerous components of histocompatibility complex (MHC) class II and phagosome presented a stronger transcription suppression after the YC-2020 infection. All results imply that YC-2020 may induce milder inflammatory responses, weaker antiviral processes, and more severe disturbance of antigen processing and presentation compared with HP-PRRSV. Additionally, LAPTM4A, GLMP, and LITAF, which were selected from weighted gene co-expression network analysis (WGCNA), could significantly inhibit PRRSV proliferation. This study provides fundamental data for understanding the biological characteristics of NADC34-like PRRSV and new insights into PRRSV evolution and prevention.
Role of gut microbiota in the pathogenesis and treatment of diabetes mullites: Advanced research-based review
Authors: Ye Junjun , Wu Zezhen , Zhao Yifei , Zhang Shuo , Liu Weiting , Su Yu
Published: October 2022

Gut microbiota plays an important role in the proper functioning of human organisms, while its dysbiosis is associated with disease in various body organs. Diabetes mellitus (DM) is a set of heterogeneous metabolic diseases characterized by hyperglycemia caused by direct or indirect insulin deficiency. There is growing evidence that gut microbiota dysbiosis is closely linked to the development of DM. Gut microbiota composition changes in type 1 diabetes mullites (T1DM) and type 2 diabetes mullites (T2DM) patients, which may cause gut leakiness and uncontrolled entry of antigens into the circulation system, triggering an immune response that damages the isle β cells or metabolic disorders. This review summarizes gut microbiota composition in healthy individuals and compares it to diabetes mullites patients. The possible pathogenesis by which gut microbiota dysbiosis causes DM, particularly gut leakiness and changes in gut microbiota metabolites is also discussed. It also presents the process of microbial-based therapies of DM.
Complete identity and expression of StfZ, the cis-antisense RNA to the mRNA of the cell division gene ftsZ, in Escherichia coli
Authors: Anand Deepak , Jakkala Kishor , Nair Rashmi Ravindran , Sharan Deepti , Pradhan Atul , Mukkayyan Nagaraja , Ajitkumar Parthasarathi
Published: October 2022

Bacteria regulate FtsZ protein levels through transcriptional and translational mechanisms for proper cell division. A cis-antisense RNA, StfZ, produced from the ftsA-ftsZ intergenic region, was proposed to regulate FtsZ level in Escherichia coli. However, its structural identity remained unknown. In this study, we determined the complete sequence of StfZ and identified the isoforms and its promoters. We find that under native physiological conditions, StfZ is expressed at a 1:6 ratio of StfZ:ftsZ mRNA at all growth phases from three promoters as three isoforms of 366, 474, and 552 nt RNAs. Overexpression of StfZ reduces FtsZ protein level, increases cell length, and blocks cell division without affecting the ftsZ mRNA stability. We did not find differential expression of StfZ under the stress conditions of heat shock, cold shock, or oxidative stress, or at any growth phase. These data indicated that the cis-encoded StfZ antisense RNA to ftsZ mRNA may be involved in the fine tuning of ftsZ mRNA levels available for translation as per the growth-phase-specific requirement at all phases of growth and cell division.
Development of machine learning models for the screening of potential HSP90 inhibitors
Authors: Khan Mohd Imran , Park Taehwan , Imran Mohammad Azhar , Gowda Saralamma Venu Venkatarame , Lee Duk Chul , Choi Jaehyuk , Baig Mohammad Hassan , Dong Jae-June
Published: October 2022

Heat shock protein 90 (Hsp90) is a molecular chaperone playing a significant role in the folding of client proteins. This cellular protein is linked to the progression of several cancer types, including breast cancer, lung cancer, and gastrointestinal stromal tumors. Several oncogenic kinases are Hsp90 clients and their activity depends on this molecular chaperone. This makes HSP90 a prominent therapeutic target for cancer treatment. Studies have confirmed the inhibition of HSP90 as a striking therapeutic treatment for cancer management. In this study, we have utilized machine learning and different in silico approaches to screen the KCB database to identify the potential HSP90 inhibitors. Further evaluation of these inhibitors on various cancer cell lines showed favorable inhibitory activity. These inhibitors could serve as a basis for future development of effective HSP90 inhibitors.
Mesenchymal stem cells and exosomes improve cognitive function in the aging brain by promoting neurogenesis
Authors: Zhang Xiaowen , Hou Xuejia , Te Liu , Zhongsheng Zhou , Jiang Jinlan , Wu Xiaodong
Published: October 2022

