Synergy of Spall Strength and Toughness in Nanograined Metals.

Under shock loading, the spall strength of nanocrystals exhibits intricate grain-size effects due to the presence of abundant grain boundary and dislocation activities. However, the influence of size on spall toughness and void evolution has been largely overlooked. This study employs molecular dynamics simulations to investigate the damage accumulation characteristics of nanocrystalline aluminum across various grain sizes. Unlike the trade-off observed in quasi-static loading conditions, our study reveals a consistency in which grain size governs both nanovoid nucleation and coalescence, yielding a novel spall strength-toughness synergy. These insights highlight grain sizes that are particularly susceptible to spall fracture, offering a crucial understanding of nanocrystal failure mechanisms in extreme environments.

Factual and counterfactual learning in major adolescent depressive disorder, evidence from an instrumental learning study.

BACKGROUND: The incidence of adolescent depressive disorder is globally skyrocketing in recent decades, albeit the causes and the decision deficits depression incurs has yet to be well-examined. With an instrumental learning task, the aim of the current study is to investigate the extent to which learning behavior deviates from that observed in healthy adolescent controls and track the underlying mechanistic channel for such a deviation. METHODS: We recruited a group of adolescents with major depression and age-matched healthy control subjects to carry out the learning task with either gain or loss outcome and applied a reinforcement learning model that dissociates valence (positive v. negative) of reward prediction error and selection (chosen v. unchosen). RESULTS: The results demonstrated that adolescent depressive patients performed significantly less well than the control group. Learning rates suggested that the optimistic bias that overall characterizes healthy adolescent subjects was absent for the depressive adolescent patients. Moreover, depressed adolescents exhibited an increased pessimistic bias for the counterfactual outcome. Lastly, individual difference analysis suggested that these observed biases, which significantly deviated from that observed in normal controls, were linked with the severity of depressive symoptoms as measured by HAMD scores. CONCLUSIONS: By leveraging an incentivized instrumental learning task with computational modeling within a reinforcement learning framework, the current study reveals a mechanistic decision-making deficit in adolescent depressive disorder. These findings, which have implications for the identification of behavioral markers in depression, could support the clinical evaluation, including both diagnosis and prognosis of this disorder.

A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. METHODS: The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. RESULTS: PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. CONCLUSIONS: Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer.

Improving Clinical Outcomes: Hightibialosteotomy Plate Placement Combined with Arthroscopic Surgery.

Objective: Our study aimed to investigate the clinical efficacy of hightibialosteotomy (HTO) posterior plate placement combined with arthroscopic surgery for degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower extremity, improve joint function or relieve pain. Methods: The case data of 98 patients with osteoarthritis of the knee admitted to the Department of Orthopedics in our hospital from January 2019 to January 2023 were selected for retrospective analysis. The patients were divided into 54 patients, each in the study group and the comparison group according to the different treatment regimens. The study group received hightibialosteotomy plate placement combined with arthroscopic surgery, while the comparison group underwent hightibialosteotomy plate placement alone. The differences in knee scores, knee Lysholm scores, Lysholm scores, Healthcare Security and Safety (HSS) scores, Tegner scores, Visual Analog Scale (VAS), lower extremity force lines, femorotibial angles, and tibial plateau were counted and compared between the two groups. Results: HSS knee function scores, Lysholm scores, and VAS scores of the study group were statistically significant compared with those of the comparison group at the final follow-up of patients, and the postoperative clinical outcomes improved significantly (P < .05). The differences in Hip-Knee-Ankle(HKA) angle andMedial-Pateral Tibial Angle (MPTA) of patients in the study group were statistically significant compared with the comparison group, and the increase in HKA (12.31±2.13)°, MPTA (11.84±2.32)° and lower limb force line was significantly improved (P < .05). Preoperatively, there was no statistically significant comparison between the visual analog scores of the knee joint in the study group and the comparison group. After surgery, the difference between the two groups was statistically significant (P < .05). The relative position of the mechanical axis of the lower limb through the tibial plateau, the femorotibial angle, and the posterior tibial plateau angle increased in patients after surgery, and the differences were statistically significant when compared with the preoperative period (P < .05). Both the tibial posterior displacement distance and the lateral knee gap opening were reduced compared with the preoperative period, and the differences were statistically significant (P < .05). Conclusion: Hightibialosteotomy after plate placement combined with arthroscopic surgery has better clinical efficacy in the early stage and can effectively treat the degenerative injury of the posterior horn of the medial meniscus with poor force lines in the lower limb, improve the joint function, and relieve the symptoms of patients.

