Achromobacter seleniivolatilans sp. nov. and Buttiauxella selenatireducens sp. nov., isolated from the rhizosphere of selenium hyperaccumulator Cardamine hupingshanesis.

Two Gram-stain-negative bacterial strains, R39T and R73T, were isolated from the rhizosphere soil of the selenium hyperaccumulator Cardamine hupingshanesis in China. Strain R39T transformed selenite into elemental and volatile selenium, whereas strain R73T transformed both selenate and selenite into elemental selenium. Phylogenetic and phylogenomic analyses indicated that strain R39T belonged to the genus Achromobacter, while strain R73T belonged to the genus Buttiauxella. Strain R39T (genome size, 6.68 Mb; G+C content, 61.6 mol%) showed the closest relationship to Achromobacter marplatensis LMG 26219T and Achromobacter kerstersii LMG 3441T, with average nucleotide identity (ANI) values of 83.6 and 83.4 %, respectively. Strain R73T (genome size, 5.22 Mb; G+C content, 50.3 mol%) was most closely related to Buttiauxella ferragutiae ATCC 51602T with an ANI value of 86.4 %. Furthermore, strain A111 from the GenBank database was found to cluster with strain R73T within the genus Buttiauxella through phylogenomic analyses. The ANI and digital DNA-DNA hybridization values between strains R73T and A111 were 97.5 and 80.0% respectively, indicating that they belong to the same species. Phenotypic characteristics also differentiated strain R39T and strain R73T from their closely related species. Based on the polyphasic analyses, strain R39T and strain R73T represent novel species of the genera Achromobacter and Buttiauxella, respectively, for which the names Achromobacter seleniivolatilans sp. nov. (type strain R39T=GDMCC 1.3843T=JCM 36009T) and Buttiauxella selenatireducens sp. nov. (type strain R73T=GDMCC 1.3636T=JCM 35850T) are proposed.

Mechanically Excellent, Notch-Insensitive, and Highly Conductive Double-Network Hydrogel for Flexible Strain Sensor.

A novel double-network conductive hydrogel based on lithium acetate/gelatin/polyacrylamide (PAAM) was synthesized by heating-cooling and subsequent γ-ray radiation-induced polymerization and cross-linking. Owing to the hydrogen bonding interaction between lithium acetate, physical cross-linked gelatin, and chemical cross-linked PAAM, the resultant hydrogel exhibited high tensile strength (1260 kPa), high ionic conductivity (35.2 mS cm-1), notch-insensitivity (tensile strength 415 kPa, elongation at break 872% with transverse notch), and extensive strain monitoring range (0.15-800%) under optimum conditions. The lithium acetate/gelatin/polyacrylamide hydrogel strain sensor attached to the skin can sensitively monitor the subtle movements of the human body. The strain sensor based on the resultant hydrogel with transverse notch can still work for 1200 cycles, due to that the covalent-cross-linked PAAm chain bridges the cracks and stabilizes the deformation, while the physical-cross-linked gelatin was unzipped to make the blunting of notch. The conductive hydrogel with high-sensitivity and high stability is expected to be used as materials for the preparation of flexible strain sensors in the future.

Comparison of neoadjuvant chemotherapy response and prognosis between HR-low/HER2-negative BC and TNBC: an exploratory real-world multicentre cohort study.

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.

Comparison of efficacy of acupuncture-related therapies in treating Acute Gouty Arthritis: A Network Meta-Analysis of Randomized Controlled Trials.

