The Closer Vicinity to Treated Vertebrae in Percutaneous Vertebroplasty, the Higher Rate of New Vertebral Compression Fractures at Follow-up.

OBJECTIVE: To investigate whether risk of new vertebral compression fractures (NVCFs) was associated with vicinity to treated vertebrae in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs). METHODS: All OVCF (T6-L5) patients treated with PVP between January 2016 and December 2020 were retrospectively reviewed. Vicinity to treated vertebrae was defined as the number of vertebrae between an untreated and its closest treated level. The closest treated level was chosen as reference vertebra. Clinical, radiologic, and surgical parameters were compared between groups of reference vertebrae for each vicinity NVCF. RESULTS: In total, 1348 patients with 1592 fractured and 14,584 normal vertebrae were enrolled. NVCF was identified in 20.1% (271 of 1348) patients in 2.2% (319 of 14584) vertebrae in a mean follow-up time of 24.3 ± 11.9 months. Rate of NVCF in vicinity 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 level were 4.6% (130 of 2808), 2.4% (62 of 2558), 1.8% (42 of 2365), 1.5% (31 of 2131), 1.3% (23 of 1739), 1.3% (17 of 1298), 0.8% (7 of 847), 0.9% (4 of 450), 0.8% (2 of 245), 0.9% (1 of 117), and 0% (0 of 26), respectively. Rate of NVCF in vicinity 1 level was significantly higher than that in vicinity 2, 3, 4, 5, 6, 7, 8, and 9 level, respectively. However, compared to reference vertebrae for vicinity 1 NVCF, any clinical, radiologic, or surgical parameters were not significantly different in those for vicinity 2, 3, and 4 NVCF, respectively. CONCLUSIONS: The closer vicinity to treated vertebrae in PVP, the higher rate of NVCF at follow-up. However, any clinical, radiologic, or surgical parameters might not matter in this phenomenon of vicinity-related NVCF.

Static and Temporal Dynamic in Functional Connectivity of Large-scale Brain Networks During Acute Stress Regulate Stress Resilience Differently: The Promotion Role of Trait Resilience.

Stress resilience has been largely regarded as a process in which individuals actively cope with and recover from stress. Over the past decade, the emergence of large-scale brain networks has provided a new perspective for the study of the neural mechanisms of stress. However, the role of inter-network functional-connectivity (FC) and its temporal fluctuations in stress resilience is still unclear. To bridge this knowledge gap, seventy-seven participants (age, 17-22 years, 37 women) were recruited for a ScanSTRESS brain imaging study. A static perspective was initially adopted, using changes in FC that obtained from stress vs. control condition during the entire stress induction phase as a static indicator. Further, changes in FC between different stress runs were analyzed as an index of temporal dynamics. Stress resilience was gauged using salivary cortisol levels, while trait resilience was measured via behavioral-activation-system (BAS) sensitivity. Results found that, for the static index, enhanced FC between the salience-network (SN), default-mode-network (DMN) and limbic-network (LBN) during acute stress could negatively signal stress resilience. For the temporal dynamics index, FC among the dorsal-attention-network (DAN), central-executive-network (CEN) and visual-network (VN) decreased significantly during repeated stress induction. Moreover, the decline of FC positively signaled stress resilience, and this relationship only exist in people with high BAS. The current research elucidates the intricate neural underpinnings of stress resilience, offering insights into the adaptive mechanisms underlying effective stress responses.

Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

A macroporous composite sponge with high water absorbency and active coagulation mechanism for traumatic hemostasis and anti-infection.

The development of a composite sponge with high water absorbency and active coagulation mechanism for traumatic hemostasis and anti-infection remains a challenge. Herein, we developed a composite sponge using gelation, swelling, and freeze-drying methods based on quaternized chitosan, succinimidyl-modified F127, and bioactive glass. The sponge exhibited macroporous structure, high porosity, and water absorbency. When exposed to blood, it strongly interacted with blood cells, promoting their adhesion, aggregation, and activation. Moreover, it activated the intrinsic coagulation pathway. The sponge/powder demonstrated superior hemostatic capacity to commercial gauze, gelatin sponge, Yunnan Baiyao, and chitosan hemostatic powder in rat tail amputation, liver superficial injury, liver resection, and liver semi-perforation wound models. The sponge also presented robust anti-infection activity against methicillin-resistantStaphylococcus aureusandEscherichia coli. Additionally, the sponge showed low cytotoxicity, hemolysis activity, inflammation response, and systemic toxicity, demonstrating its favorable biocompatibility.

