Predicting the T790M mutation in non-small cell lung cancer (NSCLC) using brain metastasis MR radiomics: a study with an imbalanced dataset.

BACKGROUND: Early detection of T790M mutation in exon 20 of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) patients with brain metastasis is crucial for optimizing treatment strategies. In this study, we developed radiomics models to distinguish NSCLC patients with T790M-positive mutations from those with T790M-negative mutations using multisequence MR images of brain metastasis despite an imbalanced dataset. Various resampling techniques and classifiers were employed to identify the most effective strategy. METHODS: Radiomic analyses were conducted on a dataset comprising 125 patients, consisting of 18 with EGFR T790M-positive mutations and 107 with T790M-negative mutations. Seventeen first- and second-order statistical features were selected from CET1WI, T2WI, T2FLAIR, and DWI images. Four classifiers (logistic regression, support vector machine, random forest [RF], and extreme gradient boosting [XGBoost]) were evaluated under 13 different resampling conditions. RESULTS: The area under the curve (AUC) value achieved was 0.89, using the SVM-SMOTE oversampling method in combination with the XGBoost classifier. This performance was measured against the AUC reported in the literature, serving as an upper-bound reference. Additionally, comparable results were observed with other oversampling methods paired with RF or XGBoost classifiers. CONCLUSIONS: Our study demonstrates that, even when dealing with an imbalanced EGFR T790M dataset, reasonable predictive outcomes can be achieved by employing an appropriate combination of resampling techniques and classifiers. This approach has significant potential for enhancing T790M mutation detection in NSCLC patients with brain metastasis.

Development and validation of a diagnostic and prognostic model for bone metastasis of intrahepatic cholangiocarcinoma: a population-based analysis.

Background: Bone metastasis (BM) is a common site of metastasis in patients with intrahepatic cholangiocarcinoma (ICC), significantly impacting the quality of life and prognosis of affected individuals. This investigation aimed to assess the risk of BM development in ICC patients and to prognosticate for patients with ICC-associated BM (ICCBM) through the construction of two nomograms. Methods: We conducted a retrospective analysis of data from 2,651 ICC patients, including 148 cases of BM, documented in the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. Independent predictors for the occurrence of BM in ICC patients were identified via univariate and multivariate logistic regression analyses; simultaneously, independent prognostic indicators for ICCBM patients were ascertained through univariate and multivariate Cox regression analyses. The utility of the nomograms was evaluated through calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and Kaplan-Meier (KM) analysis. Results: Independent risk factors for BM in ICC included sex, tumor size, lung metastasis, brain metastasis, and intrahepatic metastasis. For ICCBM patients, independent prognostic factors comprised age, chemotherapy, and radiotherapy. The prognostic nomogram exhibited C-indexes of 0.737 [95% confidential interval (CI): 0.682-0.792] for the training cohort and 0.696 (95% CI: 0.623-0.769) for the validation cohort. Calibration curves demonstrated strong concordance between predicted outcomes and observed events. The areas under the curve (AUC) for 3-, 6-, and 12-month cancer-specific survival (CSS) were 0.853, 0.781, and 0.739, respectively, in the training cohort, and 0.794, 0.822, and 0.780 in the validation cohort. DCA illustrated significant net benefits across a broad spectrum of threshold probabilities. KM analysis revealed 1-, 2-, and 3-year CSS rates of 23.91%, 7.55%, and 2.35%, respectively, with a median CSS of 6 months, underscoring the nomograms' capacity to distinctly stratify patients according to survival risk. Conclusions: The development of these nomograms offers substantial clinical utility in forecasting BM risk among ICC patients and prognosticating for those with ICCBM, thereby facilitating the formulation of more efficacious treatment modalities.

Distribution and diversity of ticks determined by environmental factors in Ningxia, China.