Background: and purpose: Acupuncture and moxibustion, as a complementary and alternative therapy, has been widely used in the treatment of acute gouty arthritis (AGA). However, there are various forms of acupuncture and moxibustion, and the curative effect of different forms is different. This study evaluated the clinical efficacy of different acupuncture therapies in treating AGA by network meta-analysis. Methods: Computer searches of English databases (including PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Embase) and Chinese databases (including China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database and China Biomedical Literature Database) were conducted for randomized controlled trials (RCTs) of acupuncture therapies in treating AGA. We set the search time from the database establishment to May 2022. Data analysis was performed using Stata14.2 software. Results: Thirty-two RCTs involving 2434 patients with AGA were screened out. The results showed that in terms of the improvement of pain visual analogue scale (VAS) scores, the top ones were acupoint application (100%), electroacupuncture + Western medicine (73.5%) and acupuncture + Western medicine (69.2%); In terms of total effective rate, acupoint application (85.2%), acupuncture (75.2%) and acupuncture + Western medicine (63%) ranked the top; In terms of reducing serum uric acid (SUA) levels, the top ones were acupoint application (95%), acupuncture + Western medicine (87.5%) and acupuncture (66.2%); In terms of the reduction of erythrocyte sedimentation rate (ESR), acupuncture (95%), acupoint application (84.7%), and electroacupuncture + Western medicine (52.8%) were the most prominent. Conclusion: The existing evidence shows that acupoint application has more advantages in improving the total effective rate, improving pain and reduce SUA levels, and acupuncture has an advantage in reducing ESR levels and adverse events. However, due to the low qualities of the original studies, the quality of this evidence is poor. Therefore, it is recommended that more scientific research be performed to confirm the efficacy of acupuncture.

MMR: A Multi-view Merge Representation model for Chemical-Disease relation extraction.

Chemical-Disease relation (CDR) extraction aims to identify the semantic relations between chemical and disease entities in the unstructured biomedical document, which provides a basis for downstream tasks such as clinical medical diagnosis and drug discovery. Compared with general domain relation extraction, it needs a more effective representation of the whole document due to the specialized nature of texts in the biomedical domain, including the biomedical entity and entity-pair representation. In this paper, we propose a novel Multi-view Merge Representation (MMR) model to thoroughly capture entity and entity-pair representation of the document. First, we utilize prior knowledge and a pre-trained transformer encoder to capture entity semantic representation. Then we employ the U-Net layer and Graph Convolution Network layer to capture global entity-pair representation. Finally, we get a specific merged representation for each entity pair to be classified. We evaluate our model on the CDR dataset published by the BioCreative-V community and achieve a state-of-the-art result.

Transcriptomic analysis of hub genes regulating albinism in light- and temperature-sensitive albino tea cultivars 'Zhonghuang 1' and 'Zhonghuang 2'.

Albino tea cultivars have high economic value because their young leaves contain enhanced free amino acids that improve the quality and properties of tea. Zhonghuang 1 (ZH1) and Zhonghuang 2 (ZH2) are two such cultivars widely planted in China; however, the environmental factors and molecular mechanisms regulating their yellow-leaf phenotype remain unclear. In this study, we demonstrated that both ZH1 and ZH2 are light- and temperature-sensitive. Under natural sunlight and low-temperature conditions, their young shoots were yellow with decreased chlorophyll and an abnormal chloroplast ultrastructure. Conversely, young shoots were green with increased chlorophyll and a normal chloroplast ultrastructure under shading and high-temperature conditions. RNA-seq analysis was performed for high light and low light conditions, and pairwise comparisons identified genes exhibiting different light responses between albino and green-leaf cultivars, including transcription factors, cytochrome P450 genes, and heat shock proteins. Weighted gene coexpression network analyses of RNA-seq data identified the modules related to chlorophyll differences between cultivars. Genes involved in chloroplast biogenesis and development, light signaling, and JA biosynthesis and signaling were typically downregulated in albino cultivars, accompanied by a decrease in JA-ILE content in ZH2 during the albino period. Furthermore, we identified the hub genes that may regulate the yellow-leaf phenotype of ZH1 and ZH2, including CsGDC1, CsALB4, CsGUN4, and a TPR gene (TEA010575.1), which were related to chloroplast biogenesis. This study provides new insights into the molecular mechanisms underlying leaf color formation in albino tea cultivars.

Effect of adaptive laboratory evolution of engineered Escherichia coli in acetate on the biosynthesis of succinic acid from glucose in two-stage cultivation.

