Correction: Preparation and characterizations of an injectable and biodegradable high-strength iron-bearing brushite cement for bone repair and vertebral augmentation applications.

Correction for 'Preparation and characterizations of an injectable and biodegradable high-strength iron-bearing brushite cement for bone repair and vertebral augmentation applications' by Luguang Ding et al., Biomater. Sci., 2023, 11, 96-107, https://doi.org/10.1039/D2BM01535H.

Hierarchical and urchin-like chitosan/hydroxyapatite microspheres as drug-laden cell carriers.

Biopolymer/hydroxyapatite (HAp) composites are one type of the most promising materials for a variety of biomedical applications. In this study, hierarchical and urchin-like chitosan/HAp nanowire (HU-CS/HAp NW) microspheres were for the first time synthesized by in situ hydrothermal treatment of chitosan/HAp (CS/HAp) microspheres in the acetic acid solution. The results indicate that HU-CS/HAp NW microspheres were spherical in morphology with a diameter of 100-300 µm. Their surface was mainly constructed by numerous HAp NWs with the diameter of 80-120 nm and showed a hierarchical and urchin-like nanofibrous architecture. It was found that the acidic hydrothermal treatment caused an in situ conversion of HAp NPs to HAp NWs. In vitro biocompatible evaluation indicates that HU-CS/HAp NW microspheres showed an enhanced cell attachment and proliferation due to the presence of hierarchical and urchin-like architecture. Furthermore, HU-CS/HAp NW microspheres showed a good adsorption capacity for tetracycline hydrochloride (model drug, one of the most representative antibiotics) with a higher adsorption capacity than CS/HAp microspheres and well maintained their antibacterial efficacy to inhibit the growth of bacteria: Escherichia coli and Staphylococcus aureus. Thus, the present HU-CS/HAp NW microspheres would be applicable as novel drug-laden cell carriers.

A therapeutic regimen of ceftazidime-avibactam for a critical patient receiving prolonged intermittent renal replacement therapy.

The present report firstly described a critically ill patient receiving a dosing regimen of ceftazidime-avibactam (CAZ-AVI) (1.875g q24h) to eliminate multidrug-resistant Klebsiella pneumoniae and a scheduled time for prolonged intermittent renal replacement therapy (PIRRT) every 48h (6h-session beginning 12h after the previous dosage on hemodialysis day). This dosing regimen for CAZ-AVI and a scheduled time for PIRRT allowed pharmacodynamic parameters of ceftazidime and avibactam to have little difference on hemodialysis and non-hemodialysis days so that we can maintain a relatively stable drug concentration. Our report highlighted not only the importance of dosing regimens in patients with PIRRT but also the significance of hemodialysis time points during the dosing interval. The innovative therapeutic plan proved to be suitable for patients infected with Klebsiella pneumoniae when on PIRRT according to the trough plasma concentrations of ceftazidime and avibactam which were maintained above the minimum inhibitory concentration during the dosing interval.

Confined Bismuth-Organic Framework Anode for High-Energy Potassium-Ion Batteries.

Metal-organic frameworks (MOFs) with inherent porosity, controllable structures, and designable components are recognized as attractive platforms for designing advanced electrodes of high-performance potassium-ion batteries (PIBs). However, the poor electrical conductivity and low theoretical capacity of many MOFs lead to inferior electrochemical performance. Herein, for the first time, a confined bismuth-organic framework with 3D porous matrix structure (Bi-MOF) as anode for PIBs via a facile wet-chemical approach is reported. Such a porous structure design with double active centers can simultaneously ensure the structure integrity and efficient charge transport to enable high-capacity electrode with super cycling life. As a result, the Bi-MOF for PIBs exhibits high reversible capacity (419 mAh g-1 at 0.1 A g-1 ), outstanding cycling stability (315 mAh g-1 at 0.5 A g-1 after 1200 cycles), and excellent full battery performance (a high energy density of 183 Wh kg-1 is achieved, outperforming all reported metal-based anodes for PIBs). Moreover, the K+ storage mechanisms of the Bi-MOF are further unveiled by in situ Raman, ex situ high-resolution transmission electron microscopy, and ex situ Fourier-transform infrared spectroscopy. This ingenious electrode design may provide further guidance for the application of MOF in energy storage systems.