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

QTc prolongation after aneurysmal subarachnoid hemorrhage might be associated with worse neurologic outcome in patients receiving microsurgical clipping or embolization of the intracranial aneurysms: a retrospective observational study.

PURPOSE: QT interval prolongation is one of the most common electrocardiographic (ECG) abnormalities in patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether corrected QT interval (QTc) prolongation is associated with perioperative cardiac events and dismal neurological outcome in mid to long-term follow-up in patients after aSAH is insufficiently studied and remains controversial. METHODS: We retrospectively studied the adult (≥ 18 years) patients admitted to our institution between Jan 2018 and Dec 2020 for aSAH who underwent intracranial aneurysm clipping or embolization. The patients were divided into 2 groups (normal and QTc prolongation groups) according to their QTc. To minimize the confounding bias, a propensity score matching (PSM) analysis was performed to compare the neurologic outcomes between patients with normal QTc and QTc prolongation. RESULTS: After screening, 908 patients were finally included. The patients were divided into 2 groups: normal QTc groups (n = 714) and long QTc group (n = 194). Female sex, hypokalemia, posterior circulation aneurysm, and higher Hunt-Hess grade were associated with QTc prolongation. In multiple regression analysis, older age, higher hemoglobin level, posterior circulation aneurysm, and higher Hunt-Hess grade were identified to be associated with worse outcome during 1-year follow-up. Before PSM, patients with QTc prolongation had higher rate of perioperative cardiac arrest or ventricular arrhythmias. After PSM, there was no statistical difference between normal and QTc prolongation groups in perioperative cardiac events. However, patients in the QTc prolongation group still had worse neurologic outcome during 1-year follow-up. CONCLUSIONS: QTc prolongation is associated with worse outcome in patients following SAH, which is independent of perioperative cardiac events.

An SSVEP-based BCI with 112 targets using frequency spatial multiplexing.

Objective.Brain-computer interface (BCI) systems with large directly accessible instruction sets are one of the difficulties in BCI research. Research to achieve high target resolution (⩾100) has not yet entered a rapid development stage, which contradicts the application requirements. Steady-state visual evoked potential (SSVEP) based BCIs have an advantage in terms of the number of targets, but the competitive mechanism between the target stimulus and its neighboring stimuli is a key challenge that prevents the target resolution from being improved significantly.Approach.In this paper, we reverse the competitive mechanism and propose a frequency spatial multiplexing method to produce more targets with limited frequencies. In the proposed paradigm, we replicated each flicker stimulus as a 2 × 2 matrix and arrange the matrices of all frequencies in a tiled fashion to form the interaction interface. With different arrangements, we designed and tested three example paradigms with different layouts. Further we designed a graph neural network that distinguishes between targets of the same frequency by recognizing the different electroencephalography (EEG) response distribution patterns evoked by each target and its neighboring targets.Main results.Extensive experiment studies employing eleven subjects have been performed to verify the validity of the proposed method. The average classification accuracies in the offline validation experiments for the three paradigms are 89.16%, 91.38%, and 87.90%, with information transfer rates (ITR) of 51.66, 53.96, and 50.55 bits/min, respectively.Significance.This study utilized the positional relationship between stimuli and did not circumvent the competing response problem. Therefore, other state-of-the-art methods focusing on enhancing the efficiency of SSVEP detection can be used as a basis for the present method to achieve very promising improvements.

CARMA3 Drives NF-κB Activation and Promotes Intervertebral Disc Degeneration: Involvement of CARMA3-BCL10-MALT1 Signalosome.

