bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel oral formulation of the melanocortin-1 receptor agonist PL8177 resolves inflammation in preclinical studies of inflammatory bowel disease and is gut restricted in rats, dogs, and humans
Authors: Dodd John , Jordan Robert , Makhlina Marie , Barnett Keith , Roffel Ad , Spana Carl , Obr Alison , Dhingra Priyanka , Kayne Paul S.
Published: February 2023

Introduction

PL8177 is a potent and selective agonist of the melanocortin 1 receptor (MC1R). PL8177 has shown efficacy in reversing intestinal inflammation in a cannulated rat ulcerative colitis model. To facilitate oral delivery, a novel, polymer-encapsulated formulation of PL8177 was developed. This formulation was tested in 2 rat ulcerative colitis models and evaluated for distribution, in vivo, in rats, dogs, and humans.

Methods

The rat models of colitis were induced by treatment with 2,4-dinitrobenzenesulfonic acid or dextran sulfate sodium. Single nuclei RNA sequencing of colon tissues was performed to characterize the mechanism of action. The distribution and concentration of PL8177 and the main metabolite within the GI tract after a single oral dose of PL8177 was investigated in rats and dogs. A phase 0 clinical study using a single microdose (70 µg) of [14C]-labeled PL8177 investigated the release of PL8177 in the colon of healthy men after oral administration.

Results

Rats treated with 50 µg oral PL8177 demonstrated significantly lower macroscopic colon damage scores and improvement in colon weight, stool consistency, and fecal occult blood vs the vehicle without active drug. Histopathology analysis resulted in the maintenance of intact colon structure and barrier, reduced immune cell infiltration, and increased enterocytes with PL8177 treatment. Transcriptome data show that oral PL8177 50 µg treatment causes relative cell populations and key gene expressions levels to move closer to healthy controls. Compared with vehicle, treated colon samples show negative enrichment of immune marker genes and diverse immune-related pathways. In rats and dogs, orally administered PL8177 was detected at higher amounts in the colon vs upper GI tract. [14C]-PL8177 and the main metabolite were detected in the feces but not in the plasma and urine in humans. This suggests that the parent drug [14C]-PL8177 was released from the polymer formulation and metabolized within the GI tract, where it would be expected to exert its effect.

Conclusion

Collectively, these findings support further research into the oral formulation of PL8177 as a possible therapeutic for GI inflammatory diseases in humans.
VISTA expression and patient selection for immune-based anticancer therapy
Authors: Martin Alexander S. , Molloy Michael , Ugolkov Andrey , von Roemeling Reinhard W. , Noelle Randolph J. , Lewis Lionel D. , Johnson Melissa , Radvanyi Laszlo , Martell Robert E.
Published: February 2023

V-domain Ig suppressor of T-cell activation (VISTA) is a B7 family member that plays key roles in maintaining T cell quiescence and regulation of myeloid cell populations, which together establish it as a novel immunotherapy target for solid tumors. Here we review the growing literature on VISTA expression in relation to various malignancies to better understand the role of VISTA and its interactions with both tumor cells and immune cells expressing other checkpoint molecules within the tumor microenvironment (TME). The biology of VISTA creates several mechanisms to maintain the TME, including supporting the function of myeloid-derived suppressor cells, regulating natural killer cell activation, supporting the survival of regulatory T cells, limiting antigen presentation on antigen-presenting cells and maintaining T cells in a quiescent state. Understanding these mechanisms is an important foundation of rational patient selection for anti-VISTA therapy. We provide a general framework to describe distinct patterns of VISTA expression in correlation with other known predictive immunotherapy biomarkers (programmed cell death ligand 1 and tumor-infiltrating lymphocytes) across solid tumors to facilitate investigation of the most efficacious TMEs for VISTA-targeted treatment as a single agent and/or in combination with anti-programmed death 1/anti-cytotoxic T lymphocyte antigen-4 therapies.
Unusual Talaromyces marneffei and Pneumocystis jirovecii coinfection in a child with a STAT1 mutation: A case report and literature review
Authors: Yang Qin , Yu Chendi , Wu Yue , Cao Ke , Li Xiaonan , Cao Weiguo , Cao Lichao , Zhang Shenrui , Ba Ying , Zheng Yuejie , Zhang Hezi , Wang Wenjian
Published: February 2023

