A review of the recombination events, mechanisms and consequences of Coxsackievirus A6.

Hand, foot, and mouth disease (HFMD) is one of the most common class C infectious diseases, posing a serious threat to public health worldwide. Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) have been regarded as the major pathogenic agents of HFMD; however, since an outbreak caused by coxsackievirus A6 (CV-A6) in France in 2008, CV-A6 has gradually become the predominant pathogen in many regions. CV-A6 infects not only children but also adults, and causes atypical clinical symptoms such as a more generalized rash, eczema herpeticum, high fever, and onychomadesis, which are different from the symptoms associated with EV-A71 and CV-A16. Importantly, the rate of genetic recombination of CV-A6 is high, which can lead to changes in virulence and the rapid evolution of other characteristics, thus posing a serious threat to public health. To date, no specific vaccines or therapeutics have been approved for CV-A6 prevention or treatment, hence it is essential to fully understand the relationship between recombination and evolution of this virus. Here, we systematically review the genetic recombination events of CV-A6 that have occurred worldwide and explore how these events have promoted virus evolution, thus providing important information regarding future HFMD surveillance and prevention.

Prediction of additional hospital days in patients undergoing cervical spine surgery with machine learning methods.

BACKGROUND: Machine learning (ML), a subset of artificial intelligence (AI), uses algorithms to analyze data and predict outcomes without extensive human intervention. In healthcare, ML is gaining attention for enhancing patient outcomes. This study focuses on predicting additional hospital days (AHD) for patients with cervical spondylosis (CS), a condition affecting the cervical spine. The research aims to develop an ML-based nomogram model analyzing clinical and demographic factors to estimate hospital length of stay (LOS). Accurate AHD predictions enable efficient resource allocation, improved patient care, and potential cost reduction in healthcare. METHODS: The study selected CS patients undergoing cervical spine surgery and investigated their medical data. A total of 945 patients were recruited, with 570 males and 375 females. The mean number of LOS calculated for the total sample was 8.64 ± 3.7 days. A LOS equal to or <8.64 days was categorized as the AHD-negative group (n = 539), and a LOS > 8.64 days comprised the AHD-positive group (n = 406). The collected data was randomly divided into training and validation cohorts using a 7:3 ratio. The parameters included their general conditions, chronic diseases, preoperative clinical scores, and preoperative radiographic data including ossification of the anterior longitudinal ligament (OALL), ossification of the posterior longitudinal ligament (OPLL), cervical instability and magnetic resonance imaging T2-weighted imaging high signal (MRI T2WIHS), operative indicators and complications. ML-based models like Lasso regression, random forest (RF), and support vector machine (SVM) recursive feature elimination (SVM-RFE) were developed for predicting AHD-related risk factors. The intersections of the variables screened by the aforementioned algorithms were utilized to construct a nomogram model for predicting AHD in patients. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and C-index were used to evaluate the performance of the nomogram. Calibration curve and decision curve analysis (DCA) were performed to test the calibration performance and clinical utility. RESULTS: For these participants, 25 statistically significant parameters were identified as risk factors for AHD. Among these, nine factors were obtained as the intersection factors of these three ML algorithms and were used to develop a nomogram model. These factors were gender, age, body mass index (BMI), American Spinal Injury Association (ASIA) scores, magnetic resonance imaging T2-weighted imaging high signal (MRI T2WIHS), operated segment, intraoperative bleeding volume, the volume of drainage, and diabetes. After model validation, the AUC was 0.753 in the training cohort and 0.777 in the validation cohort. The calibration curve exhibited a satisfactory agreement between the nomogram predictions and actual probabilities. The C-index was 0.788 (95% confidence interval: 0.73214-0.84386). On the decision curve analysis (DCA), the threshold probability of the nomogram ranged from 1 to 99% (training cohort) and 1 to 75% (validation cohort). CONCLUSION: We successfully developed an ML model for predicting AHD in patients undergoing cervical spine surgery, showcasing its potential to support clinicians in AHD identification and enhance perioperative treatment strategies.

Novel transcription and replication-competent virus-like particles system modelling the Nipah virus life cycle.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

EV71 5'UTR interacts with 3D protein affecting replication through the AKT-mTOR pathway.