Escherichia coli MLB (MG1655 ΔpflB ΔldhA), which can hardly grow on glucose with little succinate accumulation under anaerobic conditions. Two-stage fermentation is a fermentation in which the first stage is used for cell growth and the second stage is used for product production. The ability of glucose consumption and succinate production of MLB under anaerobic conditions can be improved significantly by using acetate as the solo carbon source under aerobic condition during the two-stage fermentation. Then, the adaptive laboratory evolution (ALE) of growing on acetate was applied here. We assumed that the activities of succinate production related enzymes might be further improved in this study. E. coli MLB46-05 evolved from MLB and it had an improved growth phenotype on acetate. Interestingly, in MLB46-05, the yield and tolerance of succinic acid in the anaerobic condition of two-stage fermentation were improved significantly. According to transcriptome analysis, upregulation of the glyoxylate cycle and the activity of stress regulatory factors are the possible reasons for the elevated yield. And the increased tolerance to acetate made it more tolerant to high concentrations of glucose and succinate. Finally, strain MLB46-05 produced 111 g/L of succinic acid with a product yield of 0.74 g/g glucose. SYNOPSIS.

Assessing the Function of CBF1 in Modulating the Interaction Between Phytochrome B and PIF4.

Phytochromes are red (R) and far-red (FR) light photoreceptors in plants. Upon light exposure, photoactivated phytochromes translocate into the nucleus, where they interact with their partner proteins to transduce light signals. The yeast two-hybrid (Y2H) system is a powerful technique for rapidly identifying and verifying protein-protein interactions, and PHYTOCHROME-INTERACTING FACTOR3 (PIF3), the founding member of the PIF proteins, was initially identified in a Y2H screen for phytochrome B (phyB)-interacting proteins. Recently, we developed a yeast three-hybrid (Y3H) system by introducing an additional vector into this Y2H system, and thus a new regulator could be co-expressed and its role in modulating the interactions between phytochromes and their signaling partners could be examined. By employing this Y3H system, we recently showed that both MYB30 and CBF1, two negative regulators of seedlings photomorphogenesis, act to inhibit the interactions between phyB and PIF4/PIF5. In this chapter, we will use the CBF1-phyB-PIF4 module as an example and describe the detailed procedure for performing this Y3H assay. It will be intriguing and exciting to explore the potential usage of this Y3H system in future research.

Single-cell transcriptome landscape elucidates the cellular and developmental responses to tomato chlorosis virus infection in tomato leaf.

Plant viral diseases compromise the growth and yield of the crop globally, and they tend to be more serious under extreme temperatures and drought climate changes. Currently, regulatory dynamics during plant development and in response to virus infection at the plant cell level remain largely unknown. In this study, single-cell RNA sequencing on 23 226 individual cells from healthy and tomato chlorosis virus-infected leaves was established. The specific expression and epigenetic landscape of each cell type during the viral infection stage were depicted. Notably, the mesophyll cells showed a rapid function transition in virus-infected leaves, which is consistent with the pathological changes such as thinner leaves and decreased chloroplast lamella in virus-infected samples. Interestingly, the F-box protein SKIP2 was identified to play a pivotal role in chlorophyll maintenance during virus infection in tomato plants. Knockout of the SlSKIP2 showed a greener leaf state before and after virus infection. Moreover, we further demonstrated that SlSKIP2 was located in the cytomembrane and nucleus and directly regulated by ERF4. In conclusion, with detailed insights into the plant responses to viral infections at the cellular level, our study provides a genetic framework and gene reference in plant-virus interaction and breeding in the future research.

Transcriptome data reveal beneficial effects of Rickettsia (Rickettsiales: Rickettsiaceae) on Bemisia tabaci (Hemiptera: Aleyrodidae) through nutritional factors and defense mechanisms.

Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a destructive insect pest of many crops. Rickettsia infection in different cryptic species of B. tabaci has been observed worldwide. Understanding the interactions between these 2 organisms is critical to developing Rickettsia-based strategies to control B. tabaci and thereby reduce the transmission of related vector-borne viruses. In this study, we investigated the effects of Rickettsia infection on the biological characteristics of the Middle East Asia Minor 1 (MEAM1) strain of B. tabaci through biological analysis of infected and uninfected individuals. The results of this study suggest that Rickettsia may confer fitness benefits. These benefits include increased fertility, improved survival rates, accelerated development, and resulted in female bias. We also investigated the transcriptomics impact of Rickettsia infection on B. tabaci by performing a comparative RNA-seq analysis of nymphs and adult females, both with and without the infection. Our analysis revealed 218 significant differentially expressed genes (DEGs) in infected nymphs compared to uninfected ones and 748 significant DEGs in infected female adults compared to their uninfected whiteflies. Pathway analysis further revealed that Rickettsia can affect many important metabolic pathways in whiteflies. The results suggest that Rickettsia plays an essential role in energy metabolism, and nutrient synthesis in the B. tabaci MEAM1, and depends on metabolites obtained from the host to ensure its survival. Overall, our findings suggest that Rickettsia has beneficial effects on B. tabaci and offered insights into the potential molecular mechanisms governing the interactions between Rickettsia and B. tabaci MEAM1.

Factors Associated With Radiological Lung Growth Rate After Lobectomy in Patients With Lung Cancer.

INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.

Serotonergic neurotransmission mediated cognitive dysfunction in two mouse models of sepsis-associated encephalopathy.

BACKGROUND: Patients with sepsis-associated encephalopathy (SAE) often exhibit cognitive impairments. Despite this, the underlying mechanisms of SAE remain largely unexplored. Here, we explored the role of serotonergic neurotransmission in cognitive dysfunction of two mouse models of SAE. METHODS: The mouse models of SAE were established by injection of lipopolysaccharide (LPS, 10 mg/kg, intraperitoneal) and cecal ligation puncture (CLP) respectively. Barnes maze, new object recognition test and open field test were used to evaluate the effects of fluoxetine (selective serotonin reuptake inhibitor) and cyproheptadine (nonselective 5-HT2 receptor antagonist) on cognition and motor activity of mice. Additionally, WAY100635 (5-HT1A receptor antagonist) was co-administered with fluoxetine to explore the mechanism underlying effect of fluoxetine on cognitive impairments of SAE. Enzyme-linked immunosorbent assay (ELISA) was performed to determine 5-HT levels in hippocampus, brainstem and frontal lobe of experimental groups. RESULTS: Both LPS-induced sepsis and CLP induced sepsis resulted in a notable learning deficit. Fluoxetine ameliorated, while cyproheptadine aggravated, cognitive impairment in two classic mouse models of SAE. The cognition-enhancing effect of fluoxetine is reversed by WAY100635. Decreased 5-HT levels in hippocampus, brainstem and frontal lobe were observed in LPS septic model and CLP septic model. Notably, both fluoxetine and cyproheptadine significantly increased 5-HT levels in those brain regions in LPS septic model. Additionally, fluoxetine significantly increased 5-HT levels in frontal lobe of CLP septic model. CONCLUSIONS: Our study demonstrated that serotonergic neurotransmission plays a significant role in mechanisms underlying cognitive impairment in SAE. These findings contribute to identification of novel targets to prevent and arrest cognitive impairment in SAE.

Combining cisplatin with Pinellia pedatisecta Schott lipid-soluble extract induces tumor immunogenic cell death in cervical cancer.