Talaromyces marneffei and Pneumocystis jirovecii are the common opportunistic pathogens in immunodeficient patients. There have been no reports of T. marneffei and P. jirovecii coinfection in immunodeficient children. Signal transducer and activator of transcription 1 (STAT1) is a key transcription factor in immune responses. STAT1 mutations are predominately associated with chronic mucocutaneous candidiasis and invasive mycosis. We report a 1-year-2-month-old boy diagnosed with severe laryngitis and pneumonia caused by T. marneffei and P. jirovecii coinfection, which was confirmed by smear, culture, polymerase chain reaction and metagenome next-generation sequencing of bronchoalveolar lavage fluid. He has a known STAT1 mutation at amino acid 274 in the coiled-coil domain of STAT1 according to whole exome sequencing. Based on the pathogen results, itraconazole and trimethoprim-sulfamethoxazole were administered. This patient’s condition improved, and he was discharged after two weeks of targeted therapy. In the one-year follow-up, the boy remained symptom-free without recurrence.
Gut microbiota composition in patients with advanced malignancies experiencing immune-related adverse events
Authors: Liu Xinyu , Tang Hao , Zhou Qingyang , Zeng Yanlin , Lu Bo , Chen Dan , Li Yue , Qian Jiaming , Chen Minjiang , Zhao Jing , Xu Yan , Wang Mengzhao , Tan Bei
Published: February 2023

Introduction

The gut microbiota is implicated in the occurrence and severity of immune-related adverse events (irAEs), but the role it plays as well as its causal relationship with irAEs has yet to be established.

Methods

From May 2020 to August 2021, 93 fecal samples were prospectively collected from 37 patients with advanced thoracic cancers treated with anti-PD-1 therapy, and 61 samples were collected from 33 patients with various cancers developing different irAEs. 16S rDNA amplicon sequencing was performed. Antibiotic-treated mice underwent fecal microbiota transplantation (FMT) with samples from patients with and without colitic irAEs.

Results

Microbiota composition was significantly different in patients with and without irAEs (P=0.001) and with and without colitic-type irAEs (P=0.003). Bifidobacterium, Faecalibacterium, and Agathobacter were less abundant and Erysipelatoclostridium more abundant in irAE patients, while Bacteroides and Bifidobacterium were less abundant and Enterococcus more abundant in colitis-type irAE patients. Major butyrate-producing bacteria were also less abundant in patients with irAEs than those without (P=0.007) and in colitic vs. non-colitic irAE patients (P=0.018). An irAE prediction model had an AUC of 86.4% in training and 91.7% in testing. Immune-related colitis was more common in colitic-irAE-FMT (3/9) than non-irAE-FMT mice (0/9).

Conclusions

The gut microbiota is important in dictating irAE occurrence and type, especially for immune-related colitis, possibly by modulating metabolic pathways.
The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome
Authors: Wang Yi , Zhu Cheng-long , Li Peng , Liu Qiang , Li Hui-ru , Yu Chang-meng , Deng Xiao-ming , Wang Jia-feng
Published: February 2023

Sepsis is defined as a life-threatening dysfunction due to a dysregulated host response to infection. It is a common and complex syndrome and is the leading cause of death in intensive care units. The lungs are most vulnerable to the challenge of sepsis, and the incidence of respiratory dysfunction has been reported to be up to 70%, in which neutrophils play a major role. Neutrophils are the first line of defense against infection, and they are regarded as the most responsive cells in sepsis. Normally, neutrophils recognize chemokines including the bacterial product N-formyl-methionyl-leucyl-phenylalanine (fMLP), complement 5a (C5a), and lipid molecules Leukotriene B4 (LTB4) and C-X-C motif chemokine ligand 8 (CXCL8), and enter the site of infection through mobilization, rolling, adhesion, migration, and chemotaxis. However, numerous studies have confirmed that despite the high levels of chemokines in septic patients and mice at the site of infection, the neutrophils cannot migrate to the proper target location, but instead they accumulate in the lungs, releasing histones, DNA, and proteases that mediate tissue damage and induce acute respiratory distress syndrome (ARDS). This is closely related to impaired neutrophil migration in sepsis, but the mechanism involved is still unclear. Many studies have shown that chemokine receptor dysregulation is an important cause of impaired neutrophil migration, and the vast majority of these chemokine receptors belong to the G protein-coupled receptors (GPCRs). In this review, we summarize the signaling pathways by which neutrophil GPCR regulates chemotaxis and the mechanisms by which abnormal GPCR function in sepsis leads to impaired neutrophil chemotaxis, which can further cause ARDS. Several potential targets for intervention are proposed to improve neutrophil chemotaxis, and we hope that this review may provide insights for clinical practitioners.
A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component
Authors: Yoshioka Yuya , Kobiyama Kouji , Hayashi Tomoya , Onishi Motoyasu , Yanagida Yosuke , Nakagawa Takayuki , Hashimoto Masayuki , Nishinaka Anri , Hirose Jun , Asaoka Yoshiji , Tajiri Minako , Hayata Atsushi , Ishida Satoru , Omoto Shinya , Nagira Morio , Ishii Ken J.
Published: February 2023

Background

Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.

Methods and Results

To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.

Conclusions

This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.
Pre-immunotherapy radiotherapy enhanced the efficacy of multi-line sintilimab in unresectable advanced esophageal squamous cell carcinoma
Authors: Xu Shuhui , Xu Xianxing , Zhu Hui
Published: February 2023

Background

The use of immunotherapy for the treatment of esophageal squamous cell carcinoma (ESCC) is gradually increasing. In this retrospective study, we evaluated the efficacy and explored potential factors of prognosis in multi-line sintilimab for unresectable advanced ESCC.

