bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombomodulin activation driven by LXR agonist attenuates renal injury in diabetic nephropathy
Authors: Wang Wei , Wu Song , Wang Amanda Y. , Wu Tao , Luo Haojun , Zhao Jia Wei , Chen Jin , Li Yi , Ding Hanlu
Published: January 2023

Objective

Inflammation and thrombosis are recognized as interrelated biological processes. Both thrombomodulin (TM) and factor XIII-A (FXIII-A) are involved in inflammation and coagulation process. However, their role in the pathogenesis of diabetic nephropathy (DN) remains unclear. In vitro study, the liver X receptor (LXR) agonist T0901317 can up-regulate the expression of TM in glomerular endothelial cells. Now we evaluated the interaction between TM activation and FXIII-A and their effects against renal injury.

Methods

We first evaluated the serum levels of FXIII-A and TM and the expression of TM, LXR-α and FXIII-A in renal tissues of patients with biopsy-proven DN. We then analyzed the expression of TM, LXR-α and FXIII-A in renal tissues of db/db DN mice after upregulating TM expression via T0901317 or downregulating its expression via transfection of TM shRNA-loaded adenovirus. We also investigated the serum levels of Tumor necrosis factor (TNF)-α, Interleukin (IL)-6, creatinine, and urinary microalbumin level in db/db mice.

Results

Our study showed that elevations in serum levels of FXIII-A positively correlated to the serum levels of TM and were also associated with end-stage kidney disease in patients with DN. The number of TM+ cells in the renal tissues of patients with DN negatively correlated with the number of FXIII-A+ cells and positively correlated with the number of LXR-α+ cells and estimated glomerular filtration rate (eGFR), whereas the number of FXIII-A+ cells negatively correlated with the eGFR.

Conclusion

Thrombomodulin activation with T0901317 downregulated FXIII-A expression in the kidney tissue and alleviated renal injury in db/db mice.
Melanin levels in relation to vitamin D among first-generation immigrants from different ethnic groups and origins: A comparative national Canadian cross-sectional study
Authors: Yousef Said , Papadimitropoulos Manny , Faris MoezAlIslam , Hasan Hayder , Hossain Alomgir , Colman Ian , Manuel Douglas , Wells George A.
Published: January 2023

Introduction

Immigrants to Western countries tend to have darker skin than native-born populations. We examined the relationship between skin melanin and serum vitamin D (vitD) [S-25(OH)D] levels and explored whether melanin levels explained S-25(OH)D variations between immigrants and native-born Canadians. This study offers novel findings as no such study has been conducted.

Methods

We used a national cross-sectional population-based design with data from the Canadian Health Measures Survey (CHMS). Skin melanin levels among first-generation immigrants based on their ethnicity and origin/country of birth were compared with white and native-born populations. We assessed the association between S-25(OH)D and melanin after adjusting for independent variables related to S-25(OH)D, melanin level, and immigration status.

Results

Of 11,579 participants, 21.9% were immigrants aged 3–79 years (mean age 39.23 years). Compared with non-immigrants, immigrants had lower S-25(OH)D levels (mean: 51.23 vs. 62.72; 95% CI: 8.37, 14.62; P < 0.001) but higher melanin levels (mean [SE]: 17.08 [0.25] vs. 16.29 [0.29]; 95% CI: −1.29, −0.281; P = 0.004). Melanin did not differ by length of stay in Canada but was weakly positively correlated (r = 0.088, P < 0.001) with S-25(OH)D. Sex (male), age (≥18 years), summer/fall seasons, sunlight exposure, sunscreen non-use, smoking, and alcohol consumption were associated with higher melanin levels, whereas indoor tanning use was not.

Conclusion

Skin melanin levels were associated with sociodemographic and behavioral characteristics. Immigrants had higher melanin levels, but melanin did not differ by length of stay in Canada. The weak positive correlation between melanin and S-25(OH)D suggested confounding factors may impact the relationship between melanin levels, S-25(OH)D, and immigration status.
Solitary bee larvae modify bacterial diversity of pollen provisions in the stem-nesting bee, Osmia cornifrons (Megachilidae)
Authors: Kueneman Jordan G. , Gillung Jessica , Van Dyke Maria T. , Fordyce Rachel F. , Danforth Bryan N.
Published: January 2023

Microbes, including diverse bacteria and fungi, play an important role in the health of both solitary and social bees. Among solitary bee species, in which larvae remain in a closed brood cell throughout development, experiments that modified or eliminated the brood cell microbiome through sterilization indicated that microbes contribute substantially to larval nutrition and are in some cases essential for larval development. To better understand how feeding larvae impact the microbial community of their pollen/nectar provisions, we examine the temporal shift in the bacterial community in the presence and absence of actively feeding larvae of the solitary, stem-nesting bee,Osmia cornifrons(Megachilidae). Our results indicate that theO.cornifronsbrood cell bacterial community is initially diverse. However, larval solitary bees modify the microbial community of their pollen/nectar provisions over time by suppressing or eliminating rare taxa while favoring bacterial endosymbionts of insects and diverse plant pathogens, perhaps through improved conditions or competitive release. We suspect that the proliferation of opportunistic plant pathogens may improve nutrient availability of developing larvae through degradation of pollen. Thus, the health and development of solitary bees may be interconnected with pollen bacterial diversity and perhaps with the propagation of plant pathogens.
Molluscs—A ticking microbial bomb
Authors: Kijewska Agnieszka , Koroza Aleksandra , Grudlewska-Buda Katarzyna , Kijewski Tomasz , Wiktorczyk-Kapischke Natalia , Zorena Katarzyna , Skowron Krzysztof
Published: January 2023