Ticks are important vectors of zoonotic pathogens, and represent an increasing threat for human and animal health. Considering the complex natural environments of Ningxia Hui Autonomous Region, China, we expect the diverse tick species in this region. Here, we conduct a field survey on parasitic and host-seeking ticks. A total of 10,419 ticks were collected, which belonged to nine species of four genera. There were significant differences in terms of vegetation index, altitude, and seven climatic factors among the four tick genera -Hyalomma, Dermacentor, Haemaphysalis, and Ixodes, except between Haemaphysalis and Ixodes, where no significant differences were observed in these factors. The ecological niche modelling revealed that the suitable habitats for Hyalomma asiaticum was in the northwest Ningxia, with annual ground surface temperature as the most important factor. The suitable area for Dermacentor nuttalli was in the southwest and eastern regions of Ningxia with elevation as the highest contribution. D. silvarum was best suited to the southern Ningxia also with elevation as the most important factor. The four tick species including Haemaphysalis longicornis, Hae. qinghaiensis, Hae. japonica, and Ixodes persulcatus were best suited to the southernmost Ningxia with annual precipitation as the main factors for Hae. longicornis and elevation for the other three ticks. The results of predicted potential distribution of different tick species provide a scientific basis for the prevention and control of ticks and tick-borne diseases in the region. Furthermore, the subsequent impacts of the Greening Program to regain forests and grasslands from former agricultural lands in Ningxia on tick population dynamics deserve further investigation.

Multifunctional chitosan-based composite hydrogels engineered for sensing applications.

Chitosan-based hydrogels, as natural high-molecular-weight flexible materials, are widely utilized due to their outstanding properties. In this research, we developed a one-pot method for synthesizing a novel PVA/CS@PPy-PDAx% conductive hydrogel and explored the internal bonding patterns through molecular dynamics simulations. By adding PPy-PDA nanoparticles into a hydrogel matrix, an interpenetrating conductive network established successfully. The uniform distribution of PPy-PDA nanoparticles endowed the hydrogel with good electrical conductivity (0.171 S/m), significantly enhanced mechanical properties, and strain sensing (S = 5.04), as well as near-infrared photothermal responsiveness (temperature increase of 41.9 °C within 30 s). Additionally, due to the hydrogel's significant photothermal conversion efficiency under near-infrared radiation, it exhibits rapid elimination of Escherichia coli with an antibacterial efficiency exceeding 90 %. The unique hydrogen-bonded crosslinked structure provides the hydrogel with excellent re-healing properties, allowing for restoration through a freeze-thaw process after damage. The conductivity remains nearly unchanged after re-healing, maintaining the material's integrity and functionality. The flexible sensor based on this hydrogel has a response time of 100 ms and can sensitively detect large-scale deformations (e.g., joint bending at various angles), different gravitational forces, and recognize human handwriting. These characteristics make this hydrogel a promising candidate for advancing intelligent wearable technologies and human-machine interaction systems.

Merging Ring-Opening 1,2-Metallate Shift with Asymmetric C(sp3)-H Borylation of Aziridines.

Chiral secondary alkyl amines with a vicinal quaternary stereocenter are undoubtedly important and ubiquitous subunits in natural products and pharmaceuticals. However, their asymmetric synthesis remains a formidable challenge. Herein, we merge the ring-opening 1,2-metallate shift with iridium-catalyzed enantioselective C(sp3)-H borylation of aziridines to deliver these frameworks with high enantioselectivities. We also demonstrated the synthetic application by downstream transformations, including the total synthesis of two Amaryllidaceae alkaloids, (-)-crinane and (+)-mesmebrane.

Efficacy and safety analysis of continued nursing of complications in discharged patients after percutaneous transhepatic biliary drainage.