Methods

All pathological specimens were available from our Department of Pathology. We performed PD-L1 immunohistochemical staining of surgical or puncture specimens from 133 patients. We evaluated the efficacy of multi-line sintilimab and found potential factors according to multivariate analysis. We assessed the relationship between radiotherapy and immunotherapy, and according to whether patients had received radiotherapy within 3 months prior to immunotherapy, we attempted to analyze differences in progression-free survival (PFS) and overall survival (OS).

Results

A total of 133 patients were enrolled in this retrospective study between January 2019 and December 2021. The median follow-up was 16.1 months. All patients were treated with at least two cycles of sintilimab. Of all patients, a total of 74 experienced disease progression, with a median progression-free survival of 9.0 months (95% CI 7.701–10.299). We found that pre-immunotherapy radiotherapy was a possible predictor that affected the prognosis of multi-line sintilimab and that 3 months was a significant cutoff. A total of 128 patients (96.2%) had received radiotherapy prior to immunotherapy. Of those patients, 89 (66.9%) had received radiation therapy within 3 months prior to immunotherapy. PFS was considerably longer in patients who were treated within 3 months of radiotherapy than in patients who did not receive radiation therapy within 3 months of radiation therapy prior to immunotherapy (median progression-free survival 10.0 months [95% CI 8.030–11.970] vs. 5.0 months [95% CI 2.755–7.245]). Among all patients, the median overall survival was 14.9 months (95% CI 12.558–17.242). Overall survival was significantly longer in patients who had previously received radiotherapy within 3 months prior to immunotherapy than in those who had not (median overall survival 15.3 months [95% CI 13.724–16.876] vs. 12.2 months [10.001–14.399].

Conclusion

Based on this retrospective study, sintilimab is a significant option for patients with unresectable advanced ESCC who have been previously treated, and pre-immunotherapy radiotherapy within 3 months enhanced the efficacy.
Towards effective wildlife protection law for marine species in China: A stakeholders’ perspective
Authors: Kwan Kit Yue , Chen Ruifang , Wang Chun-Chieh , Lin Shuhao , Wu Lv , Xie Xiaoyong , Weng Zhaohong , Hu Menghong , Zhou Haichao , Wu Zhou , Fu Yijian , Zhen Wenquan , Yang Xin , Wen Yulong
Published: February 2023

Introduction

As one of the megadiverse countries, the effectiveness of wildlife protection in China is of great significance to global biodiversity conservation. With continued evolution and revisions, China’s Wildlife Protection Law has listed over 140 marine species; however, it is still inclined toward terrestrial animals.

Methods

To narrow the gap between compliance and enforcement, we collected 1,309 effective responses from various coastal cities of China through an anonymous online questionnaire survey, to investigate their exposure, understanding and attitudes toward Wildlife Protection Law for marine species (mWPL).

Results

Most respondents demonstrated an overall good understanding about the context, necessity and effectiveness of mWPL. The fisher communities were found to be more aware of the dissemination and implementation of mWPL. However, they understood less of the penal system, and exhibited negative attitudes toward the necessity and punishment of the legislation, probably due to the conflicts between resource utilizations and legislative interventions. The participants also indicated that seahorses, horseshoe crabs and corals were commonly subjected to illegal exploitations.

Discussion

While most respondents suggested greater fines, tighter laws and better public enforcement, we advocate the exploration of bottom-up options such as community engagement and environmental education to improve compliance and implementation of mWPL for the benefit of marine wildlife conservation in China.
Comparison of alive and dead benthic foraminiferal fauna off the Changjiang Estuary: Understanding water-mass properties and taphonomic processes
Authors: Jiang Feng , Fan Daidu , Zhao Quanhong , Wu Yijing , Ren Fahui , Liu Yan , Li Ang
Published: February 2023

Benthic foraminifera (BF) are utilized in palaeo-environmental reconstruction based on our understanding of how living individuals respond to environmental variations. However, there is still a lack of empirical insight into how non-environmental factors, such as taphonomic processes, influence the preservations of fossil BF in strata. In this study, we compare the spatial distribution and composition of alive and dead BF fauna in surface sediments to elucidate how well fossil foraminiferal fauna mirror quasi-contemporary alive BF groups indicative of different water masses off a mega-river (Changjiang) estuary, which is characterized by intense and complex river-sea interactions. On-site measurements of bottom water salinity, temperature, and dissolved oxygen were conducted in the summer to determine water mass properties. A same-site comparison of alive (Rose Bengal stained) and dead foraminiferal fauna in surface sediment samples over 73 stations was then carried out. Q-mode Hierarchical clustering analysis was used to differentiate foraminiferal assemblages based on the relative abundance of common species. Three distinct regions with different water-mass properties were identified. The distribution pattern of dead foraminiferal fauna is mainly inherited from alive fauna, while the density and diversity of the dead fauna were found to be higher than those of the alive one. Both alive and dead fauna were clustered into four assemblages. A few common alive species (small-agglutinated and thin-calcareous) were rarely found in dead fauna, and a few common dead species (preferring low temperature and indicating allochthonous sources) were rarely present in alive fauna. The alive foraminiferal abundance and diversity were mainly determined by food resources and environmental properties of salinity and temperature. Alive foraminiferal assemblages were separated by different water masses determined by river-sea interactions off the Changjiang Estuary. The “time-averaging” effect was found to be responsible for the higher density and diversity of the dead fauna. Disintegration of agglutinated tests, dissolution of calcareous tests and selective transportation were observed to contribute to the different species compositions between the alive and dead fauna. Nevertheless, indicative species-environment relations in alive and taphocoenose fauna were found to be almost homologous among most common species. This suggests that distinct benthic foraminiferal assemblages can be used to effectively differentiate between different water masses in the study coastal seas.
Laboratory study on movement characteristics of a river plume using particle image velocimetry
Authors: Xu Zhenshan , Xu Chiyuan , Wang Gang , Zhang Jiabo , Chen Yongping
Published: February 2023

