Nonreciprocal and Nonvolatile Electric-Field Switching of Magnetism in van der Waals Heterostructure Multiferroics.

Multiferroic materials provide robust and efficient routes for the control of magnetism by electric fields, which have been diligently sought after for a long time. Construction of two-dimensional (2D) vdW multiferroics is a more exciting endeavor. To date, the nonvolatile manipulation of magnetism through ferroelectric polarization still remains challenging in a 2D vdW heterostructure multiferroic. Here, we report a van der Waals (vdW) heterostructure multiferroic comprising the atomically thin layered antiferromagnet (AFM) CrI3 and ferroelectric (FE) α-In2Se3. We demonstrate anomalously nonreciprocal and nonvolatile electric-field control of magnetization by ferroelectric polarization. The nonreciprocal electric control originates from an intriguing antisymmetric enhancement of interlayer ferromagnetic coupling in the opposite ferroelectric polarization configurations of α-In2Se3. Our work provides numerous possibilities for creating diverse heterostructure multiferroics at the limit of a few atomic layers for multistage magnetic memories and brain-inspired in-memory computing.

Corrigendum: Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

[This corrects the article DOI: 10.3389/fnmol.2023.1182005.].

Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy.

Objective: This study aims to explore whether interferon-induced transmembrane protein 3 (IFITM3) is involved in recombinant human brain natriuretic peptide (rhBNP)-mediated effects on sepsis-induced cognitive dysfunction in mice. Methods: The cellular localization and expression level of IFITM3 in the hippocampus were detected. The IFITM3 overexpression was achieved using an intracranial stereotactic system to inject an adeno-associated virus into the hippocampal CA1 region of mice. Field experiments, an elevated plus maze, and conditioned fear memory tests assessed the cognitive impairment in rhBNP-treated septic mice. Finally, in the hippocampus of septic mice, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining and Immunoblot were used to detect changes in the protein expression of cleaved Caspase-8 and cleaved Caspase-3 in apoptosis-related pathways, and toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) p65 in inflammatory pathways. Results: Fourteen days after cecal ligation and puncture (CLP) surgery, IFITM3 localized in the plasma membrane and cytoplasm of the astrocytes in the hippocampus of septic mice, partially attached to the perivascular and neuronal surfaces, but not expressed in the microglia. The expression of IFITM3 was increased in the astrocytes and neurons in the hippocampus of septic mice, which was selectively inhibited by the administration of rhBNP. Overexpression of IFITM3 resulted in elevated anxiety levels and long-term learning and memory dysfunction, completely abolished the therapeutic effect of rhBNP on cognitive impairment in septic mice, and induced an increase in the number of neuronal apoptosis in the hippocampal CA1 region. The expression levels of cleaved Caspase-3 and cleaved Caspase-8 proteins were significantly increased in the hippocampus, but the expression levels of TLR4 and NF-κB p65 were not increased. Conclusion: The activation of IFITM3 may be a potential new target for treating sepsis-associated encephalopathy (SAE), and it may be one of the key anti-apoptotic mechanisms in rhBNP exerting its therapeutic effect, providing new insight into the clinical treatment of SAE patients.

Bladder paraganglioma after kidney transplantation: A case report.

BACKGROUND: Kidney transplantation is associated with an increased risk of tumors in the urinary bladder. Among all the pathological types of tumors in the bladder, paraganglioma, which arises from extra-adrenal paraganglia and consists of chromaffin cells, is rare. Paragangliomas might cause severe clinical symptoms due to catecholamine hypersecretion or mass compression. Bladder paragangliomas are rare, especially those appearing after kidney transplantation. Here, we report a case of bladder paraganglioma developing after kidney transplantation. CASE SUMMARY: A 63-year-old woman received a kidney transplant 12 years ago and took oral immunosuppressants (cyclosporine, mizoribine, and methylprednisolone) for regular post-transplant treatment. The patient felt no discomfort and she came to the hospital for a routine checkup. A mass located in the bladder was incidentally discovered by computed tomography, and she underwent surgical treatment. A 2 cm × 2 cm invasive mass was found in the trigone of the bladder and the mass was removed. The diagnosis of paraganglioma was confirmed by morphology and immunophenotyping. The patient had a good prognosis and is still alive. CONCLUSION: Paraganglioma can grow in the bladder, which might cause no clinical symptoms. The diagnosis mainly depends on morphology and immunophenotyping. Surgical resection is an important treatment option for such patients.