BACKGROUND: Percutaneous hepatobiliary drainage (PTCD) is an effective method for the treatment of biliary obstruction and other diseases, but postoperative complications are still one of the important problems faced by patients. Continuous nursing is a comprehensive nursing model that plays an important role in postoperative recovery. The purpose of this study was to investigate the effect of continuous nursing on the incidence of complications in patients after PTCD surgery through meta-analysis and to evaluate its efficacy and safety. AIM: To evaluate the effect of extended nursing on the incidence of complications in discharged patients after percutaneous transhepatic biliary drainage (PTBD). METHODS: Randomized controlled studies on PTBD postdischarge extended care were identified in the CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase, Web of Science, and other databases. The quality of the included studies was evaluated using the Joanna Briggs Institute of Australia literature quality evaluation tool, and a meta-analysis of the included studies was performed with RevMan 5.4 software. RESULTS: Finally, 9 studies were included, with a total sample size of 854 patients (425 patients in the control group and 429 patients in the intervention group). Meta-analysis revealed that extended care effectively reduced biliary tract infection (RR: 0.42, 95%CI: 0.30-0.57), puncture wound infection (RR: 0.19, 95%CI: 0.06-0.65), catheter protrusion or displacement in discharged patients after PTBD (RR: 0.31, 95%CI: 0.18-0.54), catheter blockage (RR: 0.23, 95%CI: 0.13-0.42), skin infection around the drainage tube (RR: 0.30, 95%CI: 0.12-0.77), and catheter-related readmissions (RR: 0.34, 95%CI: 0.18-0.65) (P < 0.05). CONCLUSION: Compared with conventional discharge care, extended care can effectively reduce the occurrence of complications such as biliary tract infection, puncture wound infection, catheter prolapse or displacement, catheter blockage, skin infection around the drainage tube, and catheter-related readmission in discharged patients after PTBD.

Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial.

BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.

COAP-Pd Catalyzed Asymmetric Formal [3+2] Cycloaddition for Optically Active Multistereogenic Spiro Cyclopentane-Indandiones Bearing Cyclic N-Sulfonyl Ketimine Skeletons.

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction.

Chiral Phosphine Ligands of COAP and SKP Switched Regiodivergent Asymmetric Allylic Alkylation of MBH Adducts.

The palladium-catalyzed highly regioselective asymmetric allylic alkylation of 3'-indolyl-3-oxindole derivatives with Morita-Baylis-Hillman (MBH) carbonates was developed to facilely construct chiral 3,3'-bisindole derivatives under mild reaction conditions. The regioselectivity (α/γ) of MBH carbonates was efficiently switched in the presence of chiral oxalamide phosphine or spiroketal-based diphosphine/Pd(0) complexes as a chiral catalyst. A series of multifunctional 3,3'-bisindole derivatives with all-carbon quaternary stereogenic centers were obtained in high yields with good to excellent enantio-, diastereo-, and regioselectivity. The present process is endowed with some salient features such as broad substrate scope, N-protecting group-free, excellent stereoselectivity, as well as adjustable regioselectivity.

Anti-UV Microgel Based on Interfacial Polymerization to Decrease Skin Irritation of High Permeability UV Absorber Ethylhexyl Methoxycinnamate.

Ethylhexyl methoxycinnamate (EHMC) is frequently employed as a photoprotective agent in sunscreen formulations. EHMC has been found to potentially contribute to health complications as a result of its propensity to produce irritation and permeate the skin. A microgel carrier, consisting of poly(ethylene glycol dimethacrylate) (pEDGMA), was synthesized using interfacial polymerization with the aim of reducing the irritation and penetration of EHMC. The thermogravimetric analysis (TGA) indicated that the EHMC content accounted for 75.72% of the total composition. Additionally, the scanning electron microscopy (SEM) images depicted the microgel as exhibiting a spherical morphology. In this study, the loading of EHMC was demonstrated through FTIR and contact angle tests. The UV resistance, penetration, and skin irritation of the EHMC-pEDGMA microgel were additionally assessed. The investigation revealed that the novel sunscreen compound, characterized by limited dermal absorption, had no irritant effects and offered sufficient protection against ultraviolet radiation.

Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control.

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits.

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

The complete mitogenome of Argas vulgaris (Filippova, 1961) and its phylogenetic status in subgenus Argas (Acari: Argasidae).