Rivers are important passages for land-based materials transported to the sea, such as fresh water, sediment, pollutants, and nutrients. River discharge with land-based materials will form a river plume with a buoyancy flow. The river plume is subject to the interaction between nearshore runoff with seawater. In this study, the movement characteristics of the river plume are investigated based on particle image velocimetry (PIV) and the dye tracing method. It is found that the change of flow rate and environmental water density will shape the river plume pattern in both the plan view and the side view. The combined effect of flow rate and environmental water density could be described by the Froude number. The river plume has a free surface in the x-z plane and the horizontal velocity of the plume can be fitted with a 1/2 Gaussian distribution curve. The change of flow rate has little effect on the type of plume thickness curve, while the increase of environmental water density will change the thickness curve type of the river plume. The stable thickness of the river plume increases with the increase of the Froude number. The maximum value of turbulent kinetic energy is located in the middle layer, and the increase of the flow rate or the density difference leads to the increase in the turbulent kinetic energy.
Analytical model for the load-slip relationship of bearing-shear connectors
Authors: Qin Fengjiang , Huang Zhipeng , Zheng Zhichao , Chou Yaling , Zou Yang , Di Jin
Published: February 2023

The shear behavior of shear connectors in steel-concrete composite structures mainly depends on its load-slip relationship. The load-slip relationship not only reflects the shear capacity and slip capacity of the shear connectors, but also the degradation of shear stiffness during loading. In this study, fifteen push-out tests were carried out to investigate the load-slip relationship of the novel bearing-shear (B-S) connectors, which consist of pressuring-bearing plates and shear plates. Based on push-out tests, the influence of the shape and height of the pressure-bearing plate, and the shear plate shape on the load-slip relationship of the B-S connectors was analyzed. Then, an effective finite element model, validated by push-out tests, was used to study the influence of the concrete strength, and the thickness and tensile strength of the shear plate on the load-slip relationship of B-S connectors. Finally, based on the push-out tests, numerical analysis and theoretical analysis, an analytical model expressing the load-slip relationship of the B-S connectors was proposed.
Stability, phonon calculations, electronic structure, and optical properties of a VO2(M) nanostructure: A comprehensive density functional theory study
Authors: Mohebbi Elaheh , Pavoni Eleonora , Mencarelli Davide , Stipa Pierluigi , Laudadio Emiliano , Pierantoni Luca
Published: February 2023

This work aimed to precisely evaluate the physical properties of vanadium dioxide (M), particularly the optical characteristics. We employed different exchange-correlation functionals to determine the phase stability, band gap properties, and optical characteristics of an experimentally recognized monoclinic VO2(M) polymorph. The calculations not only correctly interpreted the VO2(M) origin but also predicted other optical properties including the extinction coefficient (k) and refractive index (n), which have not been reported in experimental measurements. Phonon dispersion calculations confirmed the presence of negative frequencies for acoustic modes in the phononic curves. When the HSE functional correctly reproduced the experimental band gap, here for the first time, our calculations based on PBE and PBEsol yielded non-zero electronic bandgaps of 0.23 and 0.15 eV for bulk VO2(M). Our predictions showed that semi-local functionals can adequately predict the semiconductor properties of VO2(M) and performed better than all previously reported theoretical works on nulled band gaps. In addition to the better prediction of the peak position in the absorption spectra with HSE hybrid functional, this method also reasonably well described the static dielectric constant of 7.54, showing an excellent match to the experimental values. In general, the results of this study reveal that hybrid functionals yield superior outcomes compared to semi-local functionals for optical properties of a VO2(M) polymorph. Our results suggest that the PBEsol + HSE approach allows the efficient characterization of smart materials for electronic and optoelectronic applications.
Antibiofilm effect of melittin alone and in combination with conventional antibiotics toward strong biofilm of MDR-MRSA and -Pseudomonas aeruginosa
Authors: Mirzaei Rasoul , Esmaeili Gouvarchin Ghaleh Hadi , Ranjbar Reza
Published: February 2023

Introduction

Multidrug-resistant (MDR) pathogens are being recognized as a critical threat to human health if they can form biofilm and, in this sense, biofilm-forming MDR-methicillin resistant Staphylococcus aureus (MRSA) and -Pseudomonas aeruginosa strains are a worse concern. Hence, a growing body of documents has introduced antimicrobial peptides (AMPs) as a substitute candidate for conventional antimicrobial agents against drug-resistant and biofilm-associated infections. We evaluated melittin’s antibacterial and antibiofilm activity alone and/or in combination with gentamicin, ciprofloxacin, rifampin, and vancomycin on biofilm-forming MDR-P. aeruginosa and MDR-MRSA strains.