BACKGROUND: EV71 is one of the important pathogens of Hand-foot-and-mouth disease (HFMD), which causes serious neurological symptoms. Several studies have speculated that there will be interaction between 5'UTR and 3D protein. However, whether 5'UTR interacts with the 3D protein in regulating virus replication has not been clarified. METHODS: Four 5'UTR mutation sites (nt88C/T, nt90-102-3C, nt157G/A and nt574T/A) and two 3D protein mutation sites (S37N and R142K) were mutated or co-mutated using virulent strains as templates. The replication of these mutant viruses and their effect on autophagy were determined. RESULTS: 5'UTR single-point mutant strains, except for EGFP-EV71(nt90-102-3C), triggered replication attenuation. The replication ability of them was weaker than that of the parent strain the virulent strain SDLY107 which is the fatal strain that can cause severe neurological complications. While the replication level of the co-mutant strains showed different characteristics. 5 co-mutant strains with interaction were screened: EGFP-EV71(S37N-nt88C/T), EGFP-EV71(S37N-nt574T/A), EGFP-EV71(R142K-nt574T/A), EGFP-EV71(R142K-nt88C/T), and EGFP-EV71(R142K-nt157G/A). The results showed that the high replicative strains significantly promoted the accumulation of autophagosomes in host cells and hindered the degradation of autolysosomes. The low replicative strains had a low ability to regulate the autophagy of host cells. In addition, the high replicative strains also significantly inhibited the phosphorylation of AKT and mTOR. CONCLUSIONS: EV71 5'UTR interacted with the 3D protein during virus replication. The co-mutation of S37N and nt88C/T, S37N and nt574T/ A, R142K and nt574T/A induced incomplete autophagy of host cells and promoted virus replication by inhibiting the autophagy pathway AKT-mTOR. The co-mutation of R142K and nt88C/T, and R142K and nt157G/A significantly reduced the inhibitory effect of EV71 on the AKT-mTOR pathway and reduced the replication ability of the virus.

Applying improved ddPCR to reliable quantification of MPXV in clinical settings.

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome.

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

Molecular self-assembled cellulose enabling durable, scalable, high-power osmotic energy harvesting.

In recent years, renewable cellulose-based ion exchange membranes have emerged as promising candidates for capturing green, abundant osmotic energy. However, the low power density and structural/performance instability are challenging for such cellulose membranes. Herein, cellulose-molecule self-assembly engineering (CMA) is developed to construct environmentally friendly, durable, scalable cellulose membranes (CMA membranes). Such a strategy enables CMA membranes with ideal nanochannels (∼7 nm) and tailored channel lengths, which support excellent ion selectivity and ion fluxes toward high-performance osmotic energy harvesting. Finite element simulations also verified the function of tailored nanochannel length on osmotic energy conversion. Correspondingly, our CMA membrane shows a high-power density of 2.27 W/m2 at a 50-fold KCl gradient and super high voltage of 1.32 V with 30-pair CMA membranes (testing area of 22.2 cm2). In addition, the CMA membrane demonstrates long-term structural and dimensional integrity in saline solution, due to their high wet strength (4.2 MPa for N-CMA membrane and 0.5 MPa for P-CMA membrane), and correspondingly generates ultrastable yet high power density more than 100 days. The self-assembly engineering of cellulose molecules constructs high-performance ion-selective membranes with environmentally friendly, scalable, high wet strength and stability advantages, which guide sustainable nanofluidic applications beyond the blue energy.

RNA binding motif 4 inhibits the replication of ebolavirus by directly targeting 3'-leader region of genomic RNA.

Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the "CU" enrichment elements located in the PE1 and TSS of the 3'-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.

Development and validation of a diagnostic model to differentiate spinal tuberculosis from pyogenic spondylitis by combining multiple machine learning algorithms.