Biologically speaking, normal aging is a spontaneous and inevitable process of organisms over time. It is a complex natural phenomenon that manifests itself in the form of degenerative changes in structures and the decline of functions, with diminished adaptability and resistance. Brain aging is one of the most critical biological processes that affect the physiological balance between health and disease. Age-related brain dysfunction is a severe health problem that contributes to the current aging society, and so far, there is no good way to slow down aging. Mesenchymal stem cells (MSCs) have inflammation-inhibiting and proliferation-promoting functions. At the same time, their secreted exosomes inherit the regulatory and therapeutic procedures of MSCs with small diameters, allowing high-dose injections and improved therapeutic efficiency. This manuscript describes how MSCs and their derived exosomes promote brain neurogenesis and thereby delay aging by improving brain inflammation.
Reactive oxygen species contribute to delirium-like behavior by activating CypA/MMP9 signaling and inducing blood-brain barrier impairment in aged mice following anesthesia and surgery
Authors: Liu Li-fang , Hu Yun , Liu Yi-nuo , Shi De-wen , Liu Chang , Da Xin , Zhu Si-hui , Zhu Qian-yun , Zhang Ji-qian , Xu Guang-hong
Published: October 2022

Postoperative delirium (POD) is common in the elderly and is associated with poor clinical outcomes. Reactive oxygen species (ROS) and blood-brain barrier (BBB) damage have been implicated in the development of POD, but the association between these two factors and the potential mechanism is not clear. Cyclophilin A (CypA) is a specifically chemotactic leukocyte factor that can be secreted in response to ROS, which activates matrix metalloproteinase 9 (MMP9) and mediates BBB breakdown. We, therefore, hypothesized that ROS may contribute to anesthesia/surgery-induced BBB damage and delirium-like behavior via the CypA/MMP9 pathway. To test these hypotheses, 16-month-old mice were subjected to laparotomy under 3% sevoflurane anesthesia (anesthesia/surgery) for 3 h. ROS scavenger (N-acetyl-cysteine) and CypA inhibitor (Cyclosporin A) were used 0.5 h before anesthesia/surgery. A battery of behavior tests (buried food test, open field test, and Y maze test) was employed to evaluate behavioral changes at 24 h before and after surgery in the mice. Levels of tight junction proteins, CypA, MMP9, postsynaptic density protein (PSD)-95, and synaptophysin in the prefrontal cortex were assessed by western blotting. The amounts of ROS and IgG in the cortex of mice were observed by fluorescent staining. The concentration of S100β in the serum was detected by ELISA. ROS scavenger prevented the reduction in TJ proteins and restored the permeability of BBB as well as reduced the levels of CypA/MMP9, and further alleviated delirium-like behavior induced by anesthesia/surgery. Furthermore, the CypA inhibitor abolished the increased levels of CypA/MMP, which reversed BBB damage and ameliorated delirium-like behavior caused by ROS accumulation. Our findings demonstrated that ROS may participate in regulating BBB permeability in aged mice with POD via the CypA/MMP9 pathway, suggesting that CypA may be a potential molecular target for preventing POD.
Nutrient responding peptide hormone CCHamide-2 consolidates appetitive memory
Authors: Yamagata Nobuhiro , Imanishi Yasuhito , Wu Hongyang , Kondo Shu , Sano Hiroko , Tanimoto Hiromu
Published: October 2022