Methods

Antibacterial tests [antibiogram, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC)], anti-biofilm tests [minimum biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC)], as well as synergistic antibiofilm activity of melittin and antibiotics, were performed. Besides, the influence of melittin alone on the biofilm encoding genes and the cytotoxicity and hemolytic effects of melittin were examined.

Results

MIC, MBC, MBIC, and MBEC indices for melittin were in the range of 0.625–5, 1.25–10, 2.5–20, and 10–40 μg/ml, respectively. The findings found that the combination of melittin AMP with antibiotics was synergistic and fractional biofilm inhibitory concentration index (FBICi) for most tested concentrations was <0.5, resulting in a significant reduction in melittin, gentamicin, ciprofloxacin, vancomycin, and rifampin concentrations by 2–256.4, 2–128, 2–16, 4–64 and 4–8 folds, respectively. This phenomenon reduced the toxicity of melittin, whereby its synergist concentration required for biofilm inhibition did not show cytotoxicity and hemolytic activity. Our findings found that melittin decreased the expression of icaA in S. aureus and LasR in P. aeruginosa genes from 0.1 to 4.11 fold for icaA, and 0.11 to 3.7 fold for LasR, respectively.

Conclusion

Overall, the results obtained from our study show that melittin alone is effective against the strong biofilm of MDR pathogens and also offers sound synergistic effects with antibiotics without toxicity. Hence, combining melittin and antibiotics can be a potential candidate for further evaluation of in vivo infections by MDR pathogens.
Biological potential of Bacillus subtilis BS45 to inhibit the growth of Fusarium graminearum through oxidative damage and perturbing related protein synthesis
Authors: Lu Ziyun , Chen Meiling , Long Xinyi , Yang Huilin , Zhu Du
Published: February 2023

Fusarium root rot (FRR) caused by Fusarium graminearum poses a threat to global food security. Biological control is a promising control strategy for FRR. In this study, antagonistic bacteria were obtained using an in-vitro dual culture bioassay with F. graminearum. Molecular identification of the bacteria based on the 16S rDNA gene and whole genome revealed that the species belonged to the genus Bacillus. We evaluated the strain BS45 for its mechanism against phytopathogenic fungi and its biocontrol potential against FRR caused by F. graminearum. A methanol extract of BS45 caused swelling of the hyphal cells and the inhibition of conidial germination. The cell membrane was damaged and the macromolecular material leaked out of cells. In addition, the mycelial reactive oxygen species level increased, mitochondrial membrane potential decreased, oxidative stress-related gene expression level increased and oxygen-scavenging enzyme activity changed. In conclusion, the methanol extract of BS45 induced hyphal cell death through oxidative damage. A transcriptome analysis showed that differentially expressed genes were significantly enriched in ribosome function and various amino acid transport pathways, and the protein contents in cells were affected by the methanol extract of BS45, indicating that it interfered with mycelial protein synthesis. In terms of biocontrol capacity, the biomass of wheat seedlings treated with the bacteria increased, and the BS45 strain significantly inhibited the incidence of FRR disease in greenhouse tests. Therefore, strain BS45 and its metabolites are promising candidates for the biological control of F. graminearum and its related root rot diseases.
A putative terpene cyclase gene (CcPtc1) is required for fungal development and virulence in Cytospora chrysosperma
Authors: Yang Yuchen , Yu Lu , Qiu Xiaolin , Xiong Dianguang , Tian Chengming
Published: February 2023