Bivalve shellfish consumption (ark shells, clams, cockles, and oysters) has increased over the last decades. Following this trend, infectious disease outbreaks associated with their consumption have been reported more frequently. Molluscs are a diverse group of organisms found wild and farmed. They are common on our tables, but unfortunately, despite their great taste, they can also pose a threat as a potential vector for numerous species of pathogenic microorganisms. Clams, in particular, might be filled with pathogens because of their filter-feeding diet. This specific way of feeding favors the accumulation of excessive amounts of pathogenic microorganisms like Vibrio spp., including Vibrio cholerae and V. parahaemolyticus, Pseudomonas aeruginosa, Escherichia coli, Arcobacter spp., and fecal coliforms, and intestinal enterococci. The problems of pathogen dissemination and disease outbreaks caused by exogenous bacteria in many geographical regions quickly became an unwanted effect of globalized food supply chains, global climate change, and natural pathogen transmission dynamics. Moreover, some pathogens like Shewanella spp., with high zoonotic potential, are spreading worldwide along with food transport. These bacteria, contained in food, are also responsible for the potential transmission of antibiotic-resistance genes to species belonging to the human microbiota. Finally, they end up in wastewater, thus colonizing new areas, which enables them to introduce new antibiotic-resistance genes (ARG) into the environment and extend the existing spectrum of ARGs already present in local biomes. Foodborne pathogens require modern methods of detection. Similarly, detecting ARGs is necessary to prevent resistance dissemination in new environments, thus preventing future outbreaks, which could threaten associated consumers and workers in the food processing industry.
Characteristics of lactic acid bacteria, microbial community and fermentation dynamics of native grass silage prepared in Inner Mongolian Plateau
Authors: Hou Meiling , Wang Zhijun , Sun Lin , Jia Yushan , Wang Shicong , Cai Yimin
Published: January 2023

Introduction

To prepare high-quality silage, we studied the chemical composition, silage fermentation, characterization, and identification of lactic acid bacteria (LAB) associated with the silage fermentation of native grass on the Inner Mongolian Plateau.

Methods

LAB were isolated from fresh native grass and their silage, and silages were prepared using a small-scale fermentation system with 2–3 cm length in plastic bags.

Results

The dominant species of native grasses used were Stipa baicalensis, Leymus chinensis, Cleistogenes squarrosa, Melissilus ruthenicus and Pulsatilla turczaninovii, which contained 47.83–59.43 % moisture, 55.12–67.74 % neutral detergent fiber (NDF), and 8.72–14.55 crude protein (CP), and these nutrients did not change greatly during ensiling. Good preservation with a relatively low pH (below 4.44) and high (p < 0.05) lactic acid content (>0.58) was obtained after ensiling. Based on the morphological and biochemical characteristics, these isolates were divided into 12 groups (A-L). All isolate strains were gram-positive and catalase-negative bacteria that produce lactic acid from glucose. Group A-K were cocci, while group L was rod-shaped. Group A-E formed D-lactic acid, but group H-K formed L-lactic acid, and other groups formed DL-lactic acid. Group A-E were heterofermentative, and Group F-L were homofermentative types of LAB. According to the 16S rRNA gene sequences analysis, strains were identified as genus Leuconostoc (A, B, and C), Weissellla (D, E), Pediococcus (F, G), Enterococcus (H, I, J and K), and Lactiplantibacillus (L). Enterococcus (E.) faecium (29.17%, percentage of total isolates) and Pediococcus (P.) acidilactici (18.75%) were the most frequently occurring dominant species.

Discussion

This study suggests that the native grasses contained abundant LAB species, and they can be used as good-quality silages in animal husbandry. In addition, the strains P. acidilactici and E. faecium were the most frequently isolated from native grass silages as dominant species which can be a potentially excellent inoculant for native grass silage.
The co-inoculation of Pseudomonas chlororaphis H1 and Bacillus altitudinis Y1 promoted soybean [Glycine max (L.) Merrill] growth and increased the relative abundance of beneficial microorganisms in rhizosphere and root
Authors: Zhang Wentao , Mao Guohao , Zhuang Jiayao , Yang Hao
Published: January 2023