Intervertebral disc degeneration (IDD) diseases are common and frequent diseases in orthopedics. The caspase recruitment domain (CARD) and membrane-associated guanylate kinase-like protein 3 (CARMA3) is crucial in the activation of the NF-κB pathway. However, the biological function of CARMA3 in IDD remains unknown. Here, CARMA3 expression was elevated in nucleus pulposus (NP) tissues of IDD rats and nutrient deprivation (ND)-induced NP cells. The main pathological manifestations observed in IDD rats were shrinkage of the NP, reduction of NP cells, fibrosis of NP tissues, and massive reduction of proteoglycans. These changes were accompanied by a decrease in the expression of collagen II and aggrecan, an increase in the expression of the extracellular matrix (ECM) catabolic proteases MMP-3, MMP-13, and metalloprotease with ADAMTS-5, and an increase in the activity of the pro-apoptotic protease caspase-3. The expression of p-IκBαSer32/36 and p-p65Ser536 was also upregulated. However, these effects were reversed with the knockdown of CARMA3. Mechanistically, CARMA3 bound to BCL10 and MALT1 to form a signalosome. Knockdown of CARMA3 reduced the CARMA3-BCL10-MALT1 signalosome-mediated NF-κB activation. CARMA3 activated the NF-κB signaling pathway in a manner that bound to BCL10 and MALT1 to form a signalosome, which affects NP cell damage and is involved in the development of IDD. This supports CARMA3-BCL10-MALT1-NF-κB as a promising targeting axis for the treatment of IDD.

A self-elastic chitosan sponge integrating active and passive hemostatic mechanisms for effectively managing uncontrolled coagulopathic hemorrhage.

Developing a self-elastic sponge integrating active and passive hemostatic mechanisms for the effective management of uncontrolled coagulopathic hemorrhage remains a challenge. We here developed a chitosan-based sponge by integrating freeze-drying, chemical decoration of alkyl chains and phosphate groups, and physical loading of thrombin. The sponge exhibited high mechanical strength, self-elasticity, and rapid shape recovery. The sponge facilitated blood cell adhesion, aggregation, and activation through hydrophobic and electrostatic interactions, as well as accelerated blood clotting. The sponge exhibited higher efficacy than commercial gauze and gelatin sponge in managing uncontrolled hemorrhage from heparinized rat tail amputation, liver superficial injury, and liver perforating wound models. In addition, the sponge exhibited favorable biodegradability and biocompatibility. These findings revealed that the developed sponge holds great potential as a novel hemostat for effectively managing uncontrolled coagulopathic hemorrhage from superficial and perforating wounds.

A novel combined therapeutic strategy of Nano-EN-IR@Lip mediated photothermal therapy and stem cell inhibition for gastric cancer.

Recurrence and metastasis of gastric cancer is a major therapeutic challenge for treatment. The presence of cancer stem cells (CSCs) is a major obstacle to the success of current cancer therapy, often leading to treatment resistance and tumor recurrence and metastasis. Therefore, it is important to develop effective strategies to eradicate CSCs. In this study, we developed a combined therapeutic strategy of photothermal therapy (PTT) and gastric cancer stem cells (GCSCs) inhibition by successfully synthesizing nanoliposomes loaded with IR780 (photosensitizer) and EN4 (c-Myc inhibitor). The nanocomposites are biocompatible and exhibit superior photoacoustic (PA) imaging properties. Under laser irradiation, IR780-mediated PTT effectively and rapidly killed tumor cells, while EN4 synergistically inhibited the self-renewal and stemness of GCSCs by suppressing the expression and activity of the pluripotent transcription factor c-Myc, preventing the tumor progression of gastric cancer. This Nano-EN-IR@Lip is expected to be a novel clinical nanomedicine for the integration of gastric cancer diagnosis, treatment and prevention.

Realization of sextuple polarization states and interstate switching in antiferroelectric CuInP2S6.

Realization of higher-order multistates with mutual interstate switching in ferroelectric materials is a perpetual drive for high-density storage devices and beyond-Moore technologies. Here we demonstrate experimentally that antiferroelectric van der Waals CuInP2S6 films can be controllably stabilized into double, quadruple, and sextuple polarization states, and a system harboring polarization order of six is also reversibly tunable into order of four or two. Furthermore, for a given polarization order, mutual interstate switching can be achieved via moderate electric field modulation. First-principles studies of CuInP2S6 multilayers help to reveal that the double, quadruple, and sextuple states are attributable to the existence of respective single, double, and triple ferroelectric domains with antiferroelectric interdomain coupling and Cu ion migration. These findings offer appealing platforms for developing multistate ferroelectric devices, while the underlining mechanism is transformative to other non-volatile material systems.