Simultaneous Determination of Four Catechins in Black Tea via NIR Spectroscopy and Feature Wavelength Selection: A Novel Approach.

As a non-destructive, fast, and cost-effective technique, near-infrared (NIR) spectroscopy has been widely used to determine the content of bioactive components in tea. However, due to the similar chemical structures of various catechins in black tea, the NIR spectra of black tea severely overlap in certain bands, causing nonlinear relationships and reducing analytical accuracy. In addition, the number of NIR spectral wavelengths is much larger than that of the modeled samples, and the small-sample learning problem is rather typical. These issues make the use of NIRS to simultaneously determine black tea catechins challenging. To address the above problems, this study innovatively proposed a wavelength selection algorithm based on feature interval combination sensitivity segmentation (FIC-SS). This algorithm extracts wavelengths at both coarse-grained and fine-grained levels, achieving higher accuracy and stability in feature wavelength extraction. On this basis, the study built four simultaneous prediction models for catechins based on extreme learning machines (ELMs), utilizing their powerful nonlinear learning ability and simple model structure to achieve simultaneous and accurate prediction of catechins. The experimental results showed that for the full spectrum, the ELM model has better prediction performance than the partial least squares model for epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). For the feature wavelengths, our proposed FIC-SS-ELM model enjoys higher prediction performance than ELM models based on other wavelength selection algorithms; it can simultaneously and accurately predict the content of EC (Rp2 = 0.91, RMSEP = 0.019), ECG (Rp2 = 0.96, RMSEP = 0.11), EGC (Rp2 = 0.97, RMSEP = 0.15), and EGCG (Rp2 = 0.97, RMSEP = 0.35) in black tea. The results of this study provide a new method for the quantitative determination of the bioactive components of black tea.

CsCuAO1 Associated with CsAMADH1 Confers Drought Tolerance by Modulating GABA Levels in Tea Plants.

Our previous study showed that COPPER-CONTAINING AMINE OXIDASE (CuAO) and AMINOALDEHYDE DEHYDROGENASE (AMADH) could regulate the accumulation of γ-aminobutyric acid (GABA) in tea through the polyamine degradation pathway. However, their biological function in drought tolerance has not been determined. In this study, Camellia sinensis (Cs) CsCuAO1 associated with CsAMADH1 conferred drought tolerance, which modulated GABA levels in tea plants. The results showed that exogenous GABA spraying effectively alleviated the drought-induced physical damage. Arabidopsis lines overexpressing CsCuAO1 and CsAMADH1 exhibited enhanced resistance to drought, which promoted the synthesis of GABA and putrescine by stimulating reactive oxygen species' scavenging capacity and stomatal movement. However, the suppression of CsCuAO1 or CsAMADH1 in tea plants resulted in increased sensitivity to drought treatment. Moreover, co-overexpressing plants increased GABA accumulation both in an Agrobacterium-mediated Nicotiana benthamiana transient assay and transgenic Arabidopsis plants. In addition, a GABA transporter gene, CsGAT1, was identified, whose expression was strongly correlated with GABA accumulation levels in different tissues under drought stress. Taken together, CsCuAO1 and CsAMADH1 were involved in the response to drought stress through a dynamic GABA-putrescine balance. Our data will contribute to the characterization of GABA's biological functions in response to environmental stresses in plants.