This study focused on the development and validation of a diagnostic model to differentiate between spinal tuberculosis (STB) and pyogenic spondylitis (PS). We analyzed a total of 387 confirmed cases, out of which 241 were diagnosed with STB and 146 were diagnosed with PS. These cases were randomly divided into a training group (n = 271) and a validation group (n = 116). Within the training group, four machine learning (ML) algorithms (least absolute shrinkage and selection operator [LASSO], logistic regression analysis, random forest, and support vector machine recursive feature elimination [SVM-RFE]) were employed to identify distinctive variables. These specific variables were then utilized to construct a diagnostic model. The model's performance was subsequently assessed using the receiver operating characteristic (ROC) curves and the calibration curves. Finally, internal validation of the model was undertaken in the validation group. Our findings indicate that PS patients had an average platelet-to-neutrophil ratio (PNR) of 277.86, which was significantly higher than the STB patients' average of 69.88. The average age of PS patients was 54.71 years, older than the 48 years recorded for STB patients. Notably, the neutrophil-to-lymphocyte ratio (NLR) was higher in PS patients at 6.15, compared to the 3.46 NLR in STB patients. Additionally, the platelet volume distribution width (PDW) in PS patients was 0.2, compared to 0.15 in STB patients. Conversely, the mean platelet volume (MPV) was lower in PS patients at an average of 4.41, whereas STB patients averaged 8.31. Hemoglobin (HGB) levels were lower in PS patients at an average of 113.31 compared to STB patients' average of 121.64. Furthermore, the average red blood cell (RBC) count was 4.26 in PS patients, which was less than the 4.58 average observed in STB patients. After evaluation, seven key factors were identified using the four ML algorithms, forming the basis of our diagnostic model. The training and validation groups yielded area under the curve (AUC) values of 0.841 and 0.83, respectively. The calibration curves demonstrated a high alignment between the nomogram-predicted values and the actual measurements. The decision curve indicated optimal model performance with a threshold set between 2% and 88%. In conclusion, our model offers healthcare practitioners a reliable tool to efficiently and precisely differentiate between STB and PS, thereby facilitating swift and accurate diagnoses.

Multi-Scale Engineered 2D Carbon Polyhedron Array with Enhanced Electrocatalytic Performance.

Electrocatalyst engineering from the atomic to macroscopic level of electrocatalysts is one of the most powerful routes to boost the performance of electrochemical devices. However, multi-scale structure engineering mainly focuses on the range of atomic-to-particle scale such as hierarchical porosity engineering, while catalyst engineering at the macroscopic level, such as the arrangement configuration of nanoparticles, is often overlooked. Here, a 2D carbon polyhedron array with a multi-scale engineered structure via facile chemical etching, ice-templating induced self-assembly, and high-temperature pyrolysis processes is reported. Controlled phytic acid etching of the carbon precursor introduces homogeneous atomic phosphorous and nitrogen doping, as well as a well-defined mesoporous structure. Subsequent ice-templated self-assembly triggers the formation of a 2D particle array superstructure. The atomic-level doping gives rise to high intrinsic activity, while the well-engineered porous structure and particle arrangement addresses the mass transport limitations at the microscopic particle level and macroscopic electrode level. As a result, the as-prepared electrocatalyst delivers outstanding performance toward oxygen reduction reaction in both acidic and alkaline media, which is better than recently reported state-of-the-art metal-free electrocatalysts. Molecular dynamics simulation together with extensive characterizations indicate that the performance enhancement originates from multi-scale structural synergy.

Case Report: First case of HIV, hepatitis B, hepatitis C, and Vibrio vulnificus coinfection.

Our patient, a 48-year-old man from Guangdong's coastal region, worked selling and processing oysters and other seafood. He started experiencing swelling and pain in his left knee on October 4, 2022, and they got worse over time. The findings of mNGS test showed Vibrio vulnificus infection. The patient had AIDS, hepatitis A and hepatitis B concurrently. He was admitted to the hospital's intensive care unit (ICU) for treatment as his symptoms worsened. We refrained from performing an amputation because the family members expressed a desire to keep the limb. The limb was managed with regular dressing changes, thorough debridement, wound closure, ongoing VSD drainage, and local antibiotic irrigation. The patient's organ function eventually returned to normal, and the systemic infection got better. On November 1, the wound's new granulation tissue had grown well and had gradually crept to cover 80% of the wound. The tissue's blood flow had also improved, indicating a trend of growth and healing.

Genomic diversity and evolution analysis of severe fever with thrombocytopenia syndrome in East Asia from 2010 to 2022.