Currently, plant growth-promoting rhizobacteria (PGPR) microbial inoculants are heavily used in agricultural production among which Pseudomonas sp. and Bacillus sp. are two excellent inoculum strains, which are widely used in plant growth promotion and disease control. However, few studies have been conducted on the combined use of the two bacteria. The aim of this study was to investigate the effects of co-inoculation of these two bacteria on soybean [Glycine max (L.) Merrill] growth and physiological indexes and further study the effect of microbial inoculants on native soil bacterial communities and plant endophyte microbiota, especially microorganisms in rhizosphere and root. A pot experiment was conducted and four treatments were designed: group without any strain inoculant (CK); group inoculated with Pseudomonas chlororaphis H1 inoculant (J); group inoculated with Bacillus altitudinis Y1 inoculant (Y) and group inoculated with equal volume of P. chlororaphis H1 inoculant and B. altitudinis Y1 inoculant (H). Compared with CK, the three inoculant groups J, Y, and H exhibited improved soybean growth and physiological indexes, and group H was the most significant (p < 0.05). In terms of rhizosphere bacterial community structure, the relative abundance of native Luteimonas (9.31%) was higher in the H group than in the J (6.07%), Y (3.40%), and CK (5.69%) groups, which has potential value of disease suppression. Besides, compared with bacterial communities of the other three groups in soybean roots, group H increased the abundance of beneficial bacterial community for the contents of Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Devosia, and Methylobacillus significantly increased (p < 0.05). In conclusion, we found that the composite inoculum of Pseudomonas chlororaphis H1 and Bacillus altitudinis Y1 could effectively promote soybean growth, increase yield and improve the beneficial bacterial community in root and rhizosphere and have certain value for soil improvement.
Comparative transcriptomic analyzes of human lung epithelial cells infected with wild-type SARS-CoV-2 and its variant with a 12-bp missing in the E gene
Authors: Sun Yi-Sheng , Sun Hao , Zhu Han-Ping , Li Gao-Lei , Xu Fang , Lu Hang-Jing , Tang An , Wu Bei-Bei , Li Yu-Dong , Yao Ping-Ping , Jiang Jian-Min
Published: January 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused a global outbreak of coronavirus disease 2019 (COVID-19) pandemic. To elucidate the mechanism of SARS-CoV-2 replication and immunogenicity, we performed a comparative transcriptome profile of mRNA and long non-coding RNAs (lncRNAs) in human lung epithelial cells infected with the SARS-CoV-2 wild-type strain (8X) and the variant with a 12-bp deletion in the E gene (F8). In total, 3,966 differentially expressed genes (DEGs) and 110 differentially expressed lncRNA (DE-lncRNA) candidates were identified. Of these, 94 DEGs and 32 DE-lncRNAs were found between samples infected with F8 and 8X. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzes revealed that pathways such as the TNF signaling pathway and viral protein interaction with cytokine and cytokine receptor were involved. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to the immune response, which might explain the different replication and immunogenicity properties of the 8X and F8 strains. These results provide a useful resource for studying the pathogenesis of SARS-CoV-2 variants.
Effect of different phosphate sources on uranium biomineralization by the Microbacterium sp. Be9 strain: A multidisciplinary approach study
Authors: Martínez-Rodríguez Pablo , Sánchez-Castro Iván , Ojeda Jesús J. , Abad María M. , Descostes Michael , Merroun Mohamed Larbi
Published: January 2023

Introduction

Industrial activities related with the uranium industry are known to generate hazardous waste which must be managed adequately. Amongst the remediation activities available, eco-friendly strategies based on microbial activity have been investigated in depth in the last decades and biomineralization-based methods, mediated by microbial enzymes (e.g., phosphatase), have been proposed as a promising approach. However, the presence of different forms of phosphates in these environments plays a complicated role which must be thoroughly unraveled to optimize results when applying this remediation process.

Methods

In this study, we have looked at the effect of different phosphate sources on the uranium (U) biomineralization process mediated by Microbacterium sp. Be9, a bacterial strain previously isolated from U mill tailings. We applied a multidisciplinary approach (cell surface characterization, phosphatase activity, inorganic phosphate release, cell viability, microscopy, etc.).

Results and Discussion

It was clear that the U removal ability and related U interaction mechanisms by the strain depend on the type of phosphate substrate. In the absence of exogenous phosphate substrate, the cells interact with U through U phosphate biomineralization with a 98% removal of U within the first 48 h. However, the U solubilization process was the main U interaction mechanism of the cells in the presence of inorganic phosphate, demonstrating the phosphate solubilizing potential of the strain. These findings show the biotechnological use of this strain in the bioremediation of U as a function of phosphate substrate: U biomineralization (in a phosphate free system) and indirectly through the solubilization of orthophosphate from phosphate (P) containing waste products needed for U precipitation.
Molecular mechanisms of Phytophthora sojae avirulence effectors escaping host recognition
Authors: Hou Xiaoyuan , He Zheng , Che Zhengzheng , Li Hengjing , Tan Xinwei , Wang Qunqing
Published: January 2023

Phytophthora sojae is a well-known destructive oomycete pathogen, which causes soybean stem and root rot and poses a serious threat to global food security. Growing soybean cultivars with the appropriate resistance to P. sojae (Rps) genes are the primary management strategy to reduce losses. In most Phytophthora pathosystems, host resistance protein encoded by a specific R gene in the plant recognizes corresponding RxLR effector protein, encoded by an avirulence gene. This gene-for-gene relationship has been exploited to help breeders and agronomists deploy soybean cultivars. To date, 6 Rps genes have been incorporated into commercial soybean germplasm and trigger plant immunity in response to 8 P. sojae avirulence effectors. The incorporation of Rps genes in the soybean population creates selection pressure in favor of novel pathotypes of P. sojae. The 8 avirulence genes evolved to evade the host immune system, driven by genetic selection pressures. Understanding the evading strategies has important reference value for the prevention and control of Phytophthora stem and root rot. This investigation primarily highlights the research on the strategies of P. sojae avirulence effector evasion of host recognition, looking forward to creating durable resistance genes and thereby enabling successful disease management.
Twisting and swiveling domain motions in Cas9 to recognize target DNA duplexes, make double-strand breaks, and release cleaved duplexes
Authors: Wang Jimin , Arantes Pablo R. , Ahsan Mohd , Sinha Souvik , Kyro Gregory W. , Maschietto Federica , Allen Brandon , Skeens Erin , Lisi George P. , Batista Victor S. , Palermo Giulia
Published: January 2023