Optimization of carbazole carboxamide RORγt agonists: Challenges in improving the metabolic stability and maintaining the agonistic activity.

Based on two previously discovered carbazole carboxamide retinoic acid receptor-related orphan receptor-γt (RORγt) agonists 6 and 7 (t1/2 = 8.7 min and 16.4 min in mouse liver microsome, respectively), new carbazole carboxamides were designed and synthesized according to the molecular mechanism of action (MOA) and metabolic site analysis with the aim of identifying novel RORγt agonists with optimal pharmacological and metabolic profiles. By modifying the "agonist lock" touching substitutions on carbazole ring, introducing heteroatoms into different parts of the molecule and attaching a side chain to the sulfonyl benzyl moiety, several potent RORγt agonists were identified with greatly improved metabolic stability. Best overall properties were achieved in compound (R)-10f with high agonistic activities in RORγt dual FRET (EC50 = 15.6 nM) and Gal4 reporter gene (EC50 = 141 nM) assays and greatly improved metabolic stability (t1/2 > 145 min) in mouse liver microsome. Besides, the binding modes of (R)-10f and (S)-10f in RORγt ligand binding domain (LBD) were also studied. Altogether, the optimization of carbazole carboxamides led to the discovery of (R)-10f as a potential small molecule therapeutics for cancer immunotherapy.

A peptide rich in glycine-serine-alanine repeats ameliorates Alzheimer-type neurodegeneration.

BACKGROUND AND PURPOSE: Repeated amino acid sequences in proteins are widely found, and the glycine-serine-alanine repeat is an element with a general propensity to form ß-sheet aggregates as found in key pathological factors, in several neurodegenerative diseases. Such properties of this repeat may guide development of disease-modifying therapies for neurodegenerative disease. However, details of its role and underlying mechanism(s) remain largely unknown. EXPERIMENTAL APPROACH: Actions of specific glycine-serine-alanine repeat peptides (SNPs), especially SNP-9, on Alzheimer's disease (AD)-like abnormalities were evaluated in transgenic mice and Caenorhabditis elegans, and in rat and cell models. Entry of SNPs into the brain, SNP activity in neuronal cells and peptide entry into cells were analysed in vivo and in vitro. Cell-free systems and the yeast two-hybrid system were also used to explore possible targets of SNP-9, and interactions of potential targets with SNP-9 were confirmed in cell-based systems. KEY RESULTS: We first identified SNP-9 as a potent neuroprotective peptide with the activity to decrease oligomeric amyloid ß (Aß) via co-assembling with the toxic Aß oligomer to form hetero-oligomers. Also, calcyclin-binding protein was found to act as a SNP-9-binding protein, by screening of a human brain cDNA library. Such binding showed that SNP-9 could regulate the abnormal hyperphosphorylation of tau via calcyclin-binding protein. CONCLUSION AND IMPLICATIONS: Our study provides a foundation for development of SNPs, especially SNP-9, as potential therapeutic interventions for AD. We propose SNP-9 as a potential therapeutic agent for the treatment of AD.

The essential role of forkhead box P4 (FOXP4) in thyroid cancer: a study related to The Cancer Genome Atlas and experimental data.

Objective: Thyroid cancer (THCA) is the most common endocrine cancer in the world. Although most patients with THCA have a good prognosis, the prognosis of those with THCA who have an extra-glandular invasion, vascular invasion, and distant metastasis is poor. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of highly aggressive THCAs. It has been identified that forkhead box P4 (FOXP4) may be a new biomarker for the proliferation and prognosis for tumor diagnosis. However, the expression and function of FOXP4 in THCA remain to be determined. Methods: In the present study, the function of FOXP4 in cells was investigated through the comprehensive analysis of data in The Cancer Genome Atlas and combined with experiments including immunohistochemistry (IHC), colony formation, Cell Counting Kit-8 assay, wound scratch healing, and transwell invasion assay. Results: In the present study, relevant bioinformatic data showed that FOXP4 was highly expressed in THCA, which was consistent with the results of the IHC and cell experiments. Meanwhile, 10 FOXP4-related hub genes were identified as potential diagnostic genes for THCA. It was found in further experiments that FOXP4 was located in the nucleus of THCA cells, and the expression of FOXP4 in the nucleus was higher than that in the cytoplasm. FOXP4 knockdown inhibited in vitro proliferation of the THCA cells, whereas overexpression promoted the proliferation and migration of THCA cells. Furthermore, deficiency of FOXP4 induced cell-cycle arrest. Conclusion: FOXP4 might be a potential target for diagnosing and treating THCA.