Background: Conducting an up-to-date analysis on the genomic diversity and evolution patterns of severe fever with thrombocytopenia syndrome virus (SFTSV) is crucial for elucidating the underlying mechanisms of its emergency and pathogenicity, as well as assessing the extent of its threat to public health. Methods: Complete genome sequences of SFTSV were obtained from GenBank until December 19, 2022. A thorough phylogenetic analysis was conducted using comprehensive bioinformatics methods to estimate the genomic diversity and evolution. Results: The phylogenetic classification of SFTSV strains yielded seven lineages (A-G) for each genome segment. SFTSV displayed notable variations in evolutionary patterns among different regions and segments, without a linear accumulation of nucleotide substitutions within segments and regions. The comprehensive analysis revealed 54 recombination events and 17 reassortment strains, including the first discovery of recombination events involving sea-crossing and species-crossing. Selection analysis identified three positive sites (2, 671, 1353) in RNA-dependent RNA polymerase, three positive sites (22, 298, 404) in glycoprotein, and two positive sites (9, 289) in nonstructural protein. No positive selection sites were found in nucleoprotein. Conclusion: Our study unveiled the existence of multiple evolutionary forces influencing SFTSV, contributing to its increasing genetic diversity, which had the potential to modify its antigenicity and pathogenicity. Furthermore, our study highlights the importance of tracking the spread of SFTSV across regions and species.

Using Machine Learning to Predict Surgical Site Infection After Lumbar Spine Surgery.

Objective: The objective of this study was to utilize machine learning techniques to analyze perioperative factors and identify blood glucose levels that can predict the occurrence of surgical site infection following posterior lumbar spinal surgery. Methods: A total of 4019 patients receiving lumbar internal fixation surgery from an institute were enrolled between June 2012 and February 2021. First, the filtered data were randomized into the test and verification groups. Second, in the test group, specific variables were screened using logistic regression analysis, Lasso regression analysis, support vector machine, and random forest. Specific variables obtained using the four methods were intersected, and a dynamic model was constructed. ROC and calibration curves were constructed to assess model performance. Finally, internal model performance was verified in the verification group using ROC and calibration curves. Results: The data from 4019 patients were collected. In total, 1327 eligible cases were selected. By combining logistic regression analysis with three machine learning algorithms, this study identified four predictors associated with SSI, namely Modic changes, sebum thickness, hemoglobin, and glucose. Using this information, a prediction model was developed and visually represented. Then, we constructed ROC and calibration curves using the test group; the area under the ROC curve was 0.988. Further, calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index of our model was 0.986 (95% CI 0.981-0.994). Finally, we used the validation group to validate the model internally; the AUC was 0.987. Calibration curve analysis revealed favorable consistency of nomogram-predicted values compared with real measurements. The C-index was 0.982 (95% CI 0.974-0.999). Conclusion: Logistic regression analysis and machine learning were employed to select four risk factors: Modic changes, sebum thickness, hemoglobin, and glucose. Then, a dynamic prediction model was constructed to help clinicians simplify the monitoring and prevention of SSI.

A Thermochromic, Viscoelastic Nacre-like Nanocomposite for the Smart Thermal Management of Planar Electronics.

Cutting-edge heat spreaders for soft and planar electronics require not only high thermal conductivity and a certain degree of flexibility but also remarkable self-adhesion without thermal interface materials, elasticity, arbitrary elongation along with soft devices, and smart properties involving thermal self-healing, thermochromism and so on. Nacre-like composites with excellent in-plane heat dissipation are ideal as heat spreaders for thin and planar electronics. However, the intrinsically poor viscoelasticity, i.e., adhesion and elasticity, prevents them from simultaneous self-adhesion and arbitrary elongation along with current flexible devices as well as incurring high interfacial thermal impedance. In this paper, we propose a soft thermochromic composite (STC) membrane with a layered structure, considerable stretchability, high in-plane thermal conductivity (~ 30 W m-1 K-1), low thermal contact resistance (~ 12 mm2 K W-1, 4-5 times lower than that of silver paste), strong yet sustainable adhesion forces (~ 4607 J m-2, 2220 J m-2 greater than that of epoxy paste) and self-healing efficiency. As a self-adhesive heat spreader, it implements efficient cooling of various soft electronics with a temperature drop of 20 °C than the polyimide case. In addition to its self-healing function, the chameleon-like behavior of STC facilitates temperature monitoring by the naked eye, hence enabling smart thermal management.