The CRISPR-associated protein 9 (Cas9) has been engineered as a precise gene editing tool to make double-strand breaks. CRISPR-associated protein 9 binds the folded guide RNA (gRNA) that serves as a binding scaffold to guide it to the target DNA duplex via a RecA-like strand-displacement mechanism but without ATP binding or hydrolysis. The target search begins with the protospacer adjacent motif or PAM-interacting domain, recognizing it at the major groove of the duplex and melting its downstream duplex where an RNA-DNA heteroduplex is formed at nanomolar affinity. The rate-limiting step is the formation of an R-loop structure where the HNH domain inserts between the target heteroduplex and the displaced non-target DNA strand. Once the R-loop structure is formed, the non-target strand is rapidly cleaved by RuvC and ejected from the active site. This event is immediately followed by cleavage of the target DNA strand by the HNH domain and product release. Within CRISPR-associated protein 9, the HNH domain is inserted into the RuvC domain near the RuvC active site via two linker loops that provide allosteric communication between the two active sites. Due to the high flexibility of these loops and active sites, biophysical techniques have been instrumental in characterizing the dynamics and mechanism of the CRISPR-associated protein 9 nucleases, aiding structural studies in the visualization of the complete active sites and relevant linker structures. Here, we review biochemical, structural, and biophysical studies on the underlying mechanism with emphasis on how CRISPR-associated protein 9 selects the target DNA duplex and rejects non-target sequences.
Computational protein design repurposed to explore enzyme vitality and help predict antibiotic resistance
Authors: Michael Eleni , Saint-Jalme Rémy , Mignon David , Simonson Thomas
Published: January 2023

In response to antibiotics that inhibit a bacterial enzyme, resistance mutations inevitably arise. Predicting them ahead of time would aid target selection and drug design. The simplest resistance mechanism would be to reduce antibiotic binding without sacrificing too much substrate binding. The property that reflects this is the enzyme “vitality”, defined here as the difference between the inhibitor and substrate binding free energies. To predict such mutations, we borrow methodology from computational protein design. We use a Monte Carlo exploration of mutation space and vitality changes, allowing us to rank thousands of mutations and identify ones that might provide resistance through the simple mechanism considered. As an illustration, we chose dihydrofolate reductase, an essential enzyme targeted by several antibiotics. We simulated its complexes with the inhibitor trimethoprim and the substrate dihydrofolate. 20 active site positions were mutated, or “redesigned” individually, then in pairs or quartets. We computed the resulting binding free energy and vitality changes. Out of seven known resistance mutations involving active site positions, five were correctly recovered. Ten positions exhibited mutations with significant predicted vitality gains. Direct couplings between designed positions were predicted to be small, which reduces the combinatorial complexity of the mutation space to be explored. It also suggests that over the course of evolution, resistance mutations involving several positions do not need the underlying point mutations to arise all at once: they can appear and become fixed one after the other.
Perspective: Disentangling the effects of tES on neurovascular unit
Authors: Arora Yashika , Dutta Anirban
Published: January 2023

Transcranial electrical stimulation (tES) can modulate the neurovascular unit, including the perivascular space morphology, but the mechanisms are unclear. In this perspective article, we used an open-source “rsHRF toolbox” and an open-source functional magnetic resonance imaging (fMRI) transcranial direct current stimulation (tDCS) data set to show the effects of tDCS on the temporal profile of the haemodynamic response function (HRF). We investigated the effects of tDCS in the gray matter and at three regions of interest in the gray matter, namely, the anodal electrode (FC5), cathodal electrode (FP2), and an independent site remote from the electrodes (PZ). A “canonical HRF” with time and dispersion derivatives and a finite impulse response (FIR) model with three parameters captured the effects of anodal tDCS on the temporal profile of the HRF. The FIR model showed tDCS onset effects on the temporal profile of HRF for verum and sham tDCS conditions that were different from the no tDCS condition, which questions the validity of the sham tDCS (placebo). Here, we postulated that the effects of tDCS onset on the temporal profile of HRF are subserved by the effects on neurovascular coupling. We provide our perspective based on previous work on tES effects on the neurovascular unit, including mechanistic grey-box modeling of the effects of tES on the vasculature that can facilitate model predictive control (MPC). Future studies need to investigate grey-box modeling of online effects of tES on the neurovascular unit, including perivascular space, neurometabolic coupling, and neurovascular coupling, that can facilitate MPC of the tES dose-response to address the momentary (“state”) and phenotypic (“trait”) factors.
Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features
Authors: Papasavva Maria , Vikelis Michail , Siokas Vasileios , Katsarou Martha-Spyridoula , Dermitzakis Emmanouil V. , Raptis Athanasios , Kalliantasi Aikaterini , Dardiotis Efthimios , Drakoulis Nikolaos
Published: January 2023

Introduction

Migraine is a complex disorder with genetic and environmental inputs. Cumulative evidence implicates oxidative stress (OS) in migraine pathophysiology while genetic variability may influence an individuals' oxidative/antioxidant capacity. Aim of the current study was to investigate the impact of eight common OS-related genetic variants [rs4880 (SOD2), rs1001179 (CAT), rs1050450 (GPX1), rs1695 (GSTP1), rs1138272 (GSTP1), rs1799983 (NOS3), rs6721961 (NFE2L2), rs660339 (UCP2)] in migraine susceptibility and clinical features in a South-eastern European Caucasian population.

Methods

Genomic DNA samples from 221 unrelated migraineurs and 265 headache-free controls were genotyped for the selected genetic variants using real-time PCR (melting curve analysis).