Chromosome-level genome assembly of a triploid poplar Populus alba 'Berolinensis'.

Many recent studies have provided significant insights into polyploid breeding, but limited research has been carried out on trees. The genomic information needed to understand growth and response to abiotic stress in polyploidy trees is largely unknown, but has become critical due to the threats to forests imposed by climate change. Populus alba 'Berolinensis,' also known "Yinzhong poplar," is a triploid poplar from northeast China. This hybrid triploid poplar is widely used as a landscape ornamental and in urban forestry owing to its adaptation to adverse environments and faster growth than its parental diploid. It is an artificially synthesized male allotriploid hybrid, with three haploid genomes of P. alba 'Berolinensis' originating from different poplar species, so it is attractive for studying polyploidy genomic mechanisms in heterosis. In this study, we focused on the allelic genomic interactions in P. alba 'Berolinensis,' and generated a high-quality chromosome-level genome assembly consisting of 19 allelic chromosomes. Its three haploid chromosome sets are polymorphic with an average of 25.73 nucleotide polymorphism sites per kilobase. We found that some stress-related genes such as RD22 and LEA7 exhibited sequence differences between different haploid genomes. The genome assembly has been deposited in our polyploid genome online analysis website TreeGenomes (https://www.treegenomes.com). These polyploid genome-related resources will provide a critical foundation for the molecular breeding of P. alba 'Berolinensis' and help us uncover the allopolyploidization effects of heterosis and abiotic stress resistance and traits of polyploidy species in the future.

Early osteoimmunomodulation by mucin hydrogels augments the healing and revascularization of rat critical-size calvarial bone defects.

The design principle of osteogenic bone grafts has shifted from immunological inertness to limiting foreign body response to combined osteoimmunomodulatory activity to promote high-quality endogenous bone regeneration. Recently developed immunomodulatory mucin hydrogels have been shown to elicit very low complement activation and suppress macrophage release and activation after implantation in vivo. However, their immunoregulatory activity has not yet been studied in the context of tissue repair. Herein, we synthesized mucin-monetite composite materials and investigated their early osteoimmunomodulation using a critical-size rat bone defect model. We demonstrated that the composites can polarize macrophages towards the M2 phenotype at weeks 1 and 2. The early osteoimmunomodulation enhanced early osteogenesis and angiogenesis and ultimately promoted fracture healing and engraftment (revascularization of the host vasculature) at weeks 6 and 12. Overall, we demonstrated the applicability of mucin-based immunomodulatory biomaterials to enhance tissue repair in tissue engineering and regenerative medicine.

Identification and Verification of Potential Biomarkers in Renal Ischemia-Reperfusion Injury by Integrated Bioinformatic Analysis.

Background: Renal ischemia-reperfusion injury (RIRI) plays an important role in the poor prognosis of patients with renal transplants. However, the potential targets and mechanism of IRI are still unclear. Method: Differential gene expression (DEG) analysis and weighted correlation network analysis (WGCNA) were performed on the GSE27274 dataset. Pathway enrichment analysis on the DEGs was performed. To identify the hub DEGs, we constructed a protein-protein interaction (PPI) network. Finally, the hub genes were verified, and candidate drugs were screened from the DsigDB database. Results: A hundred DEGs and four hub genes (Atf3, Psmb6, Psmb8, and Psmb10) were screened out. Pathway enrichment analysis revealed that 100 DEGs were mainly enriched in apoptosis and the TNF signaling pathway. The four hub genes were verified in animal models and another dataset (GSE148420). Thereafter, a PPI network was used to identify the four hub genes (Atf3, Psmb6, Psmb8, and Psmb10). Finally, eight candidate drugs were identified as potential drugs. Conclusion: Three hub genes (Psmb6, Psmb8, and Psmb10) were associated with RIRI and could be potential novel biomarkers for RIRI.