TIMELESS promotes the proliferation and migration of lung adenocarcinoma cells by activating EGFR through AMPK and SPHK1 regulation.

BACKGROUND: Lung adenocarcinoma (LUAD) has high morbidity and is prone to recurrence. TIMELESS (TIM), which regulates circadian rhythms in Drosophila, is highly expressed in various tumors. Its role in LUAD has gained attention, but the detailed function and mechanism have not been clarified completely at present. METHODS: Tumor samples from patients with LUAD patient data from public databases were used to confirm the relationship of TIM expression with lung cancer. LUAD cell lines were used and siRNA of TIM was adopted to knock down TIM expression in LUAD cells, and further cell proliferation, migration and colony formation were analyzed. By using Western blot and qPCR, we detected the influence of TIM on epidermal growth factor receptor (EGFR), sphingosine kinase 1 (SPHK1) and AMP-activated protein kinase (AMPK). With proteomics analysis, we comprehensively inspected the different changed proteins influenced by TIM and did global bioinformatic analysis. RESULTS: We found that TIM expression was elevated in LUAD and that this high expression was positively correlated with more advanced tumor pathological stages and shorter overall and disease-free survival. TIM knockdown inhibited EGFR activation and also AKT/mTOR phosphorylation. We also clarified that TIM regulated the activation of SPHK1 in LUAD cells. And with SPHK1 siRNA to knock down the expression level of SPHK1, we found that EGFR activation were inhibited greatly too. Quantitative proteomics techniques combined with bioinformatics analysis clarified the global molecular mechanisms regulated by TIM in LUAD. The results of proteomics suggested that mitochondrial translation elongation and termination were altered, which were closely related to the process of mitochondrial oxidative phosphorylation. We further confirmed that TIM knockdown reduced ATP content and promoted AMPK activation in LUAD cells. CONCLUSIONS: Our study revealed that siTIM could inhibit EGFR activation through activating AMPK and inhibiting SPHK1 expression, as well as influencing mitochondrial function and altering the ATP level; TIM's high expression in LUAD is an important factor and a potential key target in LUAD.

Natural polyphenol tannin-immobilized composites: rational design and versatile applications.

Tannins, which are natural plant polyphenols, are widely used in different fields, especially in biomedical applications due to their unique properties, including high abundance, low cost, structural diversity, protein precipitation, biocompatibility, and biodegradability. However, they fail to satisfy the requirements in some specific applications (e.g., environmental remediation) on account of their water solubility, making their separation and regeneration difficult. Inspired by the design of composite materials, tannin-immobilized composites have emerged as promising and novel materials and combine or even surpass the advantages of each of their components. This strategy can endow tannin-immobilized composites with efficient manufacturing properties, high strength, good stability, easy chelating/coordinating ability, excellent antibacterial property, biological compatibility, bioactivity, chemical/corrosion resistance, and strong adhesive performance, which significantly expand their application in various fields. In this review, initially we summarize the design strategy of tannin-immobilized composites, mainly concentrating on the choice of immobilized substrate (e.g., natural polymers, synthetic polymers, and inorganic materials) as well as the binding interaction (e.g., Mannich reaction, Schiff base reaction, graft copolymerization, oxidation coupling, electrostatic interaction, and hydrogen bonding) between them. Further, the application of tannin-immobilized composites in the biomedical (tissue engineering, wound healing, cancer therapy, and biosensors) and other (leather materials, environmental remediation, and functional food packaging) fields is highlighted. Finally, we conclude with some thoughts on the open challenges and future perspectives of tannin composites. It can be anticipated that tannin-immobilized composites will continuously draw attention from more and more researchers, and further promising applications of tannin composites will be explored.

Mep50 is essential for embryonic development in medaka fish.