Results

Although allelic and genotypic frequency distribution analysis did not support an association between migraine susceptibility and the examined variants in the overall population, subgroup analysis indicated significant correlation between NOS3 rs1799983 and migraine susceptibility in males. Furthermore, significant associations of CAT rs1001179 and GPX1 rs1050450 with disease age-at-onset and migraine attack duration, respectively, were revealed. Lastly, variability in the CAT, GSTP1 and UCP2 genes were associated with sleep/weather changes, alcohol consumption and physical exercise, respectively, as migraine triggers.

Discussion

Hence, the current findings possibly indicate an association of OS-related genetic variants with migraine susceptibility and clinical features, further supporting the involvement of OS and genetic susceptibility in migraine.
Characterization of a lactate metabolism-related signature for evaluation of immune features and prediction prognosis in glioma
Authors: Wu Zhiqiang , Wang Jing , Li Yanan , Liu Jianmin , Kang Zijian , Yan Wangjun
Published: January 2023

Background

Glioma is one of the most typical tumors in the central nervous system with a poor prognosis, and the optimal management strategy remains controversial. Lactate in the tumor microenvironment is known to promote cancer progression, but its impact on clinical outcomes of glioma is largely unknown.

Methods

Glioma RNA-seq data were obtained from TCGA and GCGA databases. Lactate metabolism genes (LMGs) were then evaluated to construct an LMG model in glioma using Cox and LASSO regression. Immune cell infiltration, immune checkpoint gene expression, enriched pathways, genetic alteration, and drug sensitivity were compared within the risk subgroups. Based on the risk score and clinicopathological features, a nomogram was developed to predict prognosis in patients with glioma.

Results

Five genes (LDHA, LDHB, MRS2, SL16A1, and SL25A12) showed a good prognostic value and were used to construct an LMG-based risk score. This risk score was shown as an independent prognostic factor with good predictive power in both training and validation cohorts (p < 0.001). The LMG signature was found to be correlated with the expression of immune checkpoint genes and immune infiltration and could shape the tumor microenvironment. Genetic alteration, dysregulated metabolism, and tumorigenesis pathways could be the underlying contributing factors that affect LMG risk stratification. The patients with glioma in the LMG high-risk group showed high sensitivity to EGFR inhibitors. In addition, our nomogram model could effectively predict overall survival with an area under the curve value of 0.894.

Conclusion

We explored the characteristics of LMGs in glioma and proposed an LMG-based signature. This prognostic model could predict the survival of patients with glioma and help clinical oncologists plan more individualized and effective therapeutic regimens.
Effectiveness of smart health-based rehabilitation on patients with poststroke dysphagia: A brief research report
Authors: Zhang Jian-Rong , Wu Yu-E , Huang Yan-Fang , Zhang Shu-Qing , Pan Wen-Li , Huang Jin-Xia , Huang Qing-Ping
Published: January 2023

Objective

This study aimed to evaluate the effectiveness of smart health-based rehabilitation on patients with poststroke dysphagia (PSD).

Methods

We recruited 60 PSD patients and randomly allocated them to the intervention (n= 30) and control (n= 30) groups. The former received the smart health-based rehabilitation for 12 weeks, whereas the latter received routine rehabilitation. Water swallow test (WST), standardized swallowing assessment (SSA), swallow quality-of-life questionnaire (SWAL-QOL), stroke self-efficacy questionnaire (SSEQ), perceived social support scale (PSSS) and nutritional measurements including body weight, triceps skinfold thickness (TSF), total protein (TP), serum albumin (ALB) and serum prealbumin (PA) in both groups were measured.

Results

When the baseline WST, SSA, SWAL-QOL, SSEQ, PSSS and nutritional measurements were examined, there was no significant difference between the intervention group and the control group (P> 0.05). After rehabilitation interventions, the WST and SSA scores in the intervention group were significantly lower than those in the control group (P< 0.01). The SWAL-QOL, SSEQ and PSSS scores in the intervention group were significantly higher than in the control group (P< 0.01). Compared with the control group, the intervention group showed an increase in the serum levels of PA (P< 0.01). However, no statistically significant difference existed between the intervention group and the control group in terms of body weight, TSF, TP or ALB (P> 0.05).

Conclusions

Overall, our data revealed that smart health-based rehabilitation is significantly beneficial to the swallowing function, quality of life, self-efficacy, and social support for PSD patients when compared with routine rehabilitation. However, nutritional measurements were not significantly improved in such patients under the smart health-based rehabilitation when compared the routine rehabilitation. In the future, it is necessary to extend the intervention time to further evaluate the long-term efficacy of smart health-based rehabilitation on nutritional measurements of PSD patients.
Lactobacillus plantarum ZJUIDS14 alleviates non-alcoholic fatty liver disease in mice in association with modulation in the gut microbiota
Authors: Cao Feiwei , Ding Qinchao , Zhuge Hui , Lai Shanglei , Chang Kaixin , Le Chunyan , Yang Guorong , Valencak Teresa G. , Li Songtao , Ren Daxi
Published: January 2023