A machine learning-derived gene signature for assessing rupture risk and circulatory immunopathologic landscape in patients with intracranial aneurysms.

Background: Intracranial aneurysm (IA) is an uncommon but severe subtype of cerebrovascular disease, with high mortality after aneurysm rupture. Current risk assessments are mainly based on clinical and imaging data. This study aimed to develop a molecular assay tool for optimizing the IA risk monitoring system. Methods: Peripheral blood gene expression datasets obtained from the Gene Expression Omnibus were integrated into a discovery cohort. Weighted gene co-expression network analysis (WGCNA) and machine learning integrative approaches were utilized to construct a risk signature. QRT-PCR assay was performed to validate the model in an in-house cohort. Immunopathological features were estimated using bioinformatics methods. Results: A four-gene machine learning-derived gene signature (MLDGS) was constructed for identifying patients with IA rupture. The AUC of MLDGS was 1.00 and 0.88 in discovery and validation cohorts, respectively. Calibration curve and decision curve analysis also confirmed the good performance of the MLDGS model. MLDGS was remarkably correlated with the circulating immunopathologic landscape. Higher MLDGS scores may represent higher abundance of innate immune cells, lower abundance of adaptive immune cells, and worse vascular stability. Conclusions: The MLDGS provides a promising molecular assay panel for identifying patients with adverse immunopathological features and high risk of aneurysm rupture, contributing to advances in IA precision medicine.

Biomechanical behavior analysis of four types of short implants with different placement depths using the finite element method.

STATEMENT OF PROBLEM: The clinical application of short implants has been increasing. However, studies on the marginal bone loss of short implants are sparse, and clinicians often choose short implants based on their own experience rather than on scientific information. PURPOSE: The purpose of this finite element analysis study was to evaluate the microstrain-stress distribution in the peri-implant bone and implant components for 4 types of short implants at different placement depths of platform switching. MATERIAL AND METHODS: By using short implants as prototypes, 4 short implant models were 1:1 modeled. The diameter and length of the implants were 5×5, 5×6, 6×5, and 6×6 mm. The restoration was identical for all implants. Three different depths of implant platform switching were set: equicrestal, 0.5-mm subcrestal, and 1-mm subcrestal. The models were then assembled and assigned an occlusal force of 200 N (vertical or 30-degree oblique). A finite element analysis was carried out to evaluate the maximum equivalent elastic strain and von Mises stress in the bone and the stress distribution in the implant components. RESULTS: The 5×5 implant group showed the largest intraosseous strain (21.921×103 µÎµ). A 1-mm increase in implant diameter resulted in a 17.1% to 37.4% reduction in maximum intraosseous strain when loaded with oblique forces. The strain in the bone tended to be much smaller than the placement depth at the equicrestal and 0.5-mm subcrestal positions than that at the 1-mm subcrestal position, especially under oblique force loading, with an increase of approximately 37.4% to 81.8%. In addition, when the cortical bone thickness was less than 4 mm, 5×6 implants caused significantly higher intraosseous stresses than 6×6 implants. CONCLUSIONS: Large implant diameters, rather than long implants, led to reduced intraosseous strain, especially under oblique loading. Regarding the implant platform switching depth, the short implant showed small intraosseous strains when the platform switching depth was equicrestal or 0.5-mm subcrestal.

DnFCA Isoforms Cooperatively Regulate Temperature-Related Flowering in Dendrobium nobile.