High glucose-upregulated PD-L1 expression through RAS signaling-driven downregulation of PTRH1 leads to suppression of T cell cytotoxic function in tumor environment.

BACKGROUND: Nearly 80% of patients with pancreatic cancer suffer from glucose intolerance or diabetes. Pancreatic cancer complicated by diabetes has a more immunosuppressive tumor microenvironment (TME) and is associated with a worse prognosis. The relationship between glucose metabolism and programmed cell death-Ligand 1 (PD-L1) is close and complex. It is important to explore the regulation of high glucose on PD-L1 expression in pancreatic cancer and its effect on infiltrating immune effectors in the tumor microenvironment. METHODS: Diabetic murine models (C57BL/6) were used to reveal different immune landscape in euglycemic and hyperglycemic pancreatic tumor microenvironment. Bioinformatics, WB, iRIP [Improved RNA Binding Protein (RBP) Immunoprecipitation]-seq were used to confirm the potential regulating role of peptidyl-tRNA hydrolase 1 homolog (PTRH1) on the stability of the PD-L1 mRNA. Postoperative specimens were used to identify the expression of PD-L1 and PTRH1 in pancreatic cancer. Co-culturing T cells with pancreatic cancer cells to explore the immunosuppressive effect of pancreatic tumor cells. RESULTS: Our results revealed that a high dose of glucose enhanced the stability of the PD-L1 mRNA in pancreatic tumor cells by downregulating PTRH1 through RAS signaling pathway activation following epidermal growth factor receptor (EGFR) stimulation. PTRH1 overexpression significantly suppressed PD-L1 expression in pancreatic cells and improved the proportion and cytotoxic function of CD8+ T cells in the pancreatic TME of diabetic mice. CONCLUSIONS: PTRH1, an RBP, plays a key role in the regulation of PD-L1 by high glucose and is closely related to anti-tumor immunity in the pancreatic TME.

The Efficacy and Safety of Surufatinib Combined with Anti PD-1 Antibody Toripalimab in Neoadjuvant Treatment of Locally Advanced Differentiated Thyroid Cancer: A Phase II Study.

BACKGROUND: Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting. METHODS: In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2. CONCLUSIONS: Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

Multifunctional Mesoporous Carbonaceous Materials Enable the High Performance of Lithium-Sulfur Batteries.

Focusing on multifunctional mesoporous carbonaceous materials (MCMs) is one of the hot research topics due to increasing demand in the high-energy-density devices of lithium-sulfur (Li-S) batteries (2600 Wh kg-1). On the premise of applying MCMs as a porous framework to load elemental sulfur, to improve the electronic conductivity of the cathode, and to trap the in situ-formed electrolyte-soluble intermediates of lithium polysulfides (LiPSs), the commercialization of MCMs-based energy storage devices still needs to solve solid/solid and solid/liquid interfacial issues such as the chemical anchoring of the electrically insulating active substances, the sluggish redox kinetics of intermediate LiPSs, and so on. Through the permutation of multifunctional MCMs serving as the primary sulfur-loading carrier of the cathode, as the secondary surface-coating layers of the separator, the cathode, and the anode separately, this Perspective highlights research challenges to clarify a comprehensive high-performance mechanism of MCM-based Li-S batteries and provides new chemical insight for potential application purposes.

Genetic characterization of HIV-1 viruses among cases with antiretroviral therapy failure in Suzhou City, China.