Soft ticks (Ixodida: Argasidae) are ectoparasites of terrestrial vertebrates with worldwide distributions. As one representative group of Argasidae, the genus Argas has an important vectorial role in transmitting zoonotic diseases. However, our knowledge of the subgenus Argas in China is still limited, as most literature only lists occurrence records or describes specific case reports without providing detailed morphological characteristics and further molecular data. This study aims to characterize Argas vulgaris through complete mitochondrial sequencing and morphological diagnostic techniques based on a batch of adult specimens collected from Ningxia Hui Autonomous Regions (NXHAR), North China. The morphology and microstructures of Ar. vulgaris and other lectotypes of argasid ticks in the subgenus Argas were also observed using a stereomicroscope. Following DNA extraction and sequencing, a complete mitochondrial sequence of Ar. vulgaris was assembled and analyzed within a phylogenetic context. The 14,479 bp mitogenome of Ar. vulgaris consists of 37 genes, including 13 genes for protein coding, two for ribosomal RNA, 22 for transfer RNA, and one for control region (D-loops). Phylogenetic analysis of Ar. vulgaris showed 98.27%-100% nucleotide identity with Ar. japonicus, indicating a close relationship between the two tick species. The morphological diagnostic features to differentiate Ar. vulgaris from other ticks within the subgenus Argas included the location of the anus and setae on the anterior lip of the female genital aperture. This study provided high-resolution scanning electron microscope images of female Ar. vulgaris and corresponding molecular data, representing valuable resources for future accurate species identification.

Virome diversity shaped by genetic evolution and ecological landscape of Haemaphysalis longicornis.

BACKGROUND: Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements. RESULTS: We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated. CONCLUSIONS: These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.

Investigating the pathogens associated with Dermacentor nuttalli and its global distribution: A study integrating metagenomic sequencing, meta-analysis and niche modeling.

Dermacentor nuttalli, a member of family Ixodidae and genus Dermacentor, is predominantly found in North Asia. It transmits various pathogens of human and animal diseases, such as Lymphocytic choriomeningitis mammarenavirus and Brucella ovis, leading to severe symptoms in patients and posing serious hazards to livestock husbandry. To profile pathogen abundances of wild D. nuttalli, metagenomic sequencing was performed of four field-collected tick samples, revealing that Rickettsia, Streptomyces, and Pseudomonas were the most abundant bacterial genera in D. nuttalli. Specifically, four nearly complete Rickettsia genomes were assembled, closely relative to Rickettsia conorii subsp. raoultii. Then, a comprehensive meta-analysis was performed to evaluate its potential threats based on detected pathogens and geographical distribution positions reported in literature, reference books, related websites, and field surveys. At least 48 pathogens were identified, including 20 species of bacteria, seven species of eukaryota, and 21 species of virus. Notably, Rickettsia conorii subsp. raoultii, Coxiella burnetii, and Brucella ovis displayed remarkably high positivity rates, which were known to cause infectious diseases in both humans and livestock. Currently, the primary distribution of D. nuttalli spans China, Mongolia, and Russia. However, an additional 14 countries in Asia and America that may also be affected by D. nuttalli were identified in our niche model, despite no previous reports of its presence in these areas. This study provides comprehensive data and analysis on the pathogens carried by D. nuttalli, along with documented and potential distribution, suggesting an emerging threat to public health and animal husbandry. Therefore, there is a need for heightened surveillance and thorough investigation of D. nuttalli.

Resistive Memory Devices at the Thinnest Limit: Progress and Challenges.

The Si-based integrated circuits industry has been developing for more than half a century, by focusing on the scaling-down of transistor. However, the miniaturization of transistors will soon reach its physical limits, thereby requiring novel material and device technologies. Resistive memory is a promising candidate for in-memory computing and energy-efficient synaptic devices that can satisfy the computational demands of the future applications. However, poor cycle-to-cycle and device-to-device uniformities hinder its mass production. 2D materials, as a new type of semiconductor, is successfully employed in various micro/nanoelectronic devices and have the potential to drive future innovation in resistive memory technology. This review evaluates the potential of using the thinnest advanced materials, that is, monolayer 2D materials, for memristor or memtransistor applications, including resistive switching behavior and atomic mechanism, high-frequency device performances, and in-memory computing/neuromorphic computing applications. The scaling-down advantages of promising monolayer 2D materials including graphene, transition metal dichalcogenides, and hexagonal boron nitride are presented. Finally, the technical challenges of these atomic devices for practical applications are elaborately discussed. The study of monolayer-2D-material-based resistive memory is expected to play a positive role in the exploration of beyond-Si electronic technologies.

Interlayer engineering of Fe3GeTe2: From 3D superlattice to 2D monolayer.

The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.

Evidence for d-wave superconductivity of infinite-layer nickelates from low-energy electrodynamics.