Cytospora chrysosperma is a destructive plant pathogenic fungus, which causes canker disease on numerous woody plants. However, knowledge concerning the interaction between C. chrysosperma and its host remains limited. Secondary metabolites produced by phytopathogens often play important roles in their virulence. Terpene cyclases (TC), polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) are the key components for the synthesis of secondary metabolites. Here, we characterized the functions of a putative terpene type secondary metabolite biosynthetic core gene CcPtc1 in C. chrysosperma, which was significantly up-regulated in the early stages of infection. Importantly, deletion of CcPtc1 greatly reduced fungal virulence to the poplar twigs and they also showed significantly reduced fungal growth and conidiation compared with the wild-type (WT) strain. Furthermore, toxicity test of the crude extraction from each strain showed that the toxicity of crude extraction secreted by ΔCcPtc1 were strongly compromised in comparison with the WT strain. Subsequently, the untargeted metabolomics analyses between ΔCcPtc1 mutant and WT strain were conducted, which revealed 193 significantly different abundant metabolites (DAMs) inΔCcPtc1 mutant compared to the WT strain, including 90 significantly downregulated metabolites and 103 significantly up-regulated metabolites, respectively. Among them, four key metabolic pathways that reported to be important for fungal virulence were enriched, including pantothenate and coenzyme A (CoA) biosynthesis. Moreover, we also detected significant alterations in a series of terpenoids, among which (+)-ar-turmerone, pulegone, ethyl chrysanthemumate, and genipin were significantly down-regulated, while cuminaldehyde and (±)-abscisic acid were significantly up-regulated. In conclusion, our results demonstrated that CcPtc1 acts as a virulence-related secondary metabolism factor and provides new insights into the pathogenesis of C. chrysosperma.
Comparative metagenomic analysis reveals rhizosphere microbial community composition and functions help protect grapevines against salt stress
Authors: Wang Bo , Wang Xicheng , Wang Zhuangwei , Zhu Kefeng , Wu Weimin
Published: February 2023

Introduction

Soil salinization is a serious abiotic stress for grapevines. The rhizosphere microbiota of plants can help counter the negative effects caused by salt stress, but the distinction between rhizosphere microbes of salt-tolerant and salt-sensitive varieties remains unclear.

Methods

This study employed metagenomic sequencing to explore the rhizosphere microbial community of grapevine rootstocks 101-14 (salt tolerant) and 5BB (salt sensitive) with or without salt stress.

Results and Discussion

Compared to the control (treated with ddH2O), salt stress induced greater changes in the rhizosphere microbiota of 101-14 than in that of 5BB. The relative abundances of more plant growth-promoting bacteria, including Planctomycetes, Bacteroidetes, Verrucomicrobia, Cyanobacteria, Gemmatimonadetes, Chloroflexi, and Firmicutes, were increased in 101-14 under salt stress, whereas only the relative abundances of four phyla (Actinobacteria, Gemmatimonadetes, Chloroflexi, and Cyanobacteria) were increased in 5BB under salt stress while those of three phyla (Acidobacteria, Verrucomicrobia, and Firmicutes) were depleted. The differentially enriched functions (KEGG level 2) in 101-14 were mainly associated with pathways related to cell motility; folding, sorting, and degradation functions; glycan biosynthesis and metabolism; xenobiotics biodegradation and metabolism; and metabolism of cofactors and vitamins, whereas only the translation function was differentially enriched in 5BB. Under salt stress, the rhizosphere microbiota functions of 101-14 and 5BB differed greatly, especially pathways related to metabolism. Further analysis revealed that pathways associated with sulfur and glutathione metabolism as well as bacterial chemotaxis were uniquely enriched in 101-14 under salt stress and therefore might play vital roles in the mitigation of salt stress on grapevines. In addition, the abundance of various sulfur cycle-related genes, including genes involved in assimilatory sulfate reduction (cysNC, cysQ, sat, and sir), sulfur reduction (fsr), SOX systems (soxB), sulfur oxidation (sqr), organic sulfur transformation (tpa, mdh, gdh, and betC), increased significantly in 101-14 after treatment with NaCl; these genes might mitigate the harmful effects of salt on grapevine. In short, the study findings indicate that both the composition and functions of the rhizosphere microbial community contribute to the enhanced tolerance of some grapevines to salt stress.
Seasonal variation of phytoplankton community assembly processes in Tibetan Plateau floodplain
Authors: Huang Zhenyu , Pan Baozhu , Soininen Janne , Liu Xinyuan , Hou Yiming , Liu Xing
Published: February 2023

Uncovering the mechanisms underlying phytoplankton community assembly remains a major challenge in freshwater ecology. The roles of environmental filtering and spatial processes in shaping phytoplankton metacommunity in Tibetan floodplain ecosystems under various hydrological conditions are still unclear. Here, multivariate statistics and a null model approach were used to compare the spatiotemporal patterns and assembly processes of phytoplankton communities in the river-oxbow lake system of Tibetan Plateau floodplain between non-flood and flood periods. The results showed that phytoplankton communities had significant seasonal and habitat variations, with the seasonal variations being more remarkable. Phytoplankton density, biomass, and alpha diversity were distinctly lower in the flood than non-flood period. The habitat differences (rivers vs. oxbow lakes) in phytoplankton community were less pronounced during the flood than non-flood period, most likely due to the increased hydrological connectivity. There was a significant distance–decay relationship only in lotic phytoplankton communities, and such relationship was stronger in the non-flood than flood period. Variation partitioning and PER-SIMPER analysis showed that the relative role of environmental filtering and spatial processes affecting phytoplankton assemblages varied across hydrological periods, with environmental filtering dominating in the non-flood period and spatial processes in the flood period. These results suggest that the flow regime plays a key role in balancing environmental and spatial factors in shaping phytoplankton communities. This study contributes to a deeper understanding of ecological phenomena in highland floodplains and provides a theoretical basis for floodplain ecosystem maintenance and ecological health management.
Longitudinal changes in participant and informant reports of subjective cognitive complaints are associated with dementia risk
Authors: Numbers Katya , Lam Ben C. P. , Crawford John D. , Kochan Nicole A. , Sachdev Perminder S. , Brodaty Henry
Published: February 2023

Background

Individuals with subjective cognitive complaints (SCCs) are at an increased risk of dementia. Questions remain about participant-reported versus informant-reported SCCs as indicators of future dementia and about longitudinal changes in participant-and informant-reported SCCs and risk of incident dementia.