BACKGROUND: This retrospective study aimed to characterize the distribution of HIV-1 genotypes and the prevalence of drug resistance mutations in people with antiretroviral treatment (ART) failure in Suzhou City, China. METHODS: Pol gene of HIV-1 viruses in blood samples of EDTA anticoagulants from 398 patients with failed antiviral treatment was successfully amplified by using an in-house assay. Drug resistance mutations were analyzed by using the Stanford HIV Drug Resistance Database system ( https://hivdb.stanford.edu/hivdb/by-mutations/ ). HIV-1 genotypes were determined by the REGA HIV subtyping tool (version 3.46, https://www.genomedetective.com/app/typingtool/hiv ). Near full-length genomes (NFLG) of HIV-1 viruses were obtained by next generation sequencing method. RESULTS: Sequences analysis of the pol gene revealed that CRF 01_AE (57.29%, 228/398) was the dominant subtype circulating in Suzhou City, followed by CRF 07_BC (17.34%, 69/398), subtype B (7.54%, 30/398), CRF 08_BC (6.53%, 26/398), CRF 67_01B (3.02%, 12/398) and CRF55_01B (2.51%, 10/398). The overall prevalence of drug-resistant mutations in cases with ART failure was 64.57% (257/398), including 45.48% (181/398) for nucleotide reverse transcriptase inhibitors (NRTIs) mutations, 63.32% (252/398) for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations, and 3.02% (12/398) for protease inhibitors (PIs) mutations. Ten near full-length genomes (NFLG) of HIV-1 viruses were identified, including six recombinants of CRF 01_AE and subtype B, two recombinants of CRF 01_AE, subtype B and subtype C sequences, one recombinant of CRF 01_AE and subtype C and one recombinant of CRF 01_AE, subtype A1 and subtype C. CONCLUSIONS: The high prevalence of drug-resistant HIV-1 viruses was a serious challenge for HIV prevention and treatment of people with HIV infection. Treatment regimens for ART failure patients should be adjusted over time based on the outcome of drug resistance tests. NFLG sequencing facilitates the identification of new recombinants of HIV-1.

Research on a Super-Resolution and Low-Complexity Positioning Algorithm Using FMCW Radar Based on OMP and FFT in 2D Driving Scene.

Multitarget positioning technology, such as FMCW millimeter-wave radar, has broad application prospects in autonomous driving and related mobile scenarios. However, it is difficult for existing correlation algorithms to balance high resolution and low complexity, and it is also difficult to ensure the robustness of the positioning algorithm using an aging antenna. This paper proposes a super-resolution and low-complexity positioning algorithm based on the orthogonal matching pursuit algorithm that can achieve more accurate distance and angle estimation for multiple objects in a low-SNR environment. The algorithm proposed in this paper improves the resolving power by two and one orders of magnitude, respectively, compared to the classical FFT and MUSIC algorithms in the same signal-to-noise environment, and the complexity of the algorithm can be reduced by about 25-30%, with the same resolving power as the OMP algorithm. Based on the positioning algorithm proposed in our paper, we use the PSO algorithm to optimize the arrangement of an aging antenna array so that its angle estimation accuracy is equivalent to that observed when the antenna is intact, improving the positioning algorithm's robustness. This paper also further realizes the use of the proposed algorithm and a single-frame intermediate frequency signal to estimate the position angle information of the object and obtain its motion trajectory and velocity, verifying the proposed algorithm's estimation ability when it comes to these qualities in a moving scene. Furthermore, this paper designs and carries out simulations and experiments. The experimental results verify that the positioning algorithm proposed in this paper can achieve accuracy, robustness, and real-time performance in autonomous driving scenarios.

Federated Meta-Learning with Attention for Diversity-Aware Human Activity Recognition.