The discovery of superconductivity in infinite-layer nickelates established another category of unconventional superconductors that shares structural and electronic similarities with cuprates. However, key issues of the superconducting pairing symmetry, gap amplitude and superconducting fluctuations are yet to be addressed. Here we utilize static and ultrafast terahertz spectroscopy to address these. We demonstrate that the equilibrium terahertz conductivity and non-equilibrium terahertz responses of an optimally Sr-doped nickelate film (superconducting transition temperature of Tc = 17 K) are in line with the electrodynamics of d-wave superconductivity in the dirty limit. The gap-to-Tc ratio (2Δ/kBTc) is found to be 3.4, indicating that the superconductivity falls in the weak coupling regime. In addition, we observed substantial superconducting fluctuations near Tc that do not extend into the deep normal state as the optimally hole-doped cuprates do. Our results support a d-wave system that closely resembles the electron-doped cuprates.

Integrated Three-Dimensional Microdevice with a Modified Surface for Enhanced DNA Separation from Biological Samples.

Functional interfaces and devices for rapid adsorption and immobilization of nucleic acids (NAs) are significant for relevant bioengineering applications. Herein, a microdevice with poly(acrylic acid) (PAA) photosensitive resin was integrated by three-dimensional (3D) printing, named DPAA for short. Precise microscale structures and abundant surface carboxyl functional groups were fabricated for fast and high-throughput deoxyribonucleic acid (DNA) separation. Surface modification was then done using polydopamine (PDA) and poly(ethylene glycol) (PEG) to obtain modified poly(acrylic acid) (PAA)-based devices DPDA-PAA and DPEG-PAA rich in amino and hydroxyl groups, respectively. The fabricated device DPAA possessed superior printing accuracy (40-50 µm). Functionalization of amino and hydroxyl was successful, and the modified devices DPDA-PAA and DPEG-PAA maintained a high thermal stability like DPAA. Surface potential analysis and molecular dynamics simulation indicated that the affinity for DNA was in the order of DPDA-PAA > DPEG-PAA > DPAA. Further DNA separation experiments confirmed the high throughput and high selectivity of DNA separation performance, consistent with the predicted affinity results. DPDA-PAA showed relatively the highest DNA extraction yield, while DPEG-PAA was the worst. An acidic binding system is more favorable for DNA separation and recovery. DPDA-PAA showed significantly better DNA extraction performance than DPAA in a weakly acidic environment (pH 5.0-7.0), and the average DNA yield of the first elution was 2.16 times that of DPAA. This work validates the possibility of modification on integrated 3D microdevices to improve their DNA separation efficiency effectively. It also provides a new direction for the rational design and functionalization of bioengineering separators based on nonmagnetic methods. It may pave a new path for the highly efficient polymerase chain reaction diagnosis.

Micro-223 Promotes Diabetic Osteoarthritis Progression by Regulating Cartilage Degeneration and Subchondral Bone Remodeling.

OBJECTIVE: Our study was performed to investigate whether micro-223 promotes diabetic Osteoarthritis (OA) progression by regulating cartilage degeneration and subchondral bone remodeling. METHODS: The expression of miR-223 in human normal cartilage, OA cartilage, and subchondral bone tissue with or without DM was detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). miR-223 mimic or inhibitor was transfected into chondrocytes. Cell viability and apoptosis were assessed by 3-(4,5)-dimethylthiahiazo(-2)-3,5-diphenyltetrazolium bromide (MTT) and Terminal Deoxynucleotidyl Transferase(TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively. RESULTS: miR-223 was significantly higher in human diabetic OA cartilage and subchondral bone compared with normal OA and healthy control. Overexpression of miR-223 accelerated cartilage degeneration and subchondral bone sclerosis in diabetic OA mice, whereas miR-223 inhibition had the opposite effect. In vitro upregulation of miR-223 decreased proliferation and enhanced apoptosis of chondrocytes. Meanwhile, downregulation of miR-223 promoted glycosaminoglycan (GAG) production in chondrocytes. CONCLUSION: miR-223 promotes diabetic OA progression by regulating cartilage degeneration and subchondral bone remodeling both in vitro and in vivo.