Method

Participants were 873 older adults (M = 78.65-years; 55% female) and 849 informants from the Sydney Memory and Ageing Study. Comprehensive assessments occurred biennially, and clinical diagnoses were made by expert consensus for 10-years. SCCs were participants’ and informants’ responses to a single binary question concerning their/the participant’s memory decline (Yes/No) over the first 6-years. Categorical latent growth curve analyses, using the logit transformation, were used to model SCC change over time. Associations of initial propensity to report SCCs at baseline, and change in propensity to report SCCs over time, with dementia risk were examined using Cox regression.

Results

70% of participants reported SCCs at baseline, with a proportional increase in the odds of reporting by 11% for each additional year in the study. In contrast, 22% of informants reported SCCs at baseline, with a proportional increase by 30% in the odds of reporting per year. Participants’ initial level of (p = 0.007), but not change in SCC reporting (p = 0.179), was associated with risk of dementia controlling for all covariates. Both informants’ initial level of (p < 0.001), and change in (p < 0.001), SCCs significantly predicted incident dementia. When modelled together, informants’ initial level of, and change in, SCCs were still independently associated with increased dementia risk (p’s < 0.001).

Conclusion

These data suggest that informants’ initial impressions, and increased reporting, of SCCs appear to be uniquely prognostic of future dementia compared to participants’, even based on a single SCC question.
High plasma complement C4 levels as a novel predictor of clinical outcome in intracerebral hemorrhage
Authors: Wu Moxin , Chen Kai , Jiang Min , Xie Fusheng , Cao Xianming , Chen Liang , Chen Zhiying , Yin Xiaoping
Published: February 2023

Objective

The complement cascade is activated and contributes to the brain injury after intracerebral hemorrhage (ICH). Complement component 4 (C4), an important component of complement cascade, has been associated with severity of neurological impairment that occurs during ICH. However, the correlation of plasma complement C4 levels with hemorrhagic severity and clinical outcome in ICH patients has not been reported.

Materials and methods

This study is a monocentric, real-world, cohort study. In this study, we measured the plasma complement C4 levels of 83 ICH patients and 78 healthy controls. The hematoma volume, the National Institutes of Health Stroke Scale (NIHSS) score, the Glasgow Coma Scale (GCS) score, and the permeability surface (PS) were used to assess and quantify neurological deficit following ICH. Logistic regression analysis was configured to determine the independent relation of plasma complement C4 levels to hemorrhagic severity and clinical outcomes. The contribution of complement C4 to secondary brain injury (SBI) was assessed by changes in plasma C4 levels between admission and at day 7 after ICH.

Results

There was a significant elevation of plasma complement C4 levels in ICH patients than in healthy controls (40.48 ± 1.07 vs. 35.25 ± 0.60, p < 0.0001), and the plasma complement C4 levels were closely related to the hemorrhagic severity. Moreover, plasma complement C4 levels of patients were positively correlated with the hematoma volume (r = 0.501, p < 0.001), NIHSS score (r = 0.362, p < 0.001), the GCS score (r = −0.490, p < 0.001), and PS (r = 0.683, p = 0.045) following ICH. Logistic regression analysis also confirmed that patients with high plasma complement C4 levels show a poor clinical outcome after ICH (p < 0.001). Meanwhile, the elevated plasma levels at day 7 after ICH indicated the correlation of complement C4 with SBI (p < 0.01).

Conclusion

Plasma complement C4 levels are significantly elevated in ICH patients and positively correlated with the illness severity. Thus, these findings highlight the importance of complement C4 in brain injury after ICH and provide a novel predictor of clinical outcome for this disease.
Energy drinks at adolescence: Awareness or unawareness?
Authors: Cadoni Cristina , Peana Alessandra Tiziana
Published: February 2023

Energy drinks (EDs) are beverages similar to soft drinks, characterized by high caffeine concentrations with additional ingredients like taurine and vitamins, marketed for boosting energy, reducing tiredness, increasing concentration, and for their ergogenic effect. The majority of consumers are children, adolescents, and young athletes. Although EDs companies claim about the ergogenic and remineralizing properties of their products, there is a serious lack of evidence at preclinical as well as clinical level to validate their benefits. The regular intake and long-term consequences of these caffeinated drinks are not well documented, especially the possible negative effects in adolescents whose brain is still developing. EDs combined with alcohol are also gaining popularity among adolescents and different publications indicate that this combined consumption might increase the risk to develop an alcohol use disorder, as well as produce serious adverse cardiovascular effects. There is an increasing need to disseminate knowledge on EDs damage on health, so that adolescents can be aware about the potential harmful outcomes of consuming these drinks.
A neural learning approach for simultaneous object detection and grasp detection in cluttered scenes
Authors: Zhang Yang , Xie Lihua , Li Yuheng , Li Yuan
Published: February 2023