This present study was designed to explore the protective role of Lactobacillus plantarum ZJUIDS14 against Non-alcoholic Fatty Liver Disease (NAFLD) in a high-fat-diet (HFD)-induced C57BL/6 mice model. The probiotic (109 CFU/every other day) was administered by oral gavage for 12 weeks. We found that L. plantarum ZJUIDS14 intervention significantly alleviated HFD related hepatic steatosis, liver damage, insulin resistance, and increased hepatic expression of peroxisome proliferator activated receptor α (PPAR-α) while stimulating the activation of AMP-activated protein kinase (AMPK). Furthermore, L. plantarum ZJUIDS14 improved mitochondrial function as reflected by an increase in dynamin related protein 1 (DRP1) and a decrease of proteins associated with oxidative phosphorylation (OXPHOS) after the treatment. Additionally, mice from the L. plantarum ZJUIDS14 group had a restored intestinal flora and homeostasis involving Coprostanoligenes group, Ruminococcaceae UCG-014, Allobaculum, Ruminiclostridium 1, and Roseburia. Meanwhile, these five genera exhibited a significant (negative or positive) association with ileum inflammation mRNA levels and SCFA contents, by Spearman’s correlation analysis. In general, our data demonstrated that L. plantarum ZJUIDS14 mitigates hepatic steatosis and liver damage induced by HFD. Specifically, they strengthened the integrity of the intestinal barrier, regulated gut microbiota, and improved mitochondrial function. Our data provide an experimental basis for L. plantarum ZJUIDS14 as a promising candidate to prevent NAFLD.
Highly catalytic nanoenzyme of covalent organic framework loaded starch- surface-enhanced Raman scattering/absorption bi-mode peptide as biosensor for ultratrace determination of cadmium
Authors: Li Jingjing , Shu Yiyi , Li Chongning , Jiang Zhiliang
Published: January 2023

High affinity peptides (PTs) have been used in nanoanalysis, but there are no reports which combine PTs with a liquid crystal (LC) covalent organic framework (COF) supported soluble starch (SS) catalytic amplification system as a biosensor recognition element. In this study, a new, highly sensitive and selective bi-mode molecular biosensor has been developed for the determination of cadmium ion (Cd2+). Specifically, a highly catalytic and stable COF supported SS nanosol catalyst was fabricated such that a nanocatalytic indicator reaction system for HAuCl4-sodium formate was established based on surface-enhanced Raman scattering (SERS). The Au nanoparticles produced exhibited a surface plasmon resonance (SPR) absorption peak at 535 nm and a SERS peak at 1,615 cm–1. Combining the nanocatalytic amplification indicator system with the specific PTs reaction permitted a sensitive and selective SERS/absorption bi-mode platform to be developed for the determination of cadmium in rice. The linear range for SERS determination was 0.025–0.95 nmol/L and the detection limit (DL) was 0.012 nmol/L.
Dietary supplement of mushrooms promotes SCFA production and moderately associates with IgA production: A pilot clinical study
Authors: Nishimoto Yuichiro , Kawai Junya , Mori Koichiro , Hartanto Tenagy , Komatsu Kaori , Kudo Toru , Fukuda Shinji
Published: January 2023

Background

Mushrooms are rich in dietary fiber, and fiber intake has been reported to increase the levels of short-chain fatty acids (SCFAs). It has also been reported that SCFAs promote immunoglobulin A (IgA) production, indicating involvement in systemic immunity.

Objectives

The objective of this study was to evaluate the effects of mushroom consumption on the amount of intestinal IgA. We also aimed to comprehensively evaluate the gut microbiota and intestinal metabolome and to conduct an exploratory analysis of their relationship with IgA.

Methods

Healthy adults (n = 80) were enrolled in a parallel group trial. Participants consumed a diet with mushrooms or a placebo diet once daily for 4 weeks. Gut microbiota profiles were assessed by sequencing the bacterial 16S ribosomal RNA-encoding gene. Intestinal metabolome profiles were analyzed using capillary electrophoresis-time of flight mass spectrometry (CE-TOFMS).

Results

Mushroom consumption tended to increase IgA levels at 4 weeks of consumption compared to those in the control group (p = 0.0807; Hedges’ g = 0.480). The mushroom group had significantly higher levels of intestinal SCFAs, such as butyrate and propionate, than the control group (p = 0.001 and 0.020; Hedges’ g = 0.824 and 0.474, respectively). Correlation analysis between the changes in the amount of intestinal IgA and the baseline features of the intestinal environment showed that the increasing amount of intestinal IgA was positively correlated with the baseline levels of SCFAs (Spearman’s R = 0.559 and 0.419 for butyrate and propionate, respectively).

Conclusion

Consumption of mushrooms significantly increased the intestinal SCFAs and IgA in some subjects. The increase in intestinal IgA levels was more prominent in subjects with higher SCFA levels at baseline. This finding provides evidence that mushroom alters the intestinal environment, but the intensity of the effect still depends on the baseline intestinal environment. This trial was registered at www.umin.ac.jp as UMIN000043979.
Canine oral squamous cell carcinoma as a spontaneous, translational model for radiation and immunology research
Authors: Boss Mary-Keara , Harrison Lauren G. , Gold Alexandra , Karam Sana D. , Regan Daniel P.
Published: January 2023

Introduction

Improving outcomes for oral squamous cell carcinoma (OSCC) patients has been hindered by a lack of effective predictive animal models. Spontaneously occurring canine OSCC could help fill this gap. The objective of this study was to characterize the immune landscape of canine OSCC to advance understanding of how dogs could serve as a surrogate for human OSCC.