BACKGROUND: Pinellia pedatisecta Schott extract (PE) is extracted from Pinellia pedatisecta Schott (PPS), a traditional Chinese medicinal plant with the potential for direct anticancer effects or eliciting an anti-tumor response by activating the immune system. PURPOSE: To explore PE's ability and mechanism to reconstruct cisplatin's immunogenicity. METHODS: Cervical cancer cells were treated with cisplatin (CDDP) and/or PE. The exposure of calreticulin (CRT) on cell membrane was investigated by flow cytometry. The extracellular of ATP and HMGB1 was investigated by Western blot analysis, immunofluorescence and ELISA assay. Changes in immune profiles were using flow cytometry in vaccination and anti-tumor assays in vivo. Lastly, the mechanism of PE influenced the ROS/ERS pathway was examined by ROS assay kit, flow cytometry and Western blotting. RESULTS: PE treatment induced translocation of CRT from the endoplasmic reticulum to the cell membrane of tumor cells, concomitantly triggering immunogenic cell death (ICD). In terms of mechanisms, endoplasmic reticulum (ER) stress relievers could impede the ability of PE to induce immunogenicity. This indicates that PE is activated by ER stress, leading to subsequent induction of ICD. Upon analyzing RNA-seq data, it was observed that PE primarily induces programmed cell death in tumors by impeding upstream antioxidant mechanisms. Additionally, it transforms dying tumor cells into vaccines, activating a series of immune responses. CONCLUSIONS: This study observed for the first time that PE-induced CRT exposure on the membrane of cervical cancer cells compensates for the defect of nonimmunogenic cell death inducer CDDP thereby stimulating potent ICD. This ability restores the immunogenicity of CDDP through ER stress induced by the ROS signal. ROS played a role in PE's ability to induce ICD, leading to increased expression of ER stress-related proteins, including ATF3 and IRE-1α. PE exerted anti-cancer effects by increasing the ROS levels, and ROS/ERS signaling may be a potential avenue for cervical cancer treatment. Hence, the synergistic use of PE and CDDP holds potential for enhancing immunochemotherapy in cancer treatment.

Automated molecular structure segmentation from documents using ChemSAM.

Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable.

From Sleep Deprivation to Severe COVID-19: A Comprehensive Analysis of Shared Differentially Expressed Genes and Potential Diagnostic Biomarkers.

BACKGROUND: This study aims to identify biomarkers through the analysis of genomic data, with the goal of understanding the potential immune mechanisms underpinning the association between sleep deprivation (SD) and the progression of COVID-19. METHODS: Datasets derived from the Gene Expression Omnibus (GEO) were employed, in conjunction with a differential gene expression analysis, and several machine learning methodologies, including models of Random Forest, Support Vector Machine, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. The molecular underpinnings of the identified biomarkers were further elucidated through Gene Set Enrichment Analysis (GSEA) and AUCell scoring. RESULTS: In the research, 41 shared differentially expressed genes (DEGs) were identified, these were associated with the severity of COVID-19 and SD. Utilizing LASSO and SVM-RFE, nine optimal feature genes were selected, four of which demonstrated high diagnostic potential for severe COVID-19. The gene CD160, exhibiting the highest diagnostic value, was linked to CD8+ T cell exhaustion and the biological pathway of ribosome biosynthesis. CONCLUSIONS: This research suggests that biomarkers CD160, QPCT, SIGLEC17P, and SLC22A4 could serve as potential diagnostic tools for SD-related severe COVID-19. The substantial association of CD160 with both CD8+ T cell exhaustion and ribosomal biogenesis highlights its potential pivotal role in the pathogenesis and progression of COVID-19.

A WRI1-dependent module is essential for the accumulation of auxin and lipid in somatic embryogenesis of Arabidopsis thaliana.