The ubiquity of smartphones equipped with multiple sensors has provided the possibility of automatically recognizing of human activity, which can benefit intelligent applications such as smart homes, health monitoring, and aging care. However, there are two major barriers to deploying an activity recognition model in real-world scenarios. Firstly, deep learning models for activity recognition use a large amount of sensor data, which are privacy-sensitive and hence cannot be shared or uploaded to a centralized server. Secondly, divergence in the distribution of sensory data exists among multiple individuals due to their diverse behavioral patterns and lifestyles, which contributes to difficulty in recognizing activity for large-scale users or 'cold-starts' for new users. To address these problems, we propose DivAR, a diversity-aware activity recognition framework based on a federated Meta-Learning architecture, which can extract general sensory features shared among individuals by a centralized embedding network and individual-specific features by attention module in each decentralized network. Specifically, we first classify individuals into multiple clusters according to their behavioral patterns and social factors. We then apply meta-learning in the architecture of federated learning, where a centralized meta-model learns common feature representations that can be transferred across all clusters of individuals, and multiple decentralized cluster-specific models are utilized to learn cluster-specific features. For each cluster-specific model, a CNN-based attention module learns cluster-specific features from the global model. In this way, by training with sensory data locally, privacy-sensitive information existing in sensory data can be preserved. To evaluate the model, we conduct two data collection experiments by collecting sensor readings from naturally used smartphones annotated with activity information in the real-life environment and constructing two multi-individual heterogeneous datasets. In addition, social characteristics including personality, mental health state, and behavior patterns are surveyed using questionnaires. Finally, extensive empirical results demonstrate that the proposed diversity-aware activity recognition model has a relatively better generalization ability and achieves competitive performance on multi-individual activity recognition tasks.

Broad tuning range, high power quantum cascade laser at λ ∼ 7.4 µm.

In this article, we report a high power quantum cascade laser (QCL) at λ∼7.4 µm with a broad tuning range. By carefully designing and optimizing the active region and waveguide structure, a continuous-wave (CW) output power up to 1.36 W and 0.5 W is achieved at 293 K and 373 K which shows the excellent temperature stability. A high wall-plug efficiency (WPE) of 8% and 13.6% in CW and pulsed mode at 293 K are demonstrated. The laser shows a characteristic temperature T0 of 224 K and T1 of 381 K over a temperature range from 283 K to 373 K. In addition, a far field of pure zero order transverse mode and a fairly wide external cavity (EC) tuning range (280 cm-1) from 6.54 µm to 8 µm are achieved in pulsed operation. In addition, an EC single mode output power of 226 mW is obtained under CW operation at 293K.

GaSb surface grating distributed feedback interband cascade laser emitting at 3.25 µm.

A second-order distributed feedback interband cascade laser emitting at 3.25 µm was designed, grown, and fabricated. By coherent epitaxy of a GaSb cap layer instead of the conventional thin InAs cap on top of the laser structure, a high-quality surface grating was made of GaSb and gold. Enough coupling strength and a significant inter-modal loss difference were predicted according to the simulation within the framework of couple-wave theory. Lasers having 2-mm-long cavities and 4.5-µm-wide ridges with high-/anti-reflection coatings were fabricated. The continuous-wave threshold current and maximum single-mode output power were 60 mA and 24 mW at 20°C, respectively. The output power of 5 mW was still kept at 55°C. Continuous tuning free from mode hopping and high single-mode suppression ratios (>20 dB) were realized at all injection currents and heat-sink temperatures, covering a spectral range of over 20 cm-1.

Super enhancer-LncRNA SENCR promoted cisplatin resistance and growth of NSCLC through upregulating FLI1.

BACKGROUND: Super enhancer-lncRNA smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) were highly overexpressed in cisplatin-resistant A549/DDP cells, while the mechanism was unclear. METHODS: SE-lncRNA SENCR and FLI1 mRNA expression in A549/DDP cell, LAD tissues were detected. SENCR knockdown of A549/DDP cell and SENCR overexpression of cisplatin-sensitive A549 cell were constructed. Experiments of cell-confirmed function of SENCR and the correlation between SENCR and FLI1 were validated. RESULTS: The expression of SENCR and FLI1 mRNA in A549/DDP cell were both upregulated and mainly localized in the nucleus. Compared with DDP-sensitive tissues with disease relief, SENCR expression was higher in DDP-resistant tissues with disease progression from LAD. Knockdown of SENCR in A549/DDP reduced proliferation ability and cisplatin resistance, consistent with the decreased levels of proteins PCNA, MDMX, and P-gp. Besides, whatever without cisplatin or with 2 µg/ml cisplatin, knockdown of SENCR reduced the migration, invasion, and colony formation abilities of A549/DDP cell and promoted apoptosis. However, when SENCR was overexpressed in A549 cell, all above results were reversed. Mechanistically, FLI1 expression was reduced after knocking down SENCR, while overexpressing SENCR increased FLI1 expression. CONCLUSION: SE-LncRNA SENCR was upregulated in A549/DDP, which could promote cisplatin resistance and growth of NSCLC cell through upregulating FLI1 expression.