Methods/Results

Canine OSCC contains a heterogenous tumor immune microenvironment. CD3+ T cells were the predominant tumor infiltrating immune cell population; however, there was a wide range CD3+ T cell density across samples. The most common CD3+ T cell micro-anatomical distribution was defined as “pre-existing immunity”, but the remaining 20% of tumors were characterized as “immunologically ignorant” or “excluded infiltrates” patterns. When compared to normal oral mucosa, the tumor gene expression pattern suggests that canine OSCC microenvironment is highly inflamed and characterized by the presence of an anti-tumor immune response dominated by cytotoxic\effector T cells and NK cells (CD8a, GZMA, OX40, and HLA-A); however, overexpression of genes associated with effector T cell exhaustion and microenvironmental immunosuppression was also identified (PD-1, LAG3, CXCL2). Correlations between CD3+ T cell density and immune gene expression revealed key genes associated with cytotoxic anti-tumor T cell responses (GZMA, GZMB, PRF1), co-stimulation of T cells (CD27, CD28, ICOS), and other immune processes, including Type I IFN response (TNF, TNFSF10), and T cell exhaustion (CTLA4, PD-1). CD3+ T cell density in canine OSCC was significantly correlated with a cytolytic activity score (mean PRF1 and GZMA expression), suggestive of active effector CD8 T cell function. CD204+ macrophages were the second most abundant tumor infiltrating immune cell, and when comparing to normal oral mucosa, two differently expressed genes linked to tumor associated macrophages and myeloid derived suppressor cells (MDSC) were identified: CXCL2, CD70. Overexpression of CXCL2 was also identified in canine OSCC “T cell-high” tumors compared to “T cell-low” tumors.

Discussion

This study identified actionable immunotherapy targets which could inform future comparative oncology trials in canine OSCC: CTLA-4, PD-1, CXCL2. These data provide a good first step towards utilizing spontaneous canine OSCC as a comparative model for human OSCC radiation and immuno-oncology research.
Artificial intelligence applied in neoantigen identification facilitates personalized cancer immunotherapy
Authors: Cai Yu , Chen Rui , Gao Shenghan , Li Wenqing , Liu Yuru , Su Guodong , Song Mingming , Jiang Mengju , Jiang Chao , Zhang Xi
Published: January 2023

The field of cancer neoantigen investigation has developed swiftly in the past decade. Predicting novel and true neoantigens derived from large multi-omics data became difficult but critical challenges. The rise of Artificial Intelligence (AI) or Machine Learning (ML) in biomedicine application has brought benefits to strengthen the current computational pipeline for neoantigen prediction. ML algorithms offer powerful tools to recognize the multidimensional nature of the omics data and therefore extract the key neoantigen features enabling a successful discovery of new neoantigens. The present review aims to outline the significant technology progress of machine learning approaches, especially the newly deep learning tools and pipelines, that were recently applied in neoantigen prediction. In this review article, we summarize the current state-of-the-art tools developed to predict neoantigens. The standard workflow includes calling genetic variants in paired tumor and blood samples, and rating the binding affinity between mutated peptide, MHC (I and II) and T cell receptor (TCR), followed by characterizing the immunogenicity of tumor epitopes. More specifically, we highlight the outstanding feature extraction tools and multi-layer neural network architectures in typical ML models. It is noted that more integrated neoantigen-predicting pipelines are constructed with hybrid or combined ML algorithms instead of conventional machine learning models. In addition, the trends and challenges in further optimizing and integrating the existing pipelines are discussed.
The risk of oral squamous cell carcinoma in patients with and without somatoform disorders including bruxism: A retrospective evaluation of 309,278 individuals
Authors: Heym Marlene , Heiland Max , Preissner Robert , Huebel Christopher , Nahles Susanne , Schmidt-Westhausen Andrea Maria , Preissner Saskia , Hertel Moritz
Published: January 2023

Background

The question arises if there is an association of psycho-emotional stress and chronic soft tissue injuries caused by bruxism somatoform disorders with oral squamous cell carcinoma (OSCC).

Methods

Patients with and without “somatoform disorders including psychogenic disturbances” (International Classification of Diseases [ICD]-10 code F45.8), and/or “unspecific behavioral syndromes” (F59), and/or “sleep related bruxism” (G47.63), and/or “other sleep disorders” (G47.8) were retrieved from the TriNetX network to gain cohort I. Cohort II was formed by patients without the aforementioned diagnoses, and by matching for age, gender, tobacco use, and alcohol abuse. After defining the primary outcome as “OSCC” (ICD-10 codes C00−C14), a Kaplan-Meier analysis was performed, and risk ratio (RR) and odds ratio (OR) were calculated.

Results

After matching, each cohort accounted for 154,639 patients (59.7% females; 40.3% males; mean current age (± standard deviation) = 43.4 ± 24.5 years). Among cohorts I and II, 907 and 763 patients, respectively, were diagnosed with OSCC within 5 years (risk of OSCC = 0.6% and 0.5%), whereby the risk difference was significant (p < 0.001; Log-Rank test). RR and OR were 1.19 (95% confidence interval (CI), lower = 1.08 and upper = 1.31) and 1.19 (95% CI, 1.08−1.31).