Object detection and grasp detection are essential for unmanned systems working in cluttered real-world environments. Detecting grasp configurations for each object in the scene would enable reasoning manipulations. However, finding the relationships between objects and grasp configurations is still a challenging problem. To achieve this, we propose a novel neural learning approach, namely SOGD, to predict a best grasp configuration for each detected objects from an RGB-D image. The cluttered background is first filtered out via a 3D-plane-based approach. Then two separate branches are designed to detect objects and grasp candidates, respectively. The relationship between object proposals and grasp candidates are learned by an additional alignment module. A series of experiments are conducted on two public datasets (Cornell Grasp Dataset and Jacquard Dataset) and the results demonstrate the superior performance of our SOGD against SOTA methods in predicting reasonable grasp configurations “from a cluttered scene.”
Headache and orofacial pain: A traffic-light prognosis-based management approach for the musculoskeletal practice
Authors: Greenbaum Tzvika , Emodi-Perlman Alona
Published: February 2023

Introduction

Headache (HA) is one of the most prevalent disabling conditions worldwide and is classified as either primary or secondary. Orofacial pain (OFP) is a frequent pain perceived in the face and/or the oral cavity and is generally distinct from a headache, according to anatomical definitions. Based on the up-to-date classification of the International Headache Society, out of more than 300 specific types of HA only two are directly attributed to the musculoskeletal system: The cervicogenic HA and HA attributed to temporomandibular disorders. Because patients with HA and/or OFP frequently seek help in the musculoskeletal practice, a clear and tailored prognosis-based classification system is required to achieve better clinical outcomes.

Purpose

The aim of perspective article is to suggest a practical traffic-light prognosis-based classification system to improve the management of patients with HA and/or OFP in the musculoskeletal practice. This classification system is based on the best available scientific knowledge based on the unique set-up and clinical reasoning process of musculoskeletal practitioners.

Implications

Implementation of this traffic-light classification system will improve clinical outcomes by helping practitioners invest their time in treating patients with significant involvement of the musculoskeletal system in their clinical presentation and avoid treating patients that are not likely to respond to a musculoskeletal based intervention. Furthermore, this framework incorporates medical screening for dangerous medical conditions, and profiling the psychosocial aspects of each patient; thus follows the biopsychosocial rehabilitation paradigm.
A scoping review of cognitive assessment tools and domains for chemotherapy-induced cognitive impairments in cancer survivors
Authors: Saita Kazuya , Amano Satoru , Kaneko Fumiko , Okamura Hitoshi
Published: February 2023

Backgrounds

Cancer survivors suffer from specific symptoms known as chemotherapy-induced cognitive impairments (CICIs). CICIs are difficult to capture with existing assessments such as the brief screening test for dementia. Although recommended neuropsychological tests (NPTs) exist, international consensus and shared cognitive domains of assessment tools are unknown. The aim of this scoping review was as follows: (1) to identify studies that assess CICIs in cancer survivors; (2) to identify shared cognitive assessment tools and domains by mapping the domains reported in studies using the International Classification of Functioning, Disability and Health (ICF) framework.

Methods

The study followed the recommendations made by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We searched the following three databases through October 2021: PubMed, CINAHL, and Web of Science. Prospective longitudinal or cross-sectional studies were selected to determine CICI-specific assessment tools for adult cancer survivors.

Results

Sixty-four prospective studies (36 longitudinal studies and 28 cross-sectional studies) were included after checking for eligibility. The NPTs were divided into seven main cognitive domains. The specific mental functions were often used in the order of memory, attention, higher-level cognitive functions, and psychomotor functions. Perceptual functions were used less frequently. In some ICF domains, shared NPTs were not clearly identified. In some different domains, the same NPTs were used, such as the trail making test and the verbal fluency test. When the association between the publishing year and the amount of NPT use was examined, it was found that the amount of tool use tended to decline over the publication years. The Functional Assessment of Cancer Therapy-Cognitive function (FACT-Cog) was a shared consensus tool among the patient-reported outcomes (PROs).

Conclusion

Chemotherapy-induced cognitive impairments are currently gaining interest. Shared ICF domains such as memory and attention were identified for NPTs. There was a gap between the publicly recommended tools and the tools actually used in the studies. For PROs, a clearly shared tool, FACT-Cog, was identified. Mapping the domains reported in studies using the ICF can help in the process of reviewing consensus on which NPTs may be used to target cognitive domains.

Systematic review registration

https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053710, identifier UMIN000047104.