Timely flowering is a determinative trait for many economically valuable species in the Dendrobium genus of the Orchidaceae family, some of which are used for ornamental and medicinal purposes. D. nobile, a representative species of nobile-type Dendrobium, normally flowers in spring after exposure to sufficient low temperatures in winter. However, flowering can be stopped or disrupted by the untimely application of high temperatures. Little is known about the regulation and the mechanisms behind this switch. In this study, we report two isoforms from the KFK09_017173 locus of the D. nobile genome, named DnFCAγ and DnFCAß, respectively, that cooperatively regulate flowering in D. nobile. These two isoforms are generated by alternative 3' polyadenylation of DnFCA (FLOWERING CONTROL LOCUS C in D. nobile) pre-mRNA and contain a distinct 3'-terminus. Both can partially rescue late flowering in the Arabidopsis fca-1 mutant, while in wild-type Arabidopsis, they tend to delay the flowering time. When introduced into the detached axillary buds or young seedlings of D. nobile, both were able to induce the transcription of DnAGL19 (AGAMOUS LIKE 19 in D. nobile) in seedlings, whereas only DnFCAγ was able to suppress the transcription of DnAPL1 (AP1-LIKE 1 in D. nobile) in axillary buds. Furthermore, the time-course change of DnFCAγ accumulation was opposite to that of DnAPL1 in axillary buds, which was remarkable under low temperatures and within a short time after the application of high temperatures, supporting the suggestion that the expression of DnAPL1 can be inhibited by a high accumulation of DnFCAγ in floral buds. In leaves, the accumulation of DnFCAß was in accordance with that of DnAGL19 and DnFT (FLOWERING LOCUS T in D. nobile) to a large extent, suggesting the activation of the DnAGL19-DnFT pathway by DnFCAß. Taken together, these results suggest that the DnFCAγ-DnAPL1 pathway in axillary buds and the DnFCAß-DnAGL19 pathway in the leaves cooperatively promote flowering under low temperatures. The long-term and constant, or untimely, application of high temperatures leads to the constitutive suppression of DnAPL1 by a high level of DnFCAγ in axillary buds, which consequently delays floral development.

PET-guided attention for prediction of microvascular invasion in preoperative hepatocellular carcinoma on PET/CT.

PURPOSE: To achieve PET/CT-based preoperative prediction of microvascular invasion in hepatocellular carcinoma by combining the advantages of PET and CT. METHODS: This retrospective study included a total of 100 patients from two institutions who underwent PET/CT imaging. The above patients were divided into a training cohort (n = 70) and a validation cohort (n = 30). This study was based on PET/CT images to evaluate the possibility of microvascular invasion (MVI) of patients. In this study, we proposed a two-branch PET-guided attention network to predict MVI. The model used a two-branch network to extract image features from PET and CT, respectively. The PET-guided attention module aimed to enable the model to focus on the lesion region and reduce the disturbance of irrelevant and redundant information. Model performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: The method outperformed the single-modality prediction model for preoperative hepatocyte microvascular invasion, achieving an AUC of 0.907. On the validation set, accuracy reached 0.846, precision reached 0.881, recall 0.793, and F1-score 0.835. CONCLUSION: The model exploits the particularities of the molecular metabolic function of PET and the anatomical structure of CT and can strongly improve the accuracy of clinical diagnosis of MVI.

History of suicide attempt associated with amygdala and hippocampus changes among individuals with schizophrenia.

Abnormalities in subcortical brain structures may reflect higher suicide risk in mood disorders, but less is known about its associations for schizophrenia. This cross-sectional imaging study aimed to explore whether the history of suicide attempts was associated with subcortical changes among individuals with schizophrenia. We recruited 44 individuals with schizophrenia and a history of suicide attempts (SZ-SA) and 44 individuals with schizophrenia but without a history of suicide attempts (SZ-NSA) and 44 healthy controls. Linear regression showed that SZ-SA had smaller volumes of the hippocampus (Cohen's d = -0.72), the amygdala (Cohen's d = -0.69), and some nuclei of the amygdala (Cohen's d, -0.57 to -0.72) than SZ-NSA after adjusting for age, sex, illness phase, and intracranial volume. There was no difference in the volume of the subfields of the hippocampus. It suggests the history of suicide attempts is associated with subcortical volume alterations in schizophrenia.

[Clinical research of acupuncture therapy combined with domperidone in treatment of diabetic gastroparesis of liver stagnation and spleen deficiency].