Association between Neutrophil Levels on Admission and All-Cause Mortality in Geriatric Patients with Hip Fractures: A Prospective Cohort Study of 2,589 Patients.

Objective: To evaluate the association between neutrophil levels and all-cause mortality in geriatric hip fractures. Methods: Elderly patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between neutrophil levels and mortality. Analyses were performed using Empower Stats and R software. Results: A total of 2,589 patients were included in this study. The mean follow-up period was 38.95 months. During the study period, 875 (33.80%) patients died due to various causes. Linear multivariate Cox regression models showed that neutrophil levels were associated with mortality after adjusting for confounding factors, when neutrophil concentration increased by 1∗109/L, the mortality risk increased by 3% (HR = 1.03, 95% CI: 1.00-1.06, and P=0210). Neutrophil concentration was used as a categorical variable; we only found statistically significant differences when neutrophil levels were high (HR = 1.27, 95% CI:1.05-1.52, and P=0.0122). In addition, the results are stable in P for trend and propensity score matching sensitivity analysis. Conclusions: Neutrophil levels are associated with mortality in geriatric hip fractures and could be considered a predictor of death risk in the long-term. This study is registered with the Chinese Clinical Trial Registry (ChiCTR) as number ChiCTR2200057323.

Thermodynamic Regulation of Dendrite-Free Li Plating on Li3Bi for Stable Lithium Metal Batteries.

Rechargeable batteries with metallic lithium (Li) anodes are attracting ever-increasing interests because of their high theoretical specific capacity and energy density. However, the dendrite growth of the Li anode during cycling leads to poor stability and severe safety issues. Here, Li3Bi alloy coated carbon cloth is rationally chosen as the substrate of the Li anode to suppress the dendrite growth from a thermodynamic aspect. The adsorption energy of a Li atom on Li3Bi is larger than the cohesive energy of bulk Li, enabling uniform Li nucleation and deposition, while the high diffusion barrier of the Li atom on Li3Bi blocks the migration of adatoms from adsorption sites to the regions of fast growth, which further ensures uniform Li deposition. With the dendrite-free Li deposition, the composite Li/Li3Bi anode enables over 250 cycles at an ultrahigh current density of 20 mA cm-2 in a symmetrical cell and delivers superior electrochemical performance in full batteries.

Roles of Proteoglycans in the Tumourigenesis and Development of Adenoid Cystic Carcinoma and Pleomorphic Adenoma of the Salivary Gland: A Systematic Review.

Salivary adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) are the most common types of salivary gland tumours; the former is malignant and the latter is benign but with features of a border tumour. Proteoglycans (PGs) produced by neoplastic myoepithelial cells are ubiquitous in both types of tumours. However, normal myoepithelial cells of salivary glands do not have the ability to secrete PGs. When the synthesis of PGs is blocked, the pulmonary metastasis and perineural growth of salivary ACC as well as the implanting growth of salivary PA are inhibited, highlighting the important functions of PGs in the tumourigenesis and development of these two tumours. In this review, we summarise literature from the past 40 years, including more recent findings from our laboratory, to clarify the pivotal roles of PGs produced by neoplastic myoepithelial cells in both the histogenesis and biological behaviours of ACC and PA.

Human antigen R-regulated mRNA metabolism promotes the cell motility of migrating mouse neurons.

Neocortex development during embryonic stages requires the precise control of mRNA metabolism. Human antigen R (HuR) is a well-studied mRNA-binding protein that regulates mRNA metabolism, and it is highly expressed in the neocortex during developmental stages. Deletion of HuR does not impair neural progenitor cell proliferation or differentiation, but it disturbs the laminar structure of the neocortex. We report that HuR is expressed in postmitotic projection neurons during mouse brain development. Specifically, depletion of HuR in these neurons led to a mislocalization of CDP+ neurons in deeper layers of the cortex. Time-lapse microscopy showed that HuR was required for the promotion of cell motility in migrating neurons. PCR array identified profilin 1 (Pfn1) mRNA as a major binding partner of HuR in neurons. HuR positively mediated the stability of Pfn1 mRNA and influenced actin polymerization. Overexpression of Pfn1 successfully rescued the migration defects of HuR-deleted neurons. Our data reveal a post-transcriptional mechanism that maintains actin dynamics during neuronal migration.

Multimodality-imaging manifestations of primary renal-allograft synovial sarcoma: First case report and literature review.