Manipulating the processing window of directed self-assembly in contact hole shrinking with binary block copolymer/homopolymer blending.

Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

Analysis of adjacent vertebral fracture after percutaneous vertebroplasty: do radiological or surgical features matter?

PURPOSE: To report the incidence and risk factors of adjacent vertebral fracture (AVF) after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fractures (OVCFs). We focused to investigate effect of radiological or surgical features on AVF. METHODS: All patients with OVCFs who were treated with PVP between January 2016 and December 2019 were retrospectively reviewed. Patients were followed up at least 12 months after procedure according to treatment protocol. AVF was defined as postoperatively recurrent intractable back pain and subsequently presence of fracture on magnetic resonance imaging (MRI) in adjacent levels. Clinical, radiological, and surgical factors potentially affecting occurrence of AVF were recorded and analyzed using univariate and multivariate analysis. RESULTS: Totally, 1077 patients with 1077 fractured vertebrae who underwent PVP were enrolled in the study, after inclusion and exclusion criteria were met. Mean follow-up time was 24.3 ± 11.9 months (range, 12-59 months). AVF was identified in 98 (9.1%) patients. Univariate analysis showed that seven significant factors related to AVF were older age, non-traumatic fracture, cortical disruption on anterior wall, cortical disruption on lateral wall, basivertebral foramen, type-B leakage and type-C leakage. In multivariate analysis, two clinical factors, older age (P = 0.031) and non-traumatic fracture (P = 0.002), were significantly associated with AVF. However, any radiological or surgical factor did not reach significance in final model analysis. CONCLUSIONS: Incidence of AVF after PVP in patients with OVCFs was 9.1% (98/1077). Older age and non-traumatic fracture were two clinical risk factors for AVF. Neither radiological nor surgical feature was significantly correlated with AVF.

Tonguedness in speech: Lateral bias in lingual bracing.

This study examines the lateral biases in tongue movements during speech production. It builds on previous research on asymmetry in various aspects of human biology and behavior, focusing on the tongue's asymmetric behavior during speech. The findings reveal that speakers have a pronounced preference toward one side of the tongue during lateral releases with a majority displaying the left-side bias. This lateral bias in tongue speech movements is referred to as tonguedness. This research contributes to our understanding of the articulatory mechanisms involved in tongue movements and underscores the importance of considering lateral biases in speech production research.

Kled: an ultra-fast and sensitive structural variant detection tool for long-read sequencing data.

Structural Variants (SVs) are a crucial type of genetic variant that can significantly impact phenotypes. Therefore, the identification of SVs is an essential part of modern genomic analysis. In this article, we present kled, an ultra-fast and sensitive SV caller for long-read sequencing data given the specially designed approach with a novel signature-merging algorithm, custom refinement strategies and a high-performance program structure. The evaluation results demonstrate that kled can achieve optimal SV calling compared to several state-of-the-art methods on simulated and real long-read data for different platforms and sequencing depths. Furthermore, kled excels at rapid SV calling and can efficiently utilize multiple Central Processing Unit (CPU) cores while maintaining low memory usage. The source code for kled can be obtained from https://github.com/CoREse/kled.

The role of personal, relational, and collective self-esteem in predicting acute salivary cortisol response and perceived stress.

Personal self-esteem (PSE) has been well recognized as a buffer against stress; however, the effects of other types of self-esteem, such as relational self-esteem (RSE) and collective self-esteem (CSE), on stress have not been adequately explored. This study investigated the roles of PSE, RSE, and CSE in reducing stress response. The Rosenberg, Relational, and Collective Self-Esteem Scales were adopted to assess PSE, RSE, and CSE, respectively. Participants underwent an acute social stress paradigm, and their acute stress response was assessed using subjective stress reports and salivary cortisol levels. Chronic stress level was estimated using the Perceived Stress Scale and hair cortisol concentration. The results showed that PSE was negatively correlated with salivary cortisol response during acute social stress; however, no significant associations were found between any type of self-esteem and subjective stress reports. For chronic stress, all types of self-esteem were negatively associated with perceived stress level, but not with hair cortisol concentration. Further hierarchical regression analyses suggested that only PSE negatively predicted acute salivary cortisol response and perceived stress level. Overall, the findings suggest the essential role of PSE in predicting acute salivary cortisol responses and perceived stress.

Optical Modulation of MoTe2/Ferroelectric Heterostructure via Interface Doping.

Optical modulation through interface doping offers a convenient and efficient way to control ferroelectric polarization, thereby advancing the utilization of ferroelectric heterostructures in nanoelectronic and optoelectronic devices. In this work, we fabricated heterostructures of MoTe2/BaTiO3/La0.7Sr0.3MnO3 (MoTe2/BTO/LSMO) and demonstrated opposite ultraviolet (UV) light-induced polarization switching behaviors depending on the varied thicknesses of MoTe2. The thickness-dependent band structure of MoTe2 film results in interface doping with opposite polarity in the respective heterostructures. The polarization field of BTO interacts with the interface charges, and an enhanced effective built-in field (Ebi) can trigger the transfer of massive UV light-induced carriers in both MoTe2 and BTO films. As a result, the interplay among the contact field of MoTe2/BTO, the polarization field, and the optically excited carriers determines the UV light-induced polarization switching behavior of the heterostructures. In addition, the electric transport characteristics of MoTe2/BTO/LSMO heterostructures reveal the interface barrier height and Ebi under opposite polarization states, as well as the presence of inherent in-gap trap states in MoTe2 and BTO films. These findings represent a further step toward achieving multifield modulation of the ferroelectric polarization and promote the potential applications in optoelectronic, logic, memory, and synaptic ferroelectric devices.

Quantitative label-free proteomic analysis of excretory-secretory proteins in different developmental stages of Trichinella spiralis.

Trichinella spiralis (T. spiralis) is a zoonotic parasitic nematode with a unique life cycle, as all developmental stages are contained within a single host. Excretory-secretory (ES) proteins are the main targets of the interactions between T. spiralis and the host at different stages of development and are essential for parasite survival. However, the ES protein profiles of T. spiralis at different developmental stages have not been characterized. The proteomes of ES proteins from different developmental stages, namely, muscle larvae (ML), intestinal infective larvae (IIL), preadult (PA) 6 h, PA 30 h, adult (Ad) 3 days post-infection (dpi) and Ad 6 dpi, were characterized via label-free mass spectrometry analysis in combination with bioinformatics. A total of 1217 proteins were identified from 9341 unique peptides in all developmental stages, 590 of which were quantified and differentially expressed. GO classification and KEGG pathway analysis revealed that these proteins were important for the growth of the larvae and involved in energy metabolism. Moreover, the heat shock cognate 71 kDa protein was the centre of protein interactions at different developmental stages. The results of this study provide comprehensive proteomic data on ES proteins and reveal that these ES proteins were differentially expressed at different developmental stages. Differential proteins are associated with parasite survival and the host immune response and may be potential early diagnostic antigen or antiparasitic vaccine candidates.

Imidazolium-Based Main-Chain Copolymers With Alternating Sequences for Broad-Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms.

In response to the escalating challenge of bacterial drug resistance, the imperative to counteract planktonic cell proliferation and eliminate entrenched biofilms underscores the necessity for cationic polymeric antibacterials. However, limited efficacy and cytotoxicity challenge their practical use. Here, novel imidazolium-based main-chain copolymers with imidazolium (PIm+) as the cationic component are introduced. By adjusting precursor molecules, hydrophobicity and cationic density of each unit are fine-tuned, resulting in broad-spectrum bactericidal activity against clinically relevant pathogens. PIm+1 stands out for its potent antibacterial performance, with a minimum inhibitory concentration of 32 µg mL-1 against Methicillin-resistant Staphylococcus aureus (MRSA), and substantial biofilm reduction in Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms. The bactericidal mechanism involves disrupting the outer and cytoplasmic membranes, depolarizing the cytoplasmic membrane, and triggering intracellular reactive oxygen species (ROS) generation. Collectively, this study postulates the potential of imidazolium-based main-chain copolymers, systematically tailored in their sequences, to serve as a promising candidate in combatting drug-resistant bacterial infections.