The potential for totipotency exists in all plant cells; however, the underlying mechanisms remain largely unknown. Earlier findings have revealed that the overexpression of LEAFY COTYLEDON 2 (LEC2) can directly trigger the formation of somatic embryos on the cotyledons of Arabidopsis. Furthermore, cotyledon cells that overexpress LEC2 accumulate significant lipid reserves typically found in seeds. The precise mechanisms and functions governing lipid accumulation in this process remain unexplored. In this study, we demonstrate that WRINKLED1 (WRI1), the key regulator of lipid biosynthesis, is essential for somatic embryo formation, suggesting that WRI1-mediated lipid biosynthesis plays a crucial role in the transition from vegetative to embryonic development. Our findings indicate a direct interaction between WRI1 and LEC2, which enhances the enrichment of LEC2 at downstream target genes and stimulates their induction. Besides, our data suggest that WRI1 forms a complex with LEC1, LEC2, and FUSCA3 (FUS3) to facilitate the accumulation of auxin and lipid for the somatic embryo induction, through strengthening the activation of YUCCA4 (YUC4) and OLEOSIN3 (OLE3) genes. Our results uncover a regulatory module controlled by WRI1, crucial for somatic embryogenesis. These findings provide valuable insights into our understanding of plant cell totipotency.

Interaction of tetracycline and copper co-intake in inducing antibiotic resistance genes and potential pathogens in mouse gut.

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life-like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.

Preclinical Evaluation of Bioactive Small Intestinal Submucosa-PMMA Bone Cement for Vertebral Augmentation.

In vertebroplasty and kyphoplasty, bioinert poly(methyl methacrylate) (PMMA) bone cement is a conventional filler employed for quick stabilization of osteoporotic vertebral compression fractures (OVCFs). However, because of the poor osteointegration, excessive stiffness, and high curing temperature of PMMA, the implant loosens, the adjacent vertebrae refracture, and thermal necrosis of the surrounding tissue occurs frequently. This investigation addressed these issues by incorporating the small intestinal submucosa (SIS) into PMMA (SIS-PMMA). In vitro analyses revealed that this new SIS-PMMA bone cement had improved porous structure, as well as reduced compressive modulus and polymerization temperature compared with the original PMMA. Furthermore, the handling properties of SIS-PMMA bone cement were not significantly different from PMMA. The in vitro effect of PMMA and SIS-PMMA was investigated on MC3T3-E1 cells via the Transwell insert model to mimic the clinical condition or directly by culturing cells on the bone cement samples. The results indicated that SIS addition substantially enhanced the proliferation and osteogenic differentiation of MC3T3-E1 cells. Additionally, the bone cement's biomechanical properties were also assessed in a decalcified goat vertebrae model with a compression fracture, which indicated the SIS-PMMA had markedly increased compressive strength than PMMA. Furthermore, it was proved that the novel bone cement had good biosafety and efficacy based on the International Standards and guidelines. After 12 weeks of implantation, SIS-PMMA indicated significantly more osteointegration and new bone formation ability than PMMA. In addition, vertebral bodies with cement were also extracted for the uniaxial compression test, and it was revealed that compared with the PMMA-implanted vertebrae, the SIS-PMMA-implanted vertebrae had greatly enhanced maximum strength. Overall, these findings indicate the potential of SIS to induce efficient fixation between the modified cement surface and the host bone, thereby providing evidence that the SIS-PMMA bone cement is a promising filler for clinical vertebral augmentation.

Roles of KCNA2 in Neurological Diseases: from Physiology to Pathology.

Potassium voltage-gated channel subfamily a member 2 (Kv1.2, encoded by KCNA2) is highly expressed in the central and peripheral nervous systems. Based on the patch clamp studies, gain-of function (GOF), loss-of-function (LOF), and a mixed type (GOF/LOF) variants can cause different conditions/disorders. KCNA2-related neurological diseases include epilepsy, intellectual disability (ID), attention deficit/hyperactive disorder (ADHD), autism spectrum disorder (ASD), pain as well as autoimmune and movement disorders. Currently, the molecular mechanisms for the reported variants in causing diverse disorders are unknown. Consequently, this review brings up to date the related information regarding the structure and function of Kv1.2 channel, expression patterns, neuronal localizations, and tetramerization as well as important cell and animal models. In addition, it provides updates on human genetic variants, genotype-phenotype correlations especially highlighting the deep insight into clinical prognosis of KCNA2-related developmental and epileptic encephalopathy, mechanisms, and the potential treatment targets for all KCNA2-related neurological disorders.