CCHamide-2 (CCHa2) is a protostome excitatory peptide ortholog known for various arthropod species. In fruit flies, CCHa2 plays a crucial role in the endocrine system, allowing peripheral tissue to communicate with the central nervous system to ensure proper development and the maintenance of energy homeostasis. Since the formation of odor-sugar associative long-term memory (LTM) depends on the nutrient status in an animal, CCHa2 may play an essential role in linking memory and metabolic systems. Here we show that CCHa2 signals are important for consolidating appetitive memory by acting on the rewarding dopamine neurons. Genetic disruption of CCHa2 using mutant strains abolished appetitive LTM but not short-term memory (STM). A post-learning thermal suppression of CCHa2 expressing cells impaired LTM. In contrast, a post-learning thermal activation of CCHa2 cells stabilized STM induced by non-nutritious sugar into LTM. The receptor of CCHa2, CCHa2-R, was expressed in a subset of dopamine neurons that mediate reward for LTM. In accordance, the receptor expression in these dopamine neurons was required for LTM specifically. We thus concluded that CCHa2 conveys a sugar nutrient signal to the dopamine neurons for memory consolidation. Our finding establishes a direct interplay between brain reward and the putative endocrine system for long-term energy homeostasis.
Temperature-dependent structural plasticity of hippocampal synapses
Authors: Feng Zhendong , Saha Lopamudra , Dritsa Clio , Wan Qi , Glebov Oleg O.
Published: October 2022

The function of the central nervous system (CNS) is strongly affected by temperature. However, the underlying processes remain poorly understood. Here, we show that hypothermia and hyperthermia trigger bidirectional re-organization of presynaptic architecture in hippocampal neurons, resulting in synaptic strengthening, and weakening, respectively. Furthermore, hypothermia remodels inhibitory postsynaptic scaffold into enlarged, sparse synapses enriched in GABAA receptors. This process does not require protein translation, and instead is regulated by actin dynamics. Induction of hypothermia in vivo enhances inhibitory synapses in the hippocampus, but not in the cortex. This is confirmed by the proteomic analysis of cortical synapses, which reveals few temperature-dependent changes in synaptic content. Our results reveal a region-specific form of environmental synaptic plasticity with a mechanism distinct from the classic temperature shock response, which may underlie functional response of CNS to temperature.
Immune checkpoint inhibitor related nephrotoxicity: Advances in clinicopathologic features, noninvasive approaches, and therapeutic strategy and rechallenge
Authors: Miao Jing , Sise Meghan E. , Herrmann Sandra M.
Published: October 2022

Immune checkpoint inhibitors (ICIs) are used increasingly to treat more than 17 cancers and have shown promising therapeutic results. However, ICI use can result in a variety of immune-related adverse events (IRAEs) which can occur in any organ, including the kidneys. Acute kidney injury (AKI) is the most common nephrotoxicity, classically related to acute interstitial nephritis. Much more diverse patterns and presentations of ICI-related kidney injury can occur, and have implications for diagnostic and therapeutic management approaches. In this review, we summarize the recently approved ICIs for cancer, the incidence and risk factors for nephrotoxicity, our current understanding of the pathophysiological mechanisms and the key clinicopathological features of ICI-related AKI, and therapeutic strategies. We also explore important knowledge that require further investigation, such as the risks/benefits of ICI rechallenge in patients who recover from an episode of ICI-related AKI, and the application of liquid biopsy and microbiome to identify noninvasive biomarkers to diagnose and predict kidney injury and guide ICI therapy.
Serum vitamin E level and functional prognosis after traumatic brain injury with intracranial injury: A multicenter prospective study
Authors: Park Gwan Jin , Ro Young Sun , Yoon Hanna , Lee Stephen Gyung Won , Jung Eujene , Moon Sung Bae , Kim Sang Chul , Shin Sang Do ,   Pan-Asia Trauma Outcomes Study for Traumatic Brain Injury (PATOS-TBI) research network
Published: October 2022

Background

Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for treatment of TBI, has not been sufficiently evaluated for predicting prognosis of TBI. This study aimed to evaluate the prognostic value of vitamin E on functional outcomes of TBI patients with intracranial injury.