OBJECTIVE: To observe the clinical efficacy of shuanggu yitong acupuncture therapy (the therapy for both replenishment and unblocking) combined with domperidone on diabetic gastroparesis (DGP) of liver stagnation and spleen deficiency pattern and explore its effect mechanism. METHODS: DGP patients differentiated as liver stagnation and spleen deficiency pattern were divided into a control group (n=42) and an observation group (n=42) according to the random number table. The patients in the control group took domperidone tablets orally, 10 mg each time, 3 times a day for 28 days. In the observation group, on the base of the treatment as the control group, shuanggu yitong acupuncture therapy was applied to Baihui (GV20), Shenting (GV24), Zhongwan (CV12), bilateral Zusanli (ST36), Hegu (LI4)and Taichong (LR3), stimulated for 30 min in each treatment. Acupuncture was given once daily, 3 times a weeks for 28 days consecutively. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA1c) were detected before and after treatment in the patients of two groups separately. The score of symptom severity index of gastroparesis (GCSI), traditional Chinese medicine (TCM) syndrome score and gastric emptying rate were assessed in the patients of two groups. Using ELISA, radioimmunoassay and colorimentry methods, the contents of motilin in plasma, gastrin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interferon-gamma (INF-γ) in serum, as well as the activity of superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum were determined in the two groups. The clinical curative effect was evaluated. RESULTS: After treatment, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM syndrome, the contents of motilin in plasma, gastrin, TNF-α and MDA, as well as the activity of ROS in serum were all reduced when compared with those before treatment in each group (P<0.05, P<0.01), while gastric emptying rate and SOD activity in the serum were higher than those before treatment (P<0.05, P<0.01). After treatment, the serological content of INF-γ was lower than that before treatment in the control group (P<0.05), and the contents of IL-6 and IL-1ß were reduced than those before treatment in the observation group (P<0.05). Compared with the control group, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM symptoms, the contents of motilin in plasma, gastrin, TNF-α, MDA, IL-6 and IL-1ß, and the activity of ROS in serum in the observation group were all lower significantly (P<0.05, P<0.01), while the SOD activity and gastric emptying rate in the observation group were higher than those in the control group (P<0.05, P<0.01). The total effective rate was 90.5% (38/42) in the observation group, better than the control group (73.8%, 31/42, P<0.05). CONCLUSION: Shuanggu yitong acupuncture therapy combined with domperidone remarkably relieves the clinical symptoms and improves the gastric emptying rate, effectively reduces motilin and gastrin and regulates oxidative stress and inflammatory responses in the patients with DGP of liver stagnation and spleen deficiency.

Cerebral Blood Flow Alterations in Sepsis-Associated Encephalopathy: A Prospective Observational Study.

BACKGROUND: The timely recognition of sepsis-associated encephalopathy (SAE) remains a challenge. This study aimed to observe the CBF changes via TCD during sepsis and explore their possible predictive value in SAE. METHODS: In this prospective observational study, septic patients were enrolled and classified according to the diagnosis of SAE into two groups: SAE group and non-SAE group. Then SAE patients were further divided into subgroup A (the type with agitation) and subgroup B (the type with depressed consciousness) based on their clinical manifestations. The clinical profiles and TCD parameters within 24 hours of onset were compared between groups and subgroups. RESULTS: Exactly 198 septic patients were enrolled including 65 patients in SAE group (36 male/29 female with a median age of 70) and 133 patients in non-SAE group (75 male/58 female with a median age of 67). Significant elevated peak-systolic velocity (VS; 107 [69-138] cm/s vs 85 [69-101] cm/s, P = .002) of the left middle cerebral artery (MCA) and pulsatility index (PI; left: 0.99 [0.81-1.34] vs 0.89 [0.76-1.00], P < .001; right: 0.99 [0.77-1.21] vs 0.88 [0.78-1.03], P = .007) of bilateral MCAs were found in SAE group compared with non-SAE group. In subgroup analysis, subgroup A (the type with agitation) showed significantly increased VS/VM/VD and lower PI/RI of bilateral MCAs compared with subgroup B (the type with depressed consciousness). The cerebral blood flow volume of subgroup A were obviously higher than subgroup B [858.7 (729.1,876.9) mL/s vs 380.9 (373.3,447.4) mL/s, P < .001]. CONCLUSIONS: This study confirmed the abnormal CBF among SAE and found different types of CBF alterations were related to different clinical features. VS and PI might help clinicians to early identify different types of SAE.

The Adaptive Evolution in the Fall Armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) Revealed by the Diversity of Larval Gut Bacteria.