Mep50 as a partner promotes the activity and substrate affinity of Prmt5. Prmt5 and Mep50 function together in multiple bioprocesses of the cells. Both Prmt5 and Mep50 are necessary for maintenance of the stem cells and are indispensable in the embryogenesis in the mammals. However, the role of Mep50 is rarely studied in fish. This study was to investigate the role of Mep50 in embryonic development of medaka. Medaka mep50 was mutated by genomic editing with CRISPR-Cas9 technology. Two mutants with a deletion of 22 and 46 bp separately in mep50 caused premature stopping of translation. The homozygotes of these mutant fish were obtained by self-crossing of the heterozygotes. These homozygotic mutants could reproduce embryos but the offspring were not viable. The apoptotic cells were significantly more in the mutant embryos than that in the wild type indicated by TUNEL assay. Quantitative RT-PCR showed that the expression of oct4 and sox2 were significantly decreased, but p53 was increased in the mutant embryos. These results suggest that disruption of mep50 severely interferes with embryogenesis and mep50 is necessary for embryonic development by maintaining stem cells and repression of apoptosis in medaka.

Reversible bipolar thermopower of ionic thermoelectric polymer composite for cyclic energy generation.

The giant thermopower of ionic thermoelectric materials has attracted great attention for waste-heat recovery technologies. However, generating cyclic power by ionic thermoelectric modules remains challenging, since the ions cannot travel across the electrode interface. Here, we reported a reversible bipolar thermopower (+20.2 mV K-1 to -10.2 mV K-1) of the same composite by manipulating the interactions of ions and electrodes. Meanwhile, a promising ionic thermoelectric generator was proposed to achieve cyclic power generation under a constant heat course only by switching the external electrodes that can effectively realize the alternating dominated thermodiffusion of cations and anions. It eliminates the necessity to change the thermal contact between material and heat, nor does it require re-establish the temperature differences, which can favor improving the efficiency of the ionic thermoelectrics. Furthermore, the developed micro-thermal sensors demonstrated high sensitivity and responsivity in light detecting, presenting innovative impacts on exploring next-generation ionic thermoelectric devices.

Influence of sleep disruption on inflammatory bowel disease and changes in circadian rhythm genes.

According to clinical investigations, sleep disruption (SD) can influence the immune system and cause inflammatory bowel disease (IBD). However, the detailed effects of sleep on IBD development and progression have not been clarified. Here, we used dextran sulfate sodium (DSS) to induce colitis in mice, and then interfered with SD (day-time 8:00 a.m. to 5:00 p.m.) to explore the influence of sleep on colitis by analyzing colon length, mouse body weight, disease activity index (DAI) score, pathology detection, and infiltration of inflammatory cells with LCA immunohistochemistry analysis. Next, we detected the mRNA levels of circadian genes and related inflammatory factors, including Bmal1, CLOCK, Cry1, Cry2, Per1, Per2, Timeless, Rev-erbα, TNF-α, IL-6, and IFN-γ. Additionally, we conducted a sleep survey in IBD patients and collected colon lesion sites to detect the mRNA levels of those eight circadian genes and three inflammatory factors. We found that SD promoted the body weight decrease, increased inflammation as shown with pathological staining of the DSS animal model, and increased expression of the clock gene Cry2 in DSS-induced colitis mice. In IBD patients with active disease, the mRNA level of circadian genes Bmal1, Cry1, Cry2, and Rev-erbα in inflammatory tissues decreased significantly compared with non-inflammatory tissues.

General Synthesis of Large Inorganic Nanosheets via 2D Confined Assembly of Nanoparticles.

Assembling nanoparticles to spatially well-defined functional nanomaterials and sophisticated architectures has been an intriguing goal for scientists. However, maintaining a long-range order of assembly to create macrostructures remains a challenge, owing to the reliance on purely interparticle interactions. Here, we present a general strategy to synthesize a class of inorganic nanosheets via a bottom-up directional freezing method. We demonstrate that, by confining a homogeneously dispersed metal-cyano colloidal suspension at the ice-water interface, followed by removal of ice crystals, large nanosheets with a lateral scale of up to several millimeters can be produced. The formation of millimeter-sized nanosheets is attributed to balanced electrostatic forces between dispersed nanoparticles, coupled with an appropriate hydrodynamic size of nanoparticles, potentially favorable lattice matching between nanoparticles and ice crystals, and the intermediate water at the ice-particle interface. The highly anisotropic growth of ice crystals can therefore guide the 2D confined assembly of nanoparticles in a long-range order, leading to well-defined 2D nanosheets. This contribution sheds light on the potential of nanoparticle assembly at larger length scales in designing families of large 2D nanoarchitectures for practical applications.