BACKGROUND: Primary renal synovial sarcoma (PRSS) is an extremely rare tumor with a poor prognosis. Its imaging and immunohistochemical characteristics may overlap with other renal tumors, which renders its early diagnosis in a dilemma. The diagnosis of primary renal synovial sarcoma requires histopathology and the confirmation of SYT-SSX gene fusion using molecular techniques. Cases of primary renal synovial sarcoma have been previously reported in the literature. However, to our knowledge, primary renal allograft synovial sarcoma was never described. CASE SUMMARY: A 43-year-old male patient who underwent kidney transplantation 9 months ago came to our hospital for regular follow-up. Traditional ultrasonography revealed multiple hypo-echo neoplasms in the renal allograft. Contrast-enhanced computed tomography (CECT) showed slightly hyper-density masses with slow homogeneous enhancement. Ultrasound-guided biopsy was conducted for accurate pathological diagnosis. The neoplasms were diagnosed as synovial sarcoma by pathological, immunohistochemical, and genetic analyses. Positron emission tomography/CT showed no evidence of metastasis. At approximately one week post biopsy, contrast-enhanced ultrasound was conducted to eliminate active hemorrhage. One month later, CECT showed that the biggest neoplasm grew from 3.3 cm to 5.7 cm in diameter. Parametric imaging was conducted with SonoLiver CAP to conduct further quantitative analysis, which showed that the enhancement pattern was heterogeneous hyper-vascular enhancement. Radical surgical resection of the whole renal allograft and ureter was conducted without additional adjuvant chemotherapy or external radiotherapy. Anlotinib was chosen for targeted therapy with a good response. CONCLUSION: We propose multimodality imaging for accurate diagnosis of renal allograft synovial sarcoma especially when it is formed by spindle-shaped cells.

HuR in the Medial Prefrontal Cortex is Critical for Stress-Induced Synaptic Dysfunction and Depressive-Like Symptoms in Mice.

Chronic stress has been observed to increase the risk of developing depression and induce neuronal alterations of synaptic plasticity, yet the underlying molecular mechanisms remain unclear. Here, we found that the ubiquitously expressed RNA-binding protein HuR was up-regulated in the medial prefrontal cortex (mPFC) of mice following chronic stress. In adult mice, AAV-Cre-mediated knockout of HuR in the mPFC prevented anxiety-like and depression-like behaviors induced by chronic stress. HuR was also required for the stress-induced dendritic spine loss and synaptic transmission deficits. Moreover, HuRflox/flox;Nex-Cre mice, which induce HuR loss of function from embryonic development, exhibited enhanced synaptic functions. Notably, we ascertained RhoA signaling to be regulated by HuR and involved in the modulation of structural synaptic plasticity in response to chronic stress. Our results demonstrate HuR is a critical modulator for the regulation of stress-induced synaptic plasticity alterations and depression, providing a potential therapeutic target for the treatment of depressive disorders.

TMFUF: a triple matrix factorization-based unified framework for predicting comprehensive drug-drug interactions of new drugs.

BACKGROUND: A significant number of adverse drug reactions is caused by unexpected Drug-drug interactions (DDIs). The identification of DDIs becomes crucial before the co-prescription of multiple drugs is made. Such a task in clinics or in drug discovery usually requires high costs and numerous limitations, while computational approaches are able to predict potential DDIs effectively by utilizing diverse drug attributes (e.g. side effects). Nevertheless, they're incapable when required to predict enhancive and degressive DDIs, which change increasingly and decreasingly the pharmacological behavior of interacting drugs respectively. The pharmacological change of DDIs is one of the most important factors when making a multi-drug prescription. RESULTS: In this work, we design a Triple Matrix Factorization-based Unified Framework (TMFUF) to address the above issue. By leveraging a group of side effect entries of drugs, TMFUF achieves the inspiring result (AUC = 0.842 and AUPR = 0.526) in the case of conventional DDI prediction under the traditional screening task. In the comparison with two state-of-the-art approaches, TMFUF demonstrates it superiority by ~ 7% and ~ 20% improvement in terms of AUC and AUPR respectively. More importantly, TMFUF shows its ability in the comprehensive DDI prediction under different screening tasks. Finally, a utilization TMFUF reveals the significant pairs of side effects, which contribute to form enhancive and degressive DDIs, for further clinical validation. CONCLUSIONS: The proposed TMFUF is first capable to predict both conventional binary DDIs and comprehensive DDIs such that it captures the pharmacological changes caused by DDIs. Furthermore, it provides a unified solution of DDI prediction for two screening scenarios, which involves newly given drugs having no prior interaction. Another advantage is its ability to indicate how significantly the pairs of drug features contribute to form DDIs.

BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.

BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far. RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC = 0.906, AUPR =0.526) and demonstrates its superiority by ~ 7% and ~ 5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA. CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).

EGFR mutations subset in Chinese lung squamous cell carcinoma patients.

Research has identified that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) possess large benefits for adenocarcinoma (ADC), although little benefit for squamous cell carcinoma (SCC). The aim of the present study was to investigate the percentage of patients with SCC with the EGFR mutations subset and the benefits of EGFR TKIs in SCC. In the present study, the EGFR mutations subset was detected with an amplification refractory mutation system in 1,359 clinical SCC tissues. The association of the EGFR mutations subset with clinicopathological parameters was evaluated using the Mann­Whitney U test, and Kruskal­Wallis H. Kaplan­Meier survival analysis was used to estimate the effect of the EGFR mutations subset on SCC patient survival rates. A total of 94 out of 1,359 SCC patients were identified as having EGFR mutations, an EGFR mutation rate of 6.92%. The EGFR mutations subset in the 94 cases was identified as follows: 37.2% (35/94) in exon 19; 39.4% (37/94) in L858R; 5.3% (5/94) in T790M; 4.3% (4/94) in G719X; 2.1% (2/94) in L861Q; and 11.7% (11/94) in other mutations. Kaplan­Meier survival analysis identified that the differentiation, pathological tumor, node, metastasis stage, lymph node metastasis and distant metastases were significantly associated with patients' survival (P>0.05; log­rank test), and no significant difference was observed between TKI therapy and chemotherapy in terms of patient survival rates (P>0.05). In addition, the overall discordant rate of the EGFR mutations subset in SCC patients was relatively low. Due to the non­significant difference between TKI therapy and chemotherapy in terms of patient survival and the lower discordance rate of the EGFR mutations subset in SCC patients, EGFR TKIs could be a recommended treatment for SCC.

[Fitting of the reconstructed craniofacial hard and soft tissues based on 2-D digital radiographs].

PURPOSE: In this study, we reconstructed the craniofacial hard and soft tissues based on the data from digital cephalometric radiographs and laser scanning. The effective fitting of the craniofacial hard and soft tissues was performed in order to increase the level of orthognathic diagnosis and treatment, and promote the communication between doctors and patients. METHODS: A small lead point was put on the face of a volunteer and frontal and lateral digital cephalometric radiographs were taken. 3-D reconstruction system of the craniofacial hard tissue based on 2-D digital radiograph was used to get the craniofacial hard tissue model by means of hard tissue deformation modeling. 3-D model of facial soft tissue was obtained by using laser scanning data. By matching the lead point coordinate, the hard tissue and soft tissue were fitted. RESULTS: The 3-D model of the craniofacial hard and soft tissues was rebuilt reflecting the real craniofacial tissue structure, and effective fitting of the craniofacial hard and soft tissues was realized. CONCLUSIONS: The effective reconstruction and fitting of the 3-D craniofacial structures have been realized, which lays a foundation for further orthognathic simulation and facial appearance prediction. The fitting result is reliable, and could be used in clinical practice.

Predicting binary, discrete and continued lncRNA-disease associations via a unified framework based on graph regression.

BACKGROUND: In human genomes, long non-coding RNAs (lncRNAs) have attracted more and more attention because their dysfunctions are involved in many diseases. However, the associations between lncRNAs and diseases (LDA) still remain unknown in most cases. While identifying disease-related lncRNAs in vivo is costly, computational approaches are promising to not only accelerate the possible identification of associations but also provide clues on the underlying mechanism of various lncRNA-caused diseases. Former computational approaches usually only focus on predicting new associations between lncRNAs having known associations with diseases and other lncRNA-associated diseases. They also only work on binary lncRNA-disease associations (whether the pair has an association or not), which cannot reflect and reveal other biological facts, such as the number of proteins involved in LDA or how strong the association is (i.e., the intensity of LDA). RESULTS: To address abovementioned issues, we propose a graph regression-based unified framework (GRUF). In particular, our method can work on lncRNAs, which have no previously known disease association and diseases that have no known association with any lncRNAs. Also, instead of only a binary answer for the association, our method tries to uncover more biological relationship between a pair of lncRNA and disease, which may provide better clues for researchers. We compared GRUF with three state-of-the-art approaches and demonstrated the superiority of GRUF, which achieves 5%~16% improvement in terms of the area under the receiver operating characteristic curve (AUC). GRUF also provides a predicted confidence score for the predicted LDA, which reveals the significant correlation between the score and the number of RNA-Binding Proteins involved in LDAs. Lastly, three out of top-5 LDA candidates generated by GRUF in novel prediction are verified indirectly by medical literature and known biological facts. CONCLUSIONS: The proposed GRUF has two advantages over existing approaches. Firstly, it can be used to work on lncRNAs that have no known disease association and diseases that have no known association with any lncRNAs. Secondly, instead of providing a binary answer (with or without association), GRUF works for both discrete and continued LDA, which help revealing the pathological implications between lncRNAs and diseases.