Insect gut microbes have important roles in host feeding, digestion, immunity, development, and coevolution with pests. The fall armyworm, Spodoptera frugiperda (Smith, 1797), is a major migratory agricultural pest worldwide. The effects of host plant on the pest's gut bacteria remain to be investigated to better understand their coevolution. In this study, differences in the gut bacterial communities were examined for the fifth and sixth instar larvae of S. frugiperda fed on leaves of different host plants (corn, sorghum, highland barley, and citrus). The 16S rDNA full-length amplification and sequencing method was used to determine the abundance and diversity of gut bacteria in larval intestines. The highest richness and diversity of gut bacteria were in corn-fed fifth instar larvae, whereas in sixth instar larvae, the richness and diversity were higher when larvae were fed by other crops. Firmicutes and Proteobacteria were dominant phyla in gut bacterial communities of fifth and sixth instar larvae. According to the LDA Effect Size (LEfSe) analysis, the host plants had important effects on the structure of gut bacterial communities in S. frugiperda. In the PICRUSt2 analysis, most predicted functional categories were associated with metabolism. Thus, the host plant species attacked by S. frugiperda larvae can affect their gut bacterial communities, and such changes are likely important in the adaptive evolution of S. frugiperda to host plants.

In situ mapping of ion distribution profiles and gene expression reveals interactions between hypoxia and Mn2+/Fe2+ availability in barley roots.

Flooding stress affects soil properties thus altering the availability, uptake, and transport of mineral nutrients in plant roots. Flooding stress also increases the amount of soluble Mn2+ and Fe2+ in the soil and their uptake by plants, causing elemental toxicity. However, as oxygen profiles in plant roots are not uniform, it is still unclear how soil flooding will affect Mn2+/Fe2+ absorption and distribution in different cell types and tissues. In this study, waterlogging sensitive barley variety NasoNijo (NN) and tolerant variety TX9425 (TX) were exposed to hypoxia, metal (Mn2+ and Fe2+), and combined hypoxia + metal treatment to map the in situ ion profiles at different regions of barley root. We found that combined hypoxia and metal stress causes significantly more reduction in plant biomass compared with the single submergence or metal stress. Despite this, more Fe and Mn were accumulated under metal stress condition than those under combined stress, regardless of variety. Cultivar NN absorbed more Fe and Mn than TX in the cortical cells of the root meristem and in the mature zone under metal stress which was also verified by histochemical detection. In the mature zone, the expressions of Fe and Mn transporter genes including HvADPRibase-Mn (Manganese-dependent ADP-ribose), HvZIP1 (zinc-regulated transporter /Fe-regulated transporter-like protein 1), HvYS1 (yellow stripe 1), HvNRAMP5 (Natural Resistance-Associated Macrophage Protein 5) were significantly downregulated under all three treatments in both barley varieties except HvADPRibase-Mn HvZIP1 cortex of TX were unchanged under metal stress. Interestingly, the transcripts of HvMTP1 (metal tolerance protein 1) were significantly downregulated by metal and combined stress in stele and upregulated by hypoxia and metal stress in cortex of TX, but not affected in NN. It is concluded that Fe and Mn absorption involving HvMTP1is associated with the extent of waterlogging tolerance in barley.

LncRNA LIMp27 Regulates the DNA Damage Response through p27 in p53-Defective Cancer Cells.

P53 inactivation occurs in about 50% of human cancers, where p53-driven p21 activity is devoid and p27 becomes essential for the establishment of the G1/S checkpoint upon DNA damage. Here, this work shows that the E2F1-responsive lncRNA LIMp27 selectively represses p27 expression and contributes to proliferation, tumorigenicity, and treatment resistance in p53-defective colon adenocarcinoma (COAD) cells. LIMp27 competes with p27 mRNA for binding to cytoplasmically localized hnRNA0, which otherwise stabilizes p27 mRNA leading to cell cycle arrest at the G0/G1 phase. In response to DNA damage, LIMp27 is upregulated in both wild-type and p53-mutant COAD cells, whereas cytoplasmic hnRNPA0 is only increased in p53-mutant COAD cells due to translocation from the nucleus. Moreover, high LIMp27 expression is associated with poor survival of p53-mutant but not wild-type p53 COAD patients. These results uncover an lncRNA mechanism that promotes p53-defective cancer pathogenesis and suggest that LIMp27 may constitute a target for the treatment of such cancers.