Methods

A multi-center prospective cohort study was conducted in five university hospitals between 2018 and 2020. Adult TBI patients who visited the emergency department (ED) with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination were eligible. Serum vitamin E levels (mg/dL) were categorized into 4 groups: low (0.0–5.4), low-normal (5.5–10.9), high-normal (11.0–16.9), and high (17.0–). Study outcomes were set as 1- and 6-month disability (Glasgow outcome scale (GOS) 1–4). Multilevel logistic regression analysis was conducted to calculate the adjusted odds ratios (AORs) of vitamin E for related outcomes.

Results

Among 550 eligible TBI patients with intracranial injury, the median (IQR) of serum vitamin E was 10.0 (8.0–12.3) mg/dL; 204/550 (37.1%) had 1-month disability and 197/544 (36.1%) had 6-month disability of GOS 1–4. Compared with the high-normal group, the odds of 1-month disability and 6-month disability increased in the low and low-normal group (AORs (95% CIs): 3.66 (1.62–8.27) and 2.60 (1.15–5.85) for the low group and 1.63 (1.08–2.48) and 1.60 (1.04–2.43) for the low-normal group, respectively).

Conclusion

Low serum vitamin E level was associated with poor prognosis at 1 and 6 months after TBI with intracranial injury.
Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults
Authors: Larsen Nicholas W. , Stiles Lauren E. , Shaik Ruba , Schneider Logan , Muppidi Srikanth , Tsui Cheuk To , Geng Linda N. , Bonilla Hector , Miglis Mitchell G.
Published: October 2022

Background

Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.

Objective

To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.

Design

Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.

Participants

2,413 adults ages 18–64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.

Main measures

The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.

Key results

Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].

Conclusions

Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.
CENPA acts as a prognostic factor that relates to immune infiltrates in gliomas
Authors: Wang Bo , Wei Wei , Long Shengrong , Wang Lesheng , Yang Bin , Wu Du , Li Zhengwei , Li Zhiqiang , Arshad Muhammad , Li Xiang , Chen Jincao
Published: October 2022

Background

Glioma is the most common primary tumor of the central nervous system (CNS). Centromere protein A (CENPA) plays an essential role in ensuring that mitosis proceeds normally. The effect of CENPA on glioma is rarely reported. However, the current study aims to explore whether aberrant CENPA expression promotes glioma progression and the potential mechanisms involved.

Methods

The GEPIA website, The Cancer Genome Atlas, and the Gene Expression Omnibus (GEO) were used to assess the expression of CENPA in glioma. The results were validated by real-time quantitative polymerase chain reaction and immunohistochemical staining of clinical samples. The relationship between the expression and prognostic value of the CENPA gene in glioma was investigated by Kaplan–Meier (KM) survival analysis with RNA-seq and clinical profiles downloaded from the Chinese Glioma Genome Atlas (CGGA) and UCSC Xena. The association between CENPA and clinical characteristics was also evaluated. Cell Counting Kit-8 (CCK8) assay, wound healing assay using two glioma cell lines, gene set enrichment analysis (GSEA), KEGG and gene ontology (GO) enrichment analysis, immune infiltration analysis, temozolomide (TMZ) sensitivity analysis, and single-cell sequence analysis were performed to explore the underlying mechanisms of high CENPA expression and its effect on glioma development. Finally, we performed a Cox analysis based on the expression of CENPA to predict patient prognosis.

Results

CENPA was significantly upregulated in glioma tissue samples and correlated with patient prognosis. Moreover, the downregulation of CENPA inhibited the migration and proliferation of glioma cells. In addition, the expression level of CENPA was significantly correlated with the grade, primary–recurrent–secondary (PRS) type, IDH mutation status, and 1p19q codeletion status. Furthermore, CENPA could serve as an independent prognostic factor for glioma that mainly interferes with the normal progression of mitosis and regulates the tumor immune microenvironment favoring glioma development.

Conclusion

CENPA may act as a prognostic factor in patients with glioma and provide a novel target for the treatment of gliomas.