Sagittal intervertebral rotational motion: a deep learning-based measurement on flexion-neutral-extension cervical lateral radiographs.

BACKGROUND: The analysis of sagittal intervertebral rotational motion (SIRM) can provide important information for the evaluation of cervical diseases. Deep learning has been widely used in spinal parameter measurements, however, there are few investigations on spinal motion analysis. The purpose of this study is to develop a deep learning-based model for fully automated measurement of SIRM based on flexion-neutral-extension cervical lateral radiographs and to evaluate its applicability for the flexion-extension (F/E), flexion-neutral (F/N), and neutral-extension (N/E) motion analysis. METHODS: A total of 2796 flexion, neutral, and extension cervical lateral radiographs from 932 patients were analyzed. Radiographs from 100 patients were randomly selected as the test set, and those from the remaining 832 patients were used for training and validation. Landmarks were annotated for measuring SIRM at five segments from C2/3 to C6/7 on F/E, F/N, and N/E motion. High-Resolution Net (HRNet) was used as the main structure to train the landmark detection network. Landmark performance was assessed according to the percentage of correct key points (PCK) and mean of the percentage of correct key points (MPCK). Measurement performance was evaluated by intra-class correlation coefficient (ICC), Pearson correlation coefficient, mean absolute error (MAE), root mean square error (RMSE), and Bland-Altman plots. RESULTS: At a 2-mm distance threshold, the PCK for the model ranged from 94 to 100%. Compared with the reference standards, the model showed high accuracy for SIRM measurements for all segments on F/E and F/N motion. On N/E motion, the model provided reliable measurements from C3/4 to C6/7, but not C2/3. Compared with the radiologists' measurements, the model showed similar performance to the radiologists. CONCLUSIONS: The developed model can automatically measure SIRM on flexion-neutral-extension cervical lateral radiographs and showed comparable performance with radiologists. It may provide rapid, accurate, and comprehensive information for cervical motion analysis.

Assembled Exciton Dynamics in Porphyrin Metal-Organic Framework Nanofilms.

Metal-organic frameworks (MOFs) provide a novel strategy to precisely control the alignment of molecules to enhance exciton diffusion for high-performance organic semiconductors. In this paper, we characterize exciton dynamics in highly ordered and crystalline porphyrin MOF nanofilms by time-resolved photoluminescence and femtosecond-resolved transient absorption spectroscopy. Results suggest that porphyrin MOF nanofilms could be a promising candidate for high-performance organic photovoltaic semiconductors in which the diffusion coefficient and diffusion length of excitons are 9.0 × 10-2 cm2 s-1 and 16.6 nm, respectively, comparable with or even beyond that of other excellent organic semiconductors. Moreover, by monitoring real-time exciton dynamics it is revealed that excitons in MOF nanofilms undergo high-efficient intermolecular hopping and multiexciton annihilation due to the short intermolecular distance and aligned molecular orientation in MOF structure, thus providing new insights into the underlying physics of exciton dynamics and many-body interaction in molecular assembled systems.