Conclusions

Psycho-emotional stress and/or chronic mucosal injuries may play a role in carcinogenesis. However, the results need to be interpreted cautiously due to limitations of the applied approach. It may thus far only be concluded that further research is necessary to investigate hypotheses regarding psychogenic carcinogenesis and tumor formation due to chronic tissue trauma.
Targeting lncRNAs of colorectal cancers with natural products
Authors: Sung Woo Jung , Hong Jaewoo
Published: January 2023

Non-coding RNA (ncRNA) is one of the functional classes of RNA that has a regulatory role in various cellular processes, such as modulation of disease onset, progression, and prognosis. ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been actively studied in recent years. The change in ncRNA levels is being actively studied in numerous human diseases, especially auto-immune disorders and cancers; however, targeting and regulating ncRNA with natural products to cure cancer has not been fully established. Recently many groups reported the relationship between ncRNA and natural products showing promising effects to serve as additional therapeutic approaches to cure cancers. This mini-review summarizes the aspects of lncRNAs related to cancer biology focusing on colorectal cancers that natural products can target.
A novel strategy for bioactive natural products targeting NLRP3 inflammasome in Alzheimer’s disease
Authors: Yang Zhiyou , Liu Junxin , Wei Shuai , Deng Jiahang , Feng Xinyue , Liu Shucheng , Liu Mingxin
Published: January 2023

Alzheimer’s disease (AD), the most common type of dementia, is an ageing-related progressive neurodegenerative brain disorder. Extracellular neuritic plaques composed of misfolded amyloid β (Aβ) proteins and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein are the two classical characteristics of AD. Aβ and tau pathologies induce neurite atrophy and neuronal apoptosis, leading to cognitive, language, and behavioral deficits. For decades, researchers have made great efforts to explore the pathogens and therapeutics of AD; however, its intrinsic mechanism remains unclear and there are still no well-established strategies to restore or even prevent this disease. Therefore, it would be beneficial for the establishment of novel therapeutic strategy to determine the intrinsic molecular mechanism that is interrelated with the initiation and progression of AD. A variety of evidence indicates that neuroinflammation plays a crucial role in the pathogenesis of AD. Nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3) is a key inflammasome sensor of cellular stress and infection that is involved in the innate immune system. In response to a wide range of stimuli like Aβ, NLRP3 assembles apoptosis-associated speck-like protein (ASC) and procaspase-1 into an inflammasome complex to induce the caspase-1 mediated secretion of interleukin (IL)-1β/IL-18 in M1 polarized microglia, triggering the pathophysiological changes and cognitive decline of AD. Therefore, targeting NLRP3 inflammasome seems an efficient path for AD treatment via regulating brain immune microenvironment. Furthermore, accumulating evidence indicates that traditional Chinese medicine (TCM) exerts beneficial effects on AD via NLRP3 inflammasome inactivation. In this review, we summarize current reports on the role and activated mechanisms of the NLRP3 inflammasome in the pathogenesis of AD. We also review the natural products for attenuating neuroinflammation by targeting NLRP3 inflammasome activation, which provides useful clues for developing novel AD treatments.
Dang Gui Bu Xue Tang, a conventional Chinese herb decoction, ameliorates radiation-induced heart disease via Nrf2/HMGB1 pathway
Authors: Huang Yifan , Cheng Minghan , Wang Xiaoye , Dong Hongliang , Gao Jian
Published: January 2023

Introduction: Radiation-induced heart disease (RIHD), characterized by cardiac dysfunction and myocardial fibrosis, is one of the most common complications after cardiothoracic radiotherapy. Dang Gui Bu Xue Tang (DBT) is a conventional Chinese herb decoction composed of Radix Astragali membranaceus (RAM) and Radix Angelicae sinensis (RAS) at a ratio of 5:1, famous for its “blood-nourishing” effect. In this study, we aimed to investigate the cardioprotective effect of DBT on RIHD.

Methods: C57BL mice at 8 weeks of age were divided into five groups, namely Control, Radiation, RDBT51 (Radiation with DBT, RAM:RAS = 5:1), RDBT11 (Radiation with DBT, RAM:RAS = 1:1), and RDBT15 (Radiation with DBT, RAM:RAS = 1:5).

Results: We mainly found that radiation in the cardiothoracic region led to significant left ventricular systolic dysfunction, myocardial fibrotic lesions and cardiac injury accompanied by abnormally increased myocardial HMGB1 protein levels. Administration of conventional DBT significantly ameliorated left ventricular systolic dysfunction, alleviated myocardial fibrosis, and counteracted cardiac injury, all of which supported the protective effect of DBT on RIHD, involving upregulation of myocardial Nrf2 protein levels and downregulation of HMGB1 protein levels as underlying mechanisms.

Conclusions: DBT exerts a significant protective effect on RIHD, and the Nrf2/ HMGB1 pathway probably plays an important role in this protective effect.
Ganoderma lucidum: Current advancements of characteristic components and experimental progress in anti-liver fibrosis
Authors: Peng Haoyuan , Zhong Lei , Cheng Lin , Chen Lu , Tong Rongsheng , Shi Jianyou , Bai Lan
Published: January 2023

Ganoderma lucidum (G. lucidum, Lingzhi) is a well-known herbal medicine with a variety of pharmacological effects. Studies have found that G. lucidum has pharmacological effects such as antioxidant, antitumor, anti-aging, anti-liver fibrosis, and immunomodulation. The main active components of G. lucidum include triterpenoids, polysaccharides, sterols, peptides and other bioactive components. Among them, the triterpenoids and polysaccharide components of G. lucidum have a wide range of anti-liver fibrotic effects. Currently, there have been more reviews and studies on the antioxidant, antitumor, and anti-aging properties of G. lucidum. Based on the current trend of increasing number of liver fibrosis patients in the world, we summarized the role of G.lucidum extract in anti-liver fibrosis and the effect of G. lucidum extract on liver fibrosis induced by different pathogenesis, which were discussed and analyzed. Research and development ideas and references are provided for the subsequent application of G. lucidum extracts in anti-liver fibrosis treatment.