Cholesterol polyps in the distal common bile duct: a case report.

RATIONALE: Cholesterol polyps are rare in the common bile duct and difficult to diagnose. PATIENT CONCERNS: The small polypoid lesions often go undetected when using routine imaging methods, such as ultrasonography. DIAGNOSES: We treated a patient with cholesterol polyps in the common bile duct. After failing to detect choleliths using ultrasonography, magnetic resonance cholangiopancreatography revealed mild dilation of the common bile duct. Choledochoscopy was performed during laparoscopic cholecystectomy, which revealed yellowish-white polyps circumferentially distributed across the luminal surface of the distal common bile duct. Histological examination of biopsy specimens indicated cholesterol polyps with characteristic foamy cells. INTERVENTIONS: The patient was treated with ursodeoxycholic acid, and the number of polyps was found to have been reduced at the 6-week follow-up based on T-tube choledochoscopic examination. OUTCOMES: Recovery was unremarkable, and the ursodeoxycholic acid treatment was discontinued at the 6-month follow-up. LESSONS SUBSECTIONS: Our findings suggest that this rare condition can be treated pharmacologically to avoid potential postsurgical complications following resection of the distal common bile duct.

[Precision validation of 3-D reconstruction of the craniofacial hard tissues based on 2-D digital radiograph].

PURPOSE: In this study, we validated the precision of 3-D craniofacial reconstruction of hard tissues based on 2-D digital cephalometric radiograph, in order to increase the level of orthognathic diagnosis and treatment, and promote communication between doctors and patients. METHODS: Deformation modeling based on 2-D digital radiograph and CT modeling was performed in 7 volunteers. 64 items were measured which described craniofacial hard tissue structure, intuitive overlapping and objective analysis were conducted. SPSS 17.0 software package was used for paired t test. RESULTS: 58 measurement items were not statistically different. Deformation modeling and CT modeling of the consistency was very high. CONCLUSIONS: Deformation modeling based on 2-D digital radiograph of craniofacial hard tissues is accurate and reliable, and basic deviation was within the allowed range. This 3-D reconstruction system could be used in clinic for diagnosis and operation simulation.

Low-dimensional ScO2 with tunable electronic and magnetic properties: first-principles studies.

Transition metal dichalcogenides (TMDs) have attracted extensive attention due to their appealing properties for device applications. In this work, we explored the structure stability, electronic structure and magnetism of low-dimensional scandium dioxides, ScO2, by using the first-principles calculations. The results demonstrate that bulk ScO2, monolayers and nanoribbons (NRs) are thermodynamically stable, implying a high possibility of fabricating ScO2 nanocrystals in experiments. Despite the metallic characteristics of bulk ScO2, low-dimensional ScO2 possesses various electronic behaviors that can be further modulated by crystal structure and dimensionality. The results also show that the ground states of ScO2 monolayers and NRs are ferromagnetic (FM) with about 1 µ B per ScO2 formula. Our studies expand a new realm in low-dimensional TMDs, with tunable electronic and magnetic properties.

Modulating the phase transition between metallic and semiconducting single-layer MoS2 and WS2 through size effects.

The first-principles calculations are performed to investigate the electronic properties and the atomic mechanism of the single layer MoS2 or WS2 homo-junction structure. The results reveal that both the stability and electronic structure of the homo-junction structure are greatly affected by the type of boundaries, which connect the different phase structures, either the semiconducting hexagonal (H) structure or the metallic trigonal (T) structure. Through tuning the size of the lateral homo-junction structure of either MoS2 or WS2, the phase transformation between H and T can occur. Interestingly, the electronic structures of homo-junction structures can be tuned between the metal and the semiconductor by changing the size of the nanoribbons.