Sulfatide Deficiency, an Early Alzheimer's Lipidomic Signature, Causes Brain Ventricular Enlargement in the Absence of Classical Neuropathological Hallmarks.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and a decline in activities of daily life. Ventricular enlargement has been associated with worse performance on global cognitive tests and AD. Our previous studies demonstrated that brain sulfatides, myelin-enriched lipids, are dramatically reduced in subjects at the earliest clinically recognizable AD stages via an apolipoprotein E (APOE)-dependent and isoform-specific process. Herein, we provided pre-clinical evidence that sulfatide deficiency is causally associated with brain ventricular enlargement. Specifically, taking advantage of genetic mouse models of global and adult-onset sulfatide deficiency, we demonstrated that sulfatide losses cause ventricular enlargement without significantly affecting hippocampal or whole brain volumes using histological and magnetic resonance imaging approaches. Mild decreases in sulfatide content and mild increases in ventricular areas were also observed in human APOE4 compared to APOE2 knock-in mice. Finally, we provided Western blot and immunofluorescence evidence that aquaporin-4, the most prevalent aquaporin channel in the central nervous system (CNS) that provides fast water transportation and regulates cerebrospinal fluid in the ventricles, is significantly increased under sulfatide-deficient conditions, while other major brain aquaporins (e.g., aquaporin-1) are not altered. In short, we unraveled a novel and causal association between sulfatide deficiency and ventricular enlargement. Finally, we propose putative mechanisms by which sulfatide deficiency may induce ventricular enlargement.

Distinct Murine Pancreatic Transcriptomic Signatures during Chronic Pancreatitis Recovery.

We have previously demonstrated that the pancreas can recover from chronic pancreatitis (CP) lesions in the cerulein-induced mouse model. To explore how pancreatic recovery is achieved at the molecular level, we used RNA-sequencing (seq) and profiled transcriptomes during CP transition to recovery. CP was induced by intraperitoneally injecting cerulein in C57BL/6 mice. Time-matched controls (CON) were given normal saline. Pancreata were harvested from mice 4 days after the final injections (designated as CP and CON) or 4 weeks after the final injections (designated as CP recovery (CPR) and control recovery (CONR)). Pancreatic RNAs were extracted for RNA-seq and quantitative (q) PCR validation. Using RNA-seq, we identified a total of 3,600 differentially expressed genes (DEGs) in CP versus CON and 166 DEGs in CPR versus CONR. There are 132 DEGs overlapped between CP and CPR and 34 DEGs unique to CPR. A number of selected pancreatic fibrosis-relevant DEGs were validated by qPCR. The top 20 gene sets enriched from DEGs shared between CP and CPR are relevant to extracellular matrix and cancer biology, whereas the top 10 gene sets enriched from DEGs specific to CPR are pertinent to DNA methylation and specific signaling pathways. In conclusion, we identified a distinct set of DEGs in association with extracellular matrix and cancer cell activities to contrast CP and CPR. Once during ongoing CP recovery, DEGs relevant to DNA methylation and specific signaling pathways were induced to express. The DEGs shared between CP and CPR and the DEGs specific to CPR may serve as the unique transcriptomic signatures and biomarkers for determining CP recovery and monitoring potential therapeutic responses at the molecular level to reflect pancreatic histological resolution.

Formulation and intestinal absorption of naringenin loaded nanostructured lipid carrier and its inhibitory effects on nonalcoholic fatty liver disease.

In this study, we prepared naringenin (NGN) loaded nanostructured lipid carrier (NGN-NLC) and investigated its characterizations, transepithelial transport, intestinal absorption and inhibitory effects on nonalcoholic fatty liver disease (NAFLD) induced by a methionine choline deficient (MCD) diet in mice. The NGN-NLC, prepared by a method of emulsion-evaporation plus low temperature-solidification, displayed high drug loading capacity of 22.5 ± 1.7%. Compared to the NGN crude drug, the NGN-NLC, at an equal NGN dose, improved NGN release rate by 3.5-fold and elevated NGN transepithelial transport and intestinal absorption through enhancing intracellular transport of clathrin pathway and escaping p-gp efflux; at an 8-fold lower NGN dose, showed comparable pharmacokinetic parameters, but elevated liver NGN distribution by 1.5-fold, reduced MCD diet-induced hepatic lipid deposition by 3-fold. These results suggest that the NLC formulation significantly increased the inhibitory effects of NGN on NAFLD because of the improved drug release rate, transepithelial transport and intestinal absorption, and the elevated oral bioavailability and